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Serum C1qTNF-Related Protein 4 Levels are Associated with Nonalcoholic Fatty Liver Disease in Type 2 Diabetic Patients.

Brain-derived neurotrophic factor in diabetes mellitus A systematic review and meta-analysis.

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor expressed in several tissues, including the brain, gut, and pancreas. Activation of the BDNFTrkBCREB reduces hepatic gluconeogenesis, induces hepatic insulin signal transduction, and protects against pancreatic beta-cell loss in diabetes mellitus (DM). Several studies have investigated the possible association between BDNF and DM and its complications, but the results have been conflicting. In the present study, we aimed at systematically reviewing the literature on the serum and plasma levels of BDNF in DM and its subgroups such as T2DM, DM patients with depression, and patients with retinopathy. A comprehensive search was conducted in PubMed, Scopus, and Web of Science. We identified 28 eligible studies and calculated the standardized mean difference (SMD) of outcomes as an effect measure. The meta-analysis included 2734 patients with DM and 6004 controls. Serum BDNF levels were significantly lower in patients with DM vs. controls (SMD -1.00, P<0.001). Plasma BDNF levels were not different in patients with DM compared with controls. When conducting subgroup analysis, serum BDNF levels were lower among patients with T2DM (SMD -1.26, P<0.001), DM and depression (SMD -1.69, P<0.001), and patients with diabetic retinopathy (DR) vs. controls (SMD -1.03, P 0.01). Serum BDNF levels were lower in patients with DM, T2DM, DM with depression, and DM and DR than the controls. Our findings are in line with the hypothesis that decreased BDNF levels might impair glucose metabolism and contribute to the pathogenesis of DM and its complications.

Melatoninnicotinamide mononucleotideubiquinol a cocktail providing superior cardioprotection against ischemiareperfusion injury in a common co-morbidities modelled rat.

The metabolic and intracellular abnormalities in aging and diabetes cause loss of cardioprotection by routine interventions against myocardial ischemiareperfusion (IR) injury. We aimed to evaluate the possible interaction of aging and type-2 diabetes mellitus with cardioprotection and the potential protective effect of a mitochondrial cocktail (melatoninnicotinamide mononucleotide (NMN)ubiquinol) on myocardial IR injury in aged diabetic rats. Male Wistar rats (n 108, 22-24 months old, 400-450 g) received high-fat dietlow dose of streptozotocin to induce type-2 diabetes, then were randomized into 9 groups of 12 rats each withwithout IR andor melatonin, NMN, and ubiquinol, alone or in dual or triple combinations. Myocardial IR was induced by LAD occlusion for 30 min followed by 24 h reperfusion. NMN (100 mgkg48 h, intraperitoneally) was administered for 28 days before IR operation. Melatonin (10 mgkg, intraperitoneally) andor ubiquinol (30 mgkg, intravenously) were administered at early reperfusion. Finally, hemodynamic index changes, infarct size, CK-MB levels, mitochondrial functional endpoints, and expression of mitochondrial biogenesis genes (SIRT-1PGC-1αNRF-2TFAM) were assessed. The solo and dual applications of melatonin, NMN, and ubiquinol did not exert remarkable cardioprotective impacts. However, the triple combination improved myocardial function and decreased infarct size and CK-MB levels following myocardial IR (P < .05 to P < .01). It also improved mitochondrial function and restored mitochondrial biogenesis genes (P < .01). Combination therapy with melatonin, NMN, and ubiquinol exerted significant cardioprotection and improved mitochondrial function and biogenesis via upregulation of SIRT-1PGC-1αNRF-2TFAM profiles in aged diabetic rats and, thus, offers a promising strategy for providing noticeable cardioprotection against IR injury also in aged diabetic patients.

Effectiveness and Safety of iGlarLixi (Insulin Glargine 100 UmL Plus Lixisenatide) in Type 2 Diabetes According to the Timing of Daily Administration Data from the REALI Pooled Analysis.

iGlarLixi (insulin glargine 100 UmL plus lixisenatide) has demonstrated glycaemic efficacy and safety in adults with inadequately controlled type 2 diabetes mellitus (T2DM). Per the European Medicines Agencys product label, iGlarLixi should be injected once a day within 1 h prior to a meal, preferably the same meal every day when the most convenient meal has been chosen. It is however unknown whether iGlarLixi administration timing affects glycaemic control and safety, as clinical trial evidence is mainly based on pre-breakfast iGlarLixi administration. Therefore, we assessed the effectiveness and safety of iGlarLixi in clinical practice, according to its administration timing. Data were pooled from two prospective observational studies including 1303 European participants with T2DM inadequately controlled on oral antidiabetic drugs with or without basal insulin who initiated iGlarLixi therapy for 24 weeks. Participants were classified into four subgroups based on daily timing of iGlarLixi injection pre-breakfast (N 436), pre-lunch (N 262), pre-dinner (N 399), and those who switched iGlarLixi injection time during the study (N 206). No meaningful differences in baseline characteristics were observed between the study groups. Least-squares mean reductions in haemoglobin A1c (HbA1c) from baseline to week 24 were substantial in all groups, with the numerically largest decrease observed in the pre-breakfast group (1.57%) compared with the pre-lunch (1.27%), pre-dinner (1.42%), or changed injection time (1.33%) groups. Pre-breakfast iGlarLixi injection also resulted in a numerically greater proportion of participants achieving HbA1c < 7.0% at week 24 (33.7% versus 19.0% for pre-lunch, 25.6% pre-dinner, and 23.2% changed injection time). iGlarLixi was well tolerated across all groups, with low rates of gastrointestinal disorders and hypoglycaemia. Mean body weight decreased similarly in all groups (by 1.3-2.3 kg). iGlarLixi was effective and safe regardless of its daily administration time. However, pre-breakfast iGlarLixi injection resulted in a more effective glycaemic control.

Plant-based diets a fad or the future of medical nutrition therapy for children with chronic kidney disease

Plant-based diets are growing in popularity worldwide due to the importance of reducing the populations ecological footprint as well as an emerging role in the prevention and treatment of chronic human diseases. In adults, plant-based diets have been shown to be beneficial for preventing and controlling conditions that are common in patients with chronic kidney disease (CKD), such as obesity, hypertension, type 2 diabetes, dyslipidemia, and metabolic acidosis. Emerging evidence suggests that the higher fiber content of plant-based diets may help to modulate production of uremic toxins through beneficial shifts in the gut microbiome. The effects of the plant-based diet on progression of CKD remain controversial, and there are no data to support this in children. However, knowledge that the bioavailability of potassium and phosphorus from plant-based foods is reduced has led to recent changes in international kidney-friendly diet recommendations for children with CKD. The new guidelines advise that high potassium fruits and vegetables should no longer be automatically excluded from the kidney-friendly diet. In fact, a plant-based diet can be safely implemented in children with CKD through building the diet around whole, high fiber foods, avoiding processed foods and using recommended cooking methods to control potassium. The health benefits of the plant-based diet compared to omnivorous diets in children with CKD need investigation.

Causal factors underlying diabetes risk informed by Mendelian randomisation analysis evidence, opportunities and challenges.

Diabetes and its complications cause a heavy disease burden globally. Identifying exposures, risk factors and molecular processes causally associated with the development of diabetes can provide important evidence bases for disease prevention and spur novel therapeutic strategies. Mendelian randomisation (MR), an epidemiological approach that uses genetic instruments to infer causal associations between an exposure and an outcome, can be leveraged to complement evidence from observational and clinical studies. This narrative review aims to summarise the evidence on potential causal risk factors for diabetes by integrating published MR studies on type 1 and 2 diabetes, and to reflect on future perspectives of MR studies on diabetes. Despite the genetic influence on type 1 diabetes, few MR studies have been conducted to identify causal exposures or molecular processes leading to increased disease risk. In type 2 diabetes, MR analyses support causal associations of somatic, mental and lifestyle factors with development of the disease. These studies have also identified biomarkers, some of them derived from the gut microbiota, and molecular processes leading to increased disease risk. These studies provide valuable data to better understand disease pathophysiology and explore potential therapeutic targets. Because genetic association studies have mostly been restricted to participants of European descent, multi-ancestry cohorts are needed to examine the role of different types of physical activity, dietary components, metabolites, protein biomarkers and gut microbiome in diabetes development.

Embracing complexity making sense of diet, nutrition, obesity and type 2 diabetes.

Nutrition therapy has been emphasised for decades for people with type 2 diabetes, and the vital importance of diet and nutrition is now also recognised for type 2 diabetes prevention. However, the complexity of diet and mixed messages on what is unhealthy, healthy or optimal have led to confusion among people with diabetes and their physicians as well as the general public. What should people eat for the prevention, management and remission of type 2 diabetes Recently, progress has been made in research evidence that has advanced our understanding in several areas of past uncertainty. This article examines some of these issues, focusing on the role of diet in weight management and in the prevention and management of type 2 diabetes. It considers nutritional strategies including low-energy, low-fat and low-carbohydrate diets, discusses inter-relationships between nutrients, foods and dietary patterns, and examines aspects of quantity and quality together with new developments, challenges and future directions.

Disrupting future discounting a commentary on an underutilised psychological approach for improving adherence to diet and physical activity interventions.

Non-communicable diseases (NCD) such as CVD and type 2 diabetes mellitus are major contributors to the burden of disease. NCD are largely driven by modifiable lifestyle factors including poor diet and insufficient physical activity, and consequently, prevention is a public health priority. Although diet and physical activity levels can be improved via lifestyle interventions, long-term adherence to such interventions remains low, which limits their effectiveness. Thus, it is critical to identify the underlying mechanisms that challenge uptake and adherence to such interventions. The current commentary discusses an important, but underexplored, psychological driver of poor adherence to lifestyle interventions, namely, future discounting, which describes the tendency to prefer smaller, short-term rewards over larger, long-term rewards. For example, in the nutrition domain, future discounting refers to valuing the immediate reward of excessive intake of energy-dense, nutrient-poor, discretionary foods high in salt, sugar, and saturated fat, and insufficient intake of low-energy, nutrient-dense, whole foods such as vegetables. Prominent theoretical models propose that excessive future discounting is a major contributor to the development of unhealthy lifestyle behaviours. Furthermore, a vast body of evidence suggests that future discounting plays a key role in risk of NCD. Thus, the evidence to date supports the idea that future discounting is an important multi-behaviour target for supporting lifestyle behaviour change however, this approach has been largely neglected in preventive health efforts. Furthermore, this commentary discusses promising techniques (e.g. Episodic Future Thinking) for disrupting future discounting to promote improved adherence to lifestyle interventions aimed at reducing NCD risk.

Collocation of metformin and dipeptidyl peptidase-4 inhibitor is associated with increased risk of diabetes-related vascular dementia A single hospital study in Northern Taiwan.

Recent studies have established a close link between diabetes mellitus (DM) and an increased risk of vascular dementia (VD). In this study, we evaluated the risk of VD in patients with type 2 diabetes who were on antidiabetic medications. There is a growing interest in observational and data-driven studies to answer specific research questions for defined populations. In line with this, 67,281 patients (age range, 61.95 ± 13.88 years length of follow up, 3.2 ± 3.4 years) diagnosed with DM were divided into two groups48,072 subjects who had not used dipeptidyl peptidase-4 (DPP-4) medication and 19,209 subjects who had taken DPP-4 medication. Each patient underwent follow-up examination after the date of the latest diagnosis. Among 10,884 DM patients with dementia, the combination therapy of metformin and DPP-4 inhibitor may increase the risk of dementia compared with that in the control group (adjusted hazard ratio, 1.11 95% confidence interval, 1.06-1.15 p ≤ 0.001). In this study, patients who received a combination therapy of metformin and DPP-4 inhibitor for DM were at a higher risk of dementia than those who received monotherapy.

The association study between changes in HbA1C with rs2250486 and rs67238751 genetic variants for SLC47A1 in newly diagnosed Iranian patients with type 2 diabetes mellitus 6 months follow-up study.

One of the most well-known oral medications for the treatment of T2DM is metformin. Variants have been found in studies to be useful in detecting new genes connected to T2DM aetiology and affecting metformins mechanism of action. In this research, we aimed to study two variations of the SLC47A1 gene rs2250486 and rs67238751, in T2DM patients who had been taking metformin for the first 6 months after the diagnosis in the Iranian population for the first time. A total of 200 individuals were recruited for the study. According to their glycosylated haemoglobin (HbA1c) levels, the patients were divided into two groups responders (HbA1c levels were reduced by at least 1% after 6 months of metformin treatment.) and non-responders. DNA was extracted from whole blood and genotyped by Tetra ARMS PCR. High-performance liquid chromatography (HPLC) was used to measure HbA1c levels at the start of the treatment and again 6 months later. rs2250486 variant in the dominant model reduces the HbA1C levels after 6 months of metformin treatment. In fact, when compared to the TC CC genotypes, the TT genotype improves HbA1C levels (p-value .014). Furthermore, in the allelic model, the T allele improves HbA1C levels in comparison to the C allele (p-value .008). After 6 months of metformin treatment, serum levels of HbA1C in responders were reduced significantly in both groups (TT and TC CC), (p-value <.0001). However, the rs67238751 variant did not reveal a meaningful relationship with lower HbA1C levels in any of the models. This study found that the rs2250486 variant could be associated with reducing HbA1C levels while the rs67238751 variant, had no relationship.

Sex differences in risk factors for end-stage kidney disease and death in type 2 diabetes A retrospective cohort study.

This study investigated the sex differences in the risk of end-stage kidney disease (ESKD) and mortality, as well as the effect modification of sex on associated factors in patients with type 2 diabetes. This multicenter observational cohort study included 4328 patients with type 2 diabetes. Hazard ratios (HRs) with 95% confidence intervals (CIs) of sex for ESKD and death were estimated using Cox proportional regression with adjustment for baseline covariates. For assessing risk modification, HRs and incidence rates for ESKD and death were compared between sexes across patient characteristics using Cox proportional and Poisson regression models. During a median follow-up of 7 years, 276 patients (70% men) developed ESKD, and 241 patients (68% men) died. Men had higher risks of ESKD (HR 1.34 95% CI 1.02-1.75 p .034) and death (HR 1.64 95% CI 1.24-2.16 p .001) versus women after adjusting for multiple covariates. Among patients with microalbuminuria, men had a substantially higher risk of ESKD versus women, compared to those with normo- and macroalbuminuria (p for interaction .04). Incidence rates were also increased in men versus women with albuminuria of around 300 mgg. No differences were detected in the association of sex and death across baseline patient subgroups. In type 2 diabetes, men had an increased risk of ESKD and death versus women. Moderately increased albuminuria was strongly associated with sex difference in developing ESKD.

Gender-associated cardiometabolic risk profiles and health behaviors in patients with type 2 diabetes a cross-sectional analysis of the Joint Asia Diabetes Evaluation (JADE) program.

In Asia, diabetes-associated death due to cardiorenal diseases were 2-3 times higher in women than men which might be due to gender disparity in quality of care and health habits. Adults with type 2 diabetes (T2D) from 11 Asian countriesareas were assessed using the same protocol (2007-2015). We compared treatment target attainment (HbA Among 106,376 patients (53.2% men median (interquartile range) diabetes duration 6.0 (2.0-12.0) years mean ± SD HbA Asian women with T2D had worse quality of care than men especially in middle-income countriesareas, calling for targeted implementation programs to close these care gaps. Asia Diabetes Foundation. Nil.

The burden of diabetic complications in subjects with type 2 diabetes attending the diabetes clinic of the Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria - a cross-sectional study.

the increasing prevalence of diabetes (DM) worldwide has resulted in an increase in the morbidity and mortality of DM. This burden is as a result of the development of the chronic complications associated with it. This study determined the burden of occurrence of microvascular and macrovascular complications of subjects with type 2 diabetes attending the out -patient clinic of a tertiary hospital in south west Nigeria. this cross-sectional study involved 400 consecutive subjects with type 2 diabetes. A study proforma was used to document the socio demographic data. While clinical assessment for anthropometric measurement, blood pressure was done. Laboratory measurement of blood glucose control and lipids were done. Assessment of the occurrence of microvascular and macrovascular complications were performed and documented. four hundred type 2 DM participants made up of 190 males and 210 females with a mean age of 60.35±9.53 years, with a mean age of 60.35(SD 9.53) years for males and 60.81(SD10.29) years for females. Median duration of DM for all subjects was 6.00(IQR 3.00 - 11.00) years. Majority (45%) of the participants were overweight. The prevalence of hypertension was 78% and poor glycaemia using HBA1C was 75.5% and 59.8% had dyslipidaemia. The occurrence of microvascular complications (diabetic neuropathy - 82%, diabetic retinopathy - 46% and diabetic nephropathy - 44%) 69.3% while macrovascular complications (peripheral arterial disease - 42.5%, stroke - 4%, electrocardiographic changes if ischaemic heart disease -9.3% and left ventricular hypertrophy - 22%) in 49%. Regression analyses showed advancing age aOR (1.18 95%CI 1.01 - 1.38) and waist circumference (aOR 1.17 95% CI 1.00 - 1.36), as significant contributors to the presence of diabetes complications. the risk factors of both microvascular and macrovascular complications remain high in our clinic and this is linked to the high burden of diabetes mellitus and its long duration.

