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The association between the reduction of body weight and new-onset type 2 diabetes remission in middle-aged Japanese men Population-based Panasonic cohort study 8.

This study aimed to investigate the association between change in body weight (BW) and type 2 diabetes remission in Japanese men with new-onset type 2 diabetes. This study enrolled 1,903 patients with new-onset type 2 diabetes between 2008 and 2013 from a medical health checkup program conducted by the Panasonic Corporation, Osaka, Japan. The baseline was defined as the year of new-onset diabetes. We assessed the type 2 diabetes remission five years after baseline and the association between the change in BW and type 2 diabetes remission using logistic regression analyses. To evaluate the predictive performance of the change in BW, we employed the receiver operating characteristic curves and the area under the receiver operating characteristic (ROC) curve (AUC). The BW loss was associated with type 2 diabetes remission in the participants with a BMI ≥25 kgm Body weight loss of ≥5% effectively achieved diabetes remission in Japanese men with a BMI ≥25 kgm

Management of Type 2 Diabetic Kidney Disease in 2022 A Narrative Review for Specialists and Primary Care.

Kidney disease is present in almost half of Canadian patients with type 2 diabetes (T2D), and it is also the most common first cardiorenal manifestation of T2D. Despite clear guidelines for testing, opportunities are being missed to identify kidney diseases, and many Canadians are therefore not receiving the best available treatments. This has become even more important given recent clinical trials demonstrating improvements in both kidney and cardiovascular (CV) endpoints with sodium-glucose cotransporter 2 (SGLT2) inhibitors and a nonsteroidal mineralocorticoid receptor antagonist, finerenone. The goal of this document is to provide a narrative review of the current evidence for the treatment of diabetic kidney disease (DKD) that supports this new standard of care and to provide practice points. An expert panel of Canadian clinicians was assembled, including 9 nephrologists, an endocrinologist, and a primary care practitioner. The information the authors used for this review consisted of published clinical trials and guidelines, selected by the authors based on their assessment of their relevance to the questions being answered. Panelists met virtually to discuss potential questions to be answered in the review and agreed on 10 key questions. Two panel members volunteered as co-leads to write the summaries and practice points for each of the identified questions. Summaries and practice points were distributed to the entire author list by email. Through 2 rounds of online voting, a second virtual meeting, and subsequent email correspondence, the authors reached consensus on the contents of the review, including all the practice points. It is critical that DKD be identified as early as possible in the course of the disease to optimally prevent disease progression and associated complications. Patients with diabetes should be routinely screened for DKD with assessments of both urinary albumin and kidney function. Treatment decisions should be individualized based on the risks and benefits, patients needs and preferences, medication access and cost, and the degree of glucose lowering needed. Patients with DKD should be treated to achieve targets for A1C and blood pressure. Renin-angiotensin-aldosterone system blockade and treatment with SGLT2 inhibitors are also key components of the standard of care to reduce the risk of kidney and CV events for these patients. Finerenone should also be considered to further reduce the risk of CV events and chronic kidney disease progression. Education of patients with diabetes prescribed SGLT2 inhibitors andor finerenone is an important component of treatment. No formal guideline process was used. The practice points are not graded and are not intended to be viewed as having the weight of a clinical practice guideline or formal consensus statement. However, most practice points are well aligned with current clinical practice guidelines. L’insuffisance rénale est présente chez près de la moitié des patients canadiens atteints de diabète de type 2 (DT2). Il s’agit également de la première manifestation cardiorénale la plus fréquente du DT2. Bien qu’il existe des lignes directrices claires pour son dépistage, des occasions de diagnostiquer l’insuffisance rénale sont manquées, ce qui fait en sorte que de nombreux Canadiens ne reçoivent pas les meilleurs traitements disponibles. Cette préoccupation a pris de l’importance puisque de récents essais cliniques ont démontré des améliorations dans les paramètres rénaux et cardiovasculaires (CV) avec la prise de finérénone, un antagoniste non stéroïdien des récepteurs minéralocorticoïdes (nsMRA), et d’inhibiteurs du cotransporteur de glucose de sodium 2 (SGLT2). L’objectif de cet article est de fournir une revue narrative des données probantes actuelles appuyant cette nouvelle norme de soins pour le traitement de l’insuffisance rénale diabétique (IRD), ainsi que des points de pratique. Un groupe d’experts composé de cliniciens canadiens, dont neuf néphrologues, un endocrinologue et un prestataire de soins primaires, a été formé. Les auteurs de cette revue ont utilisé des lignes directrices et des essais cliniques publiés comme sources ceux-ci ont été choisis sur la base d’une évaluation de leur pertinence pour les questions auxquelles ils avaient répondu. Les panélistes se sont réunis virtuellement pour discuter de potentielles questions à répondre dans le cadre de cette revue, et se sont entendus sur dix questions clés. Deux membres du panel se sont portés volontaires pour être co-responsables et rédiger les résumés et les points de pratique pour chacune des questions identifiées. Ces derniers ont été distribués par courriel à l’ensemble des auteurs. Après deux tours de vote en ligne, une deuxième réunion virtuelle et la correspondance électronique qui a suivi, les auteurs sont parvenus à un consensus sur le contenu de la revue narrative, y compris sur tous les points de pratique. Il est essentiel que l’IRD soit diagnostiquée le plus tôt possible afin de prévenir de façon optimale la progression de la maladie et les complications qui y sont associées. On devrait procéder au dépistage systématique de l’IRD chez les patients diabétiques par l’évaluation de l’albumine urinaire ET de la fonction rénale. Les décisions relatives au traitement devraient être individualisées en fonction des risques et des avantages pour le patient, de ses besoins et préférences, de l’accès aux médicaments et des coûts, ainsi que du degré nécessaire de réduction de la glycémie. Les patients atteints d’IRD devraient être traités pour atteindre les cibles d’A1c et de pression artérielle. Le blocage du SRAA et le traitement avec des inhibiteurs du SGLT2 sont également des composantes clés de la norme de soins visant à réduire le risque d’événements rénaux et CV pour ces patients. La finérénone devrait également être envisagée pour réduire encore davantage les risques d’événements CV et de progression vers l’IRC. L’éducation des patients diabétiques auxquels on prescrit des inhibiteurs du SGLT2 etou de la finérénone est un élément important du traitement. Aucun processus officiel de directives n’a été utilisé. Les points de pratique ne sont pas notés et ne sont pas destinés à être considérés comme ayant le poids d’une directive de pratique clinique ou d’une déclaration de consensus officielle. Cependant, la plupart des points de pratique sont bien alignés avec les lignes directrices actuelles de pratique clinique.

Direct comparison two fixed-ratio combination glucagon-like peptide receptor agonist and basal insulin on glycemic and non glycemic parameters in type 2 diabetes.

Two types of fixed-ratio combinations of basal insulin and a glucagon-like peptide-1 receptor agonist (GLP-1RA) have been approved for use in type 2 diabetes. One is insulin degludecliraglutide (iDergLira), and the other is insulin glarginelixisenatide (iGlarLixi). Direct comparisons between these two combination is not available. The retrospective study included 186 patients with type 2 diabetes mellitus (DM) with inadequate glycemic control on metformin and basal insulin (degludec, glargine 100, glargine 300) who were switched to fixed-ratio combination GLP-1 RA and basal insulin. Patients were divided into two groups based on the basal insulin before study group I (n 86) treated with degludec were switched to iDegLira and patients group II (n 99), treated with glargine were switched to iGlarLixi. The aim of this study was to directly compare the effects between two fixed - ratio combination on glycemic parameters and non glycemic parameters. Follow up was 6 months. Mean HbA1c decreased similarly (- 1.2% vs.-1.1%). Higher percentage patients in iDegLira group had reached the HbA1c < 7% after 6 months (22% vs. 18.2%, p < 0.05). The mean change in fasting plasma glucose (FPG) was comparable for the two groups, while mean decrease postprandial plasma glucose (PPG) level were lower in iGlarLixi group (2 vs 1.8 mmoll, p > 0.05). Change in body weight was significant in iDegLira group (1.8 kg vs. 0.7 kg, p < 0.001). At the end of the study patients showed decrease in total cholesterol (TC) and low-density lipoprotein (LDL) for 0.2 mmolL in iDegLira, 0.1 mmoll in iGlarLixi, triglycerides decreased 0.3 mmoll in both groups, high-density lipoprotein(HDL) increased 0.1 mml in iGlarLixi. Our results showed that more patients with iDegLira had HbA1c less than 7% and these combination had better effect on weight loss. There was no difference observed in FPG and PPG, lipid profile and rate of hypoglycemia.

Long-Term High-Fat Diet Decreases Renal Insulin-Degrading Enzyme Expression and Function by Inhibiting the PPARγ Pathway.

Long-term high-fat diet (HFD) causes insulin resistance, which is a primary etiological factor in the development of obesity and type 2 diabetes mellitus. Impaired insulin clearance is not only a consequence but also a cause of insulin resistance. The kidney is a major site of insulin clearance, where the insulin-degrading enzyme (IDE) plays a vital role in the proximal tubule. Thus, we investigated the role of renal IDE in the regulation of insulin resistance in HFD-induced obese mice. 24-weeks of HFD in C57BL6 mice caused insulin resistance and impaired insulin clearance, accompanied by a decrease in renal IDE expression and activity. Palmitic acid decreased IDE mRNA and protein expressions in HK-2 cells. RNA-Seq analysis found that the PPAR pathway is involved. 24-weeks of HFD decreased renal PPARγ, but not PPARα or PPARβδ mRNA expression. The inhibition of IDE expression by palmitic acid was prevented by the PPARγ agonist rosiglitazone. The amount of PPARγ bound to the promoters of IDE was decreased in palmitic acid-treated cells. Rosiglitazone improved insulin clearance and insulin resistance and increased renal IDE expression in HFD fed-mice. Long-term HFD decreases renal IDE expression and activity, and causes insulin resistance, which involves PPARγ. This article is protected by copyright. All rights reserved.

Effect of duodenal-jejunal bypass on diabetes in the early postoperative period.

Metabolic surgery is an effective treatment for patients with type 2 diabetes mellitus (T2DM). The aim of this study was to investigate the effect of duodenal-jejunal bypass (DJB) in a rat model of T2DM during the early postoperative period. A rat model of non-obese T2DM was allocated to two groups a sham group and a DJB group. On postoperative day 1 (1POD), oral glucose tolerance testing (OGTT) was performed and the changes of glucose transporter expressions in the small intestine was evaluated. 18F-fluorodeoxyglucose (18-FDG) uptake was measured in sham- and DJB-operated rats using positron emission tomography-computed tomography (PET-CT). DJB improved the glucose tolerance of the rats on 1POD. The expression of sodium-glucose cotransporter 1 (SGLT1) and glucose transporter 1 (GLUT1) was high, and that of GLUT2 was low in the alimentary limb (AL) of rats in the DJB group. PET-CT showed that 18F-FDG uptake was high in the proximal jejunum of DJB-operated rats. These results may show that DJB improve glucose tolerance in very early postoperative period as the result of glucose accumulation in the AL because of changes in glucose transporter expression.

Synthesis of new diphenyl urea-clubbed imine analogs and its Implications in diabetic management through in vitro and in silico approaches.

Type II diabetes mellitus (T2DM) is a global health issue with high rate of prevalence. The inhibition of α-glucosidase enzyme has prime importance in the management of T2DM. This study was established to synthesize Schiff bases of 1,3-dipheny urea (3a-y) and to investigate their in vitro anti-diabetic capability via inhibiting α-glucosidase, a key player in the catabolism of carbohydrates. The structures of all compounds were confirmed through various techniques including, Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) and mass-spectrometry (MS) methods. Interestingly all these compounds displayed potent inhibition IC

An Attempt to Replicate Randomized Trials of Diabetes Treatments Using a Japanese Administrative Claims and Health Checkup Database A Feasibility Study.

Use of real-world evidence (RWE) has been limited for evaluating effectiveness because of the lack of confidence in its reliability. Examining whether a rigorously designed observational study using real-world data (RWD) can reproduce the results of a randomized controlled trial (RCT) will provide insights into the implementation of high-quality RWE studies that can produce valid conclusions. We aimed to replicate published RCTs using a Japanese claims and health checkup database and examine whether the emulated RWE studies results agree with those of the original RCTs. We selected three RCTs on diabetes medications for replication in patients with type 2 diabetes. The study outcome was either the change or percentage change in HbA1c levels from baseline. We designed three observational studies using the RWD to mimic the critical study elements of the respective RCTs as closely as possible. We performed 11 propensity score nearest-neighbor matching to balance the groups for potential confounders. The differences in outcomes between the groups and their 95% confidence intervals (CIs) were calculated in each RWE study, and the results were compared with those of the RCT. Patient characteristics, such as age, sex, and duration of diabetes, differed between the RWE studies and RCTs. In Trial 1 emulation, the percentage changes in HbA1c levels were larger in the treatment group than in the comparator group (difference -6.21, 95% confidence interval (CI) -11.01 to -1.40). In Trial 2, the change in HbA1c level was larger in the treatment group (difference -0.01 95% CI -0.25 to 0.23), and in Trial 3, it was smaller in the treatment group (difference 0.46 95% CI -0.01 to 0.94). These results did not show regulatory or estimate agreement with the RCTs. None of the three emulated RWE studies using this claims and health checkup database reproduced the same conclusions as the RCTs. These discrepancies could largely be attributed to design differences between RWE studies and RCTs, primarily due to the lack of necessary data in the database. This particular RWD source may not be the best fit for evaluating treatment effects using laboratory data as the study outcome.

Association of non-alcoholic fatty liver disease with total testosterone in non-overweightobese men with type 2 diabetes mellitus.

Non-alcoholic fatty liver disease (NAFLD) is considered as both a vital risk factor and a consequence of type 2 diabetes mellitus (T2DM). Low total testosterone (TT) is common in men with T2DM, contributing to increased risks of metabolic diseases. This study aimed to investigate the association between TT levels and the prevalence of NAFLD in men with T2DM. In this cross-sectional study, 1005 men with T2DM were enrolled in National Metabolic Management Center (MMC) of First Affiliated Hospital of Wenzhou Medical University between January 2017 and August 2021. NAFLD was diagnosed using ultrasound as described by the Chinese Liver Disease Association. Overweightobesity was defined as body mass index (BMI) ≥ 25 kgm Individuals without NAFLD had higher serum TT levels than those with NAFLD. After adjustments for potential confounding factors, the top tertile was significantly associated with lower prevalence of NAFLD compared with the bottom tertile of TT level odds ratio (OR) 0.303, 95% confidence interval (CI) 0.281-0.713 P < 0.001. The association between TT with NAFLD in individuals with normal weight (OR 0.175, 95% CI 0.098-0.315 P < 0.001) was stronger than in individuals with overweightobesity (OR 0.509, 95% CI 0.267-0.971 P 0.040). There was a significant interaction of TT with overweightobesity (P for interaction 0.018 for NAFLD). Higher serum TT was significantly associated with a lower prevalence of NAFLD in men with T2DM. We found that the relationship of TT and NAFLD was stronger in individuals with non-overweightobesity.

Effects of Ramadan Fasting on Glycaemic Control Among Patients with Type 2 Diabetes Systematic Review and Meta-analysis of Observational Studies.

The prevalence of type 2 diabetes (T2D) is increasing around the world. Although Muslims with a physical illness are exempted from fasting during the month of Ramadan, a great number still choose to fast, often without medical consultations. The aim of this systematic review and meta-analysis was to investigate the impact of observing Ramadan fasting (RF) on glycaemic control in patients with T2D. The Web of Science, Scopus, EBSCOhost, CINAHL, ScienceDirect, Cochrane Library, ProQuest Central and Europe PubMed Central (Medline) databases were searched for relevant studies published between January 2000 and December 2021. Observational studies that examined the changes in body weight (BW) and glucose parameters (glycosylated haemoglobin HbA1c and fasting blood glucose FBG), before and after RF among different age groups with T2D were included in the systemic review and meta-analysis. Effect sizes for the tested outcomes were calculated as weighted mean difference (WMD), with their confidence intervals (CI). Quality assessment was examined using the National Heart, Lung, and Blood Institute (NHLBI) tool. Of the 1592 identified records, 12 studies conducted in Middle Eastern and Asian countries were eligible and included in the quantitative analyses. The quality of the retrieved studies was evaluated and found to range between fair (83%) and good (17%). These 12 studies included 5554 participants of whom 54% were males and 46% were females. Our pooled analysis demonstrated that HbA1c and FBG levels significantly decreased after RF when compared to the pre-fasting levels (WMD 0.55 mgdl, 95% CI 0.33-0.77, P < 0.00001, Ι The impact of RF on adult patients with T2D is associated with favorable outcomes. However, future studies should evaluate data from young adults separately. In addition, it is essential to identify the effects of the number of fasting days (level of exposure), diet, level of physical activity and sleeping pattern on optimal glycaemic control. This information could be utilized by medical professionals as a non-pharmacological therapeutic method for management of diabetes in patients who are willing to practice fasting during Ramadan and other months of the year. PROSPERO CRD42022314752.

Endoscopic management of obesity Impact of endoscopic sleeve gastroplasty on weight loss and co-morbidities at six months and one year.

Endoscopic sleeve gastroplasty (ESG) is one of the new minimally invasive endoscopic treatments aimed at inducing weight loss. Its effectiveness in terms of weight loss is proven. Gastric volume reduction and delayed gastric emptying are the mechanisms that drive weight loss. However, potential benefits for co-morbidities in relation to weight loss after ESG are still being investigated. This study aims to evaluate the effect of ESG procedures on major obesity-associated co-morbidities, and on some biological parameters. This is a series of consecutive cases from a prospective observational study carried out in a specialized center that follows a standardized care pathway for the multimodal management of obesity. Patients who have undergone ESG with endoscopic and laboratory follow-up at six and twelve months after this intervention were included in the study. Prospectively recorded data on weight loss, co-morbidities and laboratory parameters at six and twelve months after surgery was analyzed retrospectively. Changes in body mass index (BMI), absolute weight loss (AWL), percent of excess weight loss (%EWL) and percent total weight loss (%TWL) were assessed at six and twelve months. Reduction in various obesity-related co-morbidities (arterial hypertension AHT, type 2 diabetes mellitus T2DM, gastroesophageal reflux disease GERD, obstructive sleep apnea syndrome OSAS and dyslipidemia was also evaluated at six and twelve months. Changes in blood glucose, liver function tests and lipid blood tests were also analyzed at six and twelve months. From October 2016 to July 2021, 99 of the 227 patients who underwent ESG in our unit (43.6%) subsequently underwent a complete endoscopic and laboratory follow-up at six and twelve months. The initial BMI was 42.7±7.8kgm ESG is a well-tolerated and safe surgical procedure that is effective in terms of weight loss and reduction of obesity-related co-morbidities at six months and one year. This procedure could thus be adopted on a broader clinical scale and be more widely promoted as an effective treatment for morbid obesity.

