Datasets:

Gaborandi

/

diabetes_mellitus_type2_pubmed_abstracts

like 0

Type 2 Diabetes Mellitus Promotes the Differentiation of Adipose Tissue-Derived Mesenchymal Stem Cells into Cancer-Associated Fibroblasts, Induced by Breast Cancer Cells.

Triple-negative breast cancer (TNBC) is a highly aggressive and invasive type of breast cancer. In addition, type 2 diabetes mellitus (T2DM) is recognized as a risk factor for cancer metastasis, which is associated with mortality in patients with breast cancer. Cancer-associated fibroblasts (CAFs) generated from adipose tissue-derived mesenchymal stem cells (AT-MSCs) play a vital role in the progression of TNBC. However, to date, whether T2DM affects the ability of AT-MSCs to differentiate into CAFs is still unclear. In this study, we found that in coculture with TNBC cells breast cancer cells (BCCs) under hypoxic conditions, AT-MSCs derived from T2DM donors (dAT-MSCs) were facilitated to differentiate into CAFs, which showed fibroblastic morphology and the induced expression of fibroblastic markers, such as fibroblast activation protein, fibroblast-specific protein, and vimentin. This was involved in the higher expression of transforming growth factor beta receptor 2 (TGFβR2) and the phosphorylation of Smad23. Furthermore, T2DM affected the fate and functions of CAFs derived from dAT-MSCs. While CAFs derived from AT-MSCs of healthy donors (AT-CAFs) exhibited the markers of inflammatory CAFs, those derived from dAT-MSCs (dAT-CAFs) showed the markers of myofibroblastic CAFs. Of note, in comparison with AT-CAFs, dAT-CAFs showed a higher ability to induce the proliferation and in vivo metastasis of BCCs, which was involved in the activation of the transforming growth factor beta (TGFβ)-Smad23 signaling pathway. Collectively, our study suggests that T2DM contributes to metastasis of BCCs by inducing the myofibroblastic CAFs differentiation of dAT-MSCs. In addition, targeting the TGFβ-Smad23 signaling pathway in dAT-MSCs may be useful in cancer therapy for TNBC patients with T2DM.

Histomorphometric and oxidative evaluation of the offsprings testis from type 2 diabetic female rats treated with metformin and pentoxifylline.

Type 2 diabetes mellitus (T2D) during pregnancy is characterized by high levels of reactive oxygen species and pro-inflammatory factors in the placenta. Once these reactive species reach the foetus, they trigger physiological adaptations that allow the foetus to survive, but programme the organism to develop metabolic disorders in adulthood. The male reproductive system is highly susceptible to foetal programming. This study aimed to investigate the effects of intrauterine exposure to T2D on testicular histomorphometry and redox homeostasis of adult rats and evaluate the effects of maternal treatment with metformin and pentoxifylline. Female rats were induced to T2D, then treated with metformin and pentoxifylline, or co-treated with both drugs. The females were mated, the male offspring were sacrificed on postnatal day 90, and the testicles were collected for analysis. Metformin protected the tubular compartment, with the maintenance of the Sertoli cell population and daily sperm production. Pentoxifylline attenuated the effects of diabetes on Leydig cells, in addition to stimulating testosterone production and lowering lipid peroxidation. Intrauterine exposure to T2D results in important testicular alterations that compromise gonadal function, and the co-treatment with metformin and pentoxifylline may represent a promising therapy that attenuates these effects by combining the positive influences in both the tubular and interstitial compartments of the testicular parenchyma.

Sanghuang Tongxie Formula Ameliorates Insulin Resistance in

Insulin resistance (IR) is a pivotal pathological characteristic that affects the occurrence and development of type 2 diabetes mellitus (T2DM). Thus, the effective control of IR is of great significance for diabetes prevention and treatment. Traditional Chinese medicine (TCM) represents a valuable tool handed down to the world by the Chinese nation and has a long history of use for diabetes clinical therapy. In this study, we focused on a self-drafted TCM-patented formula, Sanghuang Tongxie Formula (SHTXF), which exhibits clinical efficacy in the treatment of diabetes. To explore the effect and molecular mechanism of SHTXF on IR

The Effect of Mild Renal Dysfunction on the Assessment of Plasma Amino Acid Concentration and Insulin Resistance in Patients with Type 2 Diabetes Mellitus.

An increase in the levels of branched-chain amino acids (BCAAs) and certain aromatic amino acids, such as alanine, in plasma is correlated with insulin resistance (IR) in type 2 diabetes mellitus (T2DM). T2DM is a leading risk factor for chronic kidney disease. Meanwhile, renal dysfunction causes changes in plasma amino acid levels. To date, no study has examined how mild renal dysfunction and IR interact with plasma amino acid levels. This study examines the effects of IR and renal dysfunction on plasma amino acid concentrations in T2DM. Data were collected from healthy male participants (controls) and male patients with T2DM between May 2018 and February 2022. Blood samples were collected after overnight fasting. IR and renal function were evaluated using the homeostasis model assessment of IR (HOMA-IR) and serum cystatin C (CysC), respectively. A total of 49 and 93 participants were included in the control and T2DM groups, respectively. In the T2DM group, eight amino acids (alanine, glutamic acid, glutamine, glycine, isoleucine, leucine, tyrosine, and valine) and total BCAA showed a significant correlation with HOMA-IR ( To use plasma BCAA concentration as a marker of IR, renal function must be considered, even in mild renal dysfunction. Increased alanine and glutamic acid levels indicate IR, regardless of mild renal dysfunction.

Bone marrow adipose tissue composition and glycemic improvements after gastric bypass surgery.

Fracture risk is increased in type 2 diabetes, which may in part be due to altered bone marrow adiposity. Cross sectional studies have reported that people with type 2 diabetes have lower unsaturated BMAT lipid levels than people without diabetes, although there are limited data on longitudinal changes. We hypothesized that Roux-en-Y gastric bypass (RYGB), which dramatically improves glycemic status, would have differential effects on BMAT composition, with increases in the unsaturated lipid index in people with diabetes. Given reports that axial BMAT is responsive to metabolic stimuli while appendicular BMAT is stable, we hypothesized that BMAT changes would occur at the spine but not the tibia. We enrolled 30 obese women, stratified by diabetes status, and used magnetic resonance spectroscopy to measure BMAT at the spine in all participants, and the tibia in a subset (

Systemic Lupus Erythematosus and Cardiovascular Disease A Mendelian Randomization Study.

Previous studies have shown that patients with systemic lupus erythematosus (SLE) tend to have a higher risk of cardiovascular disease (CVD), but the potential causal relationship between genetic susceptibility to SLE and CVD risk is not clear. This study systematically investigated the potential association between genetically determined SLE and the risk of CVD. The genetic tools were obtained from genome-wide association studies of SLE and CVD, with no overlap between their participating populations. Mendelian randomization (MR) analysis was performed using inverse variance weighting as the primary method. Simultaneously, a series of repeated analyses, sensitivity analyses, and instrumental variable strength evaluations were performed to verify the reliability of our results. MR analysis showed that genetic susceptibility to SLE was associated with a higher risk of heart failure (OR1.025, 95% CI 1.009-1.041, P0.002), ischemic stroke (OR1.020, 95% CI 1.005-1.034, P0.009), and venous thromboembolism (OR1.001, 95% CI 1.000-1.002, P0.014). However, genetic susceptibility to SLE was negatively correlated with the risk of type 2 diabetes (OR0.968, 95% CI 0.947-0.990, P0.004). Sensitivity analysis found no evidence of horizontal pleiotropy or heterogeneity. Our MR study explored the causal role of SLE in the etiology of CVD, which would help improve our understanding of the basic disease mechanisms of SLE and provide comprehensive CVD assessment and treatment for SLE patients.

Exaggerated Ventilator-Induced Lung Injury in an Animal Model of Type 2 Diabetes Mellitus A Randomized Experimental Study.

Although ventilator-induced lung injury (VILI) often develops after prolonged mechanical ventilation in normal lungs, pulmonary disorders may aggravate the development of adverse symptoms. VILI exaggeration can be anticipated in type 2 diabetes mellitus (T2DM) due to its adverse pulmonary consequences. Therefore, we determined whether T2DM modulates VILI and evaluated how T2DM therapy affects adverse pulmonary changes. Rats were randomly assigned into the untreated T2DM group receiving low-dose streptozotocin with high-fat diet (T2DM,

HNF1B-MODY Masquerading as Type 1 Diabetes A Pitfall in the Etiological Diagnosis of Diabetes.

Hepatocyte nuclear factor-1B (HNF1B) maturity-onset diabetes of the young (MODY), also referred to as renal cysts and diabetes syndrome or MODY-5, is a rare form of monogenic diabetes that is caused by a deletion or a point mutation in the HNF1B gene, a developmental gene that plays a key role in regulating urogenital and pancreatic development. HNF1B-MODY has been characterized by its association with renal, hepatic and other extrapancreatic features. We present the case of a 39-year-old female patient who was first diagnosed with type 1 diabetes, but then, owing to the absence of anti-islet autoantibodies and to the diseases progression, was labeled later on as having atypical type 2 diabetes. She was finally recognized as having HNF1B-MODY, a diagnosis that had been suggested by the lack of metabolic syndrome and by the presence of unexplained chronically disturbed liver function tests and hypomagnesemia. There was a 10-year delay between the onset of diabetes and the molecular diagnosis. An atypical form of diabetes, especially in patients with multisystem involvement, should raise suspicion for an alternative etiology. A timely diagnosis of HNF1B-MODY is of utmost importance since it can greatly impact diabetes management and disease progression as well as family history.

The rs10830963 Polymorphism of the MTNR1B Gene Association With Abnormal Glucose, Insulin and C-peptide Kinetics.

The 13 persons were diagnosed with T2DM, 119 had impaired fasting blood glucose (IFG) andor impaired glucose tolerance (IGT). 1074 participants showed normal results and formed a control group. A higher frequency of minor allele G was found in the IFGIGT group in comparison with controls. The GG constellation was present in 23% of diabetics, in 17% of IFGIGT probands and in 11% of controls. Compared to CC and CG genotypes, GG homozygotes showed higher stimulated glycemia levels during the OGTT. Homozygous as well as heterozygous carriers of the G allele showed lower very early phase of insulin and C-peptide secretion with unchanged insulin sensitivity. These differences remained significant after excluding diabetics and the IFGIGT group from the analysis. No associations of the genotype with the shape of OGTT-based trajectories, with glucagon or with chronobiological patterns were observed. However, the shape of the trajectories differed significantly between men and women. In a representative sample of the Czech population, the G allele of the rs10830963 polymorphism is associated with impaired early phase of beta cell function, and this is evident even in healthy individuals.

Increased Glycemic Variability Evaluated by Continuous Glucose Monitoring is Associated with Osteoporosis in Type 2 Diabetic Patients.