Refractory Choledocholithiasis Causing Endogenous Endophthalmitis A Case Report.

BACKGROUND Endogenous bacterial endophthalmitis is caused by a breach of the blood-ocular barrier by pathogens originating from distant infective foci. Here, we report a case of endogenous endophthalmitis due to cholangitis complicated by common bile duct stones, which is a rare source of infection. CASE REPORT A 73-year-old man with type II diabetes mellitus underwent endoscopic choledocholithotripsy 20 years ago and laparoscopic cholecystectomy 18 years ago. He had choledocholith-related cholangitis 6, 5, and 1 years previously and 4 times in the last year and underwent endoscopic choledocholithotripsy each time. Three days after the last surgery, the patient developed right endogenous endophthalmitis and vitrectomy was performed. Four months later, the patient relapsed with cholangitis and required surgery for recurrent endophthalmitis. Roux-en-Y choledochojejunostomy was performed with curative intent, and the patient was followed up for 5 years without recurrence of choledocholith, cholangitis, or endophthalmitis. CONCLUSIONS The recommended treatment strategy for patients diagnosed with common bile duct stones or choledocholithiasis is stone extraction. Endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic intervention is a widely accepted procedure. However, in cases of recurrent choledocholithiasis, the rate of recurrence increases and the interval between ERCP becomes shorter in proportion to the number of recurrences. In such intractable cases requiring numerous sessions of endoscopic stone removal, bypass Roux-en-Y choledochojejunostomy should be performed to prevent possible rare complications such as endogenous bacterial endophthalmitis.

The importance of targeting multiple risk markers in patients with type 2 diabetes a post-hoc study from the CANVAS program.

To investigate the extent to which improvements in multiple cardiovascular risk markers are associated with a lower risk of cardiovascular and kidney outcomes in patients with type 2 diabetes and high cardiovascular risk participating in the CANVAS program. Clinically relevant improvements in cardiovascular risk factors were defined as a reduction in HbA1c ≥1.0%, systolic blood pressure ≥10mmHg, body weight ≥3kg, urinary-albumin-creatinine ratio ≥30%, uric acid ≥0.5 mgdL, and an increase in hemoglobin of ≥1.0 gdL from baseline to week 26. Participants were categorized according to the number of improvements in cardiovascular risk markers zero, one, two, three, or four or more risk marker improvements). Cox proportional hazard regression adjusted for treatment assignment, demographic variables and laboratory measurements was performed to determine the association between the number of risk marker improvements and risk of a composite cardiovascular, heart failure, or kidney outcomes. We included 9487 (93.5%) participants with available data at baseline and week 26. After week 26, 566 composite cardiovascular, 370 heart failurecardiovascular death, and 153 composite kidney outcomes occurred. The multivariable adjusted hazard ratios (HR) associated with four or more improvements in risk markers versus no risk marker improvement were 0.67 (95% CI 0.48, 0.92), 0.58 (95% CI 0.39, 0.87), and 0.49 (95% CI 0.25, 0.96) for the three outcomes respectively. We observed a trend of decreased HRs across subgroups of increasing number of risk marker improvements (P for trend 0.008, 0.02 and 0.047, respectively). In patients with type 2 diabetes, improvements in multiple risk markers were associated with a reduced risk of cardiovascular and kidney outcomes as compared to no risk marker improvement. This article is protected by copyright. All rights reserved.

Comparison of simplicity, convenience, safety, and cost-effectiveness between use of insulin pen devices and disposable plastic syringes by patients with type 2 diabetes mellitus a cross-sectional study from Bangladesh.

Insulin pen devices and disposable plastic insulin syringes are two common tools for insulin administration. This study aims to compare the simplicity, convenience, safety, and cost-effectiveness of insulin pens versus syringe devices in patients with type 2 diabetes mellitus (T2DM). A cross-sectional study was conducted at 14 diabetes clinics throughout Bangladesh from November 2021 to April 2022 among adults with T2DM injecting insulin by pen devices or disposable insulin syringes at least once a day for at least one year by purposive sampling. The simplicity, convenience, and safety of insulin devices were assessed using a structured questionnaire, and the study subjects were scored based on their answers higher scores indicated a poorer response. Total scores for simplicity, convenience, and safety were obtained by adding the scores for relevant components. Their average monthly medical expense and cost of insulin therapy were recorded. The median values of the total scores and monthly expenses were compared between pen devices and disposable syringe users. 737 subjects were evaluated 406 were pen users, and 331 were vial syringe users. The pen users had lower median scores for simplicity 6.0 (5.0-8.0) vs. 7.0 (5.0-9.0), p 0.002, convenience 4.0 (3.0-6.0) vs. 5.0 (4.0-6.0), p < 0.001, and safety 7.0 (6.0-8.0) vs. 7.0 (6.0-9.0), p 0.008 than vial syringe users. Pen devices were more expensive than vial syringes in terms of average medical expense per month BDT 5000 (3500-7000) vs. 3000 (2000-5000), p < 0.001, the total cost of insulin therapy per month BDT 2000 (1500-3000) vs. 1200 (800-1700), p < 0.001 and cost per unit of insulin used BDT 2.08 (1.39-2.78) vs. 0.96 (0.64-1.39), p < 0.001. Non-significant differences in favor of pens were observed in HbA1c levels 8.7 (7.8-10) vs. 8.9 (7.9-10)%, p 0.607 and proportions of subjects having HbA1c < 7% (6.9 vs. 6.3%, p 0.991). Insulin pens are simpler, more convenient, and safe but more expensive than vial syringes. Glycemic control is comparable between pen and syringe users. Long-term follow-up studies are needed to determine the clinical and economic impacts of such benefits of insulin pens.

De novo HNF1A mutation of young maturity-onset diabetes 3 of a young girl-Case report.

Young maturity-onset diabetes of the young type3(MODY3) as a special type of diabetes, the probability of diagnosis is low. This article reports on a case and reviews the relevant knowledge of the disease. We report an 11-year-and-11-month-old girl whose grandmother died from diabetic complications while the rest of the families were non-diabetes. The proband was initially treated with insulin and metformin but the threatment proved inefficient. After an exome-targeted capture sequencing test, she was diagnosed with mature-onset diabetes of young type 3 (MODY3), and sulfonylureas make sense. The key to mody treatment is a correct and timely diagnosis, which contributes to helping patients overcome the problems of MODY3, especially for blood sugar control.

The effect of COVID-19 pandemic on diabetes care indices in Southern Iran an interrupted time series analysis.

Type 2 diabetes mellitus (T2DM) requires a continues bulk of cares. It is very probable COVID-19 pandemic is affected its healthcare coverage. The interrupted time series analysis is used to model the trend of diabetes healthcare indices, such as the health worker visits, physician visits, body mass index (MBI), fasting blood sugar (FBS), and hemoglobin A1c (HbA1c), before and after the start of COVID-19 pandemic. The reference of data was the totals of all T2DM patients living in Fars Province, Southern Iran, areas covered by Shiraz University of Medical Science (SUMS), from 2019 to 2020. A significant decrease for visits by the health workers, and physicians was observed by starting COVID-19 pandemic (β When the COVID-19 pandemic was announced, T2DM healthcare coverage drastically decreased, but it quickly began to rebound. The health monitoring system could not have any noticeable effects on diabetes outcomes.

Anxiety prevalence and its association with physical activity in patients with non-communicable diseases during COVID-19 lockdown a cross-sectional study in Shanghai, China.

Quarantine due to the COVID-19 pandemic may have created great psychological stress among vulnerable populations. We aimed to investigate the prevalence of anxiety and explore the association between physical activities (PA) and anxiety risk in people with non-communicable diseases during the period of COVID-19 lockdown. We conducted a cross-sectional telephone survey from February 25 to April 20, 2020, the period of COVID-19 lockdown in Shanghai. Up to 8000 patients with type 2 diabetes andor hypertension were selected using multi-stage cluster random sampling. PA level was measured based on the International Physical Activity Questionnaire using Metabolic Equivalent for Task scores, while symptoms of anxiety were assessed by the 7-item Generalized Anxiety Disorder scale. Multiple logistic regression analyses were performed to evaluate the associations of type and level of PA with the risk of anxiety. Of a total 4877 eligible patients, 2602 (53.4%) reported with anxiety, and 2463 (50.5%), 123 (2.5%) and 16 (0.3%) reported with mild, moderate, and severe anxiety. The prevalence of anxiety was higher in the females, the elders, non-smokers, non-drinkers, and patients with diabetes, and the associations of anxiety with sex, age, smoking, drinking and diagnosis of diabetes were significant. A significant negative association was observed for housework activities (OR 0.53, 95%CI 0.45, 0.63, p < 0.001) and trip activities (OR 0.55, 95%CI 0.48, 0.63, p < 0.001) with anxiety, but no significant was found for exercise activities (OR 1.06, 95%CI 0.94, 1.20, p 0.321). Compared with patients with a low PA level, those with a moderate (OR 0.53, 95%CI 0.44, 0.64, p < 0.001) or a high PA level (OR 0.51, 95%CI 0.43, 0.51, p < 0.001) had a lower prevalence of anxiety. This study demonstrates a higher prevalence of anxiety in patients with hypertension, diabetes, or both during the COVID-19 lockdown. The negative associations of housework and trip activities with anxiety highlight the potential benefit of PA among patients with non-communicable diseases.

The association of dietary approaches to stop hypertension (DASH) with the odds of diabetic nephropathy and metabolic markers in women a case-control study.

Epidemiologic studies have reported that diet is associated with diabetes and its complications through different pathways. We sought to examine the associations between the Dietary Approaches to Stop Hypertension (DASH) diet and the odds of diabetic nephropathy (DN) developing in Iranian women with existing type 2 diabetes. In this case-control study, 105 women with DN and 105 controls, matched for age and diabetes duration, were selected from the Kowsar Diabetes Clinic in Semnan, Iran. DASH, estimated using dietary intake, was assessed using a validated and reliable food frequency questionnaire with 147 items. Anthropometric measurements were assessed for all subjects. Logistic regression was performed to examine the association between DASH and the odds of developing DN. After controlling for potential confounders, subjects in the highest intake of DASH diet adherence have 84% lower odds of DN, compared to those with the lowest intake (OR 0.16, 95% CI 0.07-0.34, P < 0.001). Among DASH diet subcategories, intakes of vegetables (80%), fruits (88%), nuts and legumes (87%), and low-fat dairy (73%) decreased the risk of DN after adjustment for confounders (P < 0.001). This study showed that the DASH diet is associated with lower odds of DN development in women with type 2 diabetes.

Efficacy and Safety of Sotagliflozin in Patients With Type 2 Diabetes and Stage 3 Chronic Kidney Disease.

To assess the efficacy and safety of sotagliflozin, a dual inhibitor of sodium-glucose cotransporters 1 and 2, in adults with type 2 diabetes (T2D) and stage 3 chronic kidney disease (CKD3). This phase 3, randomized, placebo-controlled trial evaluated sotagliflozin 200 and 400 mg in 787 patients with T2D and estimated glomerular filtration rate (eGFR) 30-59 mLmin1.73 m At 26 weeks, placebo-adjusted mean change in HbA1c (from a baseline of 8.3% ± 1.0) was -0.1% (95% CI -0.2 to 0.05 P 0.2095) and -0.2% (-0.4 to -0.09 P 0.0021) in the sotagliflozin 200 and 400 mg groups, respectively. Significant reductions in fasting plasma glucose and body weight but not systolic blood pressure were observed. Among patients with ≥A2 albuminuria at Week 26, urine albumin creatinine ratio (UACR) was reduced with both sotagliflozin doses relative to placebo. At Week 52, UACR was reduced with sotagliflozin 200 mg in the CKD3B group. Adverse events (AEs), including serious AEs, were similar between treatment groups. After 26 weeks, HbA1c was significantly reduced with sotagliflozin 400 but not 200 mg compared with placebo in this CKD3 cohort. UACR in patients with at least A2 albuminuria was reduced with each of the two doses at 26 weeks, but changes were not sustained at Week 52. Safety findings were consistent with previous reports (NCT03242252).

Quantifying health-related quality of life in Malaysian type 2 diabetes focusing on complication types and severity.

There is a knowledge gap of health utility values for Type 2 Diabetes Mellitus (T2DM) complications in Malaysia. This study aimed to estimate EQ-5D-5L utility values and evaluate health-related quality of life (HRQoL) for Malaysian T2DM associated with complications and clinical characteristics. A cross-sectional study was conducted on T2DM patients at a tertiary hospital outpatient using the Malay and English version of the EQ-5D-5L questionnaire. Health utility values were derived using the Malaysian EQ-5D-5L value set. Ordinary least squares (OLS) multivariable regression model was used to estimate the health utility decrements associated with T2DM-related complications and clinical characteristics. A total of 513 T2DM patients were recruited. Overall, pain was the most affected of all five EQ-5D-5L dimensions. Patients with foot ulcer, amputation, severe heart failure and frequent hypoglycemia reported more problems collectively in all EQ-5D-5L dimensions. Older age, lower education level, longer duration of T2DM, urine protein creatine index (UPCI) > 0.02 gmmol, and injection therapy were significantly associated with lower EQ-5D-5L utility values (p < 0.004, Bonferroni adjusted). The lowest unadjusted utility values were reported for severe heart failure 0.65 (interquartile range, IQR 0.50), frequent hypoglycemia 0.74 (0.22) and being amputated 0.78 (0.47). In the multivariable regression model after controlling for sociodemographic and clinical characteristics, the largest utility value decrement was observed for amputation (- 0.158, SE 0.087, p 0.05), frequent hypoglycemia (- 0.101, SE 0.030, p 0.001), myocardial infarction (-0.050, SE 0.022, p 0.022) and obesity (-0.034, SE 0.016, p 0.029). Larger utility value decrements were found for severe stages of complications. These findings suggest the value of defining severity of complications in utility elicitation studies. The utility decrement quantified for different T2DM complication severity will be useful for economic evaluations within diabetic-related fields.

Poor quality of sleep in Mexican patients with type 2 diabetes and its association with lack of glycemic control.

To determine the association between sleep quality and lack of glycemic control in a Mexican population of type 2 diabetes patients. Cross-sectional study. Two hundred two patients between 20 and 60 years old with a previous diagnosis of diabetes were included. Sleep quality was assessed with the Pittsburgh Sleep Quality Index and lack of glycemic control as a glycated hemoglobin A1c level ≥ 7 %. Univariate and multivariate analyses using logistic regression were performed. The study population showed poor sleep quality and a lack of glycemic control of 70.3 % and 69.8 %, respectively. The prevalence of patients with both conditions was 52.5 %. In multivariate analysis, poor sleep quality was significantly associated with a lack of glycemic control (OR 2.3, p 0.030). Other associated variables were napping (p 0.015), diabetes duration (p 0.011), insulin use (p 0.024), and diastolic blood pressure ≥ 85 mmHg (p 0.029). The prevalence of lack of glycemic control in the study population is high. Poor sleep quality significantly doubles the risk of lack of glycemic control, even in the presence of other risk factors.

Phosphoproteomic analysis of metformin signaling in colorectal cancer cells elucidates mechanism of action and potential therapeutic opportunities.

The biguanide drug metformin is a safe and widely prescribed drug for type 2 diabetes. Interestingly, hundreds of clinical trials have been set to evaluate the potential role of metformin in the prevention and treatment of cancer including colorectal cancer (CRC). However, the metformin signaling remains controversial. To interrogate cell signaling induced by metformin in CRC and explore the druggability of the metformin-rewired phosphorylation network, we performed integrative analysis of phosphoproteomics, bioinformatics, and cell proliferation assays on a panel of 12 molecularly heterogeneous CRC cell lines. Using the high-resolute data-independent analysis mass spectrometry (DIA-MS), we monitored a total of 10,142 proteins and 56,080 phosphosites (P-sites) in CRC cells upon a short- and a long-term metformin treatment. We found that metformin tended to primarily remodel cell signaling in the long-term and only minimally regulated the total proteome expression levels. Strikingly, the phosphorylation signaling response to metformin was highly heterogeneous in the CRC panel, based on a network analysis inferring kinasephosphatase activities and cell signaling reconstruction. A MetScore was determined to assign the metformin relevance of each P-site, revealing new and robust phosphorylation nodes and pathways in metformin signaling. Finally, we leveraged the metformin P-site signature to identify pharmacodynamic interactions and confirmed a number of candidate metformin-interacting drugs, including navitoclax, a BCL-2BCL-xL inhibitor. Together, we provide a comprehensive phosphoproteomic resource to explore the metformin-induced cell signaling for potential cancer therapeutics. This resource can be accessed at httpsyslproteomics.shinyapps.ioMetformin.