Obesity surgery Which procedure should we choose and why

In the 70years that bariatric surgery has existed, many different surgical procedures have been developed. Four procedures are officially accepted by all learned societies adjustable gastric banding (AGB), sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB) and bilio-pancreatic diversion (BPD). Gastric banding has the lowest short-term surgical risk, but it has the highest re-operation rate. Compared to SG, RYGB presents about twice the risk of early complications. Late complications seem equivalent between the two procedures but studies with follow-up>10years are rarer for SG. SG has become the most commonly performed bariatric procedure worldwide, followed by RYGB, which is still the standard. BPD remains very marginal but the omega gastric bypass, an alternative technique that is still under evaluation, now competes with RYGB. The effectiveness of these different procedures on weight loss remains difficult to compare. SG and RYGB seem to be equivalent for weight loss results and remission of type-2 diabetes (T2DM). Their results are superior to AGB. Procedures that result in greater lengths of intestinal bypass (bilio-pancreatic diversion, omega bypass) seem to have a greater weight-loss effect but are burdened by more side effects. In conclusion, the choice of a procedure is conditioned firstly by the benefit-risk ratio and in relation to patient-related parameters, particularly the body mass index (BMI) and co-morbidities. Long-term results are also linked to factors other than surgery and in particular patient behavioral factors. Obesity is a chronic disease that indicates the need for real long-term medical and surgical management.

Zuogui Jiangtang Qinggan Prescription promotes recovery of intestinal mucosal barrier in mice with type 2 diabetes mellitus and nonalcoholic fatty liver disease by improving intestinal flora homeostasis.

This study aimed to investigate the recovery effect of Zuogui Jiangtang Qinggan Prescription on intestinal flora homeostasis control and intestinal mucosal barrier in type 2 diabetes mellitus(T2DM) with nonalcoholic fatty liver disease(NAFLD) induced by a high-fat diet. NAFLD was established in MKR transgenic mice(T2DM mice) by a high-fat diet(HFD), and subsequently treated for 8 weeks with Zuogui Jiangtang Qinggan Prescription(7.5, 15 g·kg(-1)) and metformin(0.067 g·kg(-1)). Triglyceride and liver function were assessed using serum. The hematoxylin-eosin(HE) staining and Masson staining were used to stain the liver tissue, while HE staining and AB-PAS staining were used to stain the intestine tissue. 16S rRNA sequencing was utilized to track the changes in the intestinal flora of the mice in each group. Polymerase chain reaction(PCR) and immunofluorescence were used to determine the protein and mRNA expression levels of ZO-1, Occludin, and Claudin-1. The results demonstrated that Zuogui Jiangtang Qinggan Prescription increased the body mass of T2DM mice with NAFLD and decreased the hepatic index. It down-regulated the serum biomarkers of liver function and dyslipidemia such as alanine aminotransferase(ALT), aspartate transaminase(AST), and triglycerides(TG), increased insulin sensitivity, and improved glucose tolerance. According to the results of 16S rRNA sequencing, the Zuogui Jiangtang Qinggan Prescription altered the composition and abundance of the intestinal flora, increasing the relative abundances of Muribaculaceae, Lactobacillaceae, Lactobacillus, Akkermansia, and Bacteroidota and decreasing the relative abundances of Lachnospiraceae, Firmicutes, Deslfobacteria, Proteobacteria, and Desulfovibrionaceae. According to the pathological examination of the intestinal mucosa, Zuogui Jiangtang Qinggan Prescritpion increased the expression levels of the tight junction proteins ZO-1, Occludin, and Claudin-1, promoted intestinal mucosa repair, protected intestinal villi, and increased the height of intestinal mucosa villi and the number of goblet cells. By enhancing intestinal mucosal barrier repair and controlling intestinal microbiota homeostasis, Zuogui Jiangtang Qinggan Prescription reduces intestinal mucosal damage induced by T2DM and NAFLD.

Association between haemoglobin A

What is the central question of this study Is the impairment in heat dissipation during exercise observed in men with type 2 diabetes related to glycaemic control (indexed by glycated haemoglobin haemoglobin A Type 2 diabetes is associated with a reduced capacity to dissipate heat. It is unknown whether this impairment is related to glycaemic control (indexed by glycated haemoglobin haemoglobin A

Retrospective Analysis of Hospitalized Patients with Type 2 Diabetes Mellitus Treated with Glucagon-Like Peptide 1 Receptor Agonist Therapy.

The use and overall benefit of glucagon-like peptide-1 (GLP-1) receptor agonist therapy for hospitalized patients with type 2 diabetes mellitus (DM) with chronic kidney disease (CKD) has limited data regarding impact and safety. We studied the impact and safety of GLP-1 receptor agonist therapy in hospitalized DM patients with CKD. Retrospective study of 51 patients using either dulaglutide (n 3) or liraglutide (n 48). Glomerular filtration rate (GFR) groups of stages 3 to 5 and 1 and 2 were compared. The primary outcome was total amount of insulin within the last 24 hours in the hospital. The secondary outcomes were glucose management and safety. Mean insulin total amount within the last 24 hours in the hospital significantly differed ( The use of GLP-1 receptor agonist therapy had better outcomes in patients with GFR stages 3 to 5 as compared with GFR stages 1 and 2. There were minimal adverse events reported for both GFR groups. This study suggests that the off-label use of GLP-1 receptor agonists for hospitalized DM patients with CKD may be useful.

Identification of potential drug candidates as TGR5 agonist to combat type II diabetes using

A cell surface bile acid receptor TGR5 being considered as a novel target for Type II diabetes found to be expressed in various tissues. A major role for TGR5 is to maintain blood sugar levels and increase in energy expenditure. These benefits make it a potential candidate for the treatment of type 2 diabetes, obesity and other metabolic disorder. To date, many novel TGR5 agonists have been synthesized and evaluated in the literature, but very few

Advanced glycation end products induce skeletal muscle atrophy and insulin resistance via activating ROS-mediated ER stress PERKFOXO1 signaling.

Skeletal muscle atrophy is often found in patients with type 2 diabetes mellitus (T2DM) which is characterized with insulin resistance. As the largest tissue in the body, skeletal muscle plays important roles in insulin resistance. Advanced glycation end products (AGEs) are representative toxic metabolites and associated with multiple pathophysiologic changes of T2DM. In this study, we investigated whether AGEs could exacerbate skeletal muscle atrophy and its related insulin resistance. Mice were exposed to AGEs. Forkhead box O1 (FOXO1) was silenced by a constructed viral vector carrying siRNA. Skeletal muscle atrophy was evaluated by HE, oil red O, myosin skeletal heavy chain (MHC) and laminin immunofluorescent stains. Reactive oxygen species (ROS) generation was assessed by DHE stain. Western blotting was used to evaluate protein expression and phosphorylation. Insulin resistance was monitored by insulin tolerance test (ITT) and glucose infusion rate (GIR). Mice exposed to AGEs showed insulin resistance which was evidenced by reduced ITT and GIR. HE and MHC immunofluorescent stains suggested reduced cross-sectional muscle fiber area. Laminin immunofluorescent and Oil red O stains indicated increased intramuscular fibrosis and lipid deposit respectively. AGEs exposure induced ROS generation, increased phosphorylation of protein kinase RNA-like endoplasmic reticulum kinase (PERK) and FOXO1, facilitated FOXO1 nuclear translocation and elevated expression of muscle atrophy F-box (MAFbx) in gastrocnemius muscle. foxo1 silencing significantly suppressed skeletal muscle atrophy and insulin resistance without affecting ROS production. AGEs exacerbated skeletal muscle atrophy and insulin resistance by activating PERKFOXO1 signaling pathway in skeletal muscle.

Differences between inflammatory cells infiltrated into tunica intima, media, and adventitia of ascending aortic aneurysms within diabetic and hypertensive patients.

The risk factors that are the most significant for the development of most cardiovascular diseases are arterial hypertension (AH), type 2 diabetes (DM), and inflammation. However, for the development of aortic aneurysms, DM is not one of them. Our study aimed to evaluate the difference between inflammatory infiltration in three individual layers of the ascending aortic aneurysm within diabetic and hypertensive patients. Forty-five patients aged 36 to 80 were divided into a group with diabetic patients without AH (group DM, N8) and hypertensive patients without DM (group AH, N37). For the histological analysis, aortic aneurysms were stained with hematoxylin eosin and Movat. We used immunochemical methods to detect pro- (M1), anti-inflammatory (M2) macrophages, T-helper, T-killer cells, B cells, and plasma cells. Statistical analysis was done by independent-samples Kruskal-Wallis test adjusted by Bonferroni correction for multiple tests (P<0.05). We found no difference in the volume density of collagen, elastin, vascular smooth muscle cells (VSMC), and ground substance between groups. In the DM group, there were significantly fewer M2, T-helpers, and T-killers in the media than in the intima and the adventitia (P<0.05). There were no significant differences in the number of M1, B, and plasma cells between all three vascular layers (P<0.05). In the AH group, there were significantly fewer B and plasma cells, T-helper, T-killer cells, M1, and M2 in the media than in the intima and adventitia (P<0.05). Our results conclude that the tunica media in the aneurismal wall of the AH group retained immune privilege. In contrast, in the DM group, all three layers were immune-privileged.

Prevalence of maturity-onset diabetes of the young in phenotypic type 2 diabetes in young adults a nationwide, multi-center, cross-sectional survey in China.

Maturity-onset diabetes of the young (MODY) is the most common monogenic diabetes. The aim of this study was to assess the prevalence of MODY in phenotypic type 2 diabetes (T2DM) among Chinese young adults. From April 2015 to October 2017, this cross-sectional study involved 2429 consecutive patients from 46 hospitals in China, newly diagnosed between 15 years and 45 years, with T2DM phenotype and negative for standardized glutamic acid decarboxylase antibody at the core laboratory. Sequencing using a custom monogenic diabetes gene panel was performed, and variants of 14 MODY genes were interpreted as per current guidelines. The survey determined 18 patients having genetic variants causing MODY (6 HNF1A, 5 GCK, 3 HNF4A, 2 INS, 1 PDX1, and 1 PAX4). The prevalence of MODY was 0.74% (95% confidence interval CI 0.40-1.08%). The clinical characteristics of MODY patients were not specific, 72.2% (1318) of them were diagnosed after 35 years, 47.1% (817) had metabolic syndrome, and only 38.9% (718) had a family history of diabetes. No significant difference in manifestations except for hemoglobin A1c levels was found between MODY and non-MODY patients. The prevalence of MODY in young adults with phenotypic T2DM was 0.74%, among which HNF1A-, GCK-, and HNF4A-MODY were the most common subtypes. Clinical features played a limited role in the recognition of MODY.

Metformin mitigates amyloid β

Metformin is an antidiabetic medicine widely used for management of type 2 diabetes with neuroprotective effects and promising potential to attenuate cognitive impairment. The efficacy of metformin in attenuation of Alzheimers disease (AD) pathology has not been well-documented. Thus, this study was designed to assess protective effect of metformin against Aβ

Relative prognostic importance of aortic and brachial blood pressures for cardiovascular and mortality outcomes in patients with resistant hypertension and diabetes a two cohorts prospective study.

The prognostic importance of derived centralaortic blood pressures (BPs) in relation to brachial office and ambulatory BPs has never been investigated in patients with resistant hypertension (RHT) or type 2 diabetes (T2D). We aimed to evaluate it in two cohorts with 532 individuals with RHT and 467 with T2D (median follow-ups 4.4 and 7.3 years, respectively). Centralaortic pressure waveforms were estimated by radial tonometry by a type 1 device (SphygmoCor devicesoftware), and other parameters of central hemodynamics (augmentation index and Buckberg indices) were calculated. Multivariate Cox regressions examined the associations between central and peripheral BPs with cardiovascular events incidence and mortality, and C-statistics and the integrated discrimination improvement index evaluated the improvement in risk discrimination. During follow-up, there were 52 cardiovascular events and 51 all-cause deaths in the RHT and 104 and 137 in the T2D cohort. No aortic BP was better than its brachial counterpart in predicting risk or improving discrimination for any outcome in either cohort. In the RHT cohort, ambulatory BPs were superior to central and office-brachial BPs. Otherwise, the augmentation index in RHT (hazard ratios 1.5, for 1-SD increment) and the Buckberg index in T2D (hazard ratios 0.7-0.8) were independent predictors of cardiovascularmortality outcomes, and improved risk discrimination (integrated discrimination improvement up to 25% in RHT and 15% in T2D). Derived aortic BPs by a type 1 device did not improve cardiovascularmortality risk prediction over brachial BPs in our cohorts of patients with RHT and T2D, but additional parameters of central hemodynamics may be useful. httplinks.lww.comHJHC137.

Gender differences in cardiovascular risk, treatment, and outcomes a post hoc analysis from the REWIND trial.

Modeling of Ultrasound Stimulation of Adolescent Pancreas for Insulin Release Therapy.

Our previous published studies have focused on safety and effectiveness of using therapeutic ultrasound (TUS) for treatment of type 2 diabetes mellitus (T2DM) in preclinical models. Here we present a set of simulation studies to explore potential ultrasound application schemes that would be feasible in a clinical setting. Using the multiphysics modeling tool OnScale, we created two-dimensional (2D) models of the human abdomen from CT images captured from one normal weight adolescent patient, and one obese adolescent patient. Based on our previous studies, the frequency of our TUS was 1 MHz delivered from a planar unfocused transducer. We tested five different insonation angles, as well as four ultrasound intensities combined with four different duty factors and five durations of application to explore how these variables effect the peak pressure and temperature delivered to the pancreas as well as surrounding tissue in the model. We determined that ultrasound applied directly from the anterior of the patient abdomen at 5 Wcm Our modeling work indicates that it may be feasible to non-invasively apply TUS in clinical treatment of T2DM.

EFFECTS OF ALPHA-LIPOIC ACID ON GLYCEMIC STATUS IN 2 TYPE DIABETES PATIENTS WITH СHRONIC CORONARY SYNDROME.

The aim To study the possibilities of alpha-lipoic acid (ALA) to control the parameters of carbohydrate metabolism. Materials and methods We examined 80 people with type 2 DM and coronary heart disease who suffered non-Q-myocardial infarction (non-Q-MI). All patients at the time of inclusion in the study received oral hypoglycemic agents, ACE inhibitor, β-blocker, statin and antiplatelet agent. 600 mg of ALA per day for 4 months was added to this treatment. After checking the patients for compliance with the criteria, they were divided into the main and experimental groups. The dosage of alpha-lipoic acid was determined for each of the groups. The results of the treatment were analyzed by determining the mean and standard deviations. Results At the end of the observation period, a significant decrease in the level of fasting glucose (FG) by 11.6% was found, which corresponded to the average size of the clinical effect. The values of glycosylated hemoglobin (HbA1c) and the insulin resistance index HOMA (HOMA-IR) showed only a tendency to decrease on the background of treatment. The effect of ALA on postprandial glycemia (PPG) and insulin levels was not detected in this study. Conclusions An additional 4-month dose of ALA in addition to baseline therapy showed a moderate effect on the decrease in FG concentration in the absence of significant dynamics in other parameters of glycemic control in the examined patients.

PROGNOSTIC ROLE OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN THE CARDIOVASCULAR COMPLICATIONS DEVELOPMENT IN PATIENTS WITH POLYMORBID PATHOLOGY THE COMBINED COURSE OF HYPERTENSION, TYPE 2 DIABETES MELLITUS AND SUBCLINICAL HYPOTHYROIDISM.

The aim To determine the prognostic value of vascular endothelial growth factor (VEGF) levels for the development of cardiovascular complications in patients with a combined course of hypertension, type 2 diabetes mellitus and subclinical hypothyroidism. Materials and methods 93 patients (mean age 61,71±0,87 years) with the combined course of hypertension, type 2 diabetes mellitus and subclinical hypothyroidism were examined. Parameters of lipid, carbohydrate metabolism, plasma insulin, VEGF (by ELISA), blood pressure levels were measured. Observation period was12 months. Results VEGF levels in the patients group were significantly higher than in the controls (482,77±21,34 pg ml vs. 121,84±11,66 pg ml, p <0,001). The results of the ROC analysis made it possible to propose the level of VEGF ≥ 512.31 pgml as an identifier for the cardiovascular complications development in patients with studied comorbidity. VEGF levels in patients who developed cardiovascular complications during observation period were significantly higher the VEGF threshold levels (650,76 ± 52,04 pg ml vs. 512,31 pgml, respectively, p 0,038) and VEGF levels in patients without cardiovascular complications were significantly lower the threshold values (420,47± 21,67 pgml vs. 512,31 pgml, respectively, p 0,047). Conclusions Determination of the vascular endothelial growth factor plasma level allows to evaluate the long-term prognosis in comorbid course of hypertension, type 2 diabetes mellitus and subclinical hypothyroidism.

BONE MINERAL DENSITY AND PROBABILITY OF OSTEOPOROTIC FRACTURES IN WOMEN WITH TYPE II DIABETES MELLITUS.

The aim To assess bone mineral density and 10-year probability of major osteoporotic and hip fractures using the Ukrainian FRAX® version for postmenopausal women with Type II diabetes mellitus and to determine the need for OP treatment according to the algorithm FRAX and BMD. Materials and methods 690 females aged 50-89 years (mean age 67.0±7.7 years) were divided into two groups Group I (n345) was made of mostly healthy women, Group II (n345) - patients with Type II diabetes mellitus. Bone mineral density was measured using dual-energy X-ray absorptiometry, 10-year probability of major osteoporotic and hip fractures was calculated using the Ukrainian FRAX® model. Results Bone mineral density and 10-year risk of major osteoporotic and hip fractures did not differ depending on the Type II diabetes mellitus presence, however the frequencies of low-energy, vertebral and all previous fractures were higher in Group II. 19% of women with diabetes mellitus and 38% of healthy ones required antiosteoporotic treatment according to dual-energy X-ray absorptiometry and only 8% and 2%, respectively, according to the FRAX. These indices became higher after recalculation of FRAX taking into account bone mineral density, however they were lower in patients with diabetes mellitus compared to the corresponding rate in the Group I (FRAX (high risk) bone mineral density 26% and 41% χ2 18.2 p<0.001). Conclusions The use of FRAX in combination with bone mineral density resulted in an increased necessity for antiosteoporotic treatment, indicating the urgency of using both indices for osteoporotic fractures prediction in patients with Type II diabetes mellitus.

Frequency of Hypoglycemia Assessed by Continuous Glucose Monitoring in Advanced Chronic Kidney Disease.

Hypoglycemia represents a risk for serious morbidity. We evaluated the prevalence and risk factors of hypoglycemia assessed by continuous glucose monitoring (CGM) in patients with chronic kidney disease (CKD) with or without diabetes. For this cross-sectional study, outpatients with CKD stages G3-G5 (including hemodialysis) and type 2 diabetes without CKD were enrolled and underwent intermittently scanned continuous glucose monitoring measurements for 7 days. The burden of CGM-measured hypoglycemia was assessed using the 7-day sum of area over the curve with glucose levels <70 mgdL and the sum of time spent <54 mgdL. A total of 366 participants (148 participants with CKD and diabetes, 115 with CKD and without diabetes, and 103 without CKD and with diabetes) were included. Low glucose levels of <54 mgdL were observed in 41% of CKD participants with diabetes, 48% of CKD without diabetes, and 14% of diabetes without CKD. However, only two participants reported hypoglycemic symptoms during CGM measurements, which were confirmed and documented by capillary blood glucose measurements. Between-group differences of 7-day area over the curve (<70 mgdl) were as follows Hemodialysis group vs. CKD stage G4 and G5 group -0.25 min·mgdLhr 95% CI -6.40 to -0.59 P < 0.001 CKD stage G4 and G5 group vs. CKD stage G3 group, -0.08 min·mgdLhr 95% CI -0.0 to -0.50 P 0.15 and CKD stage G3 group vs. Diabetes without CKD group, -0.14 min·mgdLhr 95% CI -0.0 to -0.20 P 0.01. And also in the subgroup analysis of the diabetic or nondiabetic and daytime or nighttime, the 7-day area over the curve (<70 mgdl) and time spent (<54 mgdl) increased with lowering level of kidney function. The lowering level of kidney function was strongly associated with the burden of hypoglycemia in CKD patients.