Subjects with type 2 diabetes mellitus (T2DM) are susceptible to osteoporosis. This study was conducted to evaluate the association between glycemic variability evaluated by continuous glucose monitoring (CGM) and osteoporosis in type 2 diabetic patient. A total of 362 type 2 diabetic subjects who underwent bone mineral density (BMD) measurement and were monitored by a CGM system from Jan 2019 to May 2020 were enrolled in this cross-sectional study. Glycemic variability was calculated with the Easy GV software, including 24-hour mean blood glucose (24-h MBG), the standard deviation of 24-h MBG (SDBG), coefficient of variation (CV), mean amplitude of glycemic excursions (MAGE), and time in range between 3.9 and 10.0 mmolL (TIR). Other potential influence factors for osteoporosis were also examined. Based on the T-scores of BMD measurement, there were 190 patients with normal bone mass, 132 patients with osteopenia and 40 patients with osteoporosis. T2DM patients with osteoporosis showed a higher 24-h MBG, SDBG, CV, and MAGE, but a lower TIR (all In addition to conventional influence factors including age, female gender, BMI, LDL-C and SUA, increased glycemic variability assessed by MAGE is associated with osteoporosis in type 2 diabetic patients.

Insulinotropic Effects of Neprilysin andor Angiotensin Receptor Inhibition in Mice.

Treatment of heart failure with the angiotensin receptor-neprilysin inhibitor sacubitrilvalsartan improved glycemic control in individuals with type 2 diabetes. The relative contribution of neprilysin inhibition versus angiotensin II receptor antagonism to this glycemic benefit remains unknown. Thus, we sought to determine the relative effects of the neprilysin inhibitor sacubitril versus the angiotensin II receptor blocker valsartan on beta-cell function and glucose homeostasis in a mouse model of reduced first-phase insulin secretion, and whether any beneficial effects are additivesynergistic when combined in sacubitrilvalsartan. High fat-fed C57BL6J mice treated with low-dose streptozotocin (or vehicle) were followed for eight weeks on high fat diet alone or supplemented with sacubitril, valsartan or sacubitrilvalsartan. Body weight and fed glucose levels were assessed weekly. At the end of the treatment period, insulin release in response to intravenous glucose, insulin sensitivity, and beta-cell mass were determined. Sacubitril and valsartan, but not sacubitrilvalsartan, lowered fasting and fed glucose levels and increased insulin release in diabetic mice. None of the drugs altered insulin sensitivity or beta-cell mass, but all reduced body weight gain. Effects of the drugs on insulin release were reproduced in angiotensin II-treated islets from lean C57BL6J mice, suggesting the insulin response to each of the drugs is due to a direct effect on islets and mechanisms therein. In summary, sacubitril and valsartan each exert beneficial insulinotropic, glycemic and weight-reducing effects in obese andor diabetic mice when administered alone however, when combined, mechanisms within the islet contribute to their inability to enhance insulin release.

Risk Factors for Diabetic Peripheral Neuropathy, Peripheral Artery Disease, and Foot Deformity Among the Population With Diabetes in Beijing, China A Multicenter, Cross-Sectional Study.

Diabetic peripheral neuropathy (DPN), peripheral artery disease (PAD), and foot deformity are the most common causes of diabetic foot, which can considerably worsen the patients quality of life. In this study, we aimed to investigate the prevalence and risk factors associated with DPN, PAD, and foot deformity among patients with diabetes living in Beijing, China. In total, 3,898 diabetes patients from 11 hospitals in Beijing were evaluated using questionnaires and physical examinations, and 3,758 patients were included in the analysis. We compared the demographic, clinical, biological characteristics, and comorbidities of patients with and without DPN, PAD, or foot deformity, and used binary logistic regression analysis to identify potential factors associated with these outcomes. Overall, 882 patients (23.5%) had DPN, 437 patients (11.6%) had PAD, and 1,117 patients (29.7%) had foot deformities, including callus. The risk factors for DPN included age ≥40 years, a ≥10year duration of diabetes, a body mass index of <18.5 kgm

Mixed Skin and Soft Tissue Infection Caused by

Impact of SARS-CoV-2 Pandemic on Glycaemic Control, Metabolic Status, Treatment Adherence, Quality of Life in Diabetes Mellitus Patients in Tertiary Care Hospital of Eastern India.

The Role of Changes in Cumulative Lipid Parameter Burden in the Pathogenesis of Type 2 Diabetes Mellitus A Cohort Study of People Aged 35-65 Years in Rural China.

The main purpose of this study was to examine the effect of the cumulative exposure of blood lipid parameters on type 2 diabetes mellitus (T2DM). Another purpose was to explore whether the cumulative burden of blood lipid parameters plays a certain role in the pathogenesis of diet affecting T2DM. A total of 63 cases of diabetes occurred from 2017 to 2020, with an incidence density of 3.71 person-years. The dietary intake of the residents was obtained by using a dietary frequency questionnaire (FFQ). Cumulative lipid parameter burden was calculated according to the number of years (2016-2020) multiplied by total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL) and triglyceride (TG). A Cox proportional hazard model was used to estimate the effect of cumulative lipid burden on T2DM. A mediating analysis of accelerated failure time (AFT) was used to investigate the mediating effects of certain foods, the cumulative lipid parameter burden and T2DM. A higher cumulative TG load corresponded to a higher risk of T2DM onset ( The increase in cumulative HDL burden and the decrease in cumulative HDL burden are related to the incidence of T2DM. Cumulative TG burden was shown to play a partial mediating role in the pathogenesis of red meat and diabetes.

Viphyllin

Research on plant-based formulations has drawn considerable attention in the management of diabetic neuropathy (DN) for having lesser side effects than the synthetic counterparts. Here, we have investigated for the first time the therapeutic effects of a standardized Type 2 diabetes was induced in male Wistar rats using high fat diet and a single dose of streptozotocin (60 mgkg Viphyllin treatment markedly improved the body weight and glucose tolerance in diabetic rats. Also, the extract could significantly reduce the diabetes-induced elevation in FBG, liver and kidney indices. Further, Viphyllin dose-dependently increased the nociception latency in tail flick test compared to untreated diabetic rats ( The study concludes that Viphyllin exerts antidiabetic effects and improves nerve conduction to mitigate neuropathic pain.

Intraperitoneal Hematoma After Femoral Catheterization A Case Report and Literature Review.

Central venous catheters (CVCs) are often crucial in managing severely ill patients, especially those in the intensive care unit. It is estimated that over 5 million CVCs are inserted per year in the United States. The internal jugular, subclavian, or femoral veins are the most used access sites. The catheter is advanced until its tip lies within the proximal third of the superior vena cava, the right atrium, or the inferior vena cava. Unfortunately, the use of CVCs is not without its drawbacks, and multiple immediate and delayed complications have been described. Herein, we report a case of a 70-year-old female with a past medical history significant for chronic obstructive pulmonary disease, coronavirus disease 2019, pneumonia, type 2 diabetes mellitus, and hypertension, who presented to the emergency department from a skilled nursing facility with a two-day history of dyspnea. She was later diagnosed with an intraperitoneal hematoma, an uncommon complication caused by a CVC placement.

A Rare Case of Pancreatic Cancer Undifferentiated Carcinoma of the Pancreas With Osteoclast-Like Giant Cells.

Ductal adenocarcinoma of the pancreas is the most common pancreatic cancer, but undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UC-OGCs) is an exceedingly rare tumor. Microscopically, this tumor is characterized by the presence of two different cellular elements, namely, spindle or ovoid mononuclear cells and osteoclast-like giant cells (OGCs). Here, we report a rare case of UC-OGCs in a 79-year-old male with a one-month history of epigastric abdominal pain and unintentional weight loss. A blood workup revealed new-onset type 2 diabetes mellitus, and a computed tomography scan of the abdomen showed acute pancreatitis with a hypodense lesion in the head of the pancreas concerning for malignancy. He underwent an endoscopic ultrasound that also revealed a mass in the head of the pancreas, but no lymphadenopathy was observed. Biopsy was obtained and histopathology revealed UC-OGCs. We present this case to increase awareness of this rare clinical entity in patients presenting with acute-onset pancreatitis.

A Novel Case of Metformin-Induced Pancreatitis in an Individual With Normal Dosing and No Underlying Chronic Kidney Disease.

It is well known that most medications have side effects, and many of them have gone through years of testing with thousands of test subjects before entering the market. However, as physicians it is important to assess how patients react to the initiation of new medications not only looking for known side effects but also rare ones. Our case highlights a rare presentation of metformin-induced pancreatitis in the setting of normal renal function and appropriate dosing. We are hoping our case will create more awareness and inspire future research in exploring the pathophysiology and causes of metformin-induced pancreatitis. Moreover, we aim to make healthcare professionals mindful so that they may recognize acute pancreatitis as a side effect of metformin even in a healthy patient.

Concurrent alteration in inflammatory biomarker gene expression and oxidative stress how aerobic training and vitamin D improve T2DM.

Vitamin D (Vit D) supplementation and Aerobic Training (AT) exert several beneficial effects such as antioxidant and anti-inflammatory actions. The literature on the effects of AT and Vit D supplementation on the oxidative stress biomarkers and gene expression of inflammatory cytokines in patients with Type 2 Diabetes Mellitus (T2DM) is limited. The present study aimed to examine the effects of AT and Vit D supplementation on inflammation and oxidative stress signaling pathways in T2DM patients. In this single-blinded, randomized, placebo-controlled trial, 48 men with T2DM (aged 35-50 years with Body Mass Index (BMI) of 25-30 kgm2) were randomly allocated into four groups ATVit D (n 10) AT placebo (AT n 10) Vit D (n 10), and Control placebo (C n 10). The eight-week AT program was executed for 20-40 minday, at 60-75% of heart rate maximum (HRmax), for 3 dayswks. The Vit D group received 50,000 IU of Vit D supplement capsules per week for 8 weeks. The serum levels of oxidative stress biomarkers and gene expression of inflammatory cytokines in the Peripheral Blood Mononuclear Cells (PBMCs) were evaluated using the RT-PCR method. To analyze the data, paired t-tests and one-way analysis of variance and Tukeys post hoc test were used at the significance level of P < 0.05. The result shows that serum 25-OH-Vit D, total nitrite, Total Glutathione (GSH), Total Antioxidant Capacity (TAC), Superoxide Dismutase (SOD), Catalase (CAT), and Glutathione Peroxidase (GPX) increased and insulin, Fasting Blood Glucose (FBG), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), High Sensitivity C-Reactive Protein (hs-CRP), Malondialdehyde (MDA), glycated albumin, and Urinary 8-hydroxydeoxyguanine (8-OHdG) decreased significantly in all groups after 8 weeks, except for C. In addition, results of RT-PCR showed that ATVit D, Vit D, and AT significantly downregulated the gene expression of Tumor Necrosis Factor-Alpha (TNF-α), Interleukin-1 Beta (IL-1β), Mitogen-Activated Protein Kinases 1 (MAPK1), Nuclear Factor Kappa B (NF-κB) 1 (p50). It also upregulated Interleukin-4 (IL-4) gene expression, Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) in T2DM patients compared to the C. Additionally, the ATVit D group showed significantly lower insulin, FBG, HOMA-IR, hs-CRP, MDA, glycated albumin, urinary 8-OHdG, IL-1β, TNF-α, MAPK1, and NF-κB1 (p50) levels and significantly higher serum 25-OH-Vit D, total nitrite, GSH, TAC, CAT, SOD, GPX, IL-4, and PPAR-γ levels compared to the AT and Vit D groups. In T2DM patients, 8 weeks of ATVit D had a more significant impact on certain gene expressions related to inflammation and oxidative stress than Vit D or AT alone.