Pharmacological Targeting of Mitochondria in Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) in the United States and many other countries. DKD occurs through a variety of pathogenic processes that are in part driven by hyperglycemia and glomerular hypertension, leading to gradual loss of kidney function and eventually progressing to ESRD. In type 2 diabetes, chronic hyperglycemia and glomerular hyperfiltration leads to glomerular and proximal tubular dysfunction. Simultaneously, mitochondrial dysfunction occurs in the early stages of hyperglycemia and has been identified as a key event in the development of DKD. Clinical management for DKD relies primarily on blood pressure and glycemic control through the use of numerous therapeutics that slow disease progression. Because mitochondrial function is key for renal health over time, therapeutics that improve mitochondrial function could be of value in different renal diseases. Increasing evidence supports the idea that targeting aspects of mitochondrial dysfunction, such as mitochondrial biogenesis and dynamics, restores mitochondrial function and improves renal function in DKD. We will review mitochondrial function in DKD and the effects of current and experimental therapeutics on mitochondrial biogenesis and homeostasis in DKD over time. SIGNIFICANCE STATEMENT Diabetic kidney disease (DKD) affects 20% to 40% of patients with diabetes and has limited treatment options. Mitochondrial dysfunction has been identified as a key event in the progression of DKD, and pharmacologically restoring mitochondrial function in the early stages of DKD may be a potential therapeutic strategy in preventing disease progression.

Incretin and Pancreatic β-Cell Function in Patients with Type 2 Diabetes.

To maintain normal glucose homeostasis after a meal, it is essential to secrete an adequate amount of insulin from pancreatic β-cells. However, if pancreatic β-cells solely depended on the blood glucose level for insulin secretion, a surge in blood glucose levels would be inevitable after the ingestion of a large amount of carbohydrates. To avoid a deluge of glucose in the bloodstream after a large carbohydrate- rich meal, enteroendocrine cells detect the amount of nutrient absorption from the gut lumen and secrete incretin hormones at scale. Since insulin secretion in response to incretin hormones occurs only in a hyperglycemic milieu, pancreatic β-cells can secrete a Goldilocks amount of insulin (i.e., not too much and not too little) to keep the blood glucose level in the normal range. In this regard, pancreatic β-cell sensitivity to glucose and incretin hormones is crucial for maintaining normal glucose homeostasis. In this Namgok lecture 2022, we review the effects of current anti-diabetic medications on pancreatic β-cell sensitivity to glucose and incretin hormones.

Fracture risks associated with sodium-glucose cotransporter 2 inhibitors in type 2 diabetes patients across eGFR and albuminuria categories a population-based study in Hong Kong.

To evaluate major osteoporotic fracture (MOF) risk among type 2 diabetes patients treated SGLT2i across eGFR and albuminuria categories. A population-based cohort of type 2 diabetes patients started on SGLT2i or DPP4i during 2007-2020 was identified from Hong Kong Hospital Authority database. One-to-one propensity score matching was applied to match each SGLT2i user with one DPP4i user. The primary outcomes were 180- and 365-day risks of MOF. Cox proportional hazard regression models were used to estimate hazard ratios. A total of 28,696 patients (14,348 in each group) were included. Over 180-day follow-up, MOF occurred in 25 (0.17%) SGLT2i users and 24 (0.17%) DPP4i users (incidence of 4.07 and 3.631,000 person-years, respectively). At 365 days, MOF occurred in 43 (0.30%) SGLT2i users and 44 (0.31%) DPP4i users (incidence of 4.16 and 3.641,000 person-years, respectively). Risks of MOF were comparable between two groups at both 180 days (HR1.13, 95%CI 0.65-1.98, P0.67) and 365 days (HR1.15, 95%CI 0.75-1.75, P0.52). Subgroup analyses were consistent across age, sex, eGFR, albuminuria, or KDIGO categories. Our study did not reveal a statistically significant increase in fracture risk with SGLT2i use compared with DPP4i among type 2 diabetes patients, across eGFR and albuminuria categories.

Aquatic training improves HbA1c, blood pressure and functional outcomes of patients with type 2 diabetes a systematic review with meta-analysis.

This study aimed to summarize the effects of aquatic training on the health outcomes of type 2 diabetes (T2D) patients. This is a systematic review with meta-analysis that followed the PRISMA recommendations. Searches were performed in four databases in April 2021. The following eligibility criteria were adopted adults with T2D aquatic training (AT) intervention in an upright position pre- and post-intervention assessments of the following outcomes HbA1c, SBP and DBP, functional capacity, VO Of the 375 studies, 12 studies were eligible and included in the meta-analysis. Favorable effects of AT post-intervention were observed in HbA1c (-0.62%), VO AT improves HbA1c, VO

CLINICAL AND IMMUNOLOGICAL PROFILE OF NEWLY DIAGNOSED DIABETIC PATIENTS IN A COHORT OF YOUNG ADULTS OF NATIONAL HEPATITIS C VIRUS SURVEY IN EGYPT.

T2DM (Type 2 diabetes mellitus) is considered a disease that affects old age group. Recently, it has become common in children, adolescents and adults. Aim of the work - to highlight the challenges in differentiating T1DM (type1 diabetes mellitus) from T2DM (type2 diabetes mellitus) in early onset diabetes in youth depending on clinical and laboratory characteristics. Our cross-sectional study was performed on 200 newly diagnosed diabetic patients aged (18-30) years. All patients were subjected to detailed medical history and full clinical examination. Laboratory investigations included FBS, 2hPP, HbA1C, fasting C peptide and GADA. About 59% (118) of our patients were T2DM while (82) 41% were T1DM. T1DM was more dominant than T2DM in age group less than 25 years (T1DM 79% versus T2DM 21%, P<0.001), while T2DM was more than T1DM in age group more than 25 years (T2DM 93% versus T1DM 17%, P<0.001). GADA was detected in 73.2% of T1DM patient and it was high titer while GADA was detected in only 8% of T2DM with low titer, in addition GADA positive patients were significantly younger than negative patients, age (20.9±2.5 years vs. 26.4±3.5 years respectively) (P <0.001). About 8% of phenotypically type 2 diabetic youth had GADA positive antibodies which did not confer impact on c peptide level or glycemic control yet type 1 diabetics who were GADA negative had a better glycemic control.

Common Issues in Prenatal Care Gestational Diabetes.

Two screening approaches are used to detect gestational diabetes, the 1-step and 2-step methods. The 1-step method is diagnostic and consists of a 75-g, 2-hour oral glucose tolerance test (OGTT). The 2-step method consists of a 50-g, 1-hour glucose challenge test, followed by a 100-g, 3-hr OGTT if initial test results are positive. All pregnant patients should be screened for gestational diabetes between 24 and 28 weeks gestation unless pregestational diabetes is present. Lifestyle modifications are fundamental to management, and most patients are able to control blood glucose levels with these alone. Persistent hyperglycemia should be managed with drugs. Currently, insulin is the only drug approved by the Food and Drug Administration (FDA) for gestational diabetes management. Metformin or glyburide can be reasonable alternatives. For patients who require drugs, antepartum fetal surveillance is recommended starting at 32 weeks gestation. The American College of Obstetricians and Gynecologists (ACOG) recommends delivery at 39 07 to 40 67 weeks gestation for patients with gestational diabetes controlled with diet alone. Earlier delivery is recommended for patients with gestational diabetes controlled with drugs, at 39 07 to 39 67 weeks gestation. Patients with gestational diabetes are at increased risk of type 2 diabetes later in life. These patients should be screened for prediabetes and diabetes between 4 and 12 weeks postpartum with a 75-g, 2-hour OGTT. Postpartum patients with a normal OGTT result should be screened every 1 to 3 years thereafter.

Effects of aquatic high intensity interval training on parameters of functional autonomy, mental health, and oxidative dysfunction in elderly subjects with type 2 diabetes.

The present study investigated the effects of aquatic exercise on parameters of functional autonomy, mental health, and oxidative dysfunction in elderly patients with DM2. A total of 130 elderly were included in the longitudinal clinical study and were attributed to the non-diabetic group (

Health Care Resource Utilization in Adults Living With Type 1 Diabetes Mellitus in the South African Public Health Sector Protocol for a 1-Year Retrospective Analysis With a 5-, 10-, and 25-Year Projection.

Type 1 diabetes mellitus (T1DM) is less common than type 2 diabetes mellitus but is increasing in frequency in South Africa. It tends to affect younger individuals, and upon diagnosis, exogenous insulin is essential for survival. In South Africa, the health care system is divided into private and public health care systems. The private system is well resourced, whereas the public sector, which treats more than 80% of the population, has minimal resources. There are currently no studies in South Africa, and Africa at large, that have evaluated the immediate and long-term costs of managing people living with T1DM in the public sector. The primary objective was to quantify the cost of health care resource utilization over a 12-month period in patients with controlled and uncontrolled T1DM in the public health care sector. In addition, we will project costs for 5, 10, and 25 years and determine if there are cost differences in managing subsets of patients who achieve glycemic control (hemoglobin A The study was performed in accordance with Good Epidemiological Practice. Ethical clearance and institutional permissions were acquired. Clinical data were collected from 2 tertiary hospitals in South Africa. Patients with T1DM, who provided written informed consent, and who satisfied the inclusion criteria were enrolled in the study. Data collection included demographic and clinical characteristics, acute and chronic complications, hospital admissions, and so on. We plan to perform a cost-effectiveness analysis to quantify the costs of health care utilization in the preceding 12 months. In addition, we will estimate projected costs over the next 10 years, assuming that study participants maintain their current HbA Ethical clearance and institutional approval were obtained (reference number 200407). Enrollment began on February 9, 2021, and was completed on August 24, 2021, with 224 participants. A database lock was performed on October 29, 2021. The statistical analysis and clinical study report were completed in January 2022. At present, there are no data assessing the short- and long-term costs of managing patients with T1DM in the South African public sector. It is hoped that the findings of this study will help policy makers optimally use limited resources to reduce morbidity and mortality in people living with T1DM. RR1-10.219644308.

Variation of butyrate production in the gut microbiome in type 2 diabetes patients.

Diabetes mellitus type 2 is a common disease that poses a challenge to the healthcare system. The disease is very often diagnosed late. A better understanding of the relationship between the gut microbiome and type 2 diabetes can support early detection and form an approach for therapies. Microbiome analysis offers a potential opportunity to find markers for this disease. Next-generation sequencing methods can be used to identify the bacteria present in the stool sample and to generate a microbiome profile through an analysis pipeline. Statistical analysis, e.g., using Students t-test, allows the identification of significant differences. The investigations are not only focused on single bacteria, but on the determination of a comprehensive profile. Also, the consideration of the functional microbiome is included in the analyses. The dataset is not from a clinical survey, but very extensive. By examining 946 microbiome profiles of diabetes mellitus type 2 sufferers (272) and healthy control persons (674), a large number of significant genera (25) are revealed. It is possible to identify a large profile for type 2 diabetes disease. Furthermore, it is shown that the diversity of bacteria per taxonomic level in the group of persons with diabetes mellitus type 2 is significantly reduced compared to a healthy control group. In addition, six pathways are determined to be significant for type 2 diabetes describing the fermentation to butyrate. These parameters tend to have high potential for disease detection. With this investigation of the gut microbiome of persons with diabetes type 2 disease, we present significant bacteria and pathways characteristic of this disease.

Metabolic Consequences of Pediatric Obesity A Review of Pathophysiology, Screening, and Treatment.

The prevalence of pediatric obesity has been increasing during the last 30 years, and the subsequent metabolic consequences of obesity, which were mainly seen in adults, are now presenting in childhood. Type 2 diabetes, prediabetes, metabolic syndrome, and nonalcoholic fatty liver disease are serious metabolic ramifications of pediatric obesity pediatricians need to be familiar in screening and treatment of these metabolic issues. This review will discuss the inflammation and insulin resistance involved in obesity that can lead to these conditions. We will explore the pathophysiology of type 2 diabetes and prediabetes, metabolic syndrome, and nonalcoholic fatty liver disease and review screening and treatment modalities. Finally, we will highlight other important endocrine related comorbidities in pediatric obesity, including polycystic ovary syndrome, precocious puberty, and early accelerated growth.

Comparison of Cataract Surgery Outcomes in Patients with Type 1 versus Type 2 Diabetes and Patients without Diabetes.

To report outcomes of cataract surgery in type 1 diabetes (T1DM) compared to type 2 diabetes (T2DM) and patients without diabetes (DM). Academic tertiary referral university hospital eye center, Aurora, CO, USA. Retrospective chart review using the University of Colorado Cataract Outcomes Database for all cataract surgeries between 2014-2020. Demographics, ocular history, and postoperative outcomes were compared across groups using general linear and logistic regression modeling with estimating equations to account for some patients having two eyes included. A total of 8117 patients and 13,383 eyes were included. Compared to T2DM eyes undergoing cataract surgery (n3115), T1DM eyes (n233) were more likely to have a history of diabetic retinopathy (DR) (60.5% vs 23.6%), p<0.0001), of which proliferative DR was the most common (63.1% vs 42.4%, p<0.0001). T1DM eyes were also more likely to have a history of retinal detachment (RD) (9.0% vs 2.9%, p<0.0001) and prior vitrectomy surgery (12.9% vs 4.0%, p<0.0001). Despite having similar preoperative best-corrected visual acuity (BCVA) as T2DM eyes (logMAR 0.52 vs. 0.44, p0.092), T1DM eyes had worse BCVA following cataract surgery (logMAR 0.27 vs 0.15, p0.0003). In a multivariable analysis, a history of proliferative DR and prior RD were significant predictors of worse postoperative BCVA (p<0.0001) but type of DM was not (p0.894). T1DM eyes have worse visual outcomes after cataract surgery compared to T2DM eyes. Worse postoperative visual acuity was associated with worse preoperative diabetic retinopathy and history of retinal detachment rather than type of DM.

The effects of local calf vibration on balance, blood flow, and nerve conductivity in patients with diabetic peripheral neuropathy a pilot study.

This study aimed to evaluate the effects of local calf vibration on balance, blood flow, and nerve conductivity in patients with diabetic peripheral neuropathy (DPN). An open-label controlled trial was designed. Patients with confirmed diagnoses of type 2 diabetes and DPN were enrolled in the study and underwent ten sessions of local calf vibration therapy for the dominant leg. The other leg was considered the control. Balance evaluation, nerve conduction studies, and color Doppler ultrasound were performed before and after the treatment course. The Wilcoxon signed rank test and the Mann-Whitney test were used to evaluate the differences between the test results before and after the intervention and between the intervention and control legs. Seventeen patients with a mean age of 60.3 ± 5.6 years (11 males) participated in the study. Mean Brief BESTest total scores were significantly improved (14.06 vs. 17.35 P .01, Cohens d 0.743). There were no significant differences between the treated and control legs regarding the nerve conduction and color Doppler ultrasound parameters before and after the intervention (P ≥ .054). Changes in the parameters were also not significantly different between legs (P ≥ .078), except for common peroneal nerve conduction velocity, for which there was a higher increase in its value in the treated legs compared to the control legs (4.17 vs. 0.9, P .002). Local calf vibration may positively affect balance and lower extremities nerve conduction in patients with DPN, and the findings of this study can be a basis for studies evaluating the efficacy of local calf vibration for treating DPN.

The efficacy and safety of tadalafil in the management of erectile dysfunction with diabetes and blood circulation issues.

Erectile dysfunction (ED) is a common diabetes-related complication. This study examined the effect of daily low-dose tadalafil (5 mg) on patients quality of life (including that of sex life) and blood circulation. Erectile dysfunction questionnaires were administered to 20 patients with type 2 diabetes (T2DM) and ED. The safety and efficacy of tadalafil were evaluated using laboratory tests, and the effect on blood circulation was measured through nail fold capillaroscopy. Daily tadalafil use by patients with T2DM and ED showed a statistically significant increase in the erectile reliability score from of 1.15 to 3.20 ( A small dose of daily tadalafil was shown to safely improve erectile dysfunction and peripheral blood flow in patients with T2DM, in which peripheral arterial diseases should not be considered separately but rather as complex entities.

Investigating the effects of Ceylon cinnamon water extract on HepG2 cells for Type 2 diabetes therapy.

Cinnamon and its extracts have been used as herbal remedies for many ailments, including for reducing insulin resistance and diabetes complications. Type 2 diabetes mellitus (T2DM) is a rapidly growing health concern around the world. Although many drugs are available for T2DM treatment, side effects and costs can be considerable, and there is increasing interest in natural products for managing chronic health conditions. Cinnamon may decrease the expression of genes associated with T2DM risk. The purpose of this study was to evaluate the effects of cinnamon water extract (CWE) compared with metformin on T2DM-related gene expression. HepG2 human hepatoma cells, widely used in drug metabolism and hepatotoxicity studies, were treated with different concentrations of metformin or CWE for 24 or 48 h. Cell viability was assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay and glucose uptake was compared in untreated and CWE- or metformin-treated cells under high-glucose conditions. Finally, total RNA was extracted and analyzed by RNA sequencing (RNA-seq), and bioinformatics analyses were performed to compare the transcriptional effects of CWE and metformin. We found cell viability was better in cells treated with CWE than in metformin-treated cells, demonstrating that CWE was not toxic at tested doses. CWE significantly increased glucose uptake in HepG2 cells, to the same degree as metformin (1.4-fold). RNA-seq data revealed CWE and metformin both induced significantly increased (1.3- to 1.4-fold) glucose uptake gene expression compared with untreated controls. Transcriptional differences between CWE and metformin were not significant. The effects of 0.125 mg mL

Self-management of type 2 diabetes among Turkish immigrants in Norway A focus group study.