Sulphonylureas versus metformin and the risk of ventricular arrhythmias among people with type 2 diabetes A population-based cohort study.

To determine whether the use of sulphonylurea monotherapy, compared with metformin monotherapy, is associated with an increased risk of ventricular arrhythmia (VA) among patients initiating pharmacotherapy for type 2 diabetes. We conducted a population-based cohort study using electronic health data extracted from the UKs Clinical Practice Research Datalink Aurum. Using the active comparator, new-user cohort design, we compared rates of VA among patients aged 18 years or older using sulphonylurea monotherapy with those using metformin monotherapy as their initial pharmacological treatment for type 2 diabetes from April 1998 to December 2019. We used a Cox proportional hazards model with inverse probability of treatment weighting by propensity score to estimate the adjusted hazard ratio (aHR) and a corresponding bootstrap 95% confidence interval (CI) for VA with sulphonylurea monotherapy versus metformin monotherapy. The cohort included 92 638 new users of sulphonylurea and 506 882 new users of metformin. A total of 279 VA events occurred among sulphonylurea users (rate per 10 000 person-years 25.5, 95% CI 22.7 to 28.7) and 1537 VA events occurred among metformin users (rate per 10 000 person-years 18.5, 95% CI 17.6 to 19.5). Compared with metformin, sulphonylureas were associated with an increased risk of VA (aHR 1.42, 95% CI 1.18 to 1.69). Sulphonylureas are associated with an increased risk of VA when used as first-line therapy for type 2 diabetes relative to metformin use. This increased risk should be considered when prescribing sulphonylureas as an initial treatment for type 2 diabetes.

Effects of preharvest factors on antidiabetic potential of some foods and herbal plants.

Diabetes is a metabolic disorder with no definite treatment, but it can be controlled by changing lifestyle and diet. Consumption of high-fiber and nutrient-rich foods including vegetables have been shown to reduce risks of obesity and Type II Diabetes Mellitus (T2DM). Also, many herbal plants have been associated with reduced risks of T2DM because of their composition of secondary metabolites. Antioxidant activities of some secondary metabolites have potent inhibitory effects against inflammation linked with insulin resistance and oxidative stress. More than 800 known medicinal plants are used to control diabetes and its relevant complications. However, variations in preharvest factors including plant genotype, growing medium properties, climatic factors, and management practices can influence plant growth and their accumulation of phytochemicals with health-promoting properties. However, the effects of these preharvest factors on the antidiabetic properties of plant secondary metabolites are neither explicit nor easily accessible in the literature. Therefore, this review aims to document recent studies that reported on under-exploited medicinal plants with antidiabetic properties. We reviewed several important preharvest factors that can potentially affect the synthesis of phytoconstituents which possess antidiabetic properties. This review will help identify gaps for future research in phytomedicine and functional foods.

Effects of finerenone in persons with CKD and T2D are independent of HbA1c at baseline, HbA1c variability, diabetes duration and insulin use at baseline.

Effects of glycated hemoglobin (HbA1c), HbA1c variability, diabetes duration and insulin use on cardiorenal outcomes and diabetes progression in chronic kidney disease (CKD) and type 2 diabetes (T2D) are poorly understood. This post-hoc analysis of the prespecified, pooled FIDELITY dataset investigated the efficacy and safety of finerenone by these factors. Composite efficacy outcomes included cardiovascular (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for heart failure), kidney (kidney failure, sustained ≥57% estimated glomerular filtration rate decline or renal death) and diabetes progression (new insulin initiation, increase in antidiabetic medication, 1.0% increase in HbA1c from baseline, new diabetic ketoacidosis diagnosis or uncontrolled diabetes). In 13,026 participants, risk reductions in the cardiovascular and kidney composite outcomes with finerenone vs placebo were consistent across HbA1c quartiles (P-interaction 0.52 and 0.09, respectively), HbA1c variability (P-interaction 0.48 and 0.10), diabetes duration (P-interaction 0.12 and 0.75) and insulin use (P-interaction 0.16 and 0.52). HbA1c variability in the first year of treatment was associated with higher risk of cardiovascular and kidney events (hazard ratio HR 1.20 95% confidence interval CI 1.07-1.35 P 0.0016 and HR 1.36 95% CI 1.21-1.52 P < 0.0001, respectively). There was no effect on diabetes progression with finerenone or placebo (HR 1.00 95% CI 0.95-1.04). Finerenone was well-tolerated across subgroups discontinuation and hospitalization due to hyperkalemia were low. Finerenone efficacy was not modified by baseline HbA1c, HbA1c variability, diabetes duration or baseline insulin use. Greater HbA1c variability appeared to be associated with increased risk of cardiorenal outcomes. This article is protected by copyright. All rights reserved.

Improvement of glycemic control and treatment satisfaction by switching from liraglutide or dulaglutide to subcutaneous semaglutide in patients with type 2 diabetes A multicenter, prospective, randomized, open-label, parallel-group comparison study (SWITCH-SEMA 1 study).

To investigate the effects of switching from liraglutide or dulaglutide to once-weekly semaglutide on glycemic control and treatment satisfaction in patients with type 2 diabetes. In this multicenter, open-labeled, prospective, randomized, parallel-group comparison study, patients treated with liraglutide 0.9-1.8 mgday (plan A) or dulaglutide 0.75 mgweek (plan B) were either switched to semaglutide or continued on current therapy. The primary endpoint was the mean change in glycated hemoglobin (HbA1c) over 24 weeks. The secondary endpoints included the changes of Diabetes Treatment Satisfaction Questionnaire (DTSQ) scores, body weight, and metabolic indices. In total, 110 patients were enrolled, and 10 were excluded therefore, 37 patients in plan A and 63 patients in plan B completed the study. HbA1c levels were significantly reduced in the semaglutide group in both plans (plan A, 7.8 ± 1.0% to 7.8 ± 0.7% liraglutide vs. 7.9 ± 0.7% to 7.3 ± 0.7% semaglutide, P < 0.01 plan B, 7.8 ± 1.0% to 7.9 ± 1.2% dulaglutide vs. 7.8 ± 0.8% to 7.1 ± 0.6% semaglutide, P < 0.01). Semaglutide also improved DTSQ scores in both groups (plan A, 0.1 vs. 8.3, P < 0.01 plan B, -1.2 vs. 3.5, P < 0.01). Switching from dulaglutide yielded greater reductions in body weight and improved metabolic parameters. Once-weekly semaglutide administration improved glycemic control and treatment satisfaction after switching from liraglutide or dulaglutide. These results highlighted a useful treatment option for patients with metabolic abnormalities despite GLP-1 receptor agonist treatment. This article is protected by copyright. All rights reserved.

Type 2 Diabetes and HDL dysfunction a key contributor to Glycemic Control.

High-density lipoproteins (HDL) have been shown to exert multiple cardioprotective and antidiabetic functions, such as their ability to promote cellular cholesterol efflux and their antioxidant, anti-inflammatory, and antiapoptotic properties. Type 2 diabetes (T2D) is usually associated with low high-density lipoprotein cholesterol (HDL-C) levels as well as with significant alterations in the HDL composition, thereby impairing its main functions. HDL dysfunction also negatively impacts both pancreatic β-cell function and skeletal muscle insulin sensitivity, perpetuating this adverse self-feeding cycle. The impairment of these pathways is partly dependent on cellular ATP-binding cassette transporter (ABC) A1-mediated efflux to lipid-poor apolipoprotein (apo) A-I in the extracellular space. In line with these findings, experimental interventions aimed at improving HDL functions, such as infusions of synthetic HDL or lipid-poor apoA-I, significantly improved glycemic control in T2D patients and experimental models of the disease. Cholesteryl ester transfer protein (CETP) inhibitors are specific drugs designed to increase HDL-C and HDL functions. Posthoc analyses of large clinical trials with CETP inhibitors have demonstrated their potential anti-diabetic properties. Research on HDL functionality and HDL-based therapies could be a crucial step toward improved glycemic control in T2D subjects.

Two-year trends from the LANDMARC study A 3-year, pan-India, prospective, longitudinal study on the management and real-world outcome in patients with type 2 diabetes mellitus.

There are limited data on the real-world management of diabetes in the Indian population. In this 2-year analysis of the LANDMARC study, the management of type 2 diabetes mellitus (T2DM) and related complications were assessed. This multicenter, observational, prospective study included adults aged ≥25 to ≤60 years diagnosed with T2DM (duration ≥2 years at enrollment) and controlleduncontrolled on ≥2 anti-diabetic agents. This interim analysis at 2 years reports the status of glycaemic control, diabetic complications, cardiovascular (CV) risks and therapy, pan-India including metropolitan and non-metropolitan cities. Of the 6234 evaluable patients, 5318 patients completed 2 years in the study. Microvascular complications were observed in 17.6% of patients (10966234) macrovascular complications were observed in 3.1% of patients (1956234). Higher number of microvascular complications were noted in patients from non-metropolitan than in metropolitan cities (p < .0001). In 2 years, an improvement of 0.6% from baseline (8.1%) in mean glycated haemoglobin (HbA1c) was noted 20.8% of patients met optimum glycaemic control (HbA1c < 7%). Hypertension (26793438, 77.9%) and dyslipidaemia (17763438, 51.7%) were the predominant CV risk factors in 2 years. The number of patients taking oral anti-diabetic drugs in combination with insulin increased in 2 years (baseline 14986234 24.0% vs. 2 years 19175763 33.3%). While biguanides and sulfonylureas were the most commonly prescribed, there was an evident increase in the use of dipeptidyl peptidase-IV inhibitors (baseline 30496234, 48.9% vs. 2 years 35265763, 61.2%). This longitudinal study represents the control of T2DM, its management and development of complications in Indian population. CTRI201705008452.

Ethnic differences in complement system biomarkers and their association with metabolic health in men of Black African and White European ethnicity.

Inflammation plays a fundamental role in the development of several metabolic diseases, including obesity and type 2 diabetes (T2D) the complement system has been implicated in their development. People of Black African (BA) ethnicity are disproportionately affected by T2D and other metabolic diseases but the impact of ethnicity on the complement system has not been explored. We investigated ethnic differences in complement biomarkers and activation status between men of BA and White European (WE) ethnicity and explored their association with parameters of metabolic health. We measured a panel of 15 complement components, regulators and activation products in fasting plasma from 89 BA and 96 WE men. Ethnic differences were statistically validated. Association of complement biomarkers with metabolic health indices (BMI, waist circumference, insulin resistance and HbA1c) were assessed in the groups. Plasma levels of the key complement components C3 and C4, the regulators clusterin and properdin and the activation marker iC3b were significantly higher in BA compared to WE men after age adjustment, while FD levels were significantly lower. C3 and C4 levels positively correlated with some or all markers of metabolic dysfunction in both ethnic groups while FD was inversely associated with HbA1c in both groups, and clusterin and properdin were inversely associated with some markers of metabolic dysfunction only in the WE group. Our findings of increased levels of complement components and activation products in BA compared to WE men suggest differences in complement regulation that may impact susceptibility to poor metabolic health.

Hyperglycaemic hyperosmolar state and cerebral thrombophlebitis in paediatrics A case report.

Hyperglycaemic hyperosmolar state (HHS) is a known complication of type 2 diabetes mellitus however, carbonated carbohydrate fluid intake may precipitate a more severe presentation of type 1 diabetes mellitus with hyperosmolar state. The management of these patients is not easy and can lead to severe complications such as cerebral venous thrombosis. We present the case of a 21-month-old boy admitted for consciousness disorders revealing a hyperglycaemic hyperosmolar state on a new-onset type 1 diabetes and who developed cerebral venous thrombosis. Emergency physicians should be aware of HHS in order to start the appropriate treatment as early as possible and to monitor the potential associated acute complications. This case highlights the importance of decreasing very gradually the osmolarity in order to avoid cerebral complications. Cerebral venous thrombosis in HHS paediatric patients is rarely described, and it is important to recognize that not all episodes of acute neurological deterioration in HHS or diabetic ketoacidosis are caused by cerebral oedema.

Glucagon-like peptide 1 receptor agonists in patients with type 2 diabetes with and without chronic heart failure a meta-analysis of randomized placebo-controlled outcome trials.

Glucagon-like peptide 1 receptor agonists (GLP1-RA) reduce atherosclerotic events in patients with type 2 diabetes (T2D) and a high cardiovascular risk. The effect of GLP1-RA to reduce heart failure (HF) has been inconsistent across T2D trials, and individual trials were underpowered to assess the effect of GLP1-RA according to HF history. In this meta-analysis we aim to assess the effect of GLP1-RA in patients with and without HF history in stable ambulatory patients with T2D. Random-effects meta-analysis of placebo-controlled trials. The hazard ratio (HR) and 95% confidence intervals (95%CI) were extracted from the treatment effect estimates of HF subgroup analyses reported in each individual study. The primary outcome was a composite of HF hospitalization or cardiovascular death. A total of 54092 patients with T2D from 7 randomized controlled trials were included, of whom 8460 (16%) had HF history. Compared to placebo, GLP1-RA did not reduce the composite of HF hospitalization or cardiovascular death in patients with HF history HR 0.96, 95%CI 0.84-1.08, but reduced this outcome in patients without HF history HR 0.84, 95%CI 0.76-0.92. GLP1-RA did not reduce all-cause death in patients with HF history HR 0.98, 95%CI 0.86-1.11, but reduced mortality in patients without HF history HR 0.85, 95%CI 0.79-0.92. GLP1-RA reduced atherosclerotic events regardless of HF history HR 0.85, 95%CI 0.75-0.97 with HF, and HR 0.88, 95%CI 0.83-0.93 without HF. Treatment with GLP1-RA did not reduce HF hospitalizations and mortality in patients with concomitant T2D and HF, but may prevent new-onset HF and mortality in patients with T2D without HF. The reduction of atherosclerotic events with GLP1-RA was not influenced by HF history status. This article is protected by copyright. All rights reserved.

Comparison of Serum Metabolomics Pathways and Patterns between Patients with Major Depressive Disorder with and without Type 2 Diabetes Mellitus An Exploratory Study.

A close relationship exists between major depressive disorder (MDD) and diabetes mellitus. The metabolomic difference and similarity between patients with and without diabetes mellitus have not been well studied in the context of MDD. We aimed to examine these differences and common serum metabolomics patterns, pathways and biomarkers that can comprehensively reflect the pathogenetic difference and similarity between these MDD groups. We performed a metabolomics analysis of serum samples of healthy controls (n 6), patients with MDD and type 2 diabetes mellitus (n 13), and patients with MDD without type 2 diabetes mellitus (n 27). Metabolomics analysis was conducted using capillary electrophoresis Fourier transform mass spectrometry and a candidate compound was assigned to the 496 (290 cation, 206 anion) peaks. Moreover, we evaluated the sensitivity and specificity of the candidate biomarkers for distinguishing between MDD patients with or without type 2 diabetes mellitus. Principal component analysis revealed no clear distinction among the three groups, while naive partial least squares discriminant analysis yielded three relatively good and distinct populations based on the first principal component. Energy conversion by the tricarboxylic acid cycle represented the highest percentage among the top 30 positive factors of the first principal component, and glutamate metabolism and urea cycle represented the highest percentage among the top 30 negative factors of the first principal component. Synthesis and degradation of ketone bodies had high impact in MDD with type 2 diabetes mellitus group and taurine and hypotaurine metabolism had high impact in MDD without type 2 diabetes mellitus group for the pathway. Patterns of serum metabolites may be different among MDD with type 2 diabetes mellitus, MDD without type 2 diabetes mellitus, and healthy controls groups. Specifically, comorbid type 2 diabetes mellitus could affect metabolomics pathway and alter the distribution of serum metabolites in patients with MDD. These findings may shed light on the influence of the type 2 diabetes on the pathophysiology of MDD.

Cryo-EM structure of orphan G protein-coupled receptor GPR21.

GPR21 belongs to class A orphan G protein-coupled receptor (GPCR). The endogenous ligands for human GPR21 remain unidentified. GPR21 expression is associated with developing type 2 diabetes (T2DM), a multifactorial metabolic disease caused by pancreatic β-cell dysfunction, decreasing insulin production, insulin resistance, and obesity. Animal studies suggested that GPR21 is a potential therapeutic target for T2DM treatment. The underlying mechanisms leading to GPR21 self-activation remain unknown. In our co-expression analysis, we noted that GPR21 could also form a stable complex with an unreported Gα protein subtype, Gαs. To gain further insights into the structural mechanisms of GPR21 activation, we employed cryo-electron microscopy (cryo-EM) and single-particle analysis to resolve the high-resolution structure of GPR21-Gαs complexes. The clear electron density map of the GPR21-Gαs provided direct evidence that GPR21 could couple to Gαs protein at physiological conditions. Thus, GPR21 might mediate previously unexplored pathways in normal or pathological conditions, which warrants further investigation. Structure-guided mutagenesis and biochemical analysis revealed that extracellular loop 2 (ECL2) of GPR21 is essential for the receptor transducing intracellular signal via cAMP. Together, the new structure data reveal a novel signaling cascade of human GPR21 mediated by ECL2 and provide fundamental information for future structure-based drug development.

Parachute Mitral Valve in an Adult.

Two-dimensional transthoracic echocardiography images for a 49-year-old female with a history of ventricular septal defect status post repair, type 2 diabetes mellitus, and hyperlipidemia whose evaluation of her lower extremity edema showed parachute mitral valve.

Prevalence of Sleep Disorders Among Patients With Type 2 Diabetes Mellitus in Makkah City A Cross-Sectional Study.

Due to rising rates of morbidity and mortality associated with type 2 diabetes mellitus (T2DM), Saudi Arabia is ranked second in the Middle East and seventh overall among nations with the greatest incidence of diabetes mellitus (DM). Significant sleep abnormalities have been linked to difficulties in managing blood sugar levels, suggesting a link between sleep disorders and diabetes. This study aimed to find out how common sleep disturbances were among patients with T2DM in Makkah, Saudi Arabia. This descriptive cross-sectional study was conducted between June and August 2022 in Makkah City, Saudi Arabia. Patients with T2DM who visited primary healthcare facilities in Makkah during the studys duration were included in the study. To evaluate sleep quality, the Pittsburgh Sleep Quality Index in Arabic was employed. Patients who met the inclusion criteria were given an interview questionnaire to fill out. In total, 355 patients with T2DM were enrolled in this study. The patients median age was 49.24 years. Other than DM, a majority of them (58.9%) had chronic illnesses, with hypertension (64.5%) and cardiovascular disease (65.5%) as the most prevalent comorbidities. Only 22% of the patients had controlled diabetes. Of the individuals who had sleep disorders, 63.7% stated having poor sleep quality. Sleep problems are a common occurrence in patients with T2DM. Additionally, compared to people with other chronic disorders, people with endocrine diseases had poorer sleep quality. Hence, the duration of diabetes has an impact on sleep quality.

Risk Factors of Rhino Orbital Mucormycosis.