Association of genetic polymorphisms of PCSK9 with type 2 diabetes in Uygur Chinese population.

PCSK9 gene expression is associated with biological processes such as lipid metabolism, glucose metabolism, and inflammation. In the present study, our primary objective was to assess the association between the single-nucleotide polymorphisms in the PCSK9 gene and type 2 diabetes in Uygur subjects, in Xinjiang, China. We designed a case-control study including 662 patients diagnosed with T2DM and 1220 control subjects. Four single-nucleotide polymorphisms (rs11583680, rs2483205, rs2495477 and rs562556) of PCSK9 gene were genotyped using the improved multiplex ligation detection reaction technique. For rs2483205, the distribution of genotypes, dominant model (CC vs CT TT), overdominant model (CC TT vs CT) showed significant differences between T2DM patients and the controls (P 0.011 and P 0.041 respectively). For rs2495477, the distribution of genotypes, the dominant model (AA vs GA GG) showed significant differences between T2DM patients and the controls (P 0.024). Logistic regression analysis suggested after adjustment of other confounders, the differences remained significant between the two groups for rs2483205 CC vs CT TT odds ratio (OR) 1.321, 95% confidence interval (CI) 1.078-1.617, P 0.007 CC TT vs CT OR 1.255, 95% CI 1.021-1.542, P 0.03 for rs2495477 AA vs GA GG OR 1.297, 95% CI 1.060-1.588, P 0.012. The present study indicated that CT TT genotype and CT genotype of rs2483205, as well as GA GG genotype of rs2495477 in PCSK9 gene were associated with an increased risk of type 2 diabetes in the Uygur population in Xinjiang.

High serum levels of N-epsilon-carboxymethyllysine are associated with poor coronary collateralization in type 2 diabetic patients with chronic total occlusion of coronary artery.

The formation of advanced glycation end-products (AGEs) is a crucial risk factor for the pathogenesis of cardiovascular diseases in diabetes. We investigated whether N-epsilon-carboxymethyllysine (CML), a major form of AGEs in vivo, was associated with poor coronary collateral vessel (CCV) formation in patients with type 2 diabetes mellitus (T2DM) and chronic total occlusion (CTO) of coronary artery. This study consisted of 242 T2DM patients with coronary angiographically documented CTO. Blood samples were obtained and demographicclinical characteristics were documented. The coronary collateralization of these patients was defined according to Rentrop or Werner classification. Serum CML levels were evaluated using ELISA assay. Receiver operating characteristic curve and multivariable regression analysis were performed. 242 patients were categorized into poor CCV group or good CCV group (107 vs. 135 by the Rentrop classification or 193 vs. 49 by the Werner classification, respectively). Serum CML levels were significantly higher in poor CCV group than in good CCV group (110.0 ± 83.35 vs. 62.95 ± 58.83 ngml by the Rentrop classification and 94.75 ± 78.29 ngml vs. 40.37 ± 28.69 ngml by Werner classification, both P < 0.001). Moreover, these CML levels were also significantly different across the Rentrop and Werner classification subgroups (P < 0.001). In multivariable logistic regression, CML levels (P < 0.001) remained independent determinants of poor CCV according to the Rentrop or Werner classification after adjustment of traditional risk factors. This study suggests that higher serum CML level is associated with poor collateralization in T2DM patients with CTO.

Study of ten causal genes in Turkish patients with clinically suspected maturity-onset diabetes of the young (MODY) using a targeted next-generation sequencing panel.

Maturity-onset diabetes of the young (MODY), which is the most common cause of monogenic diabetes, has an autosomal dominant pattern of inheritance and exhibits marked clinical and genetic heterogeneity. The aim of the current study was to investigate molecular defects in patients with clinically suspected MODY using a next-generation sequencing (NGS)-based targeted gene panel. Candidate patients with clinical suspicion of MODY and their parents were included in the study. Molecular genetic analyses were performed on genomic DNA by using NGS. A panel of ten MODY-causal genes involving GCK, HNF1A, HNF1B, HNF4A, ABCC8, CEL, INS, KCNJ11, NEUROD1, PDX1 was designed and subsequently implemented to screen 40 patients for genetic variants. Ten different pathogenic or likely pathogenic variants were identified in MODY-suspected patients, with a diagnostic rate of 25%. Three variants of uncertain significance were also detected in the same screen. A novel pathogenic variant in the gene HNF1A (c.505506delAA p.Lys169AlafsTer18) was described for the first time in this report. Intriguingly, we were able to detect variants associated with rare forms of MODY in our study population. Our results suggest that in heterogenous diseases such as MODY, NGS analysis enables accurate identification of underlying molecular defects in a timely and cost-effective manner. Although MODY accounts for 2-5% of all diabetic cases, molecular genetic diagnosis of MODY is necessary for optimal long-term treatment and prognosis as well as for effective genetic counseling.

Design, synthesis, in vitro α-glucosidase inhibition, docking, and molecular dynamics of new phthalimide-benzenesulfonamide hybrids for targeting type 2 diabetes.

In the present work, a new series of 14 novel phthalimide-benzenesulfonamide derivatives 4a-n were synthesized, and their inhibitory activity against yeast α-glucosidase was screened. The obtained results indicated that most of the newly synthesized compounds showed prominent inhibitory activity against α-glucosidase. Among them, 4-phenylpiperazin derivative 4m exhibited the strongest inhibition with the IC

The impact of Rhodiola rosea on biomarkers of diabetes, inflammation, and microbiota in a leptin receptor-knockout mouse model.

Type 2 diabetes is the most prevalent endocrine disease in the world, and recently the gut microbiota have become a potential target for its management. Recent studies have illustrated that this disease may predispose individuals to certain microbiome compositions, and treatments like metformin have been shown to change gut microbiota and their associated metabolic pathways. However, given the limitations and side effects associated with pharmaceuticals currently being used for therapy of diabetes, there is a significant need for alternative treatments. In this study, we investigated the effects of a root extract from Rhodiola rosea in a Leptin receptor knockout (dbdb) mouse model of type 2 diabetes. Our previous work showed that Rhodiola rosea had anti-inflammatory and gut microbiome-modulating properties, while extending lifespan in several animal models. In this study, treatment with Rhodiola rosea improved fasting blood glucose levels, altered the response to exogenous insulin, and decreased circulating lipopolysaccharide and hepatic C-reactive protein transcript levels. We hypothesize that these changes may in part reflect the modulation of the microbiota, resulting in improved gut barrier integrity and decreasing the translocation of inflammatory biomolecules into the bloodstream. These findings indicate that Rhodiola rosea is an attractive candidate for further research in the management of type 2 diabetes.

Macronutrient intake modulates impact of EcoRI polymorphism of ApoB gene on lipid profile and inflammatory markers in patients with type 2 diabetes.

We sought to examine whether dietary intakes may affect the relationship between ApoB EcoRI and lipid profile, as well as serum inflammatory markers, in patients with type 2 diabetes (T2DM). This current study consisted of 648 diabetic patients. Dietary intake was calculated by a food frequency questionnaire. Biochemical markers (high-density lipoprotein (HDL), total cholesterol (TC), LDL, TG, CRP, IL-18, PGF2α) were measured based on standard protocols. Genotyping of the Apo-B polymorphisms (rs1042031) was conducted by the PCR-RFLP method. The gene-diet interactions were evaluated using GLMs. In comparison to GG homozygotes, A-allele carriers with above the median -CHO intake (≥ 54 percent of total energy) had considerably greater TC and PGF2a concentrations. Furthermore, as compared to GG homozygotes, A-allele carriers with above the median protein intake (≥ 14 percent of total energy) had higher serum levels of TG (P 0.001), CRP (P 0.02), TGHDL (P 0.005), and LDLHDL (P 0.04) ratios. Moreover, A-allele carriers with above the median total fat intake (≥ 35 percent of total calories) had significantly higher TC level (P 0.04) and LDLHDL (P 0.04) ratios compared to GG homozygotes. Furthermore, when compared to GG homozygotes, A-allele carriers who consumed above the median cholesterol (> 196 mg) had greater TG (P 0.04), TGHDL (P 0.01) ratio, and IL-18 (P 0.02). Furthermore, diabetic patients with the GA, AA genotype who consume above the median cholesterol had lower ghrelin levels (P 0.01). In terms of LDLHDL ratio, ApoB EcoRI and dietary intakes of specific fatty acids (≥ 9 percent for SFA and ≥ 12 percent for MUFA) had significant interaction. LDLHDL ratio is greater in A-allele carriers with above the median SFA intake (P 0.04), also when they consumed above the median MUFA this association was inverse (P 0.04). Our study showed that plasma lipid levels in participants carrying the (AA or AG) genotype were found to be more responsive to increasing the percentage of energy derived from dietary fat, CHO, protein, SFA, and cholesterol consumption. Therefore, patients with a higher genetic susceptibility (AA or AG) seemed to have greater metabolic markers with a higher percentage of macronutrient consumption. Also, ApoB EcoRI correlations with metabolic markers might be attenuated with above the median MUFA consumption.

Folic acid effect on homocysteine, sortilin levels and glycemic control in type 2 diabetes mellitus patients.

The present study aimed to determine the folic acid supplement (FAS) effects on serum homocysteine and sortilin levels, glycemic indices, and lipid profile in type II diabetic patients. A double-blind randomized controlled clinical trial have been performed on 100 patients with T2DM randomly divided into two groups that received either placebo or folic acid 5 mgd for 12 weeks. FAS caused a significant decrease in homocysteine and sortilin serum levels (28.2% and 33.7%, P < 0.0001, respectively). After 3 months of intervention, 8.7% decrease in fasting blood glucose (P 0.0005), 8.2% in HbA1c (P 0.0002), 13.7% in serum insulin (P < 0.0001) and 21.7% in insulin resistance (P < 0.0001) were found in the folic acid group, however no significant difference was observed in the placebo group. Serum hs-CRP level showed significant positive associations with sortilin (r 0.237, P 0.018), homocysteine (r 0.308, P 0.002) and fasting blood glucose (r 0.342, P 0.000). There were no significant changes in lipid profile in both groups after 12 weeks. FAS might be beneficial for reducing homocysteine and sortilin levels, enhancing glycemic control, and improved insulin resistance in patients with T2DM.