The prevalence of Type 2 Diabetes Mellitus (T2DM) is higher among Turkish immigrants than the general population in Norway. The aim of the study is to describe the challenges and experiences faced by Turkish immigrants in Norway in the self-management of T2DM. The study design is based on descriptive research using a qualitative approach. The sample group contained 13 persons participating in three focus group interviews nine women and four men. A phenomenological-hermeneutical approach was employed to achieve a deeper understanding of the experience of self-management of T2DM among Turkish immigrants in Norway with regard to HL. The participants described experiences of the T2DM self-management with regard to HL and revealed three major themes (1) understanding the role and responsibility of health care staff in T2DM treatment, (2) assessing T2DM education course and information and (3) applying knowledge and motivation to adapt to life with T2DM. Findings from this study revealed that self-management of patients with T2DM among Turkish immigrants is related to their cultural, religious and socio-economical background and experiences. By understanding the cultural features, a well-tailored intervention according to the needs of Turkish immigrants regarding self-management can be developed. Health care staff are recommended to consider patients HL when interventions are developed.

Therapeutic efficacy of liraglutide versus metformin in modulating the gut microbiota for treating type 2 diabetes mellitus complicated with nonalcoholic fatty liver disease.

Metformin and liraglutide are used in the treatment of type 2 diabetes mellitus (T2DM) complicated with nonalcoholic fatty liver disease (NAFLD). Although these drugs can alter the intestinal microbiome, clinical data are required to explore their mechanisms of action. Using 16S sequencing technology, we analyzed and compared the intestinal bacterial community structure and function between patients before and after treatment (12 weeks) with the two drugs (metformin or liraglutide,

Candidate loci shared among periodontal disease, diabetes and bone density.

While periodontal disease (PD) has been associated with type 2 diabetes (T2D) and osteoporosis, the underlying genetic mechanisms for these associations remain largely unknown. The aim of this study is to apply cross-trait genetic analyses to investigate the potentially shared biology among PD, T2D, and bone mineral density (BMD) by assessing pairwise genetic correlations and searching for shared polymorphisms. We applied cross-trait genetic analyses leveraging genome-wide association study (GWAS) summary statistics for Periodontitisloose teeth from the UKBBGLIDE consortium (PerioLT, N506594), T2D from the DIAGRAM consortium (N Significant genetic correlations were identified between PerioLTT2D (Rg0.23 SE0.04 p7.4e This integrative approach identified one colocalized locus and 14 additional candidate loci that are shared between T2D and PDoral health by comparing effects across PD, T2D and BMD. Future research is needed to independently validate our findings.

Insights in diabetes Molecular mechanisms-Protectin DX, an anti-inflammatory and a stimulator of inflammation resolution metabolite of docosahexaenoic acid, protects against the development of streptozotocin-induced type 1 and type 2 diabetes mellitus in male Swiss albino mice.

Our previous studies revealed that certain endogenous low molecular weight lipids have potent anti-diabetic actions. Of all, arachidonic acid (AA) and its anti-inflammatory and inflammation resolving metabolite lipoxin A4 (LXA4) are the most potent anti-diabetic molecules. Similar anti-diabetic action is also shown by resolvins. In our efforts to identify other similar lipid based anti-diabetic molecules, we investigated potential anti-diabetic action of protectin DX that also has anti-inflammatory and inducer of inflammation resolution action(s) like LXA4. Protectin DX 10(S),17(S)-dihydroxy-4Z,7Z,11E,13Z,15E,19Z-docosahexaenoic acid, also called as 10(S),17(S)-DiHDoHE) prevented the development of streptozotocin-induced type 1 and type 2 diabetes mellitus in Swiss male albino mice. Protectin DX showed potent anti-inflammatory, antioxidant and anti-apoptotic actions that could explain its anti-diabetic action. In view of these beneficial actions, efforts need to be developed to exploit PDX and other similar compounds as potential anti-diabetic molecule in humans.

Novel nutraceutical supplements with yeast β-glucan, prebiotics, minerals, and

It is known that obesity has a multifactorial etiology that involves genetic and environmental factors. The WHO estimates the worldwide prevalence of 1.9 billion overweight adults and more than 650 million people with obesity. These alarming data highlight the high and growing prevalence of obesity and represent a risk factor for the development and aggravation of other chronic diseases, such as nonalcoholic fatty liver disease (NAFLD) that is frequently considered the hepatic outcome of type 2 diabetes. The use of non-pharmacological therapies such as food supplements, nutraceuticals, and natural integrative therapies has grown as an alternative tool for obesity-related diseases compared to conventional medications. However, it is a still little explored research field and lacks scientific evidence of therapeutic effectiveness. Considering this, the aim is to evaluate whether a new nutraceutical supplement composition can improve and supply essential mineral nutrients, providing an improvement of obesity-related metabolic and endocrine parameters. Sedentary volunteers (women and men) with body mass index (BMI) ≤34.9 kgm In the anthropometric analysis, the waist circumference in middle abdomen (WC-mid) and waist circumference in iliac crest (WC-IC) were reduced. Also, the waist-to-height ratio (WHt R) and waist-to-hip ratio (WHR) seem to slightly decrease alongside the supplementation period with both nutraceutical supplements tested as well as transaminase enzyme ratio aspartate aminotransferase (AST)alanine aminotransferase (ALT) ratio (AAR), a known as a biomarker of NAFLD, and endocrine hormones cortisol and thyroid-stimulating hormone (TSH) at 90 and 180 days post-supplementation. In a condition associated with sedentary and no nutritional intervention, the new nutraceutical supplement composition demonstrated the ability to be a strong and newfangled tool to improve important biomarkers associated with obesity and its comorbidities.

The management correlation between metabolic index, cardiovascular health, and diabetes combined with cardiovascular disease.

Cardiovascular disease (CVD) has become a major cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Although there is also evidence that multifactorial interventions to control blood glucose, blood pressure, and lipid profiles can reduce macrovascular complications and mortality in patients with T2DM, the link between these risk factors has not been established. On 10 December 2018, 1,920 people in four cities in Anhui Province were included. Latent category analysis (LCA) was used to explore the clustering mode of HRBs (health risk behaviors). The primary exposure was HRBs and exercise and diet interventions, and the primary outcome was CVD and other variables, including zMS, triglyceride-glucose index (TyG), TyG-WC (waist circumference), TyG-BMI, TGHDL, and cardiovascular health (CVH). A multivariable logistic regression model was used to establish the relationship between HRBs, exercise, diet interventions, and CVD. Moderate analysis and mediation moderation analysis were employed by the PROCESS method to explore the relationship between these variables. Sensitivity analysis explored the robustness of the model. The mean age was 57.10 ± 10.0 years old. Overall, CVD affects approximately 19.9% of all persons with T2DM. Macrovascular complications of T2DM include coronary heart disease, myocardial infarction (MI), cardiac insufficiency, and cerebrovascular disease. Elderly age ( CVD is one of the common complications in patients with type 2 diabetes, and its long-term outcome will have more or less impact on patients. Our findings suggest the potential benefits of scaling up multifactorial and multifaceted interventions to prevent CVD in patients with T2DM.

An integrated map of cell type-specific gene expression in pancreatic islets.

Pancreatic islets are comprised of multiple endocrine cell types that produce hormones required for glucose homeostasis, and islet dysfunction is a major factor in the development of type 1 and type 2 diabetes (T1D, T2D). Numerous studies have generated gene expression profiles in individual islet cell types using single cell assays. However, there is no canonical reference of gene expression in islet cell types in both health and disease that is also easily accessible for researchers to access, query, and use in bioinformatics pipelines. Here we present an integrated reference map of islet cell type-specific gene expression from 192,203 cells derived from single cell RNA-seq assays of 65 non-diabetic, T1D autoantibody positive (Aab), T1D, and T2D donors from the Human Pancreas Analysis Program. We identified 10 endocrine and non-endocrine cell types as well as sub-populations of several cell types, and defined sets of marker genes for each cell type and sub-population. We tested for differential expression within each cell type in T1D Aab, T1D, and T2D states, and identified 1,701 genes with significant changes in expression in any cell type. Most changes were observed in beta cells in T1D, and, by comparison, there were almost no genes with changes in T1D Aab. To facilitate user interaction with this reference, we provide the data using several single cell visualization and reference mapping tools as well as open-access analytical pipelines used to create this reference. The results will serve as a valuable resource to investigators studying islet biology and diabetes.

Pre-existing autoimmunity is associated with increased severity of COVID-19 A retrospective cohort study using data from the National COVID Cohort Collaborative (N3C).

Identifying individuals with a higher risk of developing severe COVID-19 outcomes will inform targeted or more intensive clinical monitoring and management. To examine, using data from the National COVID Cohort Collaborative (N3C), whether patients with pre-existing autoimmune disease (AID) diagnosis andor immunosuppressant (IS) exposure are at a higher risk of developing severe COVID-19 outcomes. A retrospective cohort of 2,453,799 individuals diagnosed with COVID-19 between January 1 Two outcomes of COVID-19 severity, derived from the World Health Organization severity score, were defined, namely life-threatening disease and hospitalization. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression models with and without adjustment for demographics (age, BMI, gender, race, ethnicity, smoking status), and comorbidities (cardiovascular disease, dementia, pulmonary disease, liver disease, type 2 diabetes mellitus, kidney disease, cancer, and HIV infection). In total, 2,453,799 (16.11% of the N3C cohort) adults (age> 18 years) were diagnosed with COVID-19, of which 191,520 (7.81%) had a prior AID diagnosis, and 278,095 (11.33%) had a prior IS exposure. Logistic regression models adjusted for demographic factors and comorbidities demonstrated that individuals with a prior AID (OR 1.13, 95% CI 1.09 - 1.17 Patients with pre-existing AID, exposure to IS, or both are more likely to have a life-threatening disease or hospitalization. These patients may thus require tailored monitoring and preventative measures to minimize negative consequences of COVID-19.

Diabetes-Induced Autophagy Dysregulation Engenders Testicular Impairment via Oxidative Stress.

Testes produce sperms, and gamete generation relies on a proper niche environment. The disruption of hierarchical regulatory homeostasis in Leydig or Sertoli cells may evoke a sterile phenotype in humans. In this study, we recapitulated type 2 diabetes mellitus by using a high-fat diet- (HFD-) fed mouse model to identify the phenotype and potential mechanism of diabetes-induced testicular impairment. At the end of the study, blood glucose levels, testosterone structure, testicular antioxidant capacity, and testosterone level and the expression of hypoxia-inducible factor- (HIF-) 1

Bioinformatic prediction of the molecular links between Alzheimers disease and diabetes mellitus.

Alzheimers disease (AD) and type 2 diabetes mellitus (DM2) are chronic degenerative diseases with complex molecular processes that are potentially interconnected. The aim of this work was to predict the potential molecular links between AD and DM2 from different sources of biological information. In this work, data mining of nine databases (DisGeNET, Ensembl, OMIM, Protein Data Bank, The Human Protein Atlas, UniProt, Gene Expression Omnibus, Human Cell Atlas, and PubMed) was performed to identify gene and protein information that was shared in AD and DM2. Next, the information was mapped to human protein-protein interaction (PPI) networks based on experimental data using the STRING web platform. Then, gene ontology biological process (GOBP) and pathway analyses with EnrichR showed its specific and shared biological process and pathway deregulations. Finally, potential biomarkers and drug targets were predicted with the Metascape platform. A total of 1,551 genes shared in AD and DM2 were identified. The highest average degree of nodes within the PPI was for DM2 (average 2.97), followed by AD (average degree 2.35). GOBP for AD was related to specific transcriptional and translation genetic terms occurring in neurons cells. The GOBP and pathway information for the association AD-DM2 were linked mainly to bioenergetics and cytokine signaling. Within the AD-DM2 association, 10 hub proteins were identified, seven of which were predicted to be present in plasma and exhibit pharmacological interaction with monoclonal antibodies in use, anticancer drugs, and flavonoid derivatives. Our data mining and analysis strategy showed that there are a plenty of biological information based on experiments that links AD and DM2, which could provide a rational guide to design further diagnosis and treatment for AD and DM2.

Genomic discoveries unveil mechanistic insights in diabetes.

Two diabetes-related papers are featured in this issue of

Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Mellitus A Single-Centre Observational Study From a Tertiary Care Hospital in South India.

Background There is a high prevalence of left ventricular diastolic dysfunction (LVDD) in patients with type 2 diabetes mellitus (T2DM). The influencing factors of LVDD in T2DM are not fully understood. Objective This study aimed at assessing the prevalence of LVDD in T2DM as well as looking at the association between various parameters related to T2DM with LVDD in patients with T2DM. Materials and methods This was a single-centre cross-sectional study in Kerala, India. The primary objective of the study was to assess the prevalence of LVDD in T2DM. The secondary objectives were to look for an association between higher glycated haemoglobin (HbA1c), complications of T2DM, age, and gender of the patient with the presence of LVDD. Results A total of 80 patients were included in the study. There were 40 patients with LVDD with a prevalence of 50%. There was a statistically significant positive association between increased age, longer duration of diabetes, higher HbA1C, the presence of diabetic neuropathy, diabetic retinopathy, and diabetic nephropathy with the prevalence of LVDD. A logistic regression analysis demonstrated that the presence of diabetic retinopathy is a risk factor for LVDD in the study subjects.

Effect of H2H management mode on blood sugar control and living ability in patients with schizophrenia and type 2 diabetes mellitus.

To explore the effect of H2H management mode on blood sugar control and living ability in patients with schizophrenia and type 2 diabetes mellitus. A retrospective analysis was conducted on 95 patients with schizophrenia and type 2 diabetes who were hospitalized in Wuhan Mental Health Center from July 2021 to February 2022. The subjects were grouped according to management mode 50 cases in group A (H2H management mode) and 45 cases in group B (conventional mode). Psychiatric symptoms were assessed with the Positive and Negative Symptoms Scale (PANSS), and changes in living ability before and after the intervention were assessed by the activity of daily living scale (ADL). Fasting blood glucose (FPG), 2-h postprandial blood glucose (2hPG), and glycosylated hemoglobin (HbA1c) were detected by high-performance liquid chromatography on a blood glucose analyzer. Schizophrenia Quality of Life Scale (SQLS) was used to evaluate changes in life quality, and Pittsburgh Sleep Quality Index (PSQI) and the Simple Roy Coping Adaptation Scale (CAPS-15) were for the sleep quality and coping adaptability of the two groups before and after intervention, respectively. Self-perceived burden scale (SPBS) was used to evaluate the self-perceived burden of the two groups before and after intervention. After intervention, PANSS score of group A was observed markedly lower than that of group B, as well as its ADL score, SQLS score and the levels of 2hPG, FPG and HbA1c (all P < 0.05). Compared to group B, the patients in group A were also assessed with evidently lower SQLS score (P < 0.05) and lower scores of physical burden, emotional burden and economic burden after intervention (all P < 0.05). H2H management model can effectively improve the mental state, quality of life, sleep quality and coping adaptability of patients with schizophrenia complicated with type 2 diabetes, as well as reducing patients blood sugar, which is worthy of clinical promotion.

Incidence and predictors of metabolic syndrome in Asian-Indians a 10-year population-based prospective cohort study.

Metabolic syndrome represents aggregation of risk factors associated with an increased risk of developing type 2 diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD). Assessing its incidence is an effective way for estimating the future burden of DM and ASCVD and understanding their secular trends and effect of public health measures on halting the evolution of risk factors. The present study aimed to estimate the incidence of metabolic syndrome and its predictors using a population-based cohort. A subset of Chandigarh Urban Diabetes Study cohort ( In the followed-up individuals ( Asian-Indians have a high incidence rate of metabolic syndrome, which is associated with sedentary lifestyle and consequent central obesity.

Effect of hydroxychloroquine on beta cell function, insulin resistance, and inflammatory markers in type 2 diabetes patients uncontrolled on glimepiride and metformin therapy.

Very few studies have assessed the impact of hydroxychloroquine (HCQ) on insulin resistance, beta cell function, and inflammatory markers in diabetics which takes paramount importance in understanding the mechanism of its anti-diabetic effect. To assess the effect of hydroxychloroquine on beta cell function and insulin resistance and inflammatory markers in type 2 diabetes patients uncontrolled on glimepiride and metformin combination. 30 T2DM patients were inadequately controlled on glimepiride and metformin combination with an HbA1c between 7.5 and 10% (both inclusive) and were given hydroxychloroquine 400 mg in addition to glimepiride and metformin during the 12-week study period. Beta cell function, insulin resistance, high-sensitivity C-reactive protein (hsCRP), adiponectin, interleukin-6 (IL6), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), and glycated hemoglobin (HbA1c) were assessed at baseline and at 12 weeks after addition of 400 mg hydroxychloroquine. With addition of HCQ, there was a significant improvement in both beta cell function and insulin resistance ( Addition of hydroxychloroquine as an add-on drug in uncontrolled diabetes significantly improves the beta cell function and the insulin resistance, along with significant improvement in adiponectin, hsCRP levels, and IL6 levels.