To determine the clinical presentation and risk factors associated with rhino orbital mucormycosis. Mucormycosis is a rapidly progressive fungal infection caused by filamentous fungi in the Mucoraceae family. In large numbers, they release spores into the air, and humans get exposed through inhalation. The spores inoculate in the paranasal sinuses and nasopharynx and subsequently spread to the orbit and intracranial cavity. The present COVID-19 pandemic has witnessed a resurgence of rhino-orbital mucormycosis cases, mainly seen in patients with immunocompromised status. Hence, our study evaluated the risk factors and clinical features of rhino orbital mucormycosis. This was a prospective, single-center, cross-sectional study. Patients attending tertiary care centers fulfilling the inclusion criteria were evaluated with a detailed history including sociodemographic profile, occupation, history of fever, COVID-19 infection, steroid or immunosuppressant use, organ transplants, diabetes mellitus and use of oxygen (O2). A complete ophthalmic evaluation was performed, including best-corrected visual acuity, anterior segment evaluation with slit lamp biomicroscopy, and posterior segment evaluation using indirect ophthalmoscopy. Computed Tomography (CT) scan of paranasal sinuses was done for all the patients, and Magnetic Resonance Imaging (MRI) for a few patients if indicated. Intraoperatively, samples were sent for Potassium Hydroxide (KOH) stain while debridement and patients with positive results were included in the study. Forty participants were included, out of which 34 (85%) were males and six (15%) were females. The mean age of the patients was 51.75 years. Out of 40 patients, 29 (72.5%) had ho COVID-19 infection, 30 (75%) were known type 2 diabetes mellitus, 25 (62.5%) had a ho steroid intake and 25 (62.5%) had a history of O2 use. 17 (42.5%) patients presented with low vision, out of which 15 had no light perception. 30 (75%) patients had ptosis, 22 (55%) patients presented with proptosis, 15 (37.5%) patients had limited ocular motility, 11 (27.5%) had complete ophthalmoplegia, and 11 (27.5%) patients had central retinal artery occlusion. Rhino orbital Mucormycosis is more prevalent in patients with COVID-19 infection, especially those who have used steroids and oxygen and with type 2 diabetes mellitus. Early presentation with treatment can prevent further ocular morbidity.

Medication Adherence Among Patients of Type II Diabetes Mellitus and Its Associated Risk Factors A Cross-Sectional Study in a Tertiary Care Hospital of Eastern India.

Type 2 diabetes mellitus is a major public health problem. Adherence to anti-diabetic medications improves glycaemic control, which in turn prevents complications as well as reduces out-of-pocket expenditure. The World Health Organization highlights that the impact of interventions directed to improve adherence has far greater implications than specific medical interventions. There are several factors that contribute to poor adherence. Not many studies have been conducted to explore adherence to diabetes medications in eastern India. To measure medication adherence among patients suffering from diabetes. To determine the various risk factors influencing adherence to medication. To find out the association of health-related quality of life with adherence to medication. A hospital-based cross-sectional study was conducted in the outpatient Department of General Medicine and Endocrinology of a tertiary care hospital in eastern India from January to March 2020. Adult subjects, who were diagnosed with type 2 diabetes mellitus for at least six months, were interviewed using a pretested, structured questionnaire containing 8-item Morisky Medication Adherence Scale (MMAS-8) to determine adherence to diabetic medications. Data were analysed in SPSS version 27 (IBM Corp., Armonk, NY, USA). The mean age of the 331 participants interviewed was 53.40 (SD 11.0) years and the majority were males (57.1%). Medication adherence of 34.14% (n113) was found among the subjects. Having any comorbidity, positive family history of diabetes and the habit of current alcohol intake increased the odds of poor adherence by 3.26 times, 1.88 times, and 2.35 times respectively in binary logistic regression analysis. Those following a diabetic diet had a protective effect, decreasing poor medication adherence by 79.6%. Poor medication adherence increased by 1.077 times with every one-day increase in unhealthy days. The medication adherence was 34.14% and as compared to other similar studies medication adherence in the study population was poor and was associated with unhealthy days.

Assessment of the Safety, Efficacy, and Benefit of Empagliflozin in Patients With Type 2 Diabetes Mellitus (T2DM) and Heart Failure With Reduced Ejection Fraction (HFrEF) at High Risk for Cardiovascular Events.

Background Since the increasing prevalence of type 2 diabetes mellitus (T2DM), heart failure coexisting with it has had a significant impact on clinical management and prognosis. Patients with T2DM and heart failure with reduced ejection fraction (HFrEF) have increased mortality and morbidity. Empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, is widely acknowledged to reduce cardiovascular risk in T2DM patients. We wanted to assess the composite outcomes of heart failure, cardiovascular death, and hospitalization following the start of empagliflozin therapy in the Saudi population. Methods This is a retrospective observational study conducted at King Fahad Armed Forces Hospital-Jeddah. We included patients aged 18 or older, male or female, with T2DM with HFrEF <40% and with a risk of cardiovascular events who were treated with empagliflozin 25 mg once daily as combination therapy and patients using other diabetic agents without empagliflozin as the comparative group. Results A total of 195 patients with T2DM and HFrEF who were at high risk for cardiovascular (CV) events were included in the study. Regarding gender, most of the patients (82.1%) were male with an average age of 61.28 ± 9.92. The patients were divided into 71 individuals who received empagliflozin and 124 who did not. When comparing the surgical procedure and comorbid status of the patients, coronary artery bypass graft (1.4%), coronary artery disease (5.6%), dyslipidemia (5.6%), and ischemic cardiomyopathy (0%) were found compared to the non-empagliflozin group. Meanwhile, hypertension was found to be 71.8% and ischemic heart disease was 50.7% in empagliflozin patients. Furthermore, only dyslipidemia differed significantly (p <0.001) between the empagliflozin and non-empagliflozin groups of patients. However, no significant differences were observed between the average low-density lipoprotein (p 0.990) and high-density lipoprotein (p 0.399). There was no significant difference observed in the primary outcome of CV deaths or hospital admission of patients between empagliflozin and non-empagliflozin. No deaths were reported in either of the comparative groups in our study. Conclusion In this study, there was no significant difference observed in hospital admission of the patients between the empagliflozin and non-empagliflozin groups. No cardiovascular mortality was reported in the study population. Further matched group comparative studies or placebo-controlled studies are required to compare the existing evidence of the impact of empagliflozin on T2DM patients with HFrEF and at high risk for CV deaths or hospital admission.

Associations Between Mean HbA1c, HbA1c Variability, and Both Mortality and Macrovascular Complications in Patients with Diabetes Mellitus A Registry-Based Cohort Study.

We investigate the association between mean HbA1c, HbA1c variability, and all-cause mortality and diabetes-related macrovascular complications in patients with diabetes. We performed a retrospective cohort study using patients present in the Singapore Health Services diabetes registry (SDR) during 2013 to 2014. We assessed mean HbA1c using three models a baseline mean HbA1c for 2013-14, the mean across the whole follow-up period, and a time-varying yearly updated mean. We assessed HbA1c variability at baseline using the patients HbA1c variability score (HVS) for 2013-14. The association between mean HbA1c, HVS, and 6 outcomes were assessed using Cox proportional hazard models. We included 43,837-53,934 individuals in the analysis 99.3% had type 2 diabetes mellitus. The data showed a J-shaped distribution in adjusted hazard ratios (HRs) for all-cause mortality, ischemic heart disease, acute myocardial infarction, peripheral arterial disease, and ischemic stroke, with an increased risk of developing these outcomes at HbA1c <6% (42 mmolmol) and ≥8% (64 mmolmol). With the addition of HVS, the J-shaped distribution was maintained for the above outcomes, but HRs were greater at HbA1c <6.0% (42 mmolmol) and reduced at HbA1c ≥8.0% (64 mmolmol) when compared to models without HVS. The risk for all outcomes increased substantially with increasing glycaemic variability. Both low (<6.0% 42 mmolmol) and high (≥8.0% 64 mmolmol) levels of glycaemic control are associated with increased all-cause mortality and diabetes-related macrovascular complications. Glycaemic variability is independently associated with increased risk for these outcomes. Therefore, patients with stable glycaemic level of 6-8% (42-64mmolmol) are at lowest risk of all-cause mortality and diabetes-related macrovascular complications.

A study protocol for a cluster randomized controlled trial to test the applicability of the South African diabetes prevention program in the Eastern Cape Province of South Africa.

Convincing evidence supports the effectiveness of lifestyle interventions in preventing the occurrence of diabetes in high-income countries, however little is known about appropriate interventions for use in African countries, where there are higher relative increases in diabetes prevalence. The South African Diabetes Prevention Programme (SA-DPP) was initiated with the aim of preventing or delaying the occurrence of diabetes among South Africans (SAs), through interventions, targeting lifestyle changes related to diet and physical activity. The purpose of the current project is to implement and evaluate the suitability and applicability of the SA-DPP developed and tailored in urban populations in the Western Cape Province, in peri-urban populations in the Eastern Cape Province of SA. The SA-DPP, which is an cluster randomized control trial, will be implemented in adults aged 30-65 years residing in the OR Tambo district, Eastern Cape, SA. Participants will be recruited using self-selected sampling techniques and 24 clusters across peri-urban communities will be randomly allocated to participate in the lifestyle intervention, facilitated by non-professional health workers (NPHW). The diabetes risk screening will follow a two-staged approach, including the community-based screening, using the African diabetes risk score (ADRS), followed by a clinic-based risk status assessment by an oral glucose tolerance test (OGTT) to exclude unknown diabetes. The lifestyle-change objectives of the current programme relate to, 1) < 30% of total energy intake from fat 2) < 10% of total energy intake from saturated fat 3) > 15 g of fibre1000 kcal 4) > 4 hweek moderate level of physical activity and 5) > 2% body mass index (BMI) reduction. The SA-DPP could represent a successful model for the prevention of diabetes and potentially other lifestyle-related diseases in SA and other countries in the region that are confronted with similar challenges. PACTR202205591282906.

Effectiveness of a diabetes program based on digital health on capacity building and quality of care in type 2 diabetes a pragmatic quasi-experimental study.

Health systems in Latin America face many challenges in controlling the increasing burden of diabetes. Digital health interventions are a promise for the provision of care, especially in developing countries where mobile technology has a high penetration. This study evaluated the effectiveness of the implementation of a Diabetes Program (DP) that included digital health interventions to improve the quality of care of persons with type 2 Diabetes (T2DM) in a vulnerable population attending the public primary care network. A quasi-experimental pre-post uncontrolled study was conducted in 19 primary care centers and hospitals in the province of Corrientes, Argentina. We included persons with T2DM, age > 18 years with access to a mobile phone. The multicomponent intervention included a mobile app with a diabetes registry, a clinical decision support tool for providers and a text messaging intervention for patients. One thousand sixty-five participants were included, 72.8% had less than 12 years of formal education and 53.5% lacked health coverage. Comorbidities were hypertension (60.8%) and overweightobesity (88.2%). During follow-up there was a significant increase in the proportion of participants who underwent laboratory check-ups (HbA1c 20.3%-64.4% p < 0.01) and foot exams (62.1%-87.2% p < 0.01). No changes were observed at 12 and 24 months in the proportion of participants with poor metabolic control. The proportion of participants with uncontrolled blood pressure (≥ 14090 mmHg) decreased from 47.2% at baseline to 30.8% at 24 months in those with a follow-up visit. The DP was innovative by integrating digital health interventions in the public primary care level. The study showed improvements in quality indicators related with diabetes care processes and in blood pressure control.

Efficacy of cardiometabolic drugs in reduction of epicardial adipose tissue a systematic review and meta-analysis.

Epicardial adipose tissue (EAT) plays an important role in cardiometabolic risk. EAT is a modifiable risk factor and could be a potential therapeutic target for drugs that already show cardiovascular benefits. The aim of this study is to evaluate the effect of cardiometabolic drugs on EAT reduction. A detailed search related to the effect on EAT reduction due to cardiometabolic drugs, such as glucagon-like peptide-1 receptor agonist (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT2-i), and statins was conducted according to PRISMA guidelines. Eighteen studies enrolling 1064 patients were included in the qualitative and quantitative analyses. All three analyzed drug classes, in particular GLP-1 RA, show a significant effect on EAT reduction (GLP-1 RA standardize mean difference (SMD) - 1.005 p < 0.001 SGLT2-i SMD - 0.552 p < 0.001, and statin SMD - 0.195 p < 0.001). The sensitivity analysis showed that cardiometabolic drugs strongly benefit EAT thickness reduction, measured by ultrasound (overall SMD of - 0.663 95%CI - 0.79, - 0.52 p < 0.001). Meta-regression analysis revealed younger age and higher BMI as significant effect modifiers of the association between cardiometabolic drugs and EAT reduction for both composite effect and effect on EAT thickness, (age Z 3.99 p < 0.001 and Z 1.97 p 0.001, respectively BMI Z - 4.40 p < 0.001 and Z - 2.85 p 0.004, respectively). Cardiometabolic drugs show a significant beneficial effect on EAT reduction. GLP-1 RA was more effective than SGLT2-i, while statins had a rather mild effect. We believe that the most effective treatment with these drugs should target younger patients with high BMI.

Using HbA1c measurements and the Finnish Diabetes Risk Score to identify undiagnosed individuals and those at risk of diabetes in primary care.

Prevalence of prediabetes and type 2 diabetes mellitus (T2DM) is increasing worldwide. The objective of this study was to determine the proportion of people in Northern Iceland with prediabetes, at risk of developing T2DM or with manifest undiagnosed T2DM, as this information is lacking in Iceland. A cross-sectional study. Clients of the three largest primary health care centres in the Health Care Institution of North Iceland (HSN) were invited to participate if fulfilling the following inclusion criteria a) aged between 18 and 75 years, b) not diagnosed with diabetes, c) speaking and understanding Icelandic or English fluently and d) living in the included service area. Data collection took place via face-to-face interviews between 1 March 2020 and 15 May 2021. Participation included answering the Finnish Diabetes Risk Score (FINDRISC), measuring the HbA1c levels and background information. Of the 220 participants, 65.9% were women. The mean age was 52.1 years (SD ± 14.1) and FINDRISC scores were as follows 47.3% scored ≤8 points, 37.2% scored between 9 and 14 points, and 15.5% scored between 15 and 26 points. The mean HbA1c levels in mmolmol, were 35.5 (SD ± 3.9) for men and 34.4 (SD ± 3.4) for women, ranging from 24 to 47. Body mass index ≥30 kgm The FINDRISC is a non-invasive and easily applied screening instrument for prediabetes. Used in advance of other more expensive and invasive testing, it can enable earlier intervention by assisting decision making, health promotion actions and prevention of the disease burden within primary health care. This study is a pre-phase of the registered study Effectiveness of Nurse-coordinated Follow up Program in Primary Care for People at risk of T2DM at www. gov (NCT01688359). Registered 30 December 2020.

Evaluation of meibomian gland dysfunction in type 2 diabetes with dry eye disease a non-randomized controlled trial.

The purpose of this investigation was to evaluate the morphology and physiological function of the meibomian glands between type 2 diabetics with dry eye disease (DED) and control subjects. Doing so will help to better reveal the pathologic mechanisms of meibomian gland dysfunction (MGD) and DED in type 2 diabetes mellitus (T2DM). Ninety subjects were divided into the following four groups DM-DED group T2DM patients with DED (n 30) DM control group DM patients without DED (n 18) DED group DED patients without DM (n 26) and normal control group normal subjects (n 16). All participants administered the ocular surface disease index (OSDI) questionnaire, tear meniscus height (TMH), noninvasive Keratograph tear film break-up time (NIKBUT), Schirmer I test (SIT), corneal fluorescein staining (CFS), eyelid margin abnormality examinations, meibum quality and meibomian gland (MG) dropout evaluations. The percentage of MG dropout in the upper and lower lids was significantly higher in the DM-DED group than the DED group (P < 0.05 or P < 0.01). However, there was no significant difference in other MG parameters between these two groups. Oppositely, Significant difference was observed in all of MG parameters except MG dropout in the lower lids comparing DM group with normal controls (P < 0.05 or P < 0.01). While the SIT values decreased in the DM-DED group compared to the DED group (P < 0.05), no significant differences were found in the values of other tear parameters. The higher prevalence and increased severity of MGD was found in patients with both T2DM and DED compared to those only with DED. Chinese Clinical Trial Registry ChiCTR1800019939, date of registration December 9, 2018, prospectively registered.

Ancestral recipes a mixed-methods analysis of MyPlate-based recipe dissemination for Latinos in rural communities.

The Latinx population experiences some of the highest rates of chronic disease, including obesity and type II diabetes. Such conditions may be especially burdensome in rural Latinx communities that often face barriers to accessing disease prevention resources and public health programs. Diverse stakeholders (i.e., patients, community members, system of healthcare clinics, community food bank) tailored an existing cookbook, based on the U.S. Department of Agriculture MyPlate healthy eating and dietary guidelines, for local ingredients, health literacy, and language for rural Latinx and Indigenous Latin Americans. The cookbook recipes were disseminated widely via virtual cooking demonstrations, food distribution events, and social media. Pre- and posttest surveys were used to assess changes in diabetes knowledge measured by the 24-item American Diabetes Association Diabetic Knowledge Questionnaire and confidence in dietary behavior change over time measured by 4 questions of the 17-item Mediterranean Diet Index. A mixed effects, repeated measures analysis was conducted with gender ID, age range and educational attainment included as covariates and assessment interval as the predictor (pretest vs posttest) and change in confidence about adhering to four specific components of the Mediterranean diet. Focus groups elicited information on participants motivation and ability to use the recipes and eat healthy foods following the virtual cooking demonstration participation. A total of 20 virtual cooking demonstrations were conducted and 60 participants completed a pretest survey and 54 a posttest survey, a subsample (n 19) participated in one of three focus groups. Most participants were female, identified as LatinxHispanic, were between the ages of 40-49, and spoke Spanish. 17% identified as Indigenous Latin American specifically as Purépecha, an indigenous group from Michoacán, Mexico. Survey and focus group findings indicated at posttest an increase in diabetes knowledge among participants with no prior diagnosis of chronic health conditions and more confidence in limiting sugary beverages and refined wheat pastawhite rice among indigenous participants. Focus group discussions explicated the quantitative findings. This study brought together patients and key stakeholders committed to addressing the social determinants of health and it mobilized the community to develop culturally vetted health education materials. The findings indicate the need for increased access to evidence-based nutrition education and to culturally appropriate food products that can be easily incorporated into daily food preparation.

Cardiopulmonary exercise testing for exercise prescription in cardiac rehabilitation.

Aerobic endurance training is a core component of exercise training (ET) during cardiac rehabilitation (CR). Improvements of cardiopulmonary performance and symptom-free exercise capacity that can be achieved by ET during CR are essential for patients prognosis and quality of life. Before initiating exercise training in CR, a detailed risk stratification including incremental exercise testing is required in order to ensure safe and effective exercise training conditions. Cardiopulmonary exercise testing (CPX) with measurement of respiratory gases is considered the gold standard of cardiopulmonary performance diagnostics. The oxygen uptake measured at the highest exercise intensity achieved (peakVO Aerobes Ausdauertraining ist ein wesentlicher Bestandteil der körperlichen Trainingstherapie in der kardiologischen Rehabilitation (KardReha). Die dadurch erzielte Verbesserung der kardiopulmonalen Leistungsfähigkeit und der symptomfreien Belastbarkeit im Alltag sind für die Lebensqualität und Prognose des Patienten von großer Bedeutung. Vor Beginn der Trainingstherapie wird eine ausführliche Risikostratifizierung inklusive Belastungsuntersuchung gefordert, damit ein sicheres und effektives Training während der KardReha gewährleistet ist. Die Spiroergometrie („cardio-pulmonary exercise testing“, CPX) gilt als Goldstand der Bestimmung der kardiopulmonalen Belastbarkeit und Leistungsdiagnostik. Die Sauerstoffaufnahme, die an der maximal erreichten Belastungsintensität gemessen wird (peakVO

Effect of the GLP-1 receptor agonist semaglutide on metabolic disturbances in clozapine-treated or olanzapine-treated patients with a schizophrenia spectrum disorder study protocol of a placebo-controlled, randomised clinical trial (SemaPsychiatry).