Nasal septal abscess following septoplasty in a patient with type 2 diabetes mellitus.

A man in his 50s with type 2 diabetes mellitus (T2DM) presented with a nasal septal abscess 3 weeks following septoplasty. Diabetes mellitus has been reported in association with nasal septal abscess, thought to be due to a relative immunodeficient state. We present an unusual, delayed presentation of nasal septal abscess following septoplasty and performed a literature review. Nasal septal abscess is rare. It is associated with significant complications if not diagnosed and management expediently. The association between T2DM and nasal septal abscess following septoplasty emphasises the importance of good perioperative blood sugar control and postoperative nasal care and raises the question of empirical antibiotics in this group.

Euglycaemic diabetic ketoacidosis in a patient with pancreatitis and type 2 diabetes on empagliflozin.

Sodium glucose cotransporter-2 (SGLT2) inhibitors are glucose-lowering drugs with proven efficacy in treating type 2 diabetes mellitus, and more recently, have been shown to improve heart failure outcomes in patients without diabetes. A rare complication of SGLT2 inhibitor use is the development of euglycaemic diabetic ketoacidosis (EDKA), characterised by euglycaemia (blood glucose level <250 mgdL), metabolic acidosis (arterial pH <7.3 and serum bicarbonate <18 mEqL), and ketonaemia. Given patients with EDKA do not present with the typical manifestations of diabetic ketoacidosis, including marked hyperglycaemia and dehydration, the diagnosis of EDKA may be missed and initiation of treatment delayed. We present the case of a man with recent SGLT2 inhibitor use and multiple other risk factors who developed EDKA.

SGLT2-inhibitors reduce the cardiac autonomic neuropathy dysfunction and vaso-vagal syncope recurrence in patients with type 2 diabetes mellitus the SCAN study.

In patients with type 2 diabetes mellitus (T2DM) the vaso-vagal syncope (VVS) recurrence could be due to the alteration of autonomic system function, evaluated by heart rate variability (HRV), and by 123I-metaiodobenzylguanidine (123I-mIBG) myocardial scintigraphy indexes Heart to Mediastinum ratio (HM In a prospective multicenter study, after propensity score matching, we studied a population of 324 T2DM patients with VVS, divided into 161 SGLT2-I-users vs. 163 Non-SGLT2-I users. In these patients as SGLT2-I-users vs. Non-SGLT2-I users, we investigated the HRV and 123I-MIBG modifications and VVS recurrence at 12 months of follow-up. At follow-up end, the SGLT2-I-users vs. Non-SGLT2-I users had best glucose homeostasis and lower values of inflammatory markers, and resting heart rate (p < 0.05). The SGLT2-I-users vs. Non-SGLT2-I users evidenced the lowest low frequencyhigh frequency ratio (LFHFr), a significant difference for all the indexes of autonomic dysfunction via ECG Holter analysis, and higher values of HM Non-SGLT2-I users vs. SGLT2-I-users had alterations of the autonomic nervous system, with a higher rate of VVS recurrence at 1 year of follow-up. The indexes of cardiac denervation predicted the VVS recurrence, while the SGLT2-I reduced the risk of VVS recurrence. NCT03717207.

Impact of a Digital Diabetes Prevention Program on Estimated 8-Year Risk of Diabetes in a Workforce Population.

We asked whether the estimated 8-year risk of diabetes could be reduced within the first 2 years of a digital Diabetes Prevention Program (dDPP) in a workforce population. Employees and spouses were eligible if they had prediabetes-range fasting glucose or hemoglobin A 1c and body mass index ≥25 kgm 2 . Diabetes risk was assessed using the Framingham diabetes risk score in the year before and the 2 years after dDPP initiation. Among participants completing at least nine dDPP lessons ( n 286), diabetes risk decreased 5.3% the year after dDPP initiation, after a 5.4% increase the year before initiation (difference in differences, -10.6% 95% confidence interval, -13.4% to -7.9% P lt 0.001), with risk maintained at reduced levels after the second year of the program. This dDPP reduced the estimated 8-year risk of diabetes over the first 2 years of the program.

Electronic health strategies to improve medication adherence in patients with cardiometabolic disease current status and future directions.

Enabled by widespread technological advancements, electronic health (eHealth) strategies have expanded rapidly over the last decade, presenting opportunities to support self-management including medication adherence for cardiometabolic disease control. eHealth can minimize access barriers to medications, enable timely assessment and shared decision-making, and provide medication reminders and health data feedback. This review summarizes current evidence for effectiveness of eHealth strategies for improving medication adherence in patients with hypertension, type 2 diabetes, andor hyperlipidemia, and identifies priorities for future research. Current research supports the effectiveness of eHealth strategies to improve medication adherence and clinical outcomes for cardiometabolic disease. Although patient acceptability of eHealth strategies is generally high, engagement may decline over time. In addition, differences in effectiveness across intervention characteristics and sociodemographic groups are understudied, limiting generalizability and tailoring of interventions to local health system resources, culture, and patient needs or preferences. eHealth is a promising tool for addressing low medication adherence. Further work incorporating rigorous evaluation, assessment of patient engagement over time and effectiveness of intervention characteristics and components, and a health equity lens addressing eHealth use in vulnerable groups will increase understanding of the full potential of eHealth for improving medication adherence in diverse patients with cardiometabolic disease.

A healthy plant-based diet is favorably associated with cardiometabolic risk factors among participants of South Asian ancestry.

Plant-based diets are recommended for chronic disease prevention, yet there has been little focus on plant-based diet quality among participants of South Asian ancestry who consume a predominantly plant-based diet. We evaluated cross-sectional and prospective associations between plant-based diet quality and cardiometabolic risks among participants of South Asian ancestry who are living in the United States. We included 891 participants of South Asian ancestry who completed the baseline visit in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study. The prospective analysis included 735 participants who completed exam 2 (∼5 years after baseline). The plant-based diet quality was assessed using 3 indices an overall plant-based diet index (PDI) that summarizes the consumption of plant foods, a healthy PDI (hPDI) that measures consumption of healthy plant foods, and an unhealthy PDI (uPDI) that reflects consumption of less healthy plant foods. At baseline, the PDI score was inversely associated with fasting glucose. We observed inverse associations between PDI and hPDI scores and HOMA-IR, LDL cholesterol, weight, and BMI (all P values < 0.05). Higher scores on the hPDI, but not PDI, were associated with lower glycated hemoglobin, higher adiponectin, a smaller visceral fat area, and a smaller pericardial fat volume. Each 5-unit higher hPDI score was associated with lower likelihoods of fatty liver (OR 0.76 95% CI 0.64, 0.90) and obesity (OR 0.88 95% CI 0.80, 0.97). There were no associations between uPDI scores and cardiometabolic risks. Prospectively, after covariate adjustment for baseline values, each 5-unit higher hPDI score was associated with an 18% lower risk of incident type 2 diabetes (OR 0.82 95% CI 0.67, 1.00). A higher intake of healthful plant-based foods was associated with a favorable cardiometabolic risk profile. Dietary recommendations to lower chronic disease risks among participants of South Asian ancestry should focus on the quality of plant-based foods.

Effect of Laparoscopic Sleeve Gastrectomy vs Roux-en-Y Gastric Bypass on Weight Loss, Comorbidities, and Reflux at 10 Years in Adult Patients With Obesity The SLEEVEPASS Randomized Clinical Trial.

Long-term results from randomized clinical trials comparing laparoscopic sleeve gastrectomy (LSG) with laparoscopic Roux-en-Y-gastric bypass (LRYGB) are limited. To compare long-term outcomes of weight loss and remission of obesity-related comorbidities and the prevalence of gastroesophageal reflux symptoms (GERD), endoscopic esophagitis, and Barrett esophagus (BE) after LSG and LRYGB at 10 years. This 10-year observational follow-up evaluated patients in the Sleeve vs Bypass (SLEEVEPASS) multicenter equivalence randomized clinical trial comparing LSG and LRYGB in the treatment of severe obesity in which 240 patients aged 18 to 60 years with median body mass index of 44.6 were randomized to LSG (n 121) or LRYGB (n 119). The initial trial was conducted from April 2008 to June 2010 in Finland, with last follow-up on January 27, 2021. LSG or LRYGB. The primary end point was 5-year percentage excess weight loss (%EWL). This current analysis focused on 10-year outcomes with special reference to reflux and BE. At 10 years, of 240 randomized patients (121 randomized to LSG and 119 to LRYGB 167 women 69.6% mean SD age, 48.4 9.4 years mean SD baseline BMI, 45.9 6.0), 2 never underwent surgery and there were 10 unrelated deaths 193 of the remaining 228 patients (85%) completed follow-up on weight loss and comorbidities, and 176 of 228 (77%) underwent gastroscopy. Median (range) %EWL was 43.5% (2.1%-109.2%) after LSG and 50.7% (1.7%-111.7%) after LRYGB. Mean estimate %EWL was not equivalent between the procedures %EWL was 8.4 (95% CI, 3.1-13.6) higher in LRYGB. After LSG and LRYGB, there was no statistically significant difference in type 2 diabetes remission (26% and 33%, respectively P .63), dyslipidemia (19% and 35%, respectively P .23), or obstructive sleep apnea (16% and 31%, respectively P .30). Hypertension remission was superior after LRYGB (8% vs 24% P .04). Esophagitis was more prevalent after LSG (31% vs 7% P < .001) with no statistically significant difference in BE (4% vs 4% P .29). The overall reoperation rate was 15.7% for LSG and 18.5% for LRYGB (P .57). At 10 years, %EWL was greater after LRYGB and the procedures were not equivalent for weight loss, but both LSG and LRYGB resulted in good and sustainable weight loss. Esophagitis was more prevalent after LSG, but the cumulative incidence of BE was markedly lower than in previous trials and similar after both procedures. ClinicalTrials.gov Identifier NCT00793143.

Scientific and ethical issues in add-on designs for antidiabetic drugs.

This editorial describes the clinical trials related to antidiabetic drugs, most of them following an add-on design of where the new drug is added to metformin and the comparative arm is metformin plus placebo. Many drugs are already approved for therapy following this design the authors believe that it is unethical to continue this trend because it makes it impossible to stratify the many antidiabetic drugs according to their efficacy and toxicity.

First-trimester prediction of gestational hypertension through the bioelectrical impedance analysis of the body composition.