Dietary weight-management for type 2 diabetes remissions in South Asians the South Asian diabetes remission randomised trial for proof-of-concept and feasibility (STANDby).

We aimed to assess whether a structured weight management programme incorporating a total diet replacement (TDR) (3-5 months ∼850 kcalday formula diet) weight loss phase is acceptable to people of South Asian ethnicity and can achieve type 2 diabetes (T2D) remissions similarly to other populations. Adults of South Asian ethnicity, aged 18-65 years, with T2D for ≤4 years, and BMI 25-45 kgm Current Controlled Trials, ISRCTN10720065. Date of Registration 27092017. Twenty-five eligible individuals were recruited. Mean baseline (SD) age was 45.8 (11.1) years, weight 88.2 (13.7) kg, BMI 32.1 (3.8) kgm In UK-based South Asians, TDR-led weight loss and T2D remission rates are comparable to those observed in white cohorts, and the intervention was acceptable in most of those recruited. There is potential to further improve outcomes, but one-third lost >10% body weight, and the mechanism underpinning T2D remission appears similar, driven by weight change with loss of excess ectopic body-fat. We gratefully acknowledge funding for the MRI scans from the, Miss MJM Smith Trust (registered charity SC040586). No other external funds were provided for this trial. NS is supported by the British Heart Foundation Research Excellence Award (RE18634217).

Association between body fat and sarcopenia in older adults with type 2 diabetes mellitus A cross-sectional study.

To investigate the association between body fat (BF%) and sarcopenia in older adults with type 2 diabetes mellitus (T2DM) and potential link with increased levels of inflammatory indicators and insulin resistance. A total of 543 older adults with T2DM were included in this cross-sectional study. Appendicular skeletal muscle (ASM), handgrip strength and gait speed were measured to diagnose sarcopenia according to the updated Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Body composition data were tested using dual-energy X-ray absorptiometry (DEXA). Levels of serum high-sensitive C-reactive protein (hs-CRP), interleukin-6, fasting blood insulin (FINS), hemoglobin A1c (HbA1c), 25-hydroxyvitamin D The prevalence of sarcopenia in all participants was 8.84%, of which 11.90% were male and 5.84% females. The Pearsons correlation analysis revealed that BF% was negatively correlated with gait speed in men and women (R -0.195, Higher BF% was linked to an increased risk of sarcopenia in older adults with T2DM, suggesting the importance of assessing BF% rather than BMI alone to manage sarcopenia.

Microbiota A potential orchestrator of antidiabetic therapy.

The gut microbiota, as a new organ of humans, has been identified to affect many biological processes, including immunity, inflammatory response, gut-brain neural circuits, and energy metabolism. Profound dysbiosis of the gut microbiome could change the metabolic pattern, aggravate systemic inflammation and insulin resistance, and exacerbate metabolic disturbance and the progression of type 2 diabetes (T2D). The aim of this review is to focus on the potential roles and functional mechanisms of gut microbiota in the antidiabetic therapy. In general, antidiabetic drugs (α-glucosidase inhibitor, biguanides, incretin-based agents, and traditional Chinese medicine) induce the alteration of microbial diversity and composition, and the levels of bacterial component and derived metabolites, such as lipopolysaccharide (LPS), short chain fatty acids (SCFAs), bile acids and indoles. The altered microbial metabolites are involved in the regulation of gut barrier, inflammation response, insulin resistance and glucose homeostasis. Furthermore, we summarize the new strategies for antidiabetic treatment based on microbial regulation, such as proprebiotics administration and fecal microbiota transplantation, and discuss the need for more basic and clinical researches to evaluate the feasibility and efficacy of the new therapies for diabetes.

Short-term effect of polyethylene glycol loxenatide on weight loss in overweight or obese patients with type 2 diabetes An open-label, parallel-arm, randomized, metformin-controlled trial.

Polyethylene glycol loxenatide (PEG-Loxe) is a novel, once-weekly glucagon-like peptide 1 receptor agonist that is approved in doses of 0.1 mg and 0.2 mg for the treatment of type 2 diabetes mellitus (T2DM). However, no clinical trials have been designed to determine the effect of 0.3 mg PEG-Loxe on weight loss in overweight or obese patients with T2DM. This trial aimed to evaluate the short-term effect of 0.3 mg PEG-Loxe, injected subcutaneously once weekly, for weight management in overweight or obese patients with T2DM. This 16-week, open-label, parallel-arm, randomized, metformin-controlled trial was conducted at Shandong Provincial Hospital in Shandong, China. Patients with T2DM, who were overweight or obese (body mass index ≥ 25.0 kgm Overall, 156 patients were randomized and exposed to treatment. Weight loss was 7.52 kg (8.37%) with PEG-Loxe and 2.96 kg (3.00%) with metformin, with a between-group difference of 4.55 kg (95% CI, 3.43 to 5.67) ( In overweight or obese patients with T2DM, a once-weekly subcutaneous administration of PEG-Loxe for 16 weeks, in addition to lifestyle interventions or oral antidiabetic drug therapy, resulted in significantly greater weight loss compared to metformin. Additional trials are necessary to establish whether these effects can be maintained in the long term. www.chictr.org.cn, identifier ChiCTR2200057800.

The effects of Sodium-glucose cotransporter 2 inhibitors on adipose tissue in patients with type 2 diabetes A meta-analysis of randomized controlled trials.

To systematically evaluate the effect of Sodium-glucose cotransporter 2 (SGLT2) inhibitors on adipose tissue in patients with type 2 diabetes. We searched PubMed, Cochrane Library, EMBASE, and Web of science databases for literature pertaining to Randomized controlled trials (RCTs) of SGLT2 inhibitors in treating type 2 diabetes patients. The retrieval time was from the date of establishment of the databases to September 1, 2022. Meta-analysis was performed using RevMan5.4 software. Totally 551 patients were included in 10 articles. Meta-analysis results showed that compared with the control group, the visceral adipose tissue (WMD -16.29 cm SGLT2 inhibitors cause significant reductions in visceral adipose tissue, subcutaneous adipose tissue, body weight and triglycerides in type 2 diabetes patients, which may be attributed to the protective effect of the inhibitors on cardiovascular system.

Association Between Depression, Diabetes Self-Care Activity and Glycemic Control in an Arab Population with Type 2 Diabetes.

Poor self-care behavior and depression are associated with worse glycemic control, but the relationship between these variables is poorly reported. The present study aimed to describe self-care behaviors and explore the association between depression, self-care and glycemic control in people with type 2 diabetes in an Arab population. This study recruited 446 patients with type-2 diabetes from an outpatient clinic in Kuwait and completed assessments of diabetes self-care using the Summary of Diabetes Self-Care Activities (SDSCA) questionnaire and depression using the Patients Health Questionnaire-9 (PHQ-9) scales. Multiple linear regression models were used to determine the associations between depression, self-care behaviors and glycemic control. Self-care behaviors were highest for medication taking (92.9%), an average for foot care (61.4%), blood glucose testing (60%) and healthy diet (55.7%), and lowest for exercise (27.1%). Depression, poor self-care activities and poor HbA1c levels were inter-correlated in univariate analysis ( Self-care activity was less than fifty percent in people with type 2 diabetes and higher activity was associated with better glycemic control. However, depression adversely affects self-care behaviors. To maintain and achieve glycemic control, diabetes educators might motivate people with type 2 diabetes to enhance their self-care activities, particularly those with depression symptoms and poor compliance with self-care activities.

Efficacy of ixekizumab in patients with moderate-to-severe plaque psoriasis and prediabetes or type 2 diabetes.

Patients with psoriasis have an increased prevalence of type 2 diabetes when compared to the general population. Research suggests that type 2 diabetes (T2D) as well as obesity may have an impact on patients response to treatment. This post-hoc analysis reports the efficacy of ixekizumab in treating moderate-to-severe psoriasis in patients with prediabetes or T2D. UNCOVER-1, UNCOVER-2, and UNCOVER-3 were three Phase 3, multicenter, randomized, double-blind, placebo-controlled trials that evaluated the efficacy and safety of ixekizumab in adult patients with moderate-to-severe psoriasis. Patients were aged ≥18 years with chronic moderate-to-severe psoriasis (defined as ≥10% body surface area affected, static Physician Global Assessment ≥3, and Psoriasis Area and Severity Index PASI ≥12 at screening and baseline) who were candidates for phototherapy or systemic therapy. UNCOVER-1, UNCOVER-2, and UNCOVER-3 participants received ixekizumab as per label (that is, an initial dose of two subcutaneous injections 160 mg in total at Week 0, followed by 80 mg every 2 weeks through Week 12 and 80 mg every 4 weeks thereafter through Week 60). The proportions of patients with prediabetes, T2D and normoglycemia that achieved PASI75, PASI90, and PASI100 at Week 60 were similar. Results suggest that patients with T2D were slower to achieve PASI100 than patients with prediabetes or those with normoglycemia. Ixekizumab had no effect on any metabolic markers in patients receiving the treatment. Despite the higher rate of obesity and extreme obesity in patients with prediabetes and T2D, ixekizumab was an efficacious treatment in treating patients with psoriasis.

Caspase-11 promotes high-fat diet-induced NAFLD by increasing glycolysis, OXPHOS, and pyroptosis in macrophages.

Non-alcoholic fatty liver disease (NAFLD) has a global prevalence of 25% of the population and is a leading cause of cirrhosis and hepatocellular carcinoma. NAFLD ranges from simple steatosis (non-alcoholic fatty liver) to non-alcoholic steatohepatitis (NASH). Hepatic macrophages, specifically Kupffer cells (KCs) and monocyte-derived macrophages, act as key players in the progression of NAFLD. Caspases are a family of endoproteases that provide critical connections to cell regulatory networks that sense disease risk factors, control inflammation, and mediate inflammatory cell death (pyroptosis). Caspase-11 can cleave gasdermin D (GSDMD) to induce pyroptosis and specifically defends against bacterial pathogens that invade the cytosol. However, its still unknown whether high fat diet (HFD)-facilitated gut microbiota-generated cytoplasmic lipopolysaccharides (LPS) activate caspase-11 and promote NAFLD. To examine this hypothesis, we performed liver pathological analysis, RNA-seq, FACS, Western blots, Seahorse mitochondrial stress analyses of macrophages and bone marrow transplantation on HFD-induced NAFLD in WT and Casp11-- mice. Our results showed that 1) HFD increases body wight, liver wight, plasma cholesterol levels, liver fat deposition, and NAFLD activity score (NAS score) in wild-type (WT) mice 2) HFD increases the expression of caspase-11, GSDMD, interleukin-1β, and guanylate-binding proteins in WT mice 3) Caspase-11 deficiency decreases fat liver deposition and NAS score 4) Caspase-11 deficiency decreases bone marrow monocyte-derived macrophage (MDM) pyroptosis (inflammatory cell death) and inflammatory monocyte (IM) surface GSDMD expression 5) Caspase-11 deficiency re-programs liver transcriptomes and reduces HFD-induced NAFLD 6) Caspase-11 deficiency decreases extracellular acidification rates (glycolysis) and oxidative phosphorylation (OXPHOS) in inflammatory fatty acid palmitic acid-stimulated macrophages, indicating that caspase-11 significantly contributes to maintain dual fuel bioenergetics-glycolysis and OXPHOS for promoting pyroptosis in macrophages. These results provide novel insights on the roles of the caspase-11-GSDMD pathway in promoting hepatic macrophage inflammation and pyroptosis and novel targets for future therapeutic interventions involving the transition of NAFLD to NASH, hyperlipidemia, type II diabetes, metabolic syndrome, metabolically healthy obesity, atherosclerotic cardiovascular diseases, autoimmune diseases, liver transplantation, and hepatic cancers.

Benefits of Physical Activity on Cardiometabolic Diseases in Obese Children and Adolescents.

In the past few decades, obesity in the pediatric population has dramatically increased and is common in many countries. Childhood obesity often causes health problems and increases the risk of cardiometabolic diseases such as type 2 diabetes, nonalcohol fatty liver, and cardiovascular diseases. Obesity in young people has been closely associated with environmental, behavioral, and genetic defects, including the availability of high-energy and sugary food and beverages, sedentary behavior, and hereditary factors. Few drugs are currently available to treat obesity in children and adolescents because it is difficult to demonstrate the safety of these drugs on the growth and development of the youth. Lifestyle modifications, such as diet control and physical exercise, are the primary approaches for preventing and treating childhood obesity. Among them, physical activity is a crucial component. This review summarizes the epidemiology, cardiometabolic risk of obesity, therapeutic strategies, and the benefits of exercise on obesity-related chronic diseases in children and adolescents.

Aberrant Energy Metabolism in Alzheimers Disease.

To maintain energy supply to the brain, a direct energy source called adenosine triphosphate (ATP) is produced by oxidative phosphorylation and aerobic glycolysis of glucose in the mitochondria and cytoplasm. Brain glucose metabolism is reduced in many neurodegenerative diseases, including Alzheimers disease (AD), where it appears presymptomatically in a progressive and region-specific manner. Following dysregulation of energy metabolism in AD, many cellular repairregenerative processes are activated to conserve the energy required for cell viability. Glucose metabolism plays an important role in the pathology of AD and is closely associated with the tricarboxylic acid cycle, type 2 diabetes mellitus, and insulin resistance. The glucose intake in neurons is from endothelial cells, astrocytes, and microglia. Damage to neurocentric glucose also damages the energy transport systems in AD. Gut microbiota is necessary to modulate bidirectional communication between the gastrointestinal tract and brain. Gut microbiota may influence the process of AD by regulating the immune system and maintaining the integrity of the intestinal barrier. Furthermore, some therapeutic strategies have shown promising therapeutic effects in the treatment of AD at different stages, including the use of antidiabetic drugs, rescuing mitochondrial dysfunction, and epigenetic and dietary intervention. This review discusses the underlying mechanisms of alterations in energy metabolism in AD and provides potential therapeutic strategies in the treatment of AD.

Impact of Lipoprotein(a) on Macrovascular Complications of Diabetes in a Multiethnic Population in the French Amazon.

In French Guiana, the prevalence of diabetes is around 10%, and cardio and neurovascular pathologies are the first medical cause of early mortality. Lipoprotein(a) (Lp(a)) is described in the literature as a risk factor independent of other cardiovascular risk factors, but there are important interindividual differences, especially according to ethnicity. The objective of this study was to investigate the association of Lp(a) and macrovascular complications in a multiethnic population of patients with diabetes in the French Amazon. Since May 2019, 1243 patients were screened 806 of whom had Lp(a) determination. We compared the prevalence of macrovascular complications in three groups according to Lp(a) concentration between 0 and 75 mgmL, between 76 and 300 mgmL, and >300 mgmL. 712 patients in the study had type 2 diabetes (88.34% of the sample). A history of hypertension was significantly associated with greater Lp(a) levels. Lp(a) concentration was greater among Creole ethnic groups. No association was found between Lp(a) levels and macrovascular complications in the Lp(a) > 300 mgmL group. These results do not replicate findings in mostly Caucasian populations suggesting that the Lp(a) threshold for, or the link with, cardiovascular risk may be different given the predominantly African origin of the French Guianese population. Further studies should study genetic polymorphisms in our population.

A cross-sectional study of the prevalence and clinical management of atherosclerotic cardiovascular diseases in patients with type 2 diabetes across the Middle East and Africa (PACT-MEA) study design and rationale.

The Middle East and Africa regions have the highest regional prevalence of type 2 diabetes (T2D) in the world. Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality for individuals with T2D. Although anti-diabetic medications providing cardiovascular protection are recommended by clinical guidelines, use of these medications is low. This study aimed to investigate the epidemiology and clinical management of patients with T2D and established ASCVD (eASCVD) or highvery high ASCVD risk, defined by the 2021 European Society of Cardiology (ESC) Guidelines, in seven countries in the Middle East and Africa (PACT-MEA NCT05317845). Additionally, the study sought to assess physicians attitudes and basis for their decision-making in the management of these patients. PACT-MEA is a cross-sectional, observational study undertaken in Bahrain, Egypt, Jordan, Kuwait, Qatar, South Africa, and United Arab Emirates based on a medical chart review of approximately 3700 patients with T2D in primary and secondary care settings, and a survey of approximately 400 physicians treating patients with T2D. The primary and secondary objectives are to determine the prevalence of eASCVD and highvery high ASCVD risk in patients with T2D. Current treatment with cardioprotective anti-diabetic medication, proportion of patients meeting treatment criteria for reimbursement in the study countries where there is an applicable reimbursement guideline, and physician-reported factors in clinical decision-making in T2D management will also be assessed. This large cross-sectional study will establish the estimated prevalence and management of patients with eASCVD and highvery high ASCVD risk in the Middle East and Africa. This article is protected by copyright. All rights reserved.