Clozapine and olanzapine are some of the most effective antipsychotics, but both are associated with weight gain and relevant metabolic disturbances, including pre-diabetes and diabetes. Non-pharmacologicalbehavioural interventions have had limited effects counteracting these adverse effects. Semaglutide, a glucagon-like peptide 1 receptor agonist, is approved for the treatment of type 2 diabetes and obesity. We will investigate the long-term effects of add-on treatment with semaglutide once a week versus placebo once a week on the metabolic status in pre-diabetic (glycated haemoglobin A1c (HbA1c) 35-47 mmolmol (5.4%-6.4%) and diabetic (HbA1c 48-57 mmolmol (6.5%-7.4%)) patients diagnosed with a schizophrenia spectrum disorder who initiated clozapine or olanzapine treatment within the last 60 months. This is a 26-week, double-blinded, randomised, placebo-controlled trial. Altogether, 104 patients diagnosed with a schizophrenia spectrum disorder, aged 18-65 years, with pre-diabetes or diabetes will be randomised to injections of 1.0 mg semaglutide once a week or placebo for 26 weeks. The primary endpoint is change from baseline in HbA1c. Secondary endpoints include changes in body weight, hip and waist circumference and plasma levels of insulin, glucagon, glucose, and C-peptide, insulin sensitivity, beta cell function, hepatic function, fibrosis-4 score, lipid profile, incretin hormones, bone markers, body composition, bone density, proteomic analyses and oxidative stress markers. Together with alcohol, tobacco and drug use, potential effects on the reward value of a sweet-fat stimulus, psychopathology, level of activity and quality of life will also be assessed. This study is approved by the Danish Medicines Agency and the regional scientific ethics committee of the Capital Region of Denmark (committee C, H-20019008) and will be carried out in accordance with International Council for Harmonisation Good Clinical Practice guidelines and the Helsinki Declaration. The results will be disseminated through peer-review publications and conference presentations. NCT04892199.

Major malformations risk following early pregnancy exposure to metformin a systematic review and meta-analysis.

Metformin is considered as first-line treatment for type 2 diabetes and an effective treatment for polycystic ovary syndrome (PCOS). However, evidence regarding its safety in pregnancy is limited. We conducted a systematic review and meta-analysis of major congenital malformations (MCMs) risk after first-trimester exposure to metformin in women with PCOS and pregestational diabetes mellitus (PGDM). Randomized controlled trials (RCTs) and observational cohort studies with a control group investigating risk of MCM after first-trimester pregnancy exposure to metformin were searched until December 2021. ORs and 95% CIs were calculated separately according to indications and study type using Mantel-Haenszel method outcome data were combined using random-effects model. Eleven studies (two RCTs nine observational cohorts) met the inclusion criteria four included pregnant women with PCOS, four included those with PGDM and three evaluated both indications separately and were considered in both indication groups. In PCOS group, there were two RCTs (57 exposed, 52 control infants) and five observational studies (472 exposed, 1892 control infants) point estimates for MCM rates in RCTs and observational studies were OR 0.93 (95% CI 0.09 to 9.21) (I

Use of sodium-glucose cotransporter 2 inhibitors in Alberta adults with chronic kidney disease a cross-sectional study identifying care gaps to inform knowledge translation.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have important kidney and cardiovascular benefits in adults with chronic kidney disease. Among adults with diabetes, we characterized the prevalence of chronic kidney disease eligible for SGLT2 inhibitor treatment, based on definitions of eligibility from trials and diabetes guidelines, and assessed the predictors of SGLT2 inhibitor use. We conducted a cross-sectional study using linked administrative data from Alberta Health in adults with diabetes (2002-2019). Chronic kidney disease was defined as an estimated glomerular filtration rate (eGFR) less than 90 mLmin1.73 m Of 446 315 adults with diabetes, 76 630 (17.2%, guideline-based definition 12 867 2.9%, trial-based definition) had chronic kidney disease eligible for SGLT2 inhibitor treatment. A total of 7.1% used SGLT2 inhibitors. Older age, lower hemoglobin A Many adults with chronic kidney disease would derive heart and kidney benefits from treatment with SGLT2 inhibitors but had low SGLT2 inhibitor use as of 2019. Efforts will be needed to address lower use of SGLT2 inhibitors among female, older and lower-income adults, and to enhance primary care and promote awareness of the benefits of SGLT2 inhibitors independent of glycemic control.

Comparative effectiveness of metformin versus sulfonylureas on kidney function decline or death among patients with reduced kidney function a retrospective cohort study.

Diabetes often causes kidney disease. In this study, we sought to evaluate if metformin use was associated with death or kidney events in patients with diabetes and concurrent reduced kidney function. We used data from the Veterans Health Administration, Medicare and National Death Index databases to assemble a national retrospective cohort of veterans who were using metformin or sulfonylureas from 2001 through 2016 and who began follow-up at an estimated glomerular filtration rate (eGFR) of less than 60 mLmin1.73 m In the first 360 days, the propensity score-weighted cohort included 24 883 patients who used metformin and 24 998 who used sulfonylureas. There were 33.5 (95% confidence interval CI 30.9-36.3) and 43.0 (95% CI 40.1-46.0) deaths or kidney events per 1000 person-years for patients who used metformin or sulfonylureas, respectively (hazard ratio HR 0.78, 95% CI 0.71-0.85). For the secondary outcome of kidney events, the HR was 0.94 (95% CI 0.67-1.33). In the second period from 361 days onward, the primary outcome event rate was 26.5 (95% CI 24.7-28.5) per 1000 person-years for those who used metformin, compared with 36.3 (95% CI 34.2-38.6) per 1000 person-years for those who used sulfonylureas (HR 0.73, 95% CI 0.67-0.79). Results were consistent for kidney events alone (HR 0.73, 95% CI 0.59-0.91). Metformin use for 361 days or longer after reaching an eGFR of less than 60 mLmin1.73 m

Anti-diabetic effects of fungal Ergosta-4, 6, 8(14), 22-tetraen-3-one from Pholiota adiposa.

Pholiota adiposa is a valuable edible and medicinal fungus. In this research, Ergosta-4, 6, 8(14), 22-tetraen-3-one (ETO) was obtained from Pholiota adiposa which is the first time to study the anti-diabetic and related mechanism. Ergosta-4, 6, 8 (14), 22-tetraen-3-one (ETO) was defined by IR and NMR. Relevant biochemical indicators were detected by ELISA assay, hematoxylin-eosin staining (H E), fasting glucose levels (FBG), oral glucose tolerance test (OGTT), tissue homogenate biochemical measurements, immunohistochemical staining and western blot. In this research, the ETO treatment groups exhibited a significant reduction in fasting blood glucose (FBG) levels, the High dose group (HD) was about 10 mmolL lower than the diabetic control group (DC), and increase in body weight, the HD group weighed about 5 g more than the DC group on average. Also, the levels of triacylglycerol (TG), total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C) were found to be decreased, while the levels of high-density superoxide dismutase (SOD), lipoproteincholesterol (HDL-C), catalase (CAT), and glutathione peroxidase (GSH-Px) were increased in the ETO treatment groups. The pancreatic and liver sections of diabetic control group (DC) exhibited several histopathological changes, but the ETO treatment groups exhibited improvements. ETO treatment led to the significant restoration of islet morphology and function. Moreover, the results of the western blot analysis indicate that ETO could be used for the treatment of diabetes, since it modifies part of the IRS1 PI3K AKT signaling pathway.

Addition of fenofibrate to statins is associated with risk reduction of diabetic retinopathy progression in patients with type 2 diabetes and metabolic syndrome A propensity-matched cohort study.

This study aimed to determine the association between fenofibrate added to statin therapy and diabetic retinopathy progression. In this propensity-matched study using the Korean National Health Insurance Service cohort (2002-2019), patients with type 2 diabetes and metabolic syndrome (≥ 30 years) receiving statin therapy were matched 12 by propensity score into the statin plus fenofibrate group (n 22,395) and statin-only group (n 43,191). The primary outcome was a composite of diabetic retinopathy progression including vitreous hemorrhage, vitrectomy, laser photocoagulation, intravitreous injection therapy and retinal detachment. The median (quartiles) follow-up duration was 44.0 (27.6-70.6) months. For the primary outcome, the incidence rate per 1,000 person-years was 9.66 in the statin-only group and 8.68 in the statin-plus-fenofibrate group. The risk of the primary outcome was significantly lower (hazard ratio HR0.88 95% confidence interval 0.810.96 P 0.005) in the statin-plus-fenofibrate group than in the statin-only group. Only patients with pre-existing retinopathy showed benefits from fenofibrate treatment (HR0.83 0.730.95 P 0.006). In addition, the statin plus fenofibrate group exhibited significantly lower risks of vitreous hemorrhage (HR 0.86 0.750.995 P 0.042), laser photocoagulation (HR0.86 0.770.96 P 0.009) and intravitreous injection therapy (HR0.73 0.590.90 P 0.003) than those in the statin-only group. There was no significant interaction between the different characteristics at baseline and the treatment effect. The addition of fenofibrate to statins was associated with significantly lower risk of diabetic retinopathy progression than statin therapy alone in patients with type 2 diabetes and metabolic syndrome.

The therapeutic potential for senescence-associated diabetes of green alga Enteromorpha prolifera polysaccharide.

DEAE-52 and Sephadex G-100 columns were used to isolate Enteromorpha prolifera polysaccharide (EPP), which contains α-L-Rhap-(1 → 4)-α-L-Arap-(1 → 2)-α-L-Rhap-(1 → 3)-β-D-Galp-(1 → structural fragment, along with α-L-Rhap-(1 → and →2)-α-L-Rhap-(1 → 3)-β-D-GlcpA-(1 → side bonds that connect to →3,6)-β-D-Galp-(1→. The anti-ageing and hypoglycemic activities of EPP were assessed using an ageing diabetic mice model, and the revealed that EPP could improve glucose metabolism-associated parameters and inhibit the expression of ageing associated genes, including p16

Diabetes mellitus secondary to growth hormone-secreting pituitary adenoma.

Growth hormone-secreting pituitary adenoma is a common intracranial benign tumor, characterized by excessive production of growth hormone, which leads to acromegaly or giant disease. An abnormal increase in growth hormone can induce glucose metabolism disorder, which is often diagnosed and treated as type 2 diabetes, because of uncontrollable hyperglycemia, delaying the treatment of the primary disease. This paper reports the diagnosis and treatment data of a patient with growth hormone-secreting pituitary adenoma who was first diagnosed as having diabetes, and reviews the related literature to facilitate a better understanding of the disease.

A Novel Anti-Osteoporosis Mechanism of VK2 Interfering with Ferroptosis via AMPKSIRT1 Pathway in Type 2 Diabetic Osteoporosis.

Type 2 diabetic osteoporosis (T2DOP) is a chronic bone metabolic disease. Compared with traditional menopausal osteoporosis, the long-term high glucose (HG) microenvironment increases patients risk of fracture and osteonecrosis. We were accumulating evidence that implicated ferroptosis as a pivotal mechanism of glucolipotoxicity-mediated death of osteocytes and osteoblast, a novel form of programmed cell death resulting from uncontrolled lipid peroxidation depending on iron. Vitamin K2 (VK2), a fat-soluble vitamin, is clinically applied to prevent osteoporosis and improve coagulation. This study aimed to clarify the role and mechanism of VK2 in HG-mediated ferroptosis. We established the mouse T2DOP model by intraperitoneal injection of streptozotocin solution and a high-fat and high-sugar diet. We also cultured bone marrow mesenchymal stem cells (BMSCs) in HG to simulate the diabetic environment in vitro. Based on our data, VK2 inhibited HG-mediated bone loss and ferroptosis, the latter manifested by decreased levels of mitochondrial reactive oxygen species, lipid peroxidation, and malondialdehyde and increased glutathione in vitro. In addition, VK2 treatment was capable of restoring bone mass and strengthening the expression of SIRT1, GPX4, and osteogenic markers in the distal femurs. As for further mechanism exploration, we found that VK2 could activate AMPKSIRT1 signaling, and knockdown of SIRT1 by siRNA prevented the VK2-mediated positive effect in HG-cultured BMSCs. Summarily, VK2 could ameliorate T2DOP through the activation of the AMPKSIRT1 signaling pathway to inhibit ferroptosis.

Cost-Utility of Liraglutide Plus Standard of Care Versus Standard of Care in People with Type 2 Diabetes and Cardiovascular Risk in Thailand.

Liraglutide has demonstrated a significant reduction in the primary major composite cardiovascular (CV) outcome (CV death, non-fatal myocardial infarction, non-fatal stroke). This study aimed to determine the cost-utility of adding liraglutide to the standard of care (SoC) for treating type 2 diabetes (T2D) in Thailand for three cohorts people with atherosclerotic cardiovascular disease (ASCVD), with no ASCVD, and all people with T2D. A Markov model was developed to capture the long-term costs and outcomes under the perspective of the healthcare system. Costs were based on local data, the transitional probabilities were derived from the LEADER trial, and utilities were derived from published studies. Future costs and outcomes were discounted at 3% annually. A series of sensitivity analyses were performed. Compared to SoC, adding liraglutide incurred higher costs and gained more quality-adjusted life-years (QALYs), yielding incremental cost-effectiveness ratios (ICERs) of above 1 million Thai baht (THB) for the three cohorts. The most influential parameter was the discount rate. When the annual cost of liraglutide reduced from 87,874 to 30,340 THB, 30,116 THB, and 31,617 THB for all people with T2D, people with ASCVD, and people without ASCVD, respectively, the ICER fell below the local threshold of 160,000 THBQALY. Compared to the SoC treatment, the liraglutide group acquired more clinical benefit in terms of fewer CVD. Sensitivity analyses revealed that with an increase in the level of willingness-to-pay (WTP) threshold, adding liraglutide had an increased chance of being a cost-effective strategy. Compared to the SoC treatment, adding liraglutide at the current cost is not cost-effective at the local WTP. People with T2D with ASCVD would have the most potential gain from adding liraglutide treatment compared to other populations.

Projecting the potential cost-effectiveness of dapagliflozin for chronic kidney disease in Kuwait.

In 2019, the prevalence of dialysis in Kuwait were 465 patientmillion population, while the annual mortality rate among dialysis patients reached 12%. To improve resource allocation within the health care system, a cost-effectiveness model was conducted from a societal perspective to assess the cost-effectiveness of the use of dapagliflozin as an add-on-therapy against SoC (ramipril) among CKD patients with or without type-2 diabetes over their lifetime. A Markov process model was utilized to assess the cost-effectiveness of dapagliflozin ramipril versus ramipril alone on a cohort of patients with an eGFR of 25 to 75 mLmin1.73, with or without type-2 diabetes and a urinary ACR of 200 to 5,000 over their lifetime. The model included nine health states (i) the six stages of CKD representing stages 1, 2, 3a, 3b, 4 and 5 (ii)ESRD, which represents RRT as dialysis or kidney transplant and (iii) death. Most of the clinical data were captured from the DAPA-CKD study. We assumed that the mortality risk of our study was similar to DAPA-CKD. The utility data were captured from different studies. Direct medical and indirect costs were captured from local data sources. Sensitivity analyses were conducted. The difference in QALY between dapagliflozin ramipril versus ramipril was 0.2. The difference in cost between the two arms was KWD -4,120 (-USD25750). Dapagliflozin ramipril generate better QALYs and lower costs than ramipril in CKD patients. Dapagliflozin improved the outcomes and generated cost savings in CKD patients. Adoption of dapagliflozin ramipril is considered to be a cost saving option in addition to the improvement in QALYs in CKD patients with or without type-2 diabetes due to its nephroprotective effect, regardless of the aetiology of CKD, which eventually leads to reduction of dialysis and the transplantation cost burden on the Kuwaiti health care system. This study was focussed only on DAPA-CKD cohort.

Continuous Glucose Monitoring to Optimize Management of Diabetes in Patients with Advanced CKD.

Treatment of patients with diabetes and CKD includes optimizing glycemic control using lifestyle modifications and drugs that safely control glycemia and improve clinical kidney and cardiovascular disease outcomes. However, patients with advanced CKD, defined as eGFR <30 mlmin per 1.73 m2 or kidney disease treated with dialysis, have limitations to the use of some preferred glucose-lowering medications, are often treated with insulin, and experience high rates of severe hypoglycemia. Moreover, hemoglobin A1c accuracy decreases as GFR deteriorates. Hence, there is a need for better glycemic monitoring tools. Continuous glucose monitoring allows for 24-hour glycemic monitoring to understand patterns and the effects of lifestyle and medications. Real-time continuous glucose monitoring can be used to guide the administration of insulin and noninsulin therapies. Continuous glucose monitoring can overcome the limitations of self-monitored capillary glucose testing and hemoglobin A1c and has been shown to prevent hypoglycemic excursions in some populations. More data are needed to understand whether similar benefits can be obtained for patients with diabetes and advanced CKD. This review provides an updated approach to management of glycemia in advanced CKD, focusing on the role of continuous glucose monitoring in this high-risk population.

Cardiorenal benefits of finerenone protecting kidney and heart.

Persons with diabetes and chronic kidney disease (CKD) have a high residual risk of developing cardiovascular (CV) complications despite treatment with renin-angiotensin system blockers and sodium-glucose cotransporter type 2 inhibitors. Overactivation of mineralocorticoid receptors plays a key role in the progression of renal and CV disease, mainly by promoting inflammation and fibrosis. Finerenone is a nonsteroidal selective mineralocorticoid antagonist. Recent clinical trials, such as FIDELIO-DKD and FIGARO-DKD and the combined analysis FIDELITY have demonstrated that finerenone decreases albuminuria, risk of CKD progression, and CV risk in subjects with type 2 diabetes (T2D) and CKD. As a result, finerenone should thus be considered as part of a holistic approach to kidney and CV risk in persons with T2D and CKD. In this narrative review, the impact of finerenone treatment on the CV system in persons with type 2 diabetes and CKD is analyzed from a practical point of view.Key messagesDespite inhibition of renin-angiotensin system and sodium-glucose cotransporter type 2, persons with type 2 diabetes (T2D) and chronic kidney disease (CKD) remain on high cardiovascular (CV) residual risk.Overactivation of mineralocorticoid receptors plays a key role in the progression of renal and CV disease, mainly by promoting inflammation and fibrosis that is not targeted by traditional treatments.Finerenone is a nonsteroidal selective mineralocorticoid antagonist that decreases not only albuminuria, but also the risk of CKD progression, and CV risk in subjects with T2D and CKD.

A lifestyle pattern characterized by high consumption of sweet and salty snacks, sugar sweetened beverages and sedentary time is associated with blood pressure in families at risk for type 2 diabetes mellitus in Europe. The Feel4Diabetes Study.