Obesity is a risk factor for the development of gestational hypertension, with important consequences for both the mother and fetus. This prospective observational study aims to propose an early prediction model of hypertensive disorders in pregnancy among obese women, through the bioelectrical impedance analysis (BIA) at the first trimester, thus allowing early recognition of obese women that are at risk to develop gestational hypertension, in order to target preventive interventions. Singleton obese women (BMI ≥ 30 kgm2) between the 9th and 12th week of pregnancy were included in the study. The exclusion criteria were chronic diseases, like type 2 diabetes mellitus, hypertension, and other medical pre-existing conditions. Eligible women were followed up at 20, 28, and 36 weeks of gestation by measuring blood pressure, weight, and body composition with the use of the BIA. The diagnosis of gestational hypertension was made after the 20th week of gestation. Pregnancy and perinatal outcomes were then recorded. Of the 479 women included in the study, 85 (17.7%) developed gestational hypertension the remaining 394 (82.3%) resulted to be normotensive. A higher rate of nulliparous women was found in the hypertensive group (50.6% vs. 37.6%, p 0.02), together with a higher rate of induction of labor (55.3% vs. 40.9%, p 0.02) and of small for gestational age (SGA) newborns (12.9% vs. 6.9%, p 0.03). Significant differences emerged in the body composition between the two groups already from the first trimester, indeed women developing gestational hypertension showed elevated values of Total body Mass, FM, FFM, TBW (p < 0.02), and of legs FM, FFM (p < 0.006). At the multivariate logistics regression, the risk of developing gestational hypertension resulted higher in women with elevated total body water levels in the first trimester (OR 1.10 95% CI 1.04 -1.92). The BIA is a rapid, easy, non-invasive, and inexpensive tool to evaluate the body composition of obese pregnant women. It represents a promising predictor of hypertensive disorders in pregnancy, which allows an early identification of the patients at risk of developing gestational hypertension, thus opening a window of opportunity for strictly monitoring and target preventive intervention.

Prediction of type 2 diabetes mellitus onset using logistic regression-based scorecards.

Type 2 diabetes (T2D) accounts for 90% of all cases of diabetes, resulting in an estimated 6.7 million deaths in 2021, according to the International Diabetes Federation. Early detection of patients with high risk of developing T2D can reduce the incidence of the disease through a change in lifestyle, diet, or medication. Since populations of lower socio-demographic status are more susceptible to T2D and might have limited resources or access to sophisticated computational resources, there is a need for accurate yet accessible prediction models. In this study, we analyzed data from 44,709 nondiabetic UK Biobank participants aged 40-69, predicting the risk of T2D onset within a selected time frame (mean of 7.3 years with an SD of 2.3 years). We started with 798 features that we identified as potential predictors for T2D onset. We first analyzed the data using gradient boosting decision trees, survival analysis, and logistic regression methods. We devised one nonlaboratory model accessible to the general population and one more precise yet simple model that utilizes laboratory tests. We simplified both models to an accessible scorecard form, tested the models on normoglycemic and prediabetes subcohorts, and compared the results to the results of the general cohort. We established the nonlaboratory model using the following covariates sex, age, weight, height, waist size, hip circumference, waist-to-hip ratio, and body mass index. For the laboratory model, we used age and sex together with four common blood tests high-density lipoprotein (HDL), gamma-glutamyl transferase, glycated hemoglobin, and triglycerides. As an external validation dataset, we used the electronic medical record database of Clalit Health Services. The nonlaboratory scorecard model achieved an area under the receiver operating curve (auROC) of 0.81 (95% confidence interval CI 0.77-0.84) and an odds ratio (OR) between the upper and fifth prevalence deciles of 17.2 (95% CI 5-66). Using this model, we classified three risk groups, a group with 1% (0.8-1%), 5% (3-6%), and the third group with a 9% (7-12%) risk of developing T2D. We further analyzed the contribution of the laboratory-based model and devised a blood test model based on age, sex, and the four common blood tests noted above. In this scorecard model, we included age, sex, glycated hemoglobin (HbA1c%), gamma glutamyl-transferase, triglycerides, and HDL cholesterol. Using this model, we achieved an auROC of 0.87 (95% CI 0.85-0.90) and a deciles OR of ×48 (95% CI 12-109). Using this model, we classified the cohort into four risk groups with the following risks 0.5% (0.4-7%) 3% (2-4%) 10% (8-12%) and a high-risk group of 23% (10-37%) of developing T2D. When applying the blood tests model using the external validation cohort (Clalit), we achieved an auROC of 0.75 (95% CI 0.74-0.75). We analyzed several additional comprehensive models, which included genotyping data and other environmental factors. We found that these models did not provide cost-efficient benefits over the four blood test model. The commonly used German Diabetes Risk Score (GDRS) and Finnish Diabetes Risk Score (FINDRISC) models, trained using our data, achieved an auROC of 0.73 (0.69-0.76) and 0.66 (0.62-0.70), respectively, inferior to the results achieved by the four blood test model and by the anthropometry models. The four blood test and anthropometric models outperformed the commonly used nonlaboratory models, the FINDRISC and the GDRS. We suggest that our models be used as tools for decision-makers to assess populations at elevated T2D risk and thus improve medical strategies. These models might also provide a personal catalyst for changing lifestyle, diet, or medication modifications to lower the risk of T2D onset. The funders had no role in study design, data collection, interpretation, or the decision to submit the work for publication.

Dynamic incorporation of real world evidence within the framework of adaptive design.

For the clinical studies in rare diseases or small patient populations, having an adequately powered randomized controlled trial is further complicated by variability. As such, sample size re-estimation can be a useful tool if at an interim look the trial sample size needs to be increased to achieve adequate power to reject the null hypothesis. Meanwhile, borrowing or extrapolating information from real-world data or real-world evidence has gained increasing use in trial design and analysis since 2014. Combining these two strategies, high-quality real-world data, if leveraged properly, has the potential to generate real-world evidence that can assist interim decision-making, lower enrollment burden, and reduce study timeline and costs. With proper borrowing from historical control, some of the challenges in these high unmet medical need studies could be resolved considerably. We examine the incorporation of real-world evidence within the framework of adaptive design strategy in pediatric type II diabetes trials where recruitment has been challenging and the completion is hardly on time. Simulations under various scenarios are conducted to assess the borrowing strategy, i.e., the matching method in combination of sample size re-estimation. Comparisons of performance metrics are presented to showcase the advantages of proposed method.

IMMUNOHISTOCHEMICAL DETECTION OF L CELLS IN GASTROINTESTINAL TRACT MUCOSA OF PATIENTS AFTER SURGICAL TREATMENT FOR CONTROL OF TYPE 2 DIABETES MELLITUS.

Type 2 diabetes mellitus (T2DM) is a disease of global impact that has led to an increase in comorbidities and mortality in several countries. Immunoexpression of the incretin hormones such as glucagon-like peptide-1 (GLP-1) and peptide YY (3-36) (PYY3-36) can be used as a scorer in the gastrointestinal tract to analyze L-cell activity in response to T2DM treatment. This study aimed to investigate the presence, location, and secretion of L cells in the small intestine of patients undergoing the form of bariatric surgery denominated adaptive gastroenteromentectomy with partial bipartition. Immunohistochemical assays, quantitative real-time polymerase chain reaction (qPCR), and Western blot analysis were performed on samples of intestinal mucosa from patients with T2DM in both the preoperative and postoperative periods. All results were consistent and indicated basal expression and secretion of GLP-1 and PYY3-36 incretins by L cells. A greater density of cells was demonstrated in the most distal portions of the small intestine. No significant difference was found between GLP-1 and PYY3-36 expression levels in the preoperative and postoperative periods because of prolonged fasting during which the samples were collected. The greater number of L cells in activity implies better peptide signaling, response, and functioning of the neuroendocrine system. O diabetes tipo 2 (DM2) é uma doença de impacto mundial que tem levado ao aumento de comorbidades e mortalidade em vários países. A imunoexpressão dos hormônios incretínicos glp-1 e pyy O presente estudo teve como objetivo investigar a presença, localização e secreção de células L no intestino delgado de pacientes submetidos à forma de cirurgia bariátrica denominada gastroenteromentectomia adaptativa com bipartição parcial. Ensaios imunohistoquímicos, reação quantitativa em cadeia de polimerase em tempo real (qPCR) e análise de manchas ocidentais foram realizados em amostras de mucosa intestinal de pacientes com diabetes tipo 2 nos períodos pré- e pós-operatório. Todos os resultados foram consistentes e indicaram expressão basal e secreção de peptídeos glucagon-1 (GLP-1) e peptídeos YY (PYY3-36) incretinas por células L. Uma maior densidade de células foi demonstrada nas porções mais distais do intestino delgado. Não foi encontrada diferença significativa entre os níveis de expressão GLP-1 e PYY3-36 nos períodos pré-operatório e pós-operatório, provavelmente devido ao estado de jejum prolongado durante o qual as amostras foram coletadas O maior número de células L em atividade implica melhor sinalização de peptídeo, resposta e funcionamento do sistema neuroendócrino.

Black bean husk and black rice anthocyanin extracts modulated gut microbiota and serum metabolites for improvement in type 2 diabetic rats.

Black rice and black bean have not yet been fully investigated as healthy foods for their therapeutic effects on type 2 diabetes mellitus (T2DM). In this study, we aimed to evaluate the antidiabetic effects of black rice, black bean husk anthocyanin extracts, and their combination on glycolipid metabolism, gut microbiota, and serum metabolites in T2DM rats. Black bean husk and black rice anthocyanin extracts were administered to T2DM rats by gavage for 4 weeks. The results showed that black rice and black bean husk anthocyanin extracts significantly improved blood glucose, insulin resistance, serum oxidative stress state, lipid metabolism and inflammatory cytokines levels in rats, and alleviated liver damage. Black rice and black bean husk anthocyanin extracts increased the abundance of short-chain fatty acid (SCFA) producing bacteria

USPSTF recommendation roundup.

Offer pregnant women behavioral counseling to promote healthy weight gain. Screen for type 2 diabetes and prediabetes in adults ages 35 to 70 years who are overweight or obese.

Side effects and treatment initiation barriers of sodium-glucose cotransporter 2 inhibitors in heart failure a systematic review and meta-analysis.

Physicians are sometimes reluctant to initiate guideline-directed therapy in patients with heart failure and reduced ejection fraction (HFrEF) due to concerns of adverse events. We explored the risk of hypotension, volume depletion, and acute kidney injury (AKI) on sodium-glucose cotransporter 2 (SGLT2) inhibitors in HFrEF populations. We determined summary risk ratios (RRs) by conducting a meta-analysis on reported aforementioned adverse events on SGLT2 inhibitors from randomized controlled trials. We explored robustness of meta-analyses by computing fragility andor reverse fragility index (FI or RFI) and its corresponding fragility quotient (FQ or RFQ) for each outcome. A total of 10 050 patients with HFrEF entered the final meta-analysis. Hypotension was reported in 4.5% (2194836) on SGLT2 inhibitors and in 4.1% (2024846) on placebo (RR 1.09, 95% confidence interval CI 0.91-1.31, p 0.36). An RFI of 21 and RFQ of 0.002 suggest robust findings for hypotension. Volume depletion occurred in 9.4% (4735019) on SGLT2 inhibitors and in 8.7% (4385031) on placebo (RR 1.07, 95% CI 0.95-1.21, p 0.25), respectively. RFI of 19 and RFQ of 0.001 suggest moderately robust findings for volume depletion. AKI was reported in fewer patients (1.9% 954888) on SGLT2 inhibitors than on placebo (2.8% 1404899) providing lower incidence of AKI (RR 0.69, 95% CI 0.51-0.93, p 0.02). FI of 14 and RFQ of 0.001 suggest moderately robust findings for AKI. Sodium-glucose cotransporter 2 inhibitor therapy is not associated with a clinically relevant risk of hypotension and volume depletion. Its use reduces the risk of AKI. This analysis supports current guideline recommendations on early use of SGLT2 inhibitors.