Epidemiological characteristics and management of NAFLDNASH in China A narrative review.

With industrialization and spread of the westernized lifestyle, the number of people affected by non-alcoholic fatty liver disease (NAFLD)non-alcoholic steatohepatitis (NASH) is growing rapidly in China this has become a major public health concern. To better understand the burden and characteristics of NAFLDNASH in China, we aim to perform a narrative review of the literature published in the past decade. The increasing rate of NAFLD prevalence in China is strikingly high, reaching more than twice that in western countries. The prevalence of NAFLD is nearly 30% of the general Chinese population, making it the leading cause of chronic liver diseases. The prevalence of NAFLDNASH varies between provincesregions, age groups, sexes, and individuals with different metabolic profiles. NAFLD co-exists in many Chinese patients with chronic hepatitis B. Since 2020, more Chinese studies have used the term metabolic-associated fatty liver disease (MAFLD), emphasizing the underlying metabolic disorders that occur concurrently with this disease. In this review, we also summarize the clinical trials of NAFLDNASH registered by Chinese investigators. Several trials involving lifestyle interventions, antidiabetic drugs, or traditional Chinese medicines have been completed or are ongoing. Moreover, several innovative targeted therapies developed in China are revolutionizing the treatment of NAFLDNASH. This article is protected by copyright. All rights reserved.

Apolipoprotein A-IV of diabetic-foot patients upregulates tumor necrosis factor α expression in microfluidic arterial models.

Diabetic peripheral arterial atherosclerosis is one of the important characteristics of diabetic foot syndrome. Apolipoprotein (Apo A-IV) participates in various physiological processes, and animal studies have shown that it has roles of anti-atherosclerosis, prevention of platelet aggregation and thrombosis. Apo A-IV glycosylation is closely related to the occurrence and development of diabetic peripheral atherosclerosis. This study aimed to explore the mechanism of diabetic peripheral arterial lesions caused by glycosylated Apo A-IV. Type 2 diabetes mellitus (T2DM) and T2DM with diabetic foot patients (T2DM-F

Evaluation of SGLT-2 inhibitor treatment in type 2 diabetes patients with very high cardiovascular risk.

To evaluate whether the prescription of SGLT2-inhibitors in primary care patients with type 2 diabetes (T2DM) and a very high risk was according to the newest updated Dutch general practitioners practice guidelines on T2DM. This observational study with routine care data was conducted in a primary care setting in the Netherlands. The very high-risk population size was identified and analyzed via descriptive statistics. In this high-risk group the percentage of patients treated with SGLT2-inhibitors was assessed. Of the 1492 T2DM patients managed in primary care, 475 (31.8%) were classified as very high-risk based on (a history of) ischemic cardiovascular disease, chronic kidney disease, andor heart failure. Of the very high-risk patients, 49 (10.3%) received SGLT2-inhibitors conform the guidelines. Of the remaining 426 high-risk patients 334 (70.3%) had no contraindication (eGFR <30 mlmin1.73 m The vast majority of very high-risk type 2 diabetes patients were not prescribed SGLT2-I. There is substantial room for improvement in the management of these critical T2DM patients because most of them had no contraindications for initiating SGLT2-I prescription.

Patient-physician alliance and patients sense of self-efficacy are negatively associated with resistance to treatment among patients with type 2 diabetes.

Resistance to treatment is prevalent among patients diagnosed with chronic conditions, including type 2 diabetes (T2DM). The current study aimed to examine the relationship between patient characteristics, patient-physician relationship, and resistance to treatment in T2DM. A sample of 120 T2DM patients were recruited by means of non-randomized sampling and through a public post on Facebook. Participants were asked to fill-in several questionnaires online Rotters Locus of Control questionnaire (short version) the General Self-efficacy (GSE) questionnaire the Working Alliance Inventory - Short Revised (WAI-SR) - evaluating patient-physician relationship and, finally, the Resistance to Treatment Questionnaire (RTQ) - which meant to capture the intensity of resistance to treatment and served as the dependent variable in this study. Interestingly, better patient-physician relationship and higher sense of self-efficacy among patients were found to negatively associate with patients resistance to treatment (r -.53, p < .001, and, r -.26, p < .01, respectively). Patient-physician relationship explained 22% of the variance of resistance to treatment, and self-efficacy explained 6% of the variance. Stronger patient-doctor relationship and higher sense of self-efficacy are shown to robustly associate with lower resistance to treatment among patients with T2DM. Current findings may instructor educate physicians as to the importance of the alliance with these chronic patients.

Genetic prediction of age at menarche, age at natural menopause and type 2 diabetes A Mendelian randomization study.

The relationship between reproductive factors and type 2 diabetes (T2D) is controversial therefore, we explored the causal relationship of age at menarche (AAM), age at natural menopause (ANM), with the risk of T2D and glycemic traits using two-sample Mendelian randomization. We used publicly available data at the summary level of genome-wide association studies, where AAM (N 329,345), ANM (N 69,360), T2D (N 464,389). The inverse variance weighting (IVW) method was employed as the primary method. To demonstrate the robustness of the results, we also conducted various sensitivity analysis methods including the MR-Egger regression, the weighted median (WM) and the MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test. After excluding IVs associated with confounders, we found a causal association between later AAM and reduced risk of T2D (OR 0.81 95% CI 0.75, 0.87 P 2.20 × 10 Our MR study showed a causal relationship between later AAM and lower risk of developing T2D, lower FI, FPG and HOMA-IR levels. This may provide new insights into the prevention of T2D in women.

Determination of light pressing pressure for improving foot skin blood flow in type 2 diabetic patients.

Traditional Thai massage is one of the alternative treatments for diabetic feet. However, the specific amount of pressing pressure applied to the foot during Thai foot massage is unknown. This study aimed to evaluate the effect of light pressing pressure on foot skin blood flow in type 2 diabetic patients. A single-arm repeated measures was conducted. Forty-three participants were recruited via the subjective examination and screening using the Michigan Neuropathy Screening Instrument. To obtain foot skin blood flow by laser doppler blood flowmetry, a probe was pasted on the 1st distal phalange of the big toe. Light pressure at a single point was applied on the plantar skin fold between the bases of the second and third toes by using the digital algometer. The pressure was applied gently, then increased slightly until the participant started to feel some minor discomfort. Patients were asked to rate their pain intensity using the visual analogue scale. The average pressing pressure without discomfort was 3.55 ± 1.04 kgcm The application of light pressing pressure could be used as a basic standard criterion for massage to improve the foot skin blood flow in type 2 diabetic patients.

Hyperglycemia promotes myocardial dysfunction via the ERS-MAPK10 signaling pathway in dbdb mice.

Recent studies have demonstrated that hyperglycemia is a major risk factor for the development and exacerbation of cardiovascular disease (CVD). However, the molecular mechanisms involved in diabetic cardiomyopathy (DCM) have not been fully elucidated. In this study, we focused on the underlying mechanism of DCM. Leptin receptor-deficient dbdb mice were used to model a type 2 diabetes mellitus (T2DM) model in our study. WT mice and dbdb mice received 4-phenylbutyric acid (4-PBA) (25 mgkgday) and saline by intraperitoneal injection every other day for 4 weeks. WT and dbdb mice were given tail vein injections of 100 μL of rAAV9-Sh-MAPK10 and rAAV9-Sh-GFP at the age of 6-8 weeks. Echocardiography was performed to measure cardiac function, histological examinations were used to evaluate ventricular hypertrophy and fibrosis. Quantitative RT-qPCR was used to assess the mRNA expression of Jun N-terminal kinase 3 (JNK3, MAPK10), atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), and collagen I and III. Immunoblotting was performed to measure the levels of cardiac hypertrophy-related proteins, fibrosis-related proteins, endoplasmic reticulum stress (ERS)-related proteins and apoptosis-related proteins. TUNEL staining was performed to examine cardiomyocyte apoptosis. In contrast to 12-week-old dbdb mice, 16-week-old dbdb mice showed the most severe myocardial dysfunction. The DCM induced by hyperglycemia was largely alleviated by 4-PBA (25 mgkgday, intraperitoneal injection). Similarly, tail vein injection of rAAV9-Sh-MAPK10 reversed the phenotype of the heart in dbdb mice including cardiac hypertrophy and apoptosis in dbdb mice. The mechanistic findings suggested that hyperglycemia initiated the ERS response through the negative regulation of sirtuin 1 (SIRT1), leading to the occurrence of myocardial dysfunction, and specific knockdown of MAPK10 in the heart directly reversed myocardial dysfunction induced by hyperglycemia. We demonstrated that hyperglycemia promotes DCM in dbdb mice through the ERS-MAPK10 signaling pathway in diabetic mice.

A diet-induced murine model for non-alcoholic fatty liver disease with obesity and insulin resistance that rapidly develops steatohepatitis and fibrosis.

Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide. Patients with NAFLD often suffer steatohepatitis, which can progress to cirrhosis and hepatocellular carcinoma. The presence of visceral obesity or type 2 diabetes mellitus (T2DM) is a major risk factor and potential therapeutic target for NAFLD. The establishment of animal models with these metabolic comorbidities and with the rapid progression of the disease is needed for developing treatments for NAFLD but remains to be archived. In the present study, KK-A

A case of recurrent Clostridium difficile infection with type 2 diabetes mellitus indicating the usefulness of metformin hydrochloride.

A 76-year-old woman undergoing insulin treatment for type 2 diabetes mellitus at our hospital was diagnosed with Clostridium difficile infection (CDI). She was treated with metronidazole, vancomycin hydrochloride, and fidaxomicin. Metformin hydrochloride in combination with fidaxomicin was administered to control the exacerbated symptoms. The diarrhea disappeared two days later, and colonoscopy confirmed the resolution of pseudomembranes eight days later. Till approximately two years after discharge, no recurrence was observed. Here metformin hydrochloride was suggested to be useful for the treatment of recurrent CDI with type 2 diabetes mellitus.

Intervention fidelity assessment A sub-study of the Norfolk Diabetes Prevention Study (NDPS).

Previous research has shown that lifestyle modification can delay or prevent the onset of type 2 diabetes in high-risk individuals. The Norfolk Diabetes Prevention Study (NDPS) was a parallel, three-arm, randomized controlled trial with up to 46 months follow-up that tested a group-delivered, theory-based lifestyle intervention to reduce the incidence of type 2 diabetes in high-risk groups. The current study aimed to evaluate if the NDPS intervention was delivered to an acceptable standard and if any part(s) of the delivery required improvement. A sub-sample of 30, 25 for inter-rater reliability and audio-recordings of the NDPS intervention education sessions were assessed independently by two reviewers (CT, TW) using a 12-item checklist. Each item was scored on a 0-5 scale, with a score of 3 being defined as adequate delivery. Inter-rater reliability was assessed. Analysis of covariance (ANCOVA) was used to assess changes in intervention fidelity as the facilitators gained experience. Inter-rater agreement was acceptable (86%). A mean score of 3.47 (SD .38) was achieved across all items of the fidelity checklist and across all intervention facilitators (n 6). There was an apparent trend for intervention fidelity scores to decrease with experience however, this trend was non-significant (p > .05) across all domains in this small sample. The NDPS was delivered to an acceptable standard by all Diabetes Prevention Facilitators. Further research is needed to better understand how the interventions delivery characteristics can be optimized and how they might vary over time.

Changes in plasma suPAR levels across pregnancy and in relation to hypertensive disorders.

Hypertensive disorders of pregnancy (HDP), including pre-eclampsia, eclampsia and gestational hypertension, are associated with excessive inflammation and are a leading cause of perinatal morbidity and mortality. Soluble urokinase plasminogen activator receptor (suPAR) belongs to the three-finger toxin family of proteins and acts a biomarker of chronic inflammation associated with autoimmune, renal, and cardiovascular disease. Compared with non-pregnant individuals, suPAR levels are elevated in the first trimester and may be involved in the pathogenesis of pregnancy complications that are in part immune-mediated, including HDP Participants included pregnant individuals enrolled in the study name removed for blinding, a prospective birth cohort designed to study an array of exposures and conditions relevant to maternal and child health. Maternal blood was collected at up to three time points during pregnancy and plasma suPAR levels were analyzed by enzyme-linked immunosorbent assay. Information on maternal HDP was abstracted from electronic medical records. Study participants with suPAR data in any trimester and information about HDP were eligible for inclusion (n393) 64 non-HDP participants who had chronic hypertension (n5), gestational diabetes mellitus (n55), lupus (n1), type 1 diabetes (n1) or type 2 diabetes (n2) were excluded, resulting in a final analytic sample of 329. The study was approved by the Institutional Review Board of the institution removed for blinding and all participants provided written informed consent. We first regressed suPAR levels on gestational age at the time of sample collection to assess change over the course of pregnancy. We did this for the sample overall and stratified by HDP status. Among the subset of participants with repeated measures, we used paired Wilcoxon signed-rank tests to assess the within-person change in suPAR across trimesters in both groups. Finally, we used Wilcoxon signed-rank tests to assess whether suPAR levels in each trimester and averaged over pregnancy were different among participants with and without HDP. The sample is multi-ethnic with 38.6% self-identifying as non-Hispanic white. Participants had a mean±standard deviation (SD) age of 31.3±5.7 years at delivery with a range from 18-49 years 22% of the sample was older than age 35 years. The median (interquartile range, IQR) pre-pregnancy body mass index (BMI) was 24.4 (6.2) kgm Although HDP is a primary cause of morbidity and mortality in pregnancy, predictive biomarkers are lacking. suPAR levels decrease with advancing gestation among healthy women, but remain stable in women with HDP, which may reflect a heightened inflammatory state. Additional research is needed to understand how suPAR correlates with other biomarkers of HDP and whether stable suPAR levels can predict HDP accurately in clinical practice.

Fit24, a digital health intervention to reduce type 2 diabetes risk among Hispanic youth Protocol for a feasibility pilot study.

Poor physical activity (PA) and sleep behaviors in Hispanic adolescents contributes to increased risk for type 2 diabetes. Commonly owned digital devices and services like smartphones and text-messaging are highly used among adolescents and are promising intervention tools for reaching this age group. Personal activity trackers assess activity and sleep, making them ideal tools for addressing these behaviors. We propose to examine the feasibility of a 12-week intervention that uses theoretically grounded text messages and a Fitbit device to improve PA and sleep among Hispanic adolescents with obesity, as compared to a wait-list control group with a Fitbit device only. Participants (N 48 14-16 years) will be randomized (11) to the intervention or wait-list control group. Youth in the intervention will receive a Fitbit Charge 5 and daily text messages. Youth in the wait-list control group will receive a Fitbit Charge 5 and information on PA and sleep guidelines. Feasibility will be examined by collecting process evaluation data on the following criteria (1) recruit 48 Hispanic adolescents 14-16 years (2) retain 85% of participants for post-assessments (3) Fitbit wear ≥4 daysweek and respond to 80% of text messages when prompted (4) ≤10% technical issues and (5) obtain 80% satisfaction from participants. This study will advance our knowledge on the feasibility of digital prevention strategies to promote PA and sleep behaviors to reduce T2D risk among Hispanic youth. If feasible, this approach has the potential to be a scalable, cost-effective diabetes prevention strategy among high-risk youth. NCT04953442, registered on July 8, 2021.

Contemporary medical, device, and surgical therapies for obesity in adults.

The goal of obesity management is to improve health. Sustained weight loss of more than 10% overall bodyweight improves many of the complications associated with obesity (eg, prevention and control of type 2 diabetes, hypertension, fatty liver disease, and obstructive sleep apnoea), as well as quality of life. Maintenance of weight loss is the major challenge of obesity management. Like all chronic diseases, managing obesity requires a long-term, multimodal approach, taking into account each individuals treatment goals, and the benefit and risk of different therapies. In conjunction with lifestyle interventions, anti-obesity medications and bariatric surgery improve the maintenance of weight loss and associated health gains. Most available anti-obesity medications act on central appetite pathways to reduce hunger and food reward. In the past 5 years, therapeutic advances have seen the development of targeted treatments for monogenic obesities and a new generation of anti-obesity medications. These highly effective anti-obesity medications are associated with weight losses of more than 10% of overall bodyweight in more than two-thirds of clinical trial participants. Long-term data on safety, efficacy, and cardiovascular outcomes are awaited. Long-term studies have shown that bariatric surgical procedures typically lead to a durable weight loss of 25% and rapid, sustained improvements in complications of obesity, although they have not yet been compared with new-generation highly effective anti-obesity medications. Further work is required to determine optimal patient-specific treatment strategies, including combinations of lifestyle interventions, anti-obesity medications, endoscopic and bariatric surgical procedures, and to ensure equitable access to effective treatments.

Dysregulation of circulating CD4 CXCR5 PD-1 T cells in diabetic retinopathy.