Individuals from families at high-risk for type 2 diabetes mellitus (T2DM) are also in high risk for hypertension and cardiovascular disease. Studies identifying lifestyle patterns combining dietary, physical activity or sedentary variables and examining their possible role to developing blood pressure (BP) are limited. This study aimed to examine the association of different lifestyle patterns (LPs) with BP levels in families at high risk for T2DM in Europe. 1844 adults (31.6% males) at high-risk for T2DM across 6 European countries were included in this cross-sectional study using data from the baseline assessment of the Feel4Diabetes Study. BP measurements, dietary and physical activity assessments were conducted, and screen times was surveyed. Lifestyle patterns were revealed with Principal Component Analysis (PCA) of various data regarding diet, physical activity, screen time and smoking. 3 LPs were identified, LP3 (high consumption of sweet salty snacks, sugar sweetened soft drinks and juices and high amount of screen time) was positively associated with diastolic BP B, 0.52 95%CI (0.05-0.99) and existence of hypertension OR,1.12 95%CI (1.00-1.25). Participants in the highest tertile of LP3 spent mean 3 hours of screen time, consumed 1.5 portions of sweet andor salty snacks and 1 liter of soft drinks on a daily basis, were associated with 12% higher risk of hypertension. Focusing on the combination of eating and lifestyle behaviors may more accurately identify, and therefore guide preventive measures tailored to the specific needs of high-risk populations. This article is protected by copyright. All rights reserved.

Significance of pancreatic duodenal homeobox-1 (

Pancreatic and duodenal homeobox factor-1 ( We performed a meal tolerance test (MTT) and hyperinsulinemic-euglycemic clamping on 63 Japanese subjects, 30 with type 2 diabetes and 33 non-diabetic. We analyzed the rs1124607 HOMA-beta (homeostatic model assessment beta-cell function) was significantly lower in the high-risk group than in the low-risk group for all subjects (72.9±54.2% vs 107.0±63.5%, p<0.05). Glucose levels and glucose area under the curve (AUC) were not significantly different between both the risk groups. The insulin levels at 60 and 120 min and the insulin AUC after MTT were remarkably lower in the high-risk group than those in the low-risk group for all subjects (AUC 75.7±36.7 vs 112.7±59.5, p<0.05). High-risk subjects with type 2 diabetes had significantly lower insulin levels at 30 and 60 min and insulin AUC than low-risk subjects. Non-diabetic high-risk subjects depicted significantly lower insulin levels at 120 and 180 min. There were negligible differences in insulin resistance between the risk groups. These results suggest that the

Efficacy and safety of intensive versus conventional glucose targets in people with type 2 diabetes a systematic review and meta-analysis.

The aim of study is to re-evaluate the risk-benefits of intensive glycemic control in the context of multi-factorial intervention in adults with T2D. We searched Ovid MEDLINE, Embase, Cochrane, and CINHAL for randomized control trials comparing standard glucose targets to intensive glucose targets with pre-specified HbA Fifty-seven publications including 19 trials were included. Compared to conventional glycemic control, intensive glycemic control decreased the risk of non-fatal myocardial infarction (0.8, 0.7-0.91), macroalbuminuria (0.72, 0.5--0.87), microalbuminuria (0.67, 0.52-0.85), major amputation (0.6, 0.38-0.96), retinopathy (0.75 ,0.63-0.9), and nephropathy (0.78, 0.63-0.97). The risk of hypoglycemia increased with intensive glycemic control than conventional treatment (2.04, 1.34-3.1). No reduction in all-cause or cardiovascular mortality was observed. However, in the context of multifactorial intervention, intensive glucose control was associated with a significant reduction in all-cause mortality (0.74, 0.57-0.95). Targeting HbA

Long-Term Risk of Cardiovascular Disease Among Type 2 Diabetes Patients According to Average and Visit-to-Visit Variations of HbA1c Levels During the First 3 Years of Diabetes Diagnosis.

It remains unclear whether a combination of glycemic variability and glycated hemoglobin (HbA1c) status leads to a higher incidence of cardiovascular disease (CVD). Therefore, to investigate CVD risk according to the glucose control status during early diabetes, we examined visit-to-visit HbA1c variability among patients with type 2 diabetes (T2DM). In this 9-year retrospective study, we measured HbA1c levels at each visit and tracked the change in HbA1c levels for 3 years after the first presentation (observation window) in newly diagnosed T2DM patients. We later assessed the occurrence of CVD in the last 3 years (target outcome window) of the study period after allowing a 3-year buffering window. The HbA1c variability score (HVS divided into quartiles, HVSQ1-4) was used to determine visit-to-visit HbA1c variability. Among 4,817 enrolled T2DM patients, the mean HbA1c level was < 7% for the first 3 years. The group with the lowest HVS had the lowest rate of CVD (9.4% 1041,109 patients). The highest incidence of CVD of 26.7% (830 patients) was found in HVS ≥ 9.0%Q3, which was significantly higher than that in HVS 6.0-6.9%Q1 ( To our knowledge, this is the first long-term study to analyze the importance of both HbA1c change and visit-to-visit HbA1c variability during outpatient visits within the first 3 years. Lowering glucose levels during early diabetes may be more critical than reducing visit-to-visit HbA1c variability.

Low Bone Turnover Associates with Lower Insulin Sensitivity in Newly Diagnosed Drug-naïve Persons with Type 2 Diabetes.

Bone turnover markers (BTMs) are lower in type 2 diabetes (T2D). The relationships between bone turnover, β-cell function, and insulin sensitivity in T2D are uncertain. To investigate if fasting levels of BTMs in persons with T2D are associated with β-cell function or insulin sensitivity. We defined three T2D phenotypes the insulinopenic (low β-cell function, high insulin sensitivity), the classical (low β-cell function, low insulin sensitivity) and the hyperinsulinemic (high β-cell function, low insulin sensitivity) phenotypes, in the Danish Centre for Strategic Research in T2D cohort, using the homeostatic assessment model. We selected age and gender matched subgroups to represent the three T2D phenotypes, yielding 326 glucose-lowering treatment naïve persons with T2D. Median values of BTMs between the three T2D phenotypes were compared. Regression models were applied to assess the association between BTMs, β-cell function and insulin sensitivity, adjusted for potential confounders. Median serum levels of procollagen type I N-terminal propeptide, C-terminal telopeptide of type I collagen and osteocalcin were higher in the insulinopenic phenotype (52.3 (μgL) IQR 41.6, 63.3, 259.4 (ngL) 163.4, 347.7, 18.0 (μgL) 14.4, 25.2, respectively) compared to the classical (41.4 31.0, 51.4, 150.4 103.5, 265.1, 13.1 10.0, 17.6, respectively) and the hyperinsulinemic (43.7 32.3, 57.3, 163.3 98.9, 273.1, 15.7 10.2, 20.8, respectively) phenotypes (all p < 0.01). These differences persisted after adjustment for age, sex, waist-to-hip ratio, or fasting plasma glucose (p < 0.01). BTMs are lower in newly diagnosed persons with T2D characterized by low insulin sensitivity.

Eligibility for sotagliflozin in a real-world heart failure population based on the SOLOIST-WHF trial enrolment criteria Data from the swedish heart failure registry.

The SOLOIST-WHF trial demonstrated efficacy of sotagliflozin in patients with type 2 diabetes mellitus (T2DM) and recent worsening heart failure (HF) regardless of ejection fraction (EF). Selection criteria in trials may limit their generalizability. Therefore, we aimed to investigate eligibility for sotagliflozin based on the SOLOIST-WHF criteria in a real-world HF population. SOLOIST-WHF criteria were applied to patients stabilized after HF hospitalization in the Swedish HF Registry according to 1) literal scenario (all inclusionexclusion criteria) or 2) pragmatic scenario (only criteria likely to influence treatment decisions). Of 5453 inpatients with T2DM and recent worsening HF, 51.4% had reduced EF (HFrEF), 19.1% mildly reduced (HFmrEF), and 29.5% preserved EF (HFpEF). Eligibility (literal) was 27.2% (32.4% in HFrEF, 24.7% in HFmrEF, 19.7% in HFpEF) and eligibility (pragmatic) was 62.8% (69.1%, 60.3%, 53.4%, respectively). In the literal scenario, criteria limiting eligibility were HF duration < 3 months, eGFR <30 mlmin1.73m2, age > 85 years, acute coronary syndrome < 3 months, and insufficiently high N-terminal pro-B-type natriuretic peptide levels. Eligible vs. non-eligible patients had more severe HF, higher cardiovascular (CV) comorbidity burden, higher use of HF treatments, and higher event rates (all-cause death 30.8 vs. 27.2 per 100 patient-years, CV death 19.1 vs. 16.6, and HF hospitalization 36.7 vs. 24.0). In this large, real-world HF cohort with T2DM, ∼13 of patients were eligible for sotagliflozin in the literal and ∼23 of patients in the pragmatic scenario. Eligible patients had more severe HF and higher event rates, in particular CV and HF events.

Comparative Study of New Biomarkers in Iraqi DM2 with and without Complications.

Recent research indicates that persistent inflammatory responses may contribute to the rise of diabetic nephropathy (DN) and diabetic cardiovascular disease (DCVD) in type 2 diabetes mellitus patients (DM2). Numerous molecules associated with inflammation and angiogenesis have been implicated in the development and progression of DN and DCVD, respectively. The subjects were separated into five groups healthy controls (n 25), type 2 diabetes mellitus patients (n 30), type 2 diabetes mellitus patients with nephropathy DN (n 30), and type 2 diabetes mellitus patients with cardiovascular disease DCVD (n 30). The blood levels of irisin, IL-8, HbA1C, urea, and creatinine were determined. In current study there was high significant increased irisin levels (p< 0.001) in DN patients than other groups and a high significant decreased IL-8 level in DCVD. Serum IL-8 and irisin levels may serve as early indicators of DM2 problems (DN, DCVD).

Role of Serum Lipids, Blood Glucose and Blood Pressure in Breast Cancer Risk for Women with Type 2 Diabetes Mellitus.

Women with type 2 diabetes mellitus (T2DM) have an increased risk of breast cancer. We aimed to determine the contribution of lipids, glucose and blood pressure to this risk based on the multifactorial nature of T2DM. This population-based cohort study used data from a Dutch database (the Groningen Initiative to Analyse Type 2 Diabetes Treatment) for the period 2004-2013. The cohort included women diagnosed with T2DM, aged 30-80 years, with no history of breast cancer and with follow-up data for at least 1 year. We used Cox proportional hazards models to estimate the associations of exposures with breast cancer occurrence, reporting adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Exposures of interest included total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, glycated hemoglobin A (HbA1c) and systolic blood pressure (SBP). During a median of 4.45 years follow-up, 183 of 10,183 included women received a breast cancer diagnosis. We observed U-shaped associations with breast cancer incidence for total cholesterol and HDL-C at baseline. Compared with moderate elevations, women had significantly higher breast cancer risks associated with high total cholesterol (aHR, 95% CI 1.72, 1.15-2.55) and HDL-C (aHR, 95% CI 1.74, 1.18-2.58) levels, while low total cholesterol (aHR, 95% CI 1.43, 0.94-2.19) and HDL-C (aHR, 95% CI 1.44, 0.95-2.17) levels produced marginal effects without significance. Women with high LDL-C levels more often received a breast cancer diagnosis than those with medium levels (aHR, 95% CI 1.56, 1.03-2.35). This real-world dataset highlights the importance of balancing lipid profiles, particularly total cholesterol and HDL-C. Dysregulation of the lipid profile, not the glucose or blood pressure profiles, may increase the risk of breast cancer in women with T2DM.

Reduced volume of diabetic pancreatic islets in rodents detected by synchrotron X-ray phase-contrast microtomography and deep learning network.

The pancreatic islet is a highly structured micro-organ that produces insulin in response to rising blood glucose. Here we develop a label-free and automatic imaging approach to visualize the islets

Factors Associated with Liver Fibrosis in Chinese Patients with Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are frequently co-occurring diseases. Liver fibrosis (LF), with increasing incidence, has a prognostic value for NAFLD mortality. Our study aimed to investigate the relevant factors for FL in T2DM individuals with NAFLD. A total of 565 T2DM patients with NAFLD from Hebei General Hospital participated in the study. Patients underwent an abdominal ultrasound, a questionnaire and laboratory tests. The fibrosis-4 index (FIB-4) was used to evaluate LF, with FIB ≥1.3 indicating LF and FIB ≥2.67 indicating F3-4 fibrosis. Compared with NLF group, LF group had higher levels of systolic blood pressure (SBP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transpeptidase (GGT). The glomerular filtration rate (GFR), low-density lipoprotein cholesterol (LDL), glycated hemoglobin (HbA1c), and platelets (PLT) in LF patients were lower than those without LF. Patients with LF were older than those without LF. ALT, AST, and GGT in patients with severe LF were higher than those with mild LF, while platelet was lower. Age, SBP, duration of diabetes, ALT, AST, and GGT were positively correlated with FIB-4, while eGFR, TC, LDL, and HbA1c were negatively correlated with FIB-4. Logistic regression showed that age, SBP, ALT, GGT, LDL, and PLT were independently associated with LF. For T2DM patients combined with NAFLD, older age, higher SBP, higher ALT, higher GGT, lower LDL, and lower PLT were relevant factors for LF.

Ghrelin regulates the proliferation and apoptosis of high glucose-induced islet cells through the PI3K-Akt signaling pathway.

Ghrelin may have therapeutic value in mitigating insulin resistance and type 2 diabetes, based on which we further explore the action mechanism of ghrelin on islet cells in this research. In the course of experiments, MIN6 cells were induced by glucose and then treated with acylated or unacylated ghrelin. The effects of ghrelin on the viability, proliferation, apoptosis, and insulin release of high glucose-induced islet cells were detected by Cell Counting Kit-8, 5-ethynyl-2-deoxyuridine, flow cytometry, and enzyme-linked immunosorbent assays, respectively. Meanwhile, cells were treated with LY294002 to explore whether and how the inhibited phosphoinositide 3-kinase-protein kinase B (PI3K-AKT) signaling pathway participated in the internal mechanism of ghrelin-regulating islet cells. Western blotting was performed to quantify the expression levels of Bcl-2, Bax, Cleaved caspase-3, PI3K, and AKT. As a result, ghrelin alleviated high glucose-induced suppression of viability and proliferation and promotion on apoptosis of MIN6 cells. Ghrelin also attenuated the inhibitory effects of high glucose on expression levels of PI3K-Akt signaling axis-related proteins and insulin release in MIN6 cells. Besides, ghrelin weakened the impacts of high glucose on boosting MIN6 cell apoptosis and hindering proliferation through the PI3K-Akt signaling axis. Collectively, ghrelin regulates the proliferation and apoptosis of high glucose-induced islet cells through the PI3K-Akt signaling pathway.

Clinical Measures of Dual task Gait Evaluation in Individuals with Type 2 Diabetes Mellitus- A Mini-review.

Background - Cognitive and motor deficits intertwined with type 2 diabetes mellitus (T2DM) alter walking patterns of the individuals. As walking is combined with various challenging cognitive tasks in daily activities, dual task testing is a promising avenue for gait evaluation and fall prediction in various conditions. However, there is a lack of clarity on the appropriate clinical measures for dual task gait evaluation in T2DM individuals. The present study aims to review and identify the appropriate clinical measures for dual task gait evaluation in T2DM Methods Electronic databases of PubMed, CINAHLPlus and scholarly platforms were searched to identify the relevant articles. Review has included studies which have subjects with T2DM, dual task testing as a part of evaluation, has used clinical measures to assess dual task gait and was available in English. 16 articles met the inclusión criteria. Four studies used cognitive timed up and go test (TUG), four studies used walking while talking test one study used extended TUG one study used walking and remembering testone study used instrumented TUG along with manual TUG and arithmetic subtractions two studies used inertial sensors for gait evaluation along with backword counting one study used two dimensional video analysis for gait along with verbal fluency task and calculation one study used TUG with arithmetic additions task one study used Manual TUG and arithmetic subtraction task while walking on GAITRITE walkway. The studies show a lack of valid and reliable clinical measures for dual task gait evaluation in T2DM.

When serum c-peptide measurement drives adequate diabetes mellitus diagnosis and therapy a case report.

Therapeutic targets in type 2 diabetes mellitus (T2D) are oriented towards nephron- and cardio-protection and the prescription of antihyperglycemic agents with proven renal and cardiovascular benefits are increasing over time. Failure to promptly diagnose insulinopenic diabetes may adversely affect the adequacy of treatment and have harmful consequences, including severe hyperglycemia and diabetic ketoacidosis. Herein we present the case of a 57-year-old woman referred to our clinic due to poor glycemic control (HbA1c 80 mmolmol, therapeutic target <53 mmolmol), class III obesity (BMI 41 kgm2 normal value <25 kgm2), and high cardiovascular risk misdiagnosed with T2D several years before. C-peptide measurement (0.3 ngdL reference range 1.1 - 4.4 ngmL) confirmed the diagnosis of an insulinopenic form of diabetes, and islet autoimmunity consequently measured (GADA 2,000 UAmL, reference range <5 UAmL IA2 17.1 UAmL, reference range <7.5 UAmL) and defined the diagnosis of an autoimmune form of diabetes. Deprescribing insulin therapy in T2D patients in favor of other antihyperglycemic medications has become a growing therapeutic opportunity to provide adequate glucose control, promote weight loss, improve insulin sensitivity, and ameliorate cardiovascular and renal outcomes. However, due to immediate problems, a blunted insulin reserve poses a significant restriction on the prescription of non-insulin agents (e.g., diabetic ketoacidosis due to gliflozins). According to our experience, the routine testing of insulin reserve provides detailed information on diabetes pathophysiology with positive implications for the appropriateness of pharmacological prescriptions. As part of our routine evaluation of diabetic patients, C-peptide measurement is a valuable and inexpensive tool to reclassify diabetes types and provide more appropriate disease management.

Non-altered incretin secretion in women with impaired fasting plasma glucose in the early stage of pregnancy a case control study.

Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) may be involved in pathogenesis of gestational diabetes mellitus (GDM). The aim was to compare GLP-1 and GIP production in fasting state and during 3 h mixed meal tolerance test (MMTT) measured by mean area under the curve (AUC) between pregnant women with normal and impaired fasting glucose in an early phase of pregnancy, and healthy non-pregnant controls. This study was undertaken as a case-control study. Repeated measurement of fasting plasma glucose ≥ 5.1 mmolL and < 7.0 mmolL during the first trimester of pregnancy and exclusion of overt diabetes according to IADSPG criteria was used to find women with impaired fasting glucose (n 22). Age-matched controls consisted of healthy pregnant (n 25) and non-pregnant (n 24) women. In addition to incretins, anthropometric parameters and markers of insulin resistance and beta-cell function were assessed. Variables were summarized as median (interquartile range). Fasting GLP-1 and GIP concentration or their AUC during MMTT did not significantly differ between pregnant women with impaired fasting plasma glucose GLP-1 Women with impaired fasting plasma glucose did not show altered incretin production in the first trimester of pregnancy. In contrast to type 2 diabetes, impaired incretin secretion does not seem to play a major role in the early development of GDM.

Impact of the gut microbiota and associated metabolites on cardiometabolic traits, chronic diseases and human longevity a Mendelian randomization study.