The effect of insulin and kruppel like factor 10 on osteoblasts in the dental implant osseointegration in diabetes mellitus patients.

Diabetes mellitus, metabolic disease, is characterized by chronic hyperglycemia. Patients with diabetes mellitus are susceptible to infection and therefore have a higher prevalence and progression rate of periodontal disease. We aimed to study the effect of insulin and kruppel like factor 10 (KLF10) on osteoblasts proliferation and differentiation, and expression of bone metabolism-related molecules and related signaling pathway molecules of AKT serinethreonine kinase 1 (AKT) and nuclear factor kappa B subunit 1 (NF-κB) through in vitro experiments, which can provide theoretical basis for the dental implant osseointegration in diabetic patients. The osteoblasts (hFOB 1.19 cells) were subdivided into KLF10 gene over expression group, KLF10 gene knockdown group, and KLF10 gene knockdown insulin treatment group. CCK-8 and ELISA were, respectively, used for analysis of cell proliferation and differentiation. In vitro experiments were applied to detect the mRNA and protein expression of bone metabolism-related molecules, respectively. GSE178351 dataset and GSE156993 dataset were utilized to explore the expression of KLF10 in periodontitis. In osteoblasts, insulin treatment increased the expression of KLF10. Insulin and KLF10 could reduce the proliferation and differentiation of osteoblasts. Knockdown of KLF10 could increase the expression of bone metabolism-related molecules and activate AKT and NF-κB pathways, whereas insulin reversed this effect. KLF10 was up-regulated in both patients with periodontitis and type 2 diabetes mellitus with periodontitis. It is assumed that knockdown of KLF10 in insulin resistance may promote osteoblasts differentiation and dental implant osseointegration in diabetic patients.

Tamoxifen induced maculopathy presenting like macular telangiectasia type 2 in a patient with breast cancer.

Drug-induced crystalline maculopathy has been reported secondary to tamoxifen use for breast cancer treatment. It could be misdiagnosed as macular telangiectasia type 2 (MacTel type 2). A 56-year-old woman with a history of diabetes mellitus and breast cancer was referred to our clinic with painless, bilateral, gradual onset of central vision loss for several months. The fundus examination showed the macular pigmentary change in both eyes and a few refractile crystalline deposits in the parafoveal area in the left eye. However, the rest of the retina was normal in both eyes. With the diagnosis of tamoxifen-induced maculopathy, the drug was discontinued and supplementary treatment was started. In this report, patient medical and drug history was an important and powerful measure. Due to the side effects of long-term use of tamoxifen, we need further studies on the need for retinal screening in these patients.

Efficacy and Safety of Insulin Glargine 300 UmL in People with Type 2 Diabetes Uncontrolled on Basal Insulin The 26-Week Interventional, Single-Arm ARTEMIS-DM Study.

The efficacy and safety of switching to insulin glargine 300 UmL (Gla-300) in type 2 diabetes mellitus (T2DM) uncontrolled on basal insulin (BI) has been demonstrated in the North American and Western European populations however, there is limited data from other geographical regions with different ethnicities. The ARTEMIS-DM study aimed to evaluate the efficacy and safety of Gla-300 in people with T2DM uncontrolled on BI from Asia, Latin America and Middle East Africa. The ARTEMIS-DM was a 26-week, prospective, interventional, single-arm, phase IV study (NCT03760991). Adults with T2DM previously uncontrolled (glycated haemoglobin HbA A total of 372 (50% male) participants were included, with mean (standard deviation SD) age 60.9 (10.0) years, duration of diabetes 13.11 (7.48) years and baseline HbA In people with T2DM uncontrolled on previous BI, switching to Gla-300 with optimal titration guided by an algorithm was associated with improved glycaemic control and low incidence of hypoglycaemia across multiple geographic regions. NCT03760991. The online version contains supplementary material available at 10.1007s13300-022-01271-7.

Liver Diseases in Latin America Current Status, Unmet Needs, and Opportunities for Improvement.

To assess the current challenges regarding liver diseases, including the burden of disease, access to care, screening, and treatment needs in Latin America. Latin America is a region with a rich multicultural heritage and important socioeconomic differences. The burden of liver diseases is high and mainly determined by a high level of alcohol intake and the surge of risk factors associated with NAFLD (i.e., sedentary lifestyles, broader access to highly processed foods, obesity, and type 2 diabetes mellitus). Hepatotropic viruses also play a role in the development of chronic liver diseases, although their comparative frequency has been decreasing over the last decades. There are important disparities in access to screening and treatment for liver diseases in Latin America, which are reflected in low access to critical treatments such as direct-acting antiviral agents and drugs to treat hepatocellular carcinoma. Also, important barriers to liver transplantation are present in multiple countries, including a low deceased donors rate and a lack of availability in several countries (especially in Central America). Our region also has disadvantages in research and education in liver diseases, which limits regional academic development and improvement in quality of care of liver diseases. In order to tackle an increasing health burden due to liver diseases, Latin America urgently needs tailored interventions aiming to control the main risk factors for these disorders through the establishment of effective public health policies. Also, development of liver transplantation programs and improvement of medical education and research capabilities as well as extensive collaboration between all stakeholders are keys to address the liver disease agenda in the region.

Novel perspectives of sodium handling in type 2 diabetes mellitus.

As a key regulator of body water, sodium homeostasis forms an essential component of human physiology. Type 2 Diabetes Mellitus (T2D)-associated sodium overload stems from chronic renal retention of sodium, contributing toward the development of adverse cardiovascular sequelae. Our traditional model of sodium regulation invokes two compartments extracellular fluid (ECF plasma and interstitial fluid) and intracellular fluid (ICF). Data from the Mars program reveal inconsistencies with this two-space model, including mismatches between net body sodium and water. Recent data utilizing Future studies should focus on novel therapeutic opportunities for sodium regulation in T2D and other conditions of sodium dysregulation. The ratio of freebound dermal sodium (reflecting sodium storage capacity) could be utilized as a clinical biomarker for salt and water balance, to improve diagnostic accuracy and facilitate clinical decision-making.

Protective effect of Ulinastatin on acute lung injury in diabetic sepsis rats.

This study explored the protective effect and its possible mechanism of ulinastatin (UTI) on acute lung injury (ALI) in type 2 diabetes mellitus (DM) sepsis rats. Following treatment with UTI, the wetdry weight (WD) ratio, pathological changes, hypoxia-inducible factor-1ɑlpha (HIF-1ɑ) protein and Toll-like receptor 4 (TLR4) mRNA expression of lung tissues, the expression levels of interleukin-1beta (IL-1ß), IL-18, and tumor necrosis factor-alpha (TNF-ɑ), the contents of malondialdehyde (MDA) and superoxide dismutase (SOD) in serum were detected in type 2 DM sepsis rats. It was found that rats with type 2 DM and sepsis showed obvious damage in lung tissues with significantly increased inflammatory cells, necrosis, and swelling of alveolar epithelial cells, but UTI decreased the lung damage induced by DM and sepsis. In addition, compared with the control, the WD ratio, serum IL-1ß, IL-18 and TNF-ɑ contents, HIF-1ɑ protein expression, TLR4 mRNA expression, pulmonary microvascular permeability, MDA content in serum in type 2 DM and sepsis groups were significantly increased in type 2 DM sepsis rats (p < 0.05). However, compared with the groups with type 2 DM sepsis, the WD ratio, serum IL-1ß, IL-18, TNF-ɑ contents, HIF-1ɑ protein expression, TLR4 mRNA expression, and pulmonary microvascular permeability in UTI-treated group were significantly decreased, but the activity of SOD increased (p < 0.05). This study indicates that UTI can effectively reduce ALI induced by diabetic sepsis in rats through inhibiting inflammatory response, reducing oxidative stress, regulating hypoxia response pathway, and improving pulmonary microvascular permeability.

A pilot study on the effect of D-allulose on postprandial glucose levels in patients with type 2 diabetes mellitus during Ramadan fasting.

During Ramadan fasting, postprandial hyperglycemia is commonly observed after iftar (break of fast at sunset) meal. D-allulose is a rare sugar and is reported to have several health benefits, including the suppression of increase in postprandial glucose levels. This study investigates whether D-allulose (a C-3 epimer of D-fructose) improves the postprandial glucose in patients with type 2 diabetes mellitus (T2DM) during Ramadan. This was a pilot, prospective single-arm study design that was conducted for 10 consecutive days 5 days of control and 5 days of consumption. The primary outcome was postprandial peak glucose levels. During the consumption period, 8.5 g of D-allulose was consumed by the participants before iftar meal. Postprandial glucose was measured using a continuous glucose monitoring system. A total of 12 participants completed the study. Significant lower (p < 0.01) postprandial glucose values and the glucose incremental area under the curve (iAUC) were observed from 0 to 180 min during the consumption period compared to the control period. The consumption period demonstrated significantly higher percentages of time in which glucose values were found in the target range (p 0.0032), and when the glucose levels above the target range were reduced (p 0.0015). The supplementation with D-allulose has the potential to improve postprandial hyperglycemia in patients with T2DM after iftar during Ramadan. Further studies are needed to confirm these findings. Trial registration ClinicalTrials.gov NCT05071950. Retrospectively registered, 8 October 2021.

The association between serum Sestrin2 and the risk of coronary heart disease in patients with type 2 diabetes mellitus.

Coronary heart disease (CHD) is one of the most common causes of morbidity and mortality in type 2 diabetes mellitus (T2DM). Oxidative stress is one of the important contributors to the pathogenesis of CHD. Sestrin2 is a stress-induced antioxidant protein that plays a important role in T2DM and CHD. However, the relationship between serum Sestrin2 levels and T2DM with CHD remains unclear. This study aimed to investigate the relationship between serum Sestrin2 levels and CHD in patients with type 2 diabetes. A total of 70 T2DM patients with CHD and 69 T2DM patients were enrolled in this study. Clinical features and metabolic indices were identified. Serum Sestrin2 was measured by ELISA. Serum Sestrin2 levels in T2DM-CHD groups were significantly lower compared with the T2DM group (11.17 (9.79, 13.14) ngmL vs 9.46 (8.34, 10.91) ngmL). Bivariate correlation analysis revealed that serum Sestrin2 levels were negatively correlated with age (r - 0.256, P 0.002), BMI (r - 0.206, P 0.015), FBG (r - 0.261, P 0.002) and Tyg index (r - 0.207, P < 0.014). Binary logistic regression suggested that low serum Sestrin2 levels were related to the increased risk of T2DM-CHD (P < 0.05). In addition, the receiver operating characteristic analysis revealed that the area under the curve of Sestrin2 was 0.724 (95% CI 0.641-0.808, P < 0.001) to predict T2DM-CHD patients (P < 0.001). The Sestrin2 levels were highly associated with CHD in diabetes patients. Serum Sestrin2 may be involved in the occurrence and development of diabetic with CHD.