We aimed to determine an association between follicular helper T (Tfh) cells and Bcl-6 and CXCL13 levels and determine the role of Tfh cells, Bcl-6, and CXCL13 serum levels in the pathogenesis of diabetic retinopathy (DR) since Tfh cells have an important role in type 1 diabetes however, their role in type 2 diabetes-related DR requires exploration. Blood samples were collected from 24 patients with non-proliferative diabetic retinopathy (NPDR), 20 with proliferative diabetic retinopathy (PDR), and 18 age- and sex-matched healthy volunteers. Flow cytometry detected CD4 CXCR5 PD1 Tfh cells. Serum Bcl-6 and CXCL13 levels were determined using enzyme-linked immunosorbent assay. CD4 CXCR5 PD-1 Tfh cell percentages in peripheral blood and serum levels of Bcl-6 and CXCL13 in the non-proliferative DR (NPDR) and proliferative DR (PDR) groups were significantly higher than those in healthy individuals. The proportion of Tfh cells in DR patients peripheral blood positively correlated with Bcl-6 and CXCL13 serum levels, DR course severity, Fasting blood glucose, glycosylated hemoglobin and body mass index. The increased circulating Tfh cells, serum Bcl-6 levels, and CXCL13 levels of DR patients with type 2 diabetes suggested that circulating Tfh cells and the germinal center response may have a role in the occurrence and development of DR.

A prediction model of CKD progression among individuals with type 2 diabetes in the United States.

CKD progression among individuals with T2D is associated with poor health outcomes and high healthcare costs, which have not been fully studied. This study aimed to predict CKD progression among individuals with diabetes. Using ACCORD trial data, a time-varying Cox model was developed to predict the risk of CKD progression among patients with CKD and T2D. CKD progression was defined as a 50 % decline, or 25 mLmin1.73 m A total of 6982 diabetes patients with CKD were used for model development, with a median follow-up of 4 years and 3346 events. The predictors for CKD progression included female sex, age at T2D diagnosis, smoking status, SBP, DBP, HR, HbA1c, alanine aminotransferase (ALT), eGFR, UACR, retinopathy event, hospitalization. The model demonstrated good discrimination (C-statistics 0.745 95 % CI 0.723-0.763) and calibration (Brier Score 0.0923 95 % CI 0.0873-0.0965) performance in the ACCORD data. The most contributing predictors for CKD progression were eGFR, HbA1c, and SBP. The model demonstrated acceptable discrimination and calibration performance in the two external data. For high-risk patients with both diabetes and CKD, the tool as a dynamic risk prediction of CKD progression may help develop novel strategies to lower the risk of CKD progression.

The other incretin - the therapeutic rediscovery of the glucose-dependent insulinotropic polypeptide.

Among the two incretins that strongly stimulate insulin secretion and are also involved in its physiological regulation in type 2 diabetes, glucagon-like peptide-1 (GLP1) has been the focus of interest for a long time, due to its retained - although reduced - secretagogue nature also in type 2 diabetes. Its receptor agonists were also included in the antidiabetic treatment toolkit. In the light of more recent studies, however, the other incretin, the glucose-dependent insulinotropic polypeptide (GIP) has also come into a different light. It turned out that by regulating glucagon and insulin production according to blood sugar levels, it acts as a bifunctional blood sugar stabilizing factor in type 2 diabetes as well. The article reviews new data on the physiology of GIP, its verifiable effects in type 2 diabetes and obesity, the so-called twincretin effect as well as the benefits of the double stimulation of the GIP and the GLP1 receptor. It describes the pharmacology of the first dual receptor agonist, tirzepatide, already incorporated in therapeutic recommendations, and the first clinical trials related to its use. In the light of the data so far, the molecule may open new horizons in the treatment of type 2 diabetes and obesity. Orv Hetil. 2023 164(6) 210-218. Az inzulinszekréciót erélyesen serkentő, élettani szabályozásában is részt vevő két inkretin közül a 2-es típusú diabetesben is megtartott – bár csökkent − secretagog természete folytán hosszú időn keresztül a glükagonszerű peptid-1 (GLP1) került az érdeklődés előterébe, kívülről bejuttatott receptoragonistái bekerültek az antidiabetikus kezelés eszköztárába is. Újabb vizsgálatok fényében a „másik” inkretin, a glükózdependens insulinotrop polipeptid (GIP) is más megvilágításba került. Kiderült, hogy a glükagon és az inzulintermelés vércukorszinthez igazodó szabályozásával bifunkcionális vércukor-stabilizáló tényezőként viselkedik 2-es típusú diabetesben is. A közlemény áttekinti a GIP élettanával kapcsolatos új adatokat, 2-es típusú diabetesben és elhízásban igazolható hatásait, a „twincretin” hatás, a GIP és a GLP1-receptor kettős stimulálásának előnyeit. Ismerteti az első, már terápiás ajánlásokban is megjelent duális receptoragonista, a tirzepatid farmakológiáját és az alkalmazásával kapcsolatos első klinikai vizsgálatokat. A molekula az eddigi adatok tükrében új távlatokat jelenthet a 2-es típusú diabetes és az elhízás kezelésében. Orv Hetil. 2023 164(6) 210–218.

Enhanced endosomal signaling and desensitization of GLP-1R versus GIPR in pancreatic beta cells.

The incretin receptors, glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR), are prime therapeutic targets for the treatment of type 2 diabetes (T2D) and obesity. They are expressed in pancreatic beta cells where they potentiate insulin release in response to food intake. Despite GIP being the main incretin in healthy individuals, GLP-1R has been favored as a therapeutic target due to blunted GIPR responses in T2D patients and conflicting effects of GIPR agonists and antagonists in improving glucose tolerance and preventing weight gain. There is, however, a recently renewed interest in GIPR biology following the realization that GIPR responses can be restored after an initial period of blood glucose normalization and the recent development of dual GLP-1RGIPR agonists with superior capacity for controlling blood glucose levels and weight. The importance of GLP-1R trafficking and subcellular signaling in the control of receptor outputs is well established, but little is known about the pattern of spatiotemporal signaling from the GIPR in beta cells. Here, we have directly compared surface expression, trafficking and signaling characteristics of both incretin receptors in pancreatic beta cells to identify potential differences that might underlie distinct pharmacological responses associated with each receptor. Our results indicate increased cell surface levels, internalization, degradation, and endosomal versus plasma membrane activity for the GLP-1R, while the GIPR is instead associated with increased plasma membrane recycling, reduced desensitization, and enhanced downstream signal amplification. These differences might have potential implications for the capacity of each incretin receptor to control beta cell function.

Markers for obese and non-obese Type 2 diabetes identified using whole blood metabolomics.

Definitive differences in blood metabolite profiles between obese and non-obese Type 2 diabetes (T2D) have not been established. We performed an LC-MS-based non-targeted metabolomic analysis of whole blood samples collected from subjects classified into 4 types, based on the presence or absence of obesity and T2D. Of the 125 compounds identified, 20, comprising mainly nucleobases and glucose metabolites, showed significant increases or decreases in the T2D group. These included cytidine, UDP-glucuronate, UMP, 6-phosphogluconate, and pentose-phosphate. Among those 20 compounds, 11 enriched in red blood cells (RBCs) have rarely been studied in the context of diabetes, indicating that RBC metabolism is more extensively disrupted than previously known. Correlation analysis revealed that these T2D markers include 15 HbA1c-associated and 5 irrelevant compounds that may reflect diabetic conditions by a different mechanism than that of HbA1c. In the obese group, enhanced protein and fatty acid catabolism causes increases in 13 compounds, including methylated or acetylated amino acids and short-chain carnitines. Our study, which may be considered a pilot investigation, suggests that changes in blood metabolism due to obesity and diabetes are large, but essentially independent.

Cumulative Consumption of Sulfur Amino Acids and Risk of Diabetes A Prospective Cohort Study.

Cross-sectional studies have suggested that consumption of sulfur amino acids (SAAs), including methionine and cysteine, is associated with a higher risk of type 2 diabetes (T2D) in humans and with T2D-related biomarkers in animals. But whether higher long-term SAA intake increases the risk of T2D in humans remains unknown. We aimed to investigate the association between long-term dietary SAA intake and risk of T2D. We analyzed data collected from 2 different cohorts of the Framingham Heart Study, a long-term, prospective, and ongoing study. The Offspring cohort (1991-2014) included participants from fifth through ninth examinations, and the Third-Generation cohort (2002-2011) included participants from first and second examinations. After excluding participants with a clinical history of diabetes, missing dietary data, or implausible total energy intake, 3222 participants in the Offspring cohort and 3205 participants in the Third-Generation cohort were included. Dietary intake was assessed using a validated FFQ. The relations between energy-adjusted total SAA (methionine and cysteine) intake or individual SAA intake (in quintiles) and risk of incident T2D were estimated via Cox proportional hazards models after adjusting for dietary and nondietary risk factors. Associations across the 2 cohorts were determined by direct combination and meta-analysis. During the 23 y of follow-up, 472 participants reported a new diagnosis of T2D in the 2 cohorts. In the meta-analysis, the HRs of T2D comparing the highest with the lowest intake of total SAAs, methionine, and cysteine were 1.8 (95% CI 1.3, 2.5), 1.7 (95% CI 1.2, 2.3), and 1.4 (95% CI 1.0, 2.1), respectively. The association of SAA intake with T2D was attenuated after adjusting animal protein intake in sensitivity analyses. Our findings show that excess intake of SAAs is associated with higher risk of T2D. Dietary patterns that are low in SAAs could help in preventing T2D.

Testing the Feasibility and Dietary Impact of a Produce Prescription Program for Adults with Undermanaged Type 2 Diabetes and Food Insecurity in Australia.

There is growing interest in Food is Medicine programs that incorporate food-based interventions into health care for patients with diet-related conditions. We aimed to test the feasibility of a produce prescription program and its impact on diet quality for people with type 2 diabetes (T2D) experiencing food insecurity in Australia. We conducted a pre-post intervention study in n 50 adults experiencing food insecurity with T2D and glycated hemoglobin (HbA1c) ≥8%. Once enrolled, participants received healthy food boxes weekly free of charge, with the contents sufficient to create 2 mealsd, 5 dwk for the entire household, over 12 wk. Participants were also provided with tailored recipes and behavioral change support. The primary outcome was change in diet quality assessed by 24-h diet recalls. Secondary outcomes included differences in cardiovascular disease risk factors blood micronutrients and feasibility indicators. Differences in the baseline and 12-wk mean primary and secondary outcomes were assessed by paired t tests. Participants were older adults with mean ± SD age 63 ± 9 y (range 40-87 y), HbA1c 9.8% ± 1.5%, and 46% were female. Overall, 92% completed the final study follow-up for the primary outcome. Compared with baseline, diet quality improved at week 12, with an increase in the mean overall diet quality (Alternate Healthy Eating Index score) of 12.9 (95% CI 8.7, 17.1 P < 0.001), driven by significant improvements in vegetables, fruits, whole grains, redprocessed meat, trans fat, sodium, and alcohol consumption. Blood lipids also improved (totalHDL cholesterol -0.48 95% CI -0.72, -0.24 P < 0.001), and there was significant weight loss (-1.74 kg 95% CI -2.80, -0.68 kg, P 0.002), but no changes in other clinical outcomes. Participants reported high levels of satisfaction with the program. These findings provide strong support for an adequately powered randomized trial to assess effects of produce prescription as an innovative approach to improve clinical management among individuals with T2D experiencing food insecurity. This trial was registered at httpsanzctr.org.au as ACTRN12621000404820.

Potential Mechanisms by Which Hydroxyeicosapentaenoic Acids Regulate Glucose Homeostasis in Obesity.

Dysregulation of glucose metabolism in response to diet-induced obesity contributes toward numerous complications, such as insulin resistance and hepatic steatosis. Therefore, there is a need to develop effective strategies to improve glucose homeostasis. In this review, we first discuss emerging evidence from epidemiological studies and rodent experiments that increased consumption of EPA (either as oily fish, or dietarypharmacological supplements) may have a role in preventing impairments in insulin and glucose homeostasis. We then review the current evidence on how EPA-derived metabolites known as hydroxyeicosapentaenoic acids (HEPEs) may be a major mode of action by which EPA exerts its beneficial effects on glucose and lipid metabolism. Notably, cell culture and rodent studies show that HEPEs prevent fat accumulation in metabolic tissues through peroxisome proliferator activated receptor (PPAR)-mediated mechanisms. In addition, activation of the resolvin E1 pathway, either by administration of EPA in the diet or via intraperitoneal administration of resolvin E1, improves hyperglycemia, hyperinsulinemia, and liver steatosis through multiple mechanisms. These mechanisms include shifting immune cell phenotypes toward resolution of inflammation and preventing dysbiosis of the gut microbiome. Finally, we present the next steps for this line of research that will drive future precision randomized clinical trials with EPA and its downstream metabolites. These include dissecting the variables that drive heterogeneity in the response to EPA, such as the baseline microbiome profile and fatty acid status, circadian rhythm, genetic variation, sex, and age. In addition, there is a critical need to further investigate mechanisms of action for HEPEs and to establish the concentration of HEPEs in differing tissues, particularly in response to consumption of oily fish and EPA-enriched supplements.

Consumption of Dairy Products and the Risk of Overweight or Obesity, Hypertension, and Type 2 Diabetes Mellitus A Dose-Response Meta-Analysis and Systematic Review of Cohort Studies.

Dairy products have been suggested to be related to the prevention of overweight or obesity, hypertension, and type 2 diabetes mellitus (T2DM). These associations are currently controversial, however, and a systematic quantitative meta-analysis is lacking. In this study, we examined the associations between dairy products and the risk of overweight or obesity, hypertension, and T2DM and tested for dose-response relations. We comprehensively searched PubMed, Embase, and Web of Science up to April 2021. Cohort studies were included if dairy food consumption was reported at a minimum of 3 levels or as continuous variables, and the associations were assessed with overweight or obesity, hypertension, and T2DM. Summary RRs and 95% CIs were estimated for the dose-response association. Restricted cubic splines were used to evaluate the linear or nonlinear relations. Among the 9887 articles retrieved, 42 articles were included. For overweight or obesity, a linear association was observed for total dairy, milk, and yogurt. The risk decreased by 25%, 7%, and 12% per 200-gd increase for total dairy, high-fat dairy, and milk, respectively, and by 13% per 50-gd increment of yogurt. For hypertension, a nonlinear association was observed with total dairy, whereas significant inverse associations were found for low-fat dairy (RR 0.94 95% CI 0.90, 0.98) and milk (RR 0.94 95% CI 0.92, 0.97) per 200-gd intake increase. For T2DM, all types of dairy food consumption except for milk and low-fat dairy products showed nonlinear associations, with total dairy and yogurt intake associated with 3% and 7% lower risk per 200-gd and 50-gd intake increase, respectively. In conclusion, our study suggests that total dairy is associated with a low risk of overweight or obesity, hypertension, and T2DM, especially milk and yogurt for overweight or obesity, low-fat dairy and milk for hypertension, and yogurt for T2DM.

Consumption of Nuts and Seeds and Health Outcomes Including Cardiovascular Disease, Diabetes and Metabolic Disease, Cancer, and Mortality An Umbrella Review.

Consumption of nuts and seeds is associated with a range of health outcomes. Summarizing the best evidence on essential health outcomes from the consumption of nuts is essential to provide optimal recommendations. Our objective is to comprehensively assess health outcome associations related to the consumption of nuts and seeds, using a culinary definition including tree nuts and peanuts (registered in PROSPERO CRD42021258300). Health outcomes of interest include cardiovascular disease, cancer, diabetes, obesity, respiratory disease, mortality, and their disease biomarkers. We present associations for high compared with low consumption, per serving, and dose-response relations. MEDLINE, Embase, Cochrane, and Epistemonikos were searched and screened for systematic reviews and meta-analyses. Evidence was extracted from 89 articles on the consumption of nuts and relevant health outcomes, including 23 articles with meta-analysis on disease and mortality, 66 articles on biomarkers for disease, and 9 articles on allergyadverse outcomes. Intake of nuts was associated with reduced risk of cardiovascular diseases and related risk factors, with moderate quality of evidence. An intake of 28 gd nuts compared with not eating nuts was associated with a 21% RR reduction of cardiovascular disease (including coronary heart disease incidence and mortality, atrial fibrillation, and stroke mortality), an 11% risk reduction of cancer deaths, and 22% reduction in all-cause mortality. Nut consumption was also inversely associated with mortality from respiratory diseases, infectious diseases, and diabetes however, associations between nut consumption and diabetes incidence were mixed. Meta-analyses of trials on biomarkers for disease generally mirrored meta-analyses from observational studies on cardiovascular disease, cancers, and diabetes. Allergy and related adverse reactions to nuts were observed in 1-2% of adult populations, with substantial heterogeneity between studies. Overall, the current evidence supports dietary recommendations to consume a handful of nuts and seeds per day for people without allergies to these foods.

Saturated Fatty Acid Intake and Risk of Type 2 Diabetes An Updated Systematic Review and Dose-Response Meta-Analysis of Cohort Studies.