Features of the gut microbiota have been associated with several chronic diseases and longevity in preclinical models as well as in observational studies. Whether these relations underlie causal effects in humans remains to be established. We aimed to determine whether the gut microbiota influences cardiometabolic traits as well as the risk of chronic diseases and human longevity using a comprehensive 2-Sample Mendelian randomization approach. We included as exposures 10 gut-associated metabolites and pathways and 57 microbial taxa abundance. We included as outcomes nine cardiometabolic traits (fasting glucose, fasting insulin, systolic blood pressure, diastolic blood pressure, HDL cholesterol, LDL cholesterol, triglycerides, estimated glomerular filtration rate, body mass index BMI), eight chronic diseases previously linked with the gut microbiota in observational studies (Alzheimers disease, depression, type 2 diabetes, non-alcoholic fatty liver disease, coronary artery disease (CAD), stroke, osteoporosis and chronic kidney disease), as well as parental lifespan and longevity. We found 7 associations with evidence of causality before and after sensitivity analyses, but not after multiple testing correction (1198 tests). Most effect sizes (47) were small. The two largest exposure-outcome effects were markedly attenuated towards the null upon inclusion of BMI or alcohol intake frequency in multivariable MR analyses. While finding robust genetic instruments for microbiota features is challenging hence potentially inflating type 2 errors, these results do not support a large causal impact of human gut microbita features on cardiometabolic traits, chronic diseases or longevity. These results also suggest that the previously documented associations between gut microbiota and human health outcomes may not always underly causal relations.

Forkhead box P3 gene polymorphisms predispose to type 2 diabetes and diabetic nephropathy in the Han Chinese populations a genetic-association and gender-based evaluation study.

Functional mutations or polymorphisms affecting forkhead box P3 (FOXP3) can lead to their abnormal FOXP3 gene expression andor defective Treg cells generation, thus resulting in autoimmune disease and inflammatory disorders. FOXP3 also plays a key role in Type 2 diabetes mellitus (T2DM) and its complications, because the disease usually involves chronic low-grade inflammatory disorders and is associated with long-term immune system imbalance. This study aimed to investigate the association between FOXP3 polymorphisms and the susceptibility to T2DM and type 2 diabetes nephropathy (T2DN) within the Han Chinese populations. Polymorphisms in rs3761548CA and rs2294021CT were examined in 400 patients (which include an equal number of T2DM and T2DN groups) and 200 healthy controls using PCR-HRM and sequence analysis. The genotype and allelic frequencies of the two single nucleotide polymorphisms (SNPs) were significantly different in T2DM and the progression of diabetes developing to T2DN. The further gender-based evaluation showed that in female subjects, rs3761548CA was associated with an approximately 3-fold higher threat for T2DM and 4.5-fold for T2DN, while there was no noticeable association with rs2294021CT in males, the promoter polymorphism showed an increased predisposition of 5.4-fold and 3.4-fold predisposition to T2DM and T2DN, respectively, while rs2294021 polymorphism could impart a nearly 2-fold risk of developing T2DN. An additional analysis of combined genotypes (rs3761548 CA-rs2294021CT) revealed that CC-CC and CC-CT can be considered protective combinations in the predisposition of males with diabetes towards T2DN, while AA-CC and AA-TT have the opposite effect. This study demonstrated the possible involvement of individual and combined genetic associations of rs3761548CA and rs2294021CT polymorphisms with the susceptibility to diabetes and diabetic nephropathy in the Han Chinese population, as well as gender bias.

Pattern of macronutrients intake among type-2 diabetes mellitus (T2DM) patients in Malaysia.

The incidence of type 2 diabetes mellitus (T2DM) is rising rapidly in Malaysia. Modifying dietary intake is key to both the prevention and treatment of T2DM. This study aims to investigate the pattern of macronutrient intake among T2DM patients in Malaysia. This study was carried out on adults aged between 35 and 70 years, residing in urban and rural Malaysian communities. A series of standardised questionnaires was used to assess the sociodemographic information, dietary intake and physical activity level of 15,353 respondents who provided informed consent to participate in this study. Blood sampling (finger prick test) and physical examination were performed to obtain blood glucose and anthropometric data, respectively. The Chi-square test was used to assess differences in the trends of macronutrient intake among T2DM patients. The total number of participants diagnosed with T2DM in this study was 2254. Of these, 453 (20.1%) were newly diagnosed, 1156 (51.3%) were diagnosed for ≤5 years and 645 (28.6%) were diagnosed for > 5 years. Male patients show that there were significant differences among the three groups of T2DM according to the following variables age, BMI, residency, participant comorbidity of hypertension, family history of T2DM and hypertension, and active smoker. Meanwhile, female patients show significant differences among the three groups of T2DM according to the following variables age, BMI, marital status, education level, residency, participant comorbidity of hypertension and family history of T2DM. Most of the male patients consumed appropriate proportions of carbohydrate (458, 60.7%) and protein (618, 81.9%). However, female patients did not show any significant differences of the macronutrients intake among the three groups of T2DM patients. The pattern of dietary intake among T2DM patients in this study showed consumption of carbohydrate and protein within the range of Malaysian RNI, coupled with high fat intake. Compliance with the Recommended Nutrient Intake (RNI) was satisfactory for both carbohydrate and protein but not for fat. The pattern indicated a preference for fat rather than protein when carbohydrate intake was restricted.

Improved prognosis with integrated care management including early rhythm control and healthy lifestyle modification in patients with concurrent atrial fibrillation and diabetes mellitus a nationwide cohort study.

Patients with concurrent atrial fibrillation (AF) and diabetes mellitus (DM) AF-DM have a high risk of cardiovascular and diabetes-related complications, but are less engaged in a comprehensive treatment approach. We evaluated the association of early rhythm control (ERC), lifestyle modification (LSM), and a combination of ERC and LSM with cardiovascular or diabetes-related complication risk in patients with AF-DM (type 2). From the National Health Information Database, 47,940 patients diagnosed with AF-DM in 2009-2016 were included. We defined ERC as rhythm control therapy within two years of AF diagnosis and LSM as adherence to ≥ 2 of the healthy behaviors among non-current smoking, non-drinking, and regular exercise. We compared the primary (ischemic stroke) and secondary (macro- and microvascular complications, glycemic emergency, and all-cause death) outcomes in four groups non-ERC and non-LSM (group 1), LSM only (group 2), ERC only (group 3), and both ERC and LSM (group 4). Of total, 10,617 (22%), 26,730 (55.8%), 2,903 (6.1%), and 7,690 (16.0%) were classified into groups 1 to 4, in sequence. The mean duration from AF diagnosis to ERC was 25.6 ± 75.5 days. During 4.0 (interquartile range 2.5-6.2) years follow-up, groups 2 and 3 were associated with 23% and 33% lower risks of stroke than group 1, respectively. Group 4 was associated with the lowest risk of stroke hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.51-0.67, p < 0.001. Regarding secondary outcomes, the lowest risks were also observed in group 4 macro- and microvascular complications, glycemic emergency, and all-cause death had HRs (95% CIs) of 0.63 (0.56-0.70), 0.88 (0.82-0.94), 0.72 (0.62-0.84), and 0.80 (0.73-0.87), respectively, all p < 0.001. For AF-DM patients, ERC and LSM exert a synergistic effect in preventing cardiovascular and diabetes-related complications with the greatest lowered risk of stroke. A comprehensive treatment approach should be pursued in AF-DM patients.

Understanding integrated service delivery a scoping review of models for noncommunicable disease and mental health interventions in low-and-middle income countries.

Noncommunicable diseases (NCDs) and mental health conditions represent a growing proportion of disease burden in low- and middle-income countries (LMICs). While past efforts have identified interventions to be delivered across health system levels to address this burden, the challenge remains of how to deliver heterogenous interventions in resource-constrained settings. One possible solution is the Integration of interventions within existing care delivery models. This study reviews and summarizes published literature on models of integrated NCD and mental health care in LMICs. We searched Pubmed, African Index Medicus and reference lists to conduct a scoping review of studies describing an integrated model of NCD or neuropsychiatric conditions (NPs) implemented in a LMIC. Conditions of interest were grouped into common and severe NCDs and NPs. We identified domains of interest and types of service integration, conducting a narrative synthesis of study types. Studies were screened and characteristics were extracted for all relevant studies. Results are reported using PRISMA-ScR. Our search yielded 5004 studies, we included 219 models of integration from 188 studies. Most studies were conducted in middle-income countries, with the majority in sub-Saharan Africa. Health services were offered across all health system levels, with most models implemented at health centers. Common NCDs (including type 2 diabetes and hypertension) were most frequently addressed by these models, followed by common NPs (including depression and anxiety). Conditions andor services were often integrated into existing primary healthcare, HIV, maternal and child health programs. Services provided for conditions of interest varied and frequency of these services differed across health system levels. Many models demonstrated decentralization of services to lower health system levels, and task shifting to lower cadre providers. While integrated service design is a promising method to achieve ambitious global goals, little is known about what works, when, and why. This review characterizing care integration programs is an initial step toward developing a structured study of care integration.

Metabolic dysfunction-associated fatty liver disease is associated with an increase in systolic blood pressure over time linear mixed-effects model analyses.

Metabolic dysfunction-associated fatty liver disease (MAFLD), a new feature of fatty liver (FL) disease that is defined as FL with overweightobesity, type 2 diabetes mellitus or metabolic dysregulation, has been reported to be associated with the development of diabetes mellitus, chronic kidney disease and cardiovascular disease. However, the association between MAFLD and hypertension remains unclear. We investigated the association between MAFLD and systolic blood pressure (SBP) over a 10-year period in 28,990 Japanese subjects who received annual health examinations. After exclusion of subjects without data for SBP and abdominal ultrasonography at baseline, a total of 17,021 subjects (menwomen 10,9736048 mean age 49 years) were recruited. Linear mixed-effects model analyses using diagnoses of FL, nonalcoholic fatty liver disease (NAFLD) or MAFLD and age, sex, SBP, use of anti-hypertensive drugs, levels of uric acid and estimated glomerular filtration rate, family history of hypertension and habits of current smoking and alcohol drinking at baseline as well as the duration of the observation period and the interaction between each covariate and the duration of the observation period showed that the significant association of change in SBP over time with diagnosis of MAFLD (estimate 0.223 mmHgyear, P < 0.001) was greater than that with diagnoses of FL (estimate 0.196 mmHgyear, P < 0.001) and NAFLD (estimate 0.203 mmHgyear, P < 0.001). Furthermore, the rate of increase in SBP over time was higher in subjects with MAFLD than in subjects without FL and subjects with FL who had no MAFLD. In conclusion, MAFLD is significantly associated with an increase in SBP over time. The presence of metabolic dysfunction-associated fatty liver disease (MAFLD) is significantly associated with an increase in systolic blood pressure over time.

Prevalence of atherogenic dyslipidemia, related factors and level of lipid control in the general population of Galicia. GALIPEMIAS study.

GALIPEMIAS is a study designed to establish the prevalence of familial dyslipidemia in the general population of Galicia. The objective of the present study was to assess the prevalence of atherogenic dyslipidemia (AD), its relationship with other cardiovascular risk (CVR) factors, and the degree of lipid control. Cross-sectional study carried out in the general population over 18 years of age residing in Galicia and with a health card from the Galician Health Service (N1,000). Selection of the sample by means of random sampling by conglomerates. The AD prevalence adjusted for age and sex and the related variables were analyzed. The prevalence of AD adjusted for age and sex was 6.6% (95% CI 5.0-8.3%). Arterial hypertension, altered basal glycemia, type 2 diabetes mellitus and cardiovascular disease were more frequent in subjects with AD than in the rest of the population. 47.5% of the subjects with AD had a high or very high CVR. Lipid-lowering drugs were received by 38.9% (30.5% statins) of the participants with AD (46.1% of those with high and 71.4% of those with very high CVR). 25.4% of the subjects with AD had target LDL-c levels, all of them with low or moderate CVR. The prevalence of AD in the general adult population of Galicia is not negligible, and it was related to several CVR factors and cardiovascular disease. Despite this, this lipid alteration was underdiagnosed and undertreated.

Resting-state network functional connectivity before and after bariatric surgery.

Bariatric surgery is an increasingly popular treatment for patients with severe obesity and related health issues (e.g., diabetes, cardiovascular disease). Studies have identified alterations in functional connectivity both in obesity and following surgical treatment for severe obesity. This study aimed to assess brain function via resting-state within-network connectivity in bariatric surgery patients with severe obesity. University hospital. Thirty-four bariatric surgery patients completed functional neuroimaging at baseline and postoperatively (goal, 12 weeks actual, 16 weeks, on average). They also self-reported health information. Baseline resting-state functional connectivity (RSFC) was predicted by baseline age, body mass index (BMI), continuous positive airway pressure use, and reported history of rheumatoid arthritis and type 2 diabetes. Change in RSFC was assessed using the same predictors. This model was run with and without controlling for baseline RSFC. Higher baseline BMI predicted lower baseline RSFC in 3 networks. Lower baseline RSFC also was related to rheumatoid arthritis and type 2 diabetes. Difference between baseline and follow-up RSFC was strongly negatively associated with baseline RSFC. Controlling for baseline RSFC, type 2 diabetes negatively predicted RSFC difference. RSFC may reflect brain dysfunction in patients with obesity and related diseases. That less connectivity at baseline predicted greater positive change suggests that RSFC may be a biomarker of neurocognitive improvement following bariatric surgery. Diseases more prevalent in patients with obesity (e.g., rheumatoid arthritis and type 2 diabetes) along with elevated BMI negatively affect RSFC likely through inflammatory pathways.

mTORC1 syndrome (TorS) unified paradigm for diabetesmetabolic syndrome.

Glucolipotoxicity and insulin resistance are claimed to drive type 2 diabetes (T2D) and the non-glycemic diseases of the metabolic syndrome (MetS) (obesity, dyslipidemia, hypertension). In line with that, glycemic andor insulin control are considered to be primary goal in treating T2DMetS. However, recent standard-of-care (SOC) treatments of T2D, initially designed to control T2D hyperglycemia, appear now to alleviate the cardio-renal and non-glycemic diseases of T2DMetS independently of glucose lowering and insulin resistance, and in non-T2D patients altogether, calling for an alternative unifying pathophysiologytreatment paradigm for T2DMetS. This opinion article proposes to replace the current glucolipotoxicinsulin-resistance paradigm of T2DMetS with an mammalian target of rapamycin complex 1 (mTORC1) syndrome (TorS) paradigm, implying an exhaustive cohesive disease entity driven by an upstream hyperactive mTORC1, and which includes diabetic hyperglycemia, diabetic dyslipidemia, hypertension, diabetic macrovascular and microvascular disease, non-alcoholic fatty liver disease, some cancers, neurodegeneration, polycystic ovary syndrome (PCOS), psoriasis, and others. The TorS paradigm may account for the insulin-resistant glycemic context of TorS, combined with response to insulin of the non-glycemic diseases of TorS. The TorS paradigm may account for the efficacy of current antidiabetic SOC treatments in diabetic and nondiabetic patients. Most importantly, the TorS paradigm may generate novel treatments for TorS.

Structural studies identify angiotensin II receptor blocker-like compounds as branched chain ketoacid dehydrogenase kinase inhibitors.

The mammalian mitochondrial branched chain ketoacid dehydrogenase (BCKD) complex is a multienzyme complex involved in the catabolism of branched chain amino acids. BCKD is regulated by the BCKD kinase, or BCKDK, which binds to the E2 subunit of BCKD, phosphorylates its E1 subunit, and inhibits enzymatic activity. Inhibition of the BCKD complex results in increased levels of branched chain amino acids and branched chain ketoacids, and this buildup has been associated with heart failure, type 2 diabetes mellitus, and non-alcoholic fatty liver disease. To find BCKDK inhibitors for potential treatment of these diseases, we performed both NMR and virtual fragment screening and identified tetrazole-bearing fragments that bind BCKDK at multiple sites. Through structure-based virtual screening expanding from these fragments, the angiotensin receptor blocker (ARB) class anti-hypertension drugs, and ARB-like compounds, were discovered to be potent BCKDK inhibitors, suggesting potential new avenues for heart failure treatment combining BCKDK inhibition and anti-hypertension.

The global syndemic of metabolic diseases in the young adult population A consortium of trends and projections from the Global Burden of Disease 2000-2019.

A significant proportion of premature deaths globally are related to metabolic diseases in young adults. We examined the global trends and mortality of metabolic diseases in individuals aged below 40 years using data from the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019. From 2000 to 2019, global estimates of deaths and disability-adjusted life years (DALYs) were described for metabolic diseases (type 2 diabetes mellitus T2DM, hyperlipidemia, hypertension, obesity, non-alcoholic fatty liver disease NAFLD). Subgroup analyses were performed based on sex, geographical regions and Socio-Demographic Index (SDI). Age-standardised death and DALYs were presented per 100,000 population with 95 % uncertainty intervals (UI). Projections of mortality and DALYs were estimated using regression models based on the GBD 2019 data and combining them with Institute for Health Metrics and Evaluation projection counts for years up to 2050. In 2019, the highest age-standardised death rates were observed in hypertension (133·88 121·25-155·73), followed by obesity (62·59 39·92-89·13), hyperlipidemia (56·51 41·83-73·62), T2DM (18·49 17·18-19·66) and NAFLD (2·09 1·61-2·60). Similarly, obesity (1932·54 1276·61-2639·74) had the highest age-standardised DALYs, followed by hypertension (2885·57 2580·75-3201·05), hyperlipidemia (1207·15 975·07-1461·11), T2DM (801·55 670·58-954·43) and NAFLD (53·33 40·73-68·29). Mortality rates decreased over time in hyperlipidemia (-0·6 %), hypertension (-0·47 %), NAFLD (-0·31 %) and T2DM (-0·20 %), but not in obesity (1·07 % increase). The highest metabolic-related mortality was observed in Eastern Mediterranean and low SDI countries. By 2050, obesity is projected to contribute to the largest number of deaths (102·8 % increase from 2019), followed by hypertension (61·4 % increase), hyperlipidemia (60·8 % increase), T2DM (158·6 % increase) and NAFLD (158·4 % increase), with males continuing to bear the greatest burden across all metabolic diseases. The growing burden of metabolic diseases, increasing obesity-related mortality trends, and the sex-regional-socioeconomic disparities evident in young adulthood, underlie the concerning growing global burden of metabolic diseases now and in future.

Inhibition of VEGF-B signaling prevents non-alcoholic fatty liver disease development by targeting lipolysis in the white adipose tissue.

Hepatosteatosis is a hallmark of Non-alcoholic fatty liver disease (NAFLD), a common co-morbidity in Type 2 diabetes (T2DM). The pathogenesis of NAFLD is complex and involves the crosstalk between the liver and the white adipose tissues (WAT). Vascular Endothelial Growth Factor B (VEGF-B) has been described to control tissue lipid accumulation by regulating the transport properties of the vasculature. The role of VEGF-B-signaling and the contribution to hepatosteatosis and NAFLD in T2DM is currently not understood. C57BL6J mice treated with a neutralizing antibody against VEGF-B, or mice with adipocyte-specific overexpression- or under-expression of VEGF-B (Adipoq Pharmacological inhibition of VEGF-B signaling in diabetic mice reduced hepatosteatosis and NAFLD by blocking WAT lipolysis. Mechanistically we show, by using HFD-fed Adipoq Taken together, our data from mouse models and human subjects suggest that VEGF-B antagonism may represent an approach to combat NAFLD by targeting hepatosteatosis through suppression of lipolysis. NAFLD is a common co-morbidity in type 2 diabetes mellitus (T2DM), and the global prevalence is between 25-29 %. There are currently no approved medicines for treating NAFLD, and given the enormous proportions of the ongoing diabetes epidemics, there is an urgent need to identify new treatment options. Our work suggest that VEGF-B antagonism may represent an approach to combat NAFLD by targeting hepatosteatosis through suppression of lipolysis. The neutralizing anti-VEGF-B antibody, which was used in this study, has already entered clinical trials in diabetic patients. Therefore, we believe that our results are of great general interest to a broad audience, including patients and patient organizations, the medical community, academia, the life science industry and the public.