Body fluid regulation via chronic inhibition of sodium-glucose cotransporter-2 in patients with heart failure a post hoc analysis of the CANDLE trial.

In patients with chronic heart failure (CHF) and type 2 diabetes (T2D), sodium-glucose cotransporter-2 (SGLT2) inhibition improves cardiorenal outcomes, but details of the effects on distinct subsets of body fluid volume remain incomplete. This was a post hoc analysis of patients with CHF and T2D in the CANDLE trial (UMIN000017669), an investigator-initiated, multi-center, randomized open-label trial that compared the effect of canagliflozin (100 mg, n 113) with glimepiride (starting dose 0.5 mg, n 120) on changes in N-terminal pro-brain natriuretic peptide. The estimated plasma volume (ePV, calculated with the Straus formula) and estimated extracellular volume (eEV, determined by the body surface area) were compared between treatment groups at weeks 4, 12, and 24. Among 233 patients analyzed, 166 (71.2%) had an ejection fraction (EF) > 50%. Reductions in ePV and eEV were observed only in the canagliflozin group until week 12 (change from baseline at week 12, ePV - 7.63% 95% confidence interval CI, - 10.71 to - 4.55%, p < 0.001, eEV - 123.15 mL 95% CI, - 190.38 to - 55.92 mL, p < 0.001). While ePV stopped falling after week 12, eEV continued to fall until week 24 (change from baseline at week 24 - change from baseline at week 12, ePV 1.01% 95%CI, - 2.30-4.32%, p 0.549, eEV - 125.15 mL 95% CI, - 184.35 to - 65.95 mL, p < 0.001). Maintenance of a modest reduction in ePV and continuous removal of eEV via chronic SGLT2 inhibition suggests that favorable body fluid regulation contributes to the cardiorenal benefits of SGLT2 inhibitors in patients with CHF, irrespective of EF. UMIN000017669.

The role of mental disorders in precision medicine for diabetes a narrative review.

This narrative review aims to examine the value of addressing mental disorders as part of the care of people with type 1 and type 2 diabetes in terms of four components of precision medicine. First, we review the empirical literature on the role of common mental disorders in the development and outcomes of diabetes (precision prevention and prognostics). We then review interventions that can address mental disorders in individuals with diabetes or at risk of diabetes (precision treatment) and highlight recent studies that have used novel methods to individualise interventions, in person and through applications, based on mental disorders. Additionally, we discuss the use of detailed assessment of mental disorders using, for example, mobile health technologies (precision monitoring). Finally, we discuss future directions in research and practice and challenges to addressing mental disorders as a factor in precision medicine for diabetes. This review shows that several mental disorders are associated with a higher risk of type 2 diabetes and its complications, while there is suggestive evidence indicating that treating some mental disorders could contribute to the prevention of diabetes and improve diabetes outcomes. Using technologically enabled solutions to identify mental disorders could help individuals who stand to benefit from particular treatments. However, there are considerable gaps in knowledge and several challenges to be met before we can stratify treatment recommendations based on mental disorders. Overall, this review demonstrates that addressing mental disorders as a facet of precision medicine could have considerable value for routine diabetes care and has the potential to improve diabetes outcomes.

MicroRNA-21 promotes pancreatic β cell function through modulating glucose uptake.

Pancreatic β cell dysfunction contributes to the pathogenesis of type 2 diabetes. MiR-21 has been shown to be induced in the islets of glucose intolerant patients and type 2 diabetic mice. However, the role of miR-21 in the regulation of pancreatic β cell function remains largely elusive. In the current study, we identify the pathway by which miR-21 regulates glucose-stimulated insulin secretion utilizing mice lacking miR-21 in their β cells (miR-21βKO). We find that miR-21βKO mice develop glucose intolerance due to impaired glucose-stimulated insulin secretion. Mechanistic studies reveal that miR-21 enhances glucose uptake and subsequently promotes insulin secretion by up-regulating Glut2 expression in a miR-21-Pdcd4-AP-1 dependent pathway. Over-expression of Glut2 in knockout islets results in rescue of the impaired glucose-stimulated insulin secretion. Furthermore, we demonstrate that delivery of miR-21 into the pancreas of type 2 diabetic dbdb male mice is able to promote Glut2 expression and reduce blood glucose level. Taking together, our results reveal that miR-21 in islet β cell promotes insulin secretion and support a role for miR-21 in the regulation of pancreatic β cell function in type 2 diabetes.

A multi-ethnic polygenic risk score is associated with hypertension prevalence and progression throughout adulthood.

In a multi-stage analysis of 52,436 individuals aged 17-90 across diverse cohorts and biobanks, we train, test, and evaluate a polygenic risk score (PRS) for hypertension risk and progression. The PRS is trained using genome-wide association studies (GWAS) for systolic, diastolic blood pressure, and hypertension, respectively. For each trait, PRS is selected by optimizing the coefficient of variation (CV) across estimated effect sizes from multiple potential PRS using the same GWAS, after which the 3 trait-specific PRSs are combined via an unweighted sum called PRSsum, forming the HTN-PRS. The HTN-PRS is associated with both prevalent and incident hypertension at 4-6 years of follow up. This association is further confirmed in age-stratified analysis. In an independent biobank of 40,201 individuals, the HTN-PRS is confirmed to be predictive of increased risk for coronary artery disease, ischemic stroke, type 2 diabetes, and chronic kidney disease.

Diagnosis of non-alcoholic fatty liver disease and its active screening in risk groups.

Non-alcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease in developed countries, where it affects up to a quarter of the population. The groups at most risk are diabetics, obese and patients with dyslipidemia, i. e. individuals with advanced metabolic syndrome, in whom the prevalence of NAFLD exceeds 50 %. Some of these patients develop inflammation, so-called steatohepatitis, and subsequent fibroproduction, which in turn can lead to liver cirrhosis with all the complications, especially liver failure, portal hypertension (ascites, esophageal varices) and hepatocellular carcinoma. Therefore recently great emphasis has been placed on actively searching for advanced forms of NAFLD in this population in order to identify and adequately treat these patients in a timely manner. Today, diagnostic methods are widely available and the development of effective therapies for advanced forms of NAFLD is at the forefront of research interest.

Nonalcoholic steatohepatitis and mechanisms by which it is ameliorated by activation of the CNC-bZIP transcription factor Nrf2.

Non-alcoholic steatohepatitis (NASH) represents a global health concern. It is characterised by fatty liver, hepatocyte cell death and inflammation, which are associated with lipotoxicity, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, iron overload and oxidative stress. NF-E2 p45-related factor 2 (Nrf2) is a transcription factor that combats oxidative stress. Remarkably, Nrf2 is downregulated during the development of NASH, which probably accelerates disease, whereas in pre-clinical studies the upregulation of Nrf2 inhibits NASH. We now review the scientific literature that proposes Nrf2 downregulation during NASH involves its increased ubiquitylation and proteasomal degradation, mediated by Kelch-like ECH-associated protein 1 (Keap1) andor β-transducin repeat-containing protein (β-TrCP) andor HMG-CoA reductase degradation protein 1 (Hrd1, also called synoviolin (SYVN1)). Additionally, downregulation of Nrf2-mediated transcription during NASH may involve diminished recruitment of coactivators by Nrf2, due to increased levels of activating transcription factor 3 (ATF3) and nuclear factor-kappaB (NF-κB) p65, or competition for promoter binding due to upregulation of BTB and CNC homology 1 (Bach1). Many processes that downregulate Nrf2 are triggered by transforming growth factor-beta (TGF-β), with oxidative stress amplifying its signalling. Oxidative stress may also increase suppression of Nrf2 by β-TrCP through facilitating formation of the DSGIS-containing phosphodegron in Nrf2 by glycogen synthase kinase-3. In animal models, knockout of Nrf2 increases susceptibility to NASH, while pharmacological activation of Nrf2 by inducing agents that target Keap1 inhibits development of NASH. These inducing agents probably counter Nrf2 downregulation affected by β-TrCP, Hrd1SYVN1, ATF3, NF-κB p65 and Bach1, by suppressing oxidative stress. Activation of Nrf2 is also likely to inhibit NASH by ameliorating lipotoxicity, inflammation, ER stress and iron overload. Crucially, pharmacological activation of Nrf2 in mice in which NASH has already been established supresses liver steatosis and inflammation. There is therefore compelling evidence that pharmacological activation of Nrf2 provides a comprehensive multipronged strategy to treat NASH.

A randomized clinical trial of genetic testing and personalized risk counselling in patients with type 2 diabetes receiving integrated care -The genetic testing and patient empowerment (GEM) trial.

We evaluated the effect of personalized risk counseling incorporating clinical and genetic risk factors on patient empowerment and risk factor control in diabetes. Patients with type 2 diabetes (T2D) with suboptimal glycaemic control (HbA1c ≥ 7.5%) were randomized to a genetic counselling (GC) or control group. All patients underwent genetic testing for alleles at three loci associated with diabetic complications. The GC group received additional explanation of the joint associations of genetic and modifiable risk factors on risk of complications. All patients were reassessed at 12 months including validated questionnaires for patient reported outcomes. The primary outcome was proportion of patients reaching ≥ 3 of 5 predefined treatment targets (HbA1c < 7%, BP < 13080 mmHg, LDL-C < 2.6 mmolL, Triglyceride < 2.0 mmolL, use of renin-angiotensin system inhibitors). Secondary outcomes included new-onset chronic kidney disease or microalbuminuria and patient reported outcome measures. A total of 435 patients were randomized and 420 patients were included in the modified intention-to-treat analysis. At 12 months, the proportion of patients who attained ≥ 3 targets increased from 41.6% to 52.3% in the GC group (p 0.007) versus 49.5% to 62.6% in the control group (p 0.003), without between-group difference. Both groups had similar reduction in HbA1c, LDL-C and increased use of medications. In per protocol analysis, the GC group had higher diabetes empowerment, with reduced diabetes distress. In the GC group, the greatest improvement in positive attitude and self-care activities was observed in the intermediate to high genetic risk score (GRS) groups. In patients with T2D receiving integrated care, additional counselling on genetic risk of complications did not further improve risk factor control, although the improvement in self-efficacy warrants long-term evaluation.