This systematic review and meta-analysis was conducted to pool findings of cohort studies that investigated hazards of type 2 diabetes mellitus (T2DM) in relation to intakes of SFAs. A systematic search was conducted in the PubMed, Scopus, and Embase databases up to June 2021 to find eligible studies. Review articles or commentaries, clinical trials, cross-sectional studies, studies on gestational or type 1 diabetes patients, animal studies, articles with no access to full-texts, articles published in non-English languages, and articles with missing critical data needed for the systematic review were excluded from the meta-analysis. A random-effects model was used to combine study-specific results. Thirteen cohort studies with 361,686 participants and 11,865 T2DM events were included. Dietary total SFA intake, as well as dietary palmitic acid (PA) or stearic acid (SA) were not associated with risk of T2DM when the highest was compared with the lowest intake category (HR 0.99 95% CI 0.91, 1.09 n 13 for total SFAs HR 0.96 95% CI 0.79, 1.15 n 4 for PA and HR 1.08 95% CI 0.79, 1.49 n 4 for SA). However, the risk of T2DM decreased by 11% in the highest compared with the lowest category of dietary lauric acid (HR 0.89 95% CI 0.82, 0.97 n 2), and by 17% in the highest compared with lowest category of dietary myristic acid (MA) (HR 0.83 95% CI 0.74, 0.92 n 3). There was evidence of publication bias among studies on dietary total SFAs and T2DM. Our results indicated no significant association between dietary total SFA and risk of T2DM. However, dietary intake of MA was negatively associated with developing T2DM.

Poultry Consumption and Human Health How Much Is Really Known A Systematically Searched Scoping Review and Research Perspective.

This scoping review was conducted to systematically search and chronicle scientific literature pertinent to poultry intake and human health. The protocol (uploaded to Open Science Framework, httpsosf.io2k7bj) was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews guidelines. Articles with observational and experimental research, narrative and systematic reviews, and meta-analyses were included. Among 13,141 articles identified, 525 met inclusion criteria. Among these 525 articles, 212 focused on cancer morbidity and mortality 41 on cardiovascular disease (CVD) morbidity and mortality 52 on CVD risk factors 32 on type 2 diabetes mellitus (T2DM) morbidity and mortality 33 on T2DM risk factors and 42 on body weight and body composition. An Other category (181 articles) included nutrient status, psychological well-beingmental health, cognition, microbiome, chronic kidney disease, nonalcoholic fatty liver disease, skin disorders, and fertility, among others. Among the 525 included articles, 366 were observational, 64 were experimental, and 76 were reviews and meta-analyses. Eighty-three percent of articles focused on adults or older adults. A paucity of research exists to support poultry as health-promoting foods, with most research only indirectly assessing poultry intake compared with other foods of interest (e.g., red meats or plant-based protein foods). No randomized controlled trials and only 1% of OBS assessed the influence of processed poultry intake on human health. In the future, the relative health effects of consuming poultry will be compared with a widening array of traditional and new protein-rich food products, necessitating the need for research to assess poultry as foods of choice. Science and health professionals, the poultry industry, and the public will benefit from new observational and experimental research to address cutting-edge scientific, public policy, and consumer topics pertinent to poultry intake and human health.

Prevalence of microvascular complications among patients with type 2 diabetes mellitus who visited diabetes clinics in Saudi Arabia.

To determine the microvascular complications prevalence in patients with type 2 diabetes mellitus (DM) in the eastern province of the Kingdom of Saudi Arabia. The participants in this retrospective, cross-sectional study included patients with type 2 DM who visited the diabetes clinics of primary health care centers of 2 National Guard Hospitals, Eastern Province, Saudi Arabia. This study included 935 patients with type 2 diabetes (54.1% women versus 45.9% men). Oral hypoglycemic medication was the most common treatment (90.3%). Overall, 55.1% of patients visited the ophthalmology clinic for retinopathy screening. The last glycated hemoglobin A1c result (mean 8.04%) was higher than the second-to-last result (mean 8.03%), or the third-to-last result (mean 7.99%). The prevalence of microvascular complications of DM was 55.1%. Independent significant factors linked with a higher risk of microvascular issues of DM were higher age, visits to an ophthalmology clinic, and the use of injection therapy. The most typical complications that our patients experienced was nephropathy (80.2%), followed by retinopathy (32.7%), and neuropathy (8.4%). Microvascular complications were extremely common in type 2 DM patients in our region. Being older, regularly visiting an ophthalmologist, and using injection therapy were predictive factors correlated with a higher chance of experiencing these complications.

A peripherally restricted cannabinoid-1 receptor inverse agonist promotes insulin secretion and protects from cytokine toxicity in human pancreatic islets.

The cannabinoid receptor CB1R is expressed in pancreatic β-cells CB1R increased activity is associated with diabetes, obesity, cardiovascular disorders as well as decreased insulin secretion and insulin resistance. CB1R was shown to signal through G-protein coupling as well as β-arrestins in β-cells. Peripherally restricted CB1R inverse agonists purportedly have beneficial effects on insulin secretion in β-cells, without the unwanted effects in the central nervous system. Here we show that a peripherally restricted CB1R inverse agonist, MRI-1891, augments glucose stimulated insulin secretion in isolated human pancreatic islets and mouse islets. The insulin secretion enhancing effect of MRI-1891 is comparable to exendin-4, an analogue of the glucagon like peptide-1 (GLP1). Moreover, MRI-1891 treatment protects isolated human islet cells against cytokine-induced apoptosis, similar to exendin-4. Thus, MRI-1891, a new class of CB1R inverse agonist, may be considered a potential therapeutic for both type 1 and type 2 diabetes because of its ability to protect pancreatic β-cells from cytokine toxicity and to promote insulin secretion.

Severe Distress Denial among Asian Patients with Type 2 Diabetes Mellitus in the Primary Care A prospective, multicentre study.

To determine the point-prevalence and distribution of diabetes distress among primary care Asians with Type 2 Diabetes Mellitus (T2DM) and evaluate its association with cardiovascular risk. This was a prospective, multicentre study conducted in two outpatient clinics. Patients aged ≥21years with uncontrolled T2DM (HbA1c>7.0% 53mmolmol) and polypharmacy were stratified based on their Framingham Risk Score (FRS-high ≥10%, low <10%) and matched in accordance to their baseline HbA1c. Cardiovascular risk was estimated using FRS while diabetes distress was measured using Problem Areas in Diabetes (PAID) scale (denial 0-10, severe distress ≥40). Of 1940 patients approached, 210 were recruited. A final 132 (62.9%) participants were eligible for analysis. Median PAID score was 17.5 (IQR 6.25-41.56), with an even distribution in each distress category. There was no significant difference in PAID scores between the high and low FRS groups (20.00vs13.75, p0.446). Additionally, PAID score distribution within each group was similar (McNemar-Bowker test, p0.477). However, a high prevalence of severe distress (31.4%) and denial (33.8%) was detected. Among those in denial, 58.7% had accompanying intermediate-high 10-year cardiovascular risk. In our sample of Asian primary care patients, a high prevalence of severe diabetes distress and denial was detected although no clear association between cardiovascular risk and diabetes distress was found. Future studies should assess the longitudinal changes and impact of other risk factors in diabetes distress. (Abstract 199 words).

Circulating Asprosin Concentrations in Patients with Obesity and Carbohydrate Disturbances.

Asprosin is a fasting-induced glucogenic hormone, secreted by white adipose tissue in response to starvation.The aim of the current study was to determine the levels of asprosin in subjects from the entire spectrum of the carbohydrate metabolism. A total of 153 causcasian subjects participated in this study group 1, healthy volunteers group 2, obese subjects without glycemic disturbances group 3- subjects with prediabetes and group 4, patients with newly identified type 2 diabetes. Subject with body mass index ≥30kgm2 and dysglycemia (prediabetes and diabetes) showed significantly high levels of asprosin (1.40 ngml IQR0.98-1.94 1.27 ngml IQR0.86-2.12 1.09 ngml IQR0.89-1.58) compared to the control group (0.71 ngml IQR0.54-0.92 p<0.001). Correlation analysis showed that serum asprosin also had significant positive associations with some anthropometric parameters, liver enzymes, fasting and post load glucose and insulin, LDL and triglycerides. Furthermore, we estimated a markedly relationship between asprosin concentrations and intima media thickness of the common carotid artery as well as neuropathy disability and vibration sensitivity. The circulating asprosin levels for differentiating subjects with carbohydrate disturbances and those with obesity were determined by ROC analysis. The AUC for disturbances of the glucose metabolism was 0.672 (p<0.001 95% CI 0.581-0.751) and for obesity AUC was 0.849 (p<0.001 95 % CI 0.785-0.919). Circulatin asprosin could be used as a predictive factor for early carbohydrate disorders and might be a potential new therapeutic target for the treatment of dysglycemia and obesity. Further prospective studies are needed to confirm this observation.

Candesartan protects against unilateral peripheral limb ischemia in type-2 diabetic rats Possible contribution of PI3K-Akt-eNOS-VEGF angiogenic signaling pathway.

Type-2 diabetes (T2DM) is known to be highly associated with increased risk for vascular complications including peripheral arterial diseases (PAD). Critical limb ischemia (CLI) is the most advanced stage of PAD. Current therapeutic options for diabetic patients experiencing vascular complications are limited to surgical revascularization with no effective pharmacotherapy available for clinical settings. This study is dedicated to evaluate the angiogenic potential of candesartan an angiotensin-II receptor blocker in an experimental model of vascular complications associating T2DM. T2DM was induced in rats through feeding with high fat diet for 6 weeks, followed by injection with streptozotocin (STZ, 30 mgkg i.p). After establishment of T2DM, unilateral CLI was induced through the ligation and excision of superficial femoral artery. Candesartan treatment (10 or 30 mgkg orally) was initiated one day post CLI and thereafter once daily for up to 14 days. T2DM rats that underwent CLI demonstrated impaired angiogenic signaling, increased inflammation and apoptosis in gastrocnemius muscle (GC). Candesartan reversed ischemic insult in T2DM rats subjected to unilateral CLI and induced reparative angiogenesis that was evident by increase in p-PI3KPI3K, p-AktAkt, p-eNOSeNOS, p-VEGFR2VEGFR2 ratios, and VEGF levels. Candesartan treatment also increased levels of HO-1 while decreased caspase-3 apoptotic marker and levels of inflammatory markers NF-κB and TNF-α, all of which were accompanied by preserved histological manifestations of GC muscles. Candesartan was able to combat limb ischemia under diabetic conditions which could pave the way for its therapeutic utility for diabetic patients experiencing vascular complications in clinical setting.

Plasma microRNA expression profiles associated with zinc exposure and type 2 diabetes mellitus Exploring potential role of miR-144-3p in zinc-induced insulin resistance.

Zinc exposure has been linked with disordered glucose metabolism and type 2 diabetes mellitus (T2DM) development. However, the underlying mechanism remains unclear. We conducted population-based studies and in vitro experiments to explore potential role of microRNAs (miRNAs) in zinc-related hyperglycemia and T2DM. In the discovery stage, we identified plasma miRNAs expression profile for zinc exposure based on 87 community residents from the Wuhan-Zhuhai cohort through next-generation sequencing. MiRNAs profiling for T2DM was also performed among 9 pairs newly diagnosed T2DM-healthy controls. In the validating stage, plasma miRNA related to both of zinc exposure and T2DM among the discovery population was measured by qRT-PCR in 161 general individuals derived from the same cohort. Furthermore, zinc treated HepG2 cells with mimic or inhibitor were used to verify the regulating role of miR-144-3p. Based on the discovery and validating populations, we observed that miR-144-3p was positively associated with urinary zinc, hyperglycemia, and risk of T2DM. In vitro experiments confirmed that zinc-induced increase in miR-144-3p expression suppressed the target gene Nrf2 and downstream antioxidant enzymes, and aggravated insulin resistance. Our findings provided a novel clue for mechanism underlying zinc-induced glucose dysmetabolism and T2DM development, emphasizing the important role of miR-144-3p dysregulation.

Aerobic exercise in the treatment of PTSD An examination of preclinical and clinical laboratory findings, potential mechanisms, clinical implications, and future directions.

Posttraumatic stress disorder (PTSD) is associated with heightened emotional responding, avoidance of trauma related stimuli, and physical health concerns (e.g., metabolic syndrome, type 2 diabetes, cardiovascular disease). Existing treatments such as exposure-based therapies (e.g., prolonged exposure) aim to reduce anxiety symptoms triggered by trauma reminders, and are hypothesized to work via mechanisms of extinction learning. However, these conventional gold standard psychotherapies do not address physical health concerns frequently presented in PTSD. In addition to widely documented physical and mental health benefits of exercise, emerging preclinical and clinical evidence supports the hypothesis that precisely timed administration of aerobic exercise can enhance the consolidation and subsequent recall of fear extinction learning. These findings suggest that aerobic exercise may be a promising adjunctive strategy for simultaneously improving physical health while enhancing the effects of exposure therapies, which is desirable given the suboptimal efficacy and remission rates. Accordingly, this review 1) encompasses an overview of preclinical and clinical exercise and fear conditioning studies which form the basis for this claim 2) discusses several plausible mechanisms for enhanced consolidation of fear extinction memories following exercise, and 3) provides suggestions for future research that could advance the understanding of the potential importance of incorporating exercise into the treatment of PTSD.

Development and Validation of Type 2 Diabetic Zebrafish Model for Cell-Based Treatments.

Diabetes mellitus can be categorized as one of the prolonged metabolic disorders that are associated with inappropriately elevated blood glucose levels. Among the subgroups of this disease, type 2 diabetes accounts for the most patients. Although pharmaceutical and non-pharmaceutical treatments have been employed to control the progression of the disease, as with any treatment approach, both therapeutic approaches are associated with side effects and challenges. Nowadays, the emergence of treatment methods based on stem cells has attracted the attention of researchers in order to treat diabetes fundamentally and provide a long-term solution. Since there are still blind spots regarding the positive and negative effects of these types of treatments, animal studies can give researchers a detailed insight into the effects of stem cell-based treatments. Recently, zebrafish has been proposed as a valuable animal model due to its outstanding genetic and physiological characteristics in biomedical studies including diabetes. Hereupon, in this protocol, the development and validation of type 2 diabetic zebrafish model for cell-based treatments have been explained.

OAGB with shortened excluded ileal loop as an effective treatment for type 2 diabetes mellitus in the cases of Caucasian men and women with obesity of the first degree (BMI 30-35 kgm

The aim of the study is to assess the effect of shortening the excluded loop of the small intestine to 150 cm on the effectiveness of one anastomosis gastric bypass (OAGB) in remission of type 2 diabetes with I The study included 25 patients with a body mass index (BMI) 30-35 kgm There were no deaths in the study group, bleeding during the postoperative period requiring reoperation, anastomotic leakageleakage throught mechanical stitching. The mean a glycated haemoglobin (HbA1C) level 12 months after surgery was 6.16 ± 0.96%, corresponding to a 2.29 ± 3.3% decrease. In more than 85% of the patients taking insulin before surgery, the insulin was discontinued in the postoperative period. Additionally, the level of glycaemia was assessed in patients on the day of surgery (163 ± 58 mgdl) and on the day of discharge from the hospital (4.7 ± 1.3 days)-it was lower by over 18% (133 ± 39.2 mg). Over the period of 12 months following OAGB, there was a reduction in the mean BMI value from 33.5 ± 2 to 25.5 ± 2.5 kgm OAGB with excluded 150 cm of the small intestine has beneficial effect on the remission of T2DM in patients with a BMI of 30-35kgm

Highly Miniaturized, Low-Power CMOS ASIC Chip for Long-Term Continuous Glucose Monitoring.

The objective of this work is to develop a highly miniaturized, low-power, biosensing platform for continuous glucose monitoring (CGM). This platform is based on an application-specific integrated circuit (ASIC) chip that interfaces with an amperometric glucose-sensing element. To reduce both size and power requirements, this custom ASIC chip was implemented using 65-nm complementary metal oxide semiconductor (CMOS) technology node. Interfacing this chip to a frequency-counting microprocessor with storage capabilities, a miniaturized transcutaneous CGM system can be constructed for small laboratory animals, with long battery life. A 0.45 mm × 1.12 mm custom ASIC chip was first designed and implemented using the Taiwan Semiconductor Manufacturing Company (TSMC) 65-nm CMOS technology node. This ASIC chip was then interfaced with a multi-layer amperometric glucose-sensing element and a frequency-counting microprocessor with storage capabilities. Variation in glucose levels generates a linear increase in frequency response of this ASIC chip. In vivo experiments were conducted in healthy Sprague Dawley rats. This highly miniaturized, 65-nm custom ASIC chip has an overall power consumption of circa 36 µW. In vitro testing shows that this ASIC chip produces a linear ( The miniature footprint of the biosensor platform, together with its low-power consumption, renders this CMOS ASIC chip a versatile platform for a variety of highly miniaturized devices, intended to improve the quality of life of patients with type 1 and type 2 diabetes.