Ten-year prognostic value of coronary CT angiography in asymptomatic patients with type 2 diabetes.

The United Kingdom Prospective Diabetes Study (UKPDS) risk score has limited value for predicting coronary artery disease (CAD) events. We investigated the additive value of coronary computed tomography angiography (CCTA) on top of the UKPDS risk score in predicting 10-year adverse cardiac events in asymptomatic patients with type 2 diabetes. We evaluated 589 asymptomatic diabetic patients without a history of CAD who underwent CCTA. The primary outcome was a composite of cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, and revascularization. We estimated the discrimination and reclassification ability for the prediction models, which included combinations of the UKPDS category, severity of stenosis, and coronary artery calcium score by CCTA. The incidence of the primary outcome was 12.4%. During 10 years of follow-up, patients without plaque by CCTA tended to have a low CAD event rate, while those with obstructive CAD tended to have a high event rate, irrespective of the baseline UKPDS risk category. The model that included only the UKPDS category had a Harrells c-index of 0.658 adding the degree of stenosis to the model significantly increased the c-index by 0.066 (P .004), while adding coronary artery calcium score increased the c-index by only 0.039 (P .056). Overall, CCTA information in addition to the UKPDS risk category improved the reclassification rate for predicting the primary outcome. In asymptomatic patients with type 2 diabetes, CCTA information for CAD provided significant incremental discriminatory power beyond the UKPDS risk score category for predicting 10-year adverse coronary events.

A method for comparing multiple imputation techniques A case study on the U.S. national COVID cohort collaborative.

Healthcare datasets obtained from Electronic Health Records have proven to be extremely useful for assessing associations between patients predictors and outcomes of interest. However, these datasets often suffer from missing values in a high proportion of cases, whose removal may introduce severe bias. Several multiple imputation algorithms have been proposed to attempt to recover the missing information under an assumed missingness mechanism. Each algorithm presents strengths and weaknesses, and there is currently no consensus on which multiple imputation algorithm works best in a given scenario. Furthermore, the selection of each algorithms parameters and data-related modeling choices are also both crucial and challenging. In this paper we propose a novel framework to numerically evaluate strategies for handling missing data in the context of statistical analysis, with a particular focus on multiple imputation techniques. We demonstrate the feasibility of our approach on a large cohort of type-2 diabetes patients provided by the National COVID Cohort Collaborative (N3C) Enclave, where we explored the influence of various patient characteristics on outcomes related to COVID-19. Our analysis included classic multiple imputation techniques as well as simple complete-case Inverse Probability Weighted models. Extensive experiments show that our approach can effectively highlight the most promising and performant missing-data handling strategy for our case study. Moreover, our methodology allowed a better understanding of the behavior of the different models and of how it changed as we modified their parameters. Our method is general and can be applied to different research fields and on datasets containing heterogeneous types.

Phosphoethanolamine cytidyltransferase ameliorates mitochondrial function and apoptosis in hepatocytes in T2DM in vitro.

Liver function indicators are often impaired in patients with type 2 diabetes mellitus (T2DM), who present higher concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT) than individuals without diabetes. However, the mechanism of liver injury in patients with T2DM has not been clearly elucidated. In this study, we performed a lipidomics analysis on the liver of T2DM mice, and we found that phosphatidylethanolamine (PE) levels were low in T2DM, along with an increase in diglyceride (DG), which may be due to a decrease in the levels of phosphoethanolamine cytidyltransferase (Pcyt2), thus likely affecting the de novo synthesis of PE. The phosphatidylserine decarboxylase (PISD) pathway did not change significantly in the T2DM model, although both pathways are critical sources of PE. Supplementation with cytidine-5-diphosphate-ethanolamine (CDP-etn) to increase the production of PE from the CDP-ethanolamine pathway reversed HGFFA-induced mitochondrial damage including increased apoptosis, decreased ATP synthesis, decreased mitochondrial membrane potential, and increased reactive oxygen species, whereas supplementation with lysophosphatidylethanolamine, which can increase PE production in the PISD pathway, did not. Additionally, we found that overexpression of Pcyt2 significantly ameliorated ATP synthesis and abnormal mitochondrial morphology induced by HGFFA. Finally, the BAXBcl-2caspase3 apoptosis pathway was activated in hepatocytes of the T2DM model, which could also be reversed by CDP-etn supplements and Pcyt2 overexpression. In summary, in the liver of T2DM mice, Pcyt2 reduction may lead to a decrease in the levels of PE, whereas CDP-etn supplementation and Pcyt2 overexpression ameliorate partial mitochondrial function and apoptosis in HGFFA-stimulated L02 cells.

Hepatalin The missing link in prediabetes, obesity, and type 2 diabetes.

Hepatalin is a hormone secreted by the liver in response to pulses of insulin after a mixed nutrient meal, but only if the liver receives two permissive synergistic feeding signals from the stomach. Hepatalin stimulates glucose uptake and storage as glycogen in skeletal muscle, heart, and kidney but not liver, intestines, or adipocytes. Insulin acts primarily on liver and fat. Reduced hepatalin action results in postprandial hyperglycemia, compensatory elevation of insulin secretion, and a resultant shift in partitioning of nutrient energy storage from glycogen in muscle, to fat. Chronic hepatalin suppression leads to a predictable chronology of dysfunctions, first diagnosable as Absence of Meal-induced Insulin Sensitization (AMIS) which progresses to prediabetes, adiposity, and type 2 diabetes. The focus on nutrient partitioning and the role of hepatalin allows AMIS to be diagnosed, prevented, and treated, including through the use of lifestyle interventions.

Age-specific population attributable risk factors for all-cause and cause-specific mortality in type 2 diabetes An analysis of a 6-year prospective cohort study of over 360,000 people in Hong Kong.

The prevalence of type 2 diabetes has increased in both young and old people. We examined age-specific associations and population attributable fractions (PAFs) of risk factors for all-cause and cause-specific mortality in people with type 2 diabetes. We analysed data from 360,202 Chinese with type 2 diabetes who participated in a territory-wide diabetes complication screening programme in Hong Kong between January 2000 and December 2019. We compared the hazard ratios and PAFs of eight risk factors, including three major comorbidities (cardiovascular disease CVD, chronic kidney disease CKD, all-site cancer) and five modifiable risk factors (suboptimal HbA1c, suboptimal blood pressure, suboptimal low-density lipoprotein cholesterol, smoking, and suboptimal weight), for mortality across four age groups (18 to 54, 55 to 64, 65 to 74, and ≥75 years). During a median 6.0 years of follow-up, 44,396 people died, with cancer, CVD, and pneumonia being the leading causes of death. Despite a higher absolute mortality risk in older people (crude all-cause mortality rate 59.7 versus 596.2 per 10,000 person-years in people aged 18 to 54 years versus those aged ≥75 years), the relative risk of all-cause and cause-specific mortality associated with most risk factors was higher in younger than older people, after mutually adjusting for the eight risk factors and other potential confounders including sex, diabetes duration, lipid profile, and medication use. The eight risk factors explained a larger proportion of mortality events in the youngest (PAF 51.6%, 95% confidence interval CI 39.1%, 64.0%, p < 0.001) than the oldest (PAF 35.3%, 95% CI 27.2%, 43.4%, p < 0.001) age group. Suboptimal blood pressure (PAF 16.9%, 95% CI 14.7%, 19.1%, p < 0.001) was the leading attributable risk factor for all-cause mortality in the youngest age group, while CKD (PAF 15.2%, 95% CI 14.0%, 16.4%, p < 0.001) and CVD (PAF 9.2%, 95% CI 8.3%, 10.1%, p < 0.001) were the leading attributable risk factors in the oldest age group. The analysis was restricted to Chinese, which might affect the generalisability to the global population with differences in risk profiles. Furthermore, PAFs were estimated under the assumption of a causal relationship between risk factors and mortality. However, reliable causality was difficult to establish in the observational study. Major comorbidities and modifiable risk factors were associated with a greater relative risk for mortality in younger than older people with type 2 diabetes and their associations with population mortality burden varied substantially by age. These findings highlight the importance of early control of blood pressure, which could reduce premature mortality in young people with type 2 diabetes and prevent the onset of later CKD and related mortality at older ages.

Association of sarcopenia with important health conditions among community-dwelling Asian women.

This study aimed to examine sarcopenia prevalence using the Asian Working Group for Sarcopenia 2019 (AWGS) and the Foundation for the National Institutes of Health (FNIH) definitions, and their associations with important health conditions affecting midlife Singaporean women. Muscle mass and function were objectively assessed in 1201 healthy community-dwelling subjects aged 45-69 years under the Integrated Womens Health Program (IWHP). Dual-energy X-ray absorptiometry (DXA), handgrip strength and the Short Physical Performance Battery (SPPB) were measured, and the relationship between sarcopenia with hypertension, type 2 diabetes (T2DM), osteoporosis, depressionanxiety, and urinary incontinence were examined using binary logistic regression models. Sarcopenia prevalence was 18.0% and 7.7% by the AWGS and FNIH criteria respectively. Osteoporosis (aOR 1.74, 95% CI 1.02, 2.94) and T2DM (aOR 1.98, 95% CI 1.14, 3.42) was positively associated with AWGS- and FNIH-defined sarcopenia respectively, while hypertension was not, after adjustment for age, ethnicity, education levels and menopausal status. A negative percent agreement of 95.6% suggests good agreement between the criteria in the absence of sarcopenia. Even though they represent a single concept, sarcopenia by either criterion differed in their relationships with diabetes and osteoporosis, suggesting the need for further rationalization of diagnostic criteria.

Empagliflozin is associated with lower risk of cardiovascular events and all-cause mortality in routine care in East Asia Results from the EMPRISE study.

The EMPA-REG OUTCOME® trial demonstrated benefits of empagliflozin, a sodium-glucose cotransporter-2 inhibitor (SGLT2i), on cardiovascular, renal outcomes and all-cause mortality in patients with type 2 diabetes and established cardiovascular disease. The EMPRISE study program evaluates how these effects translate in a broad population of patients with type 2 diabetes in routine clinical care across countries. The study included patients ≥18 years with type 2 diabetes initiating empagliflozin or any dipeptidyl peptidase-4 inhibitors (DPP-4i) from large administrative databases in Japan, South Korea, and Taiwan. Propensity score-matched (11) as-treated analyses comparing the risk of cardiovascular outcomes and all-cause mortality between empagliflozin and DPP-4i use were performed in each country. Pooled hazard ratios (pHR) with 95% confidence intervals (CI) were computed using random effects meta-analysis models comparing both empagliflozin and SGLT2i with DPP-4i use, respectively. Intention-to-treat and subgroup analyses in patients withwithout cardiovascular disease and in patients receiving 10 mg empagliflozin were performed. The study included 28,712 and 70,233 matched patient pairs for empagliflozinDPP-4i and SGLT2iDPP-4i analyses, respectively. The risk of composite outcomes including (i) hospitalization for heart failure (HHF) and all-cause mortality was lower with empagliflozin (pHR 0.76, 95% CI 0.67-0.86) and SGLT2i (0.71, 0.65-0.77) (ii) combined myocardial infarction, stroke, and all-cause mortality was also lower with empagliflozin (0.74, 0.61-0.88) and SGLT2i (0.69, 0.60-0.78) compared to DPP-4i. The intention-to-treat and three subgroup analyses were consistent with results of the main analyses. The results suggest that both empagliflozin and SGLT2i compared with DPP-4i are associated with a lower risk of cardiovascular events and all-cause mortality in routine clinical care in East Asia.

Association Between Autism Spectrum Disorders and Cardiometabolic Diseases A Systematic Review and Meta-analysis.

Although the increased risk of obesity among individuals with autism has been well established, evidence on the association between autism, cardiometabolic disorders, and obesity remains inconclusive. To examine the association between autism spectrum disorders and cardiometabolic diseases in a systematic review and meta-analysis. PubMed, Scopus, Web of Science, ProQuest, Embase, and Ovid databases were searched from inception through July 31, 2022, without restrictions on date of publication or language. Observational or baseline data of interventional studies reporting the prevalence of cardiometabolic risk factors (ie, diabetes, hypertension, dyslipidemia, atherosclerotic macrovascular disease) among children andor adults with autism and matched with participants without autism were included. Screening, data extraction, and quality assessment were performed independently by at least 2 researchers. DerSimonian-Laird random-effects meta-analyses were performed using the meta package in R. Relative risks (RRs) of diabetes, hypertension, dyslipidemia, and atherosclerotic macrovascular disease among individuals with autism were the primary outcomes. Secondary outcomes included the RR of type 1 and type 2 diabetes, heart disease, stroke, and peripheral vascular disease. A total of 34 studies were evaluated and included 276 173 participants with autism and 7 733 306 participants without autism (mean range age, 31.2 3.8-72.8 years pooled proportion range of female individuals, 47% 0-66%). Autism was associated with greater risks of developing diabetes overall (RR, 1.57 95% CI, 1.23-2.01 20 studies), type 1 diabetes (RR, 1.64 95% CI, 1.06-2.54 6 studies), and type 2 diabetes (RR, 2.47 95% CI, 1.30-4.70 3 studies). Autism was also associated with increased risks of dyslipidemia (RR, 1.69 95% CI, 1.20-2.40 7 studies) and heart disease (RR, 1.46 95% CI, 1.42-1.50 3 studies). Yet, there was no significantly associated increased risk of hypertension and stroke with autism (RR, 1.22 95% CI, 0.98-1.52 12 studies and RR, 1.19 95% CI, 0.63-2.24 4 studies, respectively). Meta-regression analyses revealed that children with autism were at a greater associated risk of developing diabetes and hypertension compared with adults. High between-study heterogeneity was a concern for several meta-analyses. Results suggest that the associated increased risk of cardiometabolic diseases should prompt clinicians to vigilantly monitor individuals with autism for potential contributors, signs of cardiometabolic disease, and their complications.

After Dinner Rest a While, After Supper Walk a Mile A Systematic Review with Meta-analysis on the Acute Postprandial Glycemic Response to Exercise Before and After Meal Ingestion in Healthy Subjects and Patients with Impaired Glucose Tolerance.

The most effective way to cope with high blood sugar spikes is to engage in physical activity in temporal proximity to food intake. However, so far, it is unclear as to whether there is an optimal time for physical activity around food intake. We aimed to identify the impact of pre- and post-meal exercise on postprandial glucose excursions in humans with and without type 2 diabetes mellitus. We conducted a systematic review with meta-analysis, PROSPERO registration number CRD42022324070. We screened MEDLINEPubMed, CochraneCINAHLEMBASE, and Web of Knowledge until 1 May, 2022. We used the risk of bias rating with the crossover extension of the Cochrane risk of bias assessment tool II. Standardized mean differences (SMDs, Hedges g) with 95% confidence intervals (CIs) were calculated as pooled effect estimates of a random-effects meta-analysis. Eligibility criteria included three-armed randomized controlled trials comparing the acute effects of pre- and post-meal exercise to a no-exercise control in humans. Eight randomized controlled trials (crossover trials, high risk of bias) with 30 interventions in 116 participants (47 diagnosed with type 2 diabetes, 69 without type 2 diabetes) were eligible. Exercise after meal ingestion (real food or meal replacement drinks) led to a reduction in postprandial glucose excursions compared with exercise before eating (15 effect sizes SMD 0.47 95% CI 0.23, 0.70) and an inactive control condition (15 effect sizes SMD 0.55 95% CI 0.34, 0.75. Pre-meal exercise did not lead to significantly lower postprandial glucose compared to an inactive control (15 effect sizes SMD - 0.13 95% CI - 0.42, 0.17). The time between meal and exercise (estimate - 0.0151 standard error 0.00473 Z - 3.19 p 0.001 95% CI - 0.024, - 0.006) had a moderating influence on postprandial glucose excursions. Exercise, i.e., walking, has a greater acute beneficial impact on postprandial hyperglycemia when undertaken as soon as possible after a meal rather than after a longer interval or before eating. The review was pre-registered in the PROSPERO database (CRD42022324070). The date of submission was 07.04.2022, with the registration on 08.05.2022.

Long-term HbA1c variability and macro-micro-vascular complications in type 2 diabetes mellitus a meta-analysis update.

The aim of the present study was to evaluate, by means of a meta-analysis approach, whether new available data, appeared on qualified literature, can support the effectiveness of an association of HbA1c variability with the risk of macro- andor micro-vascular complications in type 2 diabetes mellitus (T2DM). The meta-analysis was conducted according to PRISMA Statement guidelines and considered published studies on T2DM, presenting HbA1c variability as standard deviation (SD) or its derived coefficient of variation (CV). Literature search was performed on PubMed in the time range 2015-July 2022, with no restrictions of language. Twenty-three selected studies fulfilled the aims of the present investigation. Overall, the analysis of the risk as hazard ratios (HR) indicated a significant association between the HbA1c variability, expressed either as SD or CV, and the complications, except for neuropathy. Macro-vascular complications were all significantly associated with HbA1c variability, with HR 1.40 (95%CI 1.31-1.50, p < 0.0001) for stroke, 1.30 (95%CI 1.25-1.36, p < 0.0001) for transient ischaemic attackcoronary heart diseasemyocardial infarction, and 1.32 (95%CI 1.13-1.56, p 0.0007) for peripheral arterial disease. Micro-vascular complications yielded HR 1.29 (95%CI 1.22-1.36, p < 0.0001) for nephropathy, 1.03 (95%CI 0.99-1.08, p 0.14) for neuropathy, and 1.15 (95%CI 1.08-1.24, p < 0.0001) for retinopathy. For all-cause mortality, HR was 1.33 (95%CI 1.27-1.39, p < 0.0001), and for cardiovascular mortality 1.25 (95%CI 1.17-1.34, p < 0.0001). Our meta-analysis on HbA1c variability performed on the most recent published data since 2015 indicates positive association between HbA1c variability and macro-micro-vascular complications, as well as mortality events, in T2DM, suggesting that this long-term glycaemic parameter merits further attention as a predictive, independent risk factor for T2DM population.

Normal range CAG repeat size variations in the HTT gene are associated with an adverse lipoprotein profile partially mediated by body mass index.

Tandem CAG repeat sizes of 36 or more in the huntingtin gene (HTT) cause Huntington disease. Apart from neuropsychiatric complications, the disease is also accompanied by metabolic dysregulation and weight loss, which contribute to a progressive functional decline. Recent studies also reported an association between repeats below the pathogenic threshold (<36) for Huntingtons disease and body mass index (BMI), suggesting that HTT repeat sizes in the non-pathogenic range are associated with metabolic dysregulation. In this study we hypothesized that HTT repeat sizes < 36 are associated with metabolite levels, possibly mediated through reduced BMI. We pooled data from three European cohorts (n 10 228) with genotyped HTT CAG repeat size and metabolomic measurements. All 145 metabolites were measured on the same targeted platform in all studies. Multilevel mixed-effects analysis using the CAG repeat size in HTT identified 67 repeat size-metabolite associations. Overall, the metabolomic profile associated with larger CAG repeat sizes in HTT were unfavorable-similar to those of higher risk of coronary artery disease and type 2 diabetes-and included elevated levels of amino acids, fatty acids, LDL, VLDL and IDL related metabolites whilst with decreased levels of very large HDL related metabolites. Furthermore, the associations of 50 metabolites, in particular specific very large HDL related metabolites, were mediated by lower BMI. However, no mediation effect was found for 17 metabolites related to LDL and IDL. In conclusion, our findings indicate that large non-pathogenic CAG repeat sizes in HTT are associated with an unfavorable metabolomic profile despite their association with a lower BMI.