The protective effects of curcumin on metabolic syndrome and its components In-silico analysis for genes, transcription factors, and microRNAs involved.

We aimed to identify the molecular mechanisms behind curcumins therapeutic benefits for metabolic syndrome (MetS) and its components. The Comparative Toxicogenomics Database, MIENTURNET, Metascape, GeneMania, and Cytoscape software were critical analytic tools. Curcumin may have therapeutic effects on MetS and its components via the following genes NOS3, IL6, INS, and ADIPOQ, particularly PPARG. Curcumin has higher docking scores than other genes with INS and PPARG (docking scores -8.3 and -5.8, respectively). Physical interactions (56%) were found to be the most prevalent for dyslipidemia, co-expression for hypertension, obesity, T2DM, and MetS. Galanin receptor pathway, lipid particles composition, IL-18 signaling pathway, response to extracellular stimulus, and insulin resistance were listed in the first of the key pathways for MetS, dyslipidemia, hypertension, obesity, and diabetes, respectively. The protein-protein interaction enrichment analysis study also identified vitamin B12 metabolism, folate metabolism, and selenium micronutrient network as three major molecular pathways linked to MetS targeted by curcumin. PPARG was the key transcription factor that regulated practically all curcumin-targeted genes linked to MetS and its components. Curcumin targeted hsa-miR-155-5p, which has been linked to T2DM, hypertension, and MetS, as well as hsa-miR-130b-3p and hsa-miR-22-3p, which have been linked to dyslipidemia and obesity, respectively. In silico, sponges that regulated hsa-miR-155-5p were developed and evaluated. Curcumin, MetS, and its components have been found to target adipocytes, cardiac myocytes, smooth muscle, the liver, and pancreas. Curcumins physicochemical properties and pharmacokinetics are closely connected with its therapeutic advantages in MetS and its components due to its high gastrointestinal absorption, drug-likeness, water solubility, and lipophilic nature. Curcumin is a CYP1A9 and CYP3A4 inhibitor. Although curcumin has a low bioavailability, it can be synthesized and administered to increase its pharmacokinetic features. Curcumin needs to undergo therapeutic optimization and further study into its pharmacological structure before it can be used to treat MetS and its components.

A comprehensive look into the association of vitamin D levels and vitamin D receptor gene polymorphism with obesity in children.

Childhood obesity accounts for several psychosocial and clinical consequences. Psychosocial consequences include lower self-esteem, social isolation, poor academic achievement, peer problems, and depression, whereas clinical consequences are cardiovascular diseases, type 2 diabetes, dyslipidemia, cancer, autoimmune diseases, girls early polycystic ovarian syndrome (PCOS), asthma, bone deformities, etc. A growing number of studies have uncovered the association of childhood obesity and its consequences with vitamin-D (vit-D) deficiency and vitamin-D receptor (VDR) gene polymorphisms such as single nucleotide polymorphisms (SNPs), e.g., TaqI, BsmI, ApaI, FokI, and Cdx2. Considering the impact of vit-D deficiency and VDR gene polymorphisms, identifying associated factors and risk groups linked to lower serum vit-D levels and prevention of obesity-related syndromes in children is of utmost importance. Previously published review articles mainly focused on the association of vit-D deficiency with obesity or other non-communicable diseases in children. The nature of the correlation between vit-D deficiency and VDR gene polymorphisms with obesity in children is yet to be clarified. Therefore, this review attempts to delineate the association of obesity with these two factors by identifying the molecular mechanism of the relationship.

Variation in open access vildagliptin use in Waikato patients with type 2 diabetes.

To determine what the variation was in the initial use of vildagliptin in patients with type 2 diabetes following approval of open access funding in October 2018, including by ethnicity, gender, age, funding model and patient HbA1c levels. Data were collected from 31 general practices for all adult patients with type 2 diabetes. National Health Index-matched medication data were obtained from the national Pharmaceutical Collection. Patients were included for analysis if they had received at least one diabetes medication in the 12 months prior to funding approval for vildagliptin. The proportion of patients who initiated vildagliptin therapy following open access funding approval was then evaluated, as was the time taken until the first dispensing (days since funding approval). A total of 724 of 3,971 (18.2%) of patients initiated vildagliptin therapy mean time to first dispensing was 192.1±112.4 days. In logistic regression, Asian patients were more likely and Māori less likely to receive vildagliptin than Europeans. Younger patients and those with an HbA1c of >64mmolmol were also more likely to initiate therapy. Vildagliptin use by general practice ranged from 0.0-82.4%. Despite open access funding, there was inequity in the initial use of vildagliptin. Substantial variation by general practice indicates that practitioner education may be needed to ensure appropriate and early adoption of new diabetes medications.

The intestinal immune system and gut barrier function in obesity and ageing.

Obesity and ageing predispose to numerous, yet overlapping chronic diseases. For example, metabolic abnormalities, including insulin resistance (IR) and type 2 diabetes (T2D) are important causes of morbidity and mortality. Low-grade chronic inflammation of tissues, such as the liver, visceral adipose tissue and neurological tissues, is considered a significant contributor to these chronic diseases. Thus, it is becoming increasingly important to understand what drives this inflammation in affected tissues. Recent evidence, especially in the context of obesity, suggests that the intestine plays an important role as the gatekeeper of inflammatory stimuli that ultimately fuels low-grade chronic tissue inflammation. In addition to metabolic diseases, abnormalities in the intestinal mucosal barrier have been linked to a range of other chronic inflammatory conditions, such as neurodegeneration and ageing. The flow of inflammatory stimuli from the gut is in part controlled by local immunological inputs impacting the intestinal barrier. Here, we will review the impact of obesity and ageing on the intestinal immune system and its downstream consequences on gut barrier function, which is strongly implicated in the pathogenesis of obesity and age-related diseases. In particular, we will discuss the effects of age-related intestinal dysfunction on neurodegenerative diseases.

Bilirubin levels and kidney function decline An analysis of clinical trial and real world data.

To evaluate if previously found associations between low serum bilirubin concentration and kidney function decline is independent of hemoglobin and other key confounders. Clinical trial data from the SAVOR-TIMI 53 trial as well as the UK primary care electronic healthcare records, Clinical Practice Research Datalink (CPRD), were used to construct three cohorts of patients at risk of chronic kidney disease (CKD). The randomized clinical trial (RCT) cohort from the subset of SAVOR-TIMI 53 trial consisted of 10,555 type-2 diabetic patients with increased risk of cardiovascular disease. The two observational data cohorts from CPRD consisted of 71,104 newly diagnosed type-2 diabetes (CPRD-DM2) and 82,065 newly diagnosed hypertensive (CPRD-HT) patients without diabetes. Cohorts were stratified according to baseline circulating total bilirubin levels to determine association on the primary end point of a 30% reduction from baseline in estimated glomerular filtration rate (eGFR) and the secondary end point of albuminuria. The confounder adjusted hazard ratios of the subpopulation with lower than median bilirubin levels compared to above median bilirubin levels for the primary end point were 1.18 (1.02-1.37), 1.12 (1.05-1.19) and 1.09 (1.01-1.17), for the secondary end point were 1.26 (1.06-1.52), 1.11 (1.01-1.21) and 1.18 (1.01-1.39) for SAVOR-TIMI 53, CPRD-DM2, CPRD-HT, respectively. Our findings are consistent across all cohorts and endpoints lower serum bilirubin levels are associated with a greater kidney function decline independent of hemoglobin and other key confounders. This suggests that increased monitoring of kidney health in patients with lower bilirubin levels may be considered, especially for diabetic patients.

Associations Between Implementation of the Caregiver Advise Record Enable (CARE) Act and Health Service Utilization for Older Adults with Diabetes Retrospective Observational Study.

The Caregiver Advise Record Enable (CARE) Act is a state level law that requires hospitals to identify and educate caregivers (family members or friends) upon discharge. This study examined the association between the implementation of the CARE Act in a Pennsylvania health system and health service utilization (ie, reducing hospital readmission, emergency department ED visits, and mortality) for older adults with diabetes. The key elements of the CARE Act were implemented and applied to the patients discharged to home. The data between May and October 2017 were pulled from inpatient electronic health records. Likelihood-ratio chi-square tests and multivariate logistic regression models were used for statistical analysis. The sample consisted of 2591 older inpatients with diabetes with a mean age of 74.6 (SD 7.1) years. Of the 2591 patients, 46.1% (n1194) were female, 86.9% (n2251) were White, 97.4% (n2523) had type 2 diabetes, and 69.5% (n1801) identified a caregiver. Of the 1801 caregivers identified, 399 (22.2%) received discharge education and training. We compared the differences in health service utilization between pre- and postimplementation of the CARE Act however, no significance was found. No significant differences were detected from the bivariate analyses in any outcomes between individuals who identified a caregiver and those who declined to identify a caregiver. After adjusting for risk factors (multivariate analysis), those who identified a caregiver (12.2%, 2191801) was associated with higher rates of 30-day hospital readmission than those who declined to identify a caregiver (9.9%, 78790 odds ratio OR 1.38, 95% CI 1.04-1.87 P.02). Significantly lower rates were detected in 7-day readmission (P.02), as well as 7-day (P.03) and 30-day (P.01) ED visits, among patients with diabetes whose identified caregiver received education and training than those whose identified caregiver did not receive education and training in the bivariate analyses. However, after adjusting for risk factors, no significance was found in 7-day readmission (OR 0.53, 95% CI 0.27-1.05 P.07), 7-day ED visit (OR 0.63, 95% CI 0.38-1.03 P.07), and 30-day ED visit (OR 0.73, 95% CI 0.52-1.02 P.07). No significant associations were found for other outcomes (ie, 30-day readmission and 7-day and 30-day mortality) in both the bivariate and multivariate analyses. Our study found that the implementation of the CARE Act was associated with certain health service utilization. The identification of caregivers was associated with higher rates of 30-day hospital readmission in the multivariate analysis, whereas having identified caregivers who received discharge education was associated with lower rates of readmission and ED visit in the bivariate analysis.

Efficacy and Safety of Varenicline for Smoking Cessation in Patients With Type 2 Diabetes A Randomized Clinical Trial.

Evidence of effective smoking cessation interventions in patients with diabetes is limited. The unique behavioral and metabolic characteristics of smokers with type 2 diabetes warrants a randomized clinical trial of the smoking cessation drug varenicline. To evaluate the efficacy and safety of varenicline in patients with type 2 diabetes with an intention to quit smoking. This multicenter, double-blind, placebo-controlled randomized clinical trial recruited patients from 6 outpatient clinics in 5 hospitals in Catania, Italy. Patients with type 2 diabetes, who were smoking at least 10 cigarettes a day, and who intended to quit smoking were screened for eligibility. Eligible patients were randomized to either varenicline or placebo treatment. The trial consisted of a 12-week treatment phase followed by a 40-week follow-up, nontreatment phase. Intention-to-treat data analysis was performed from December 2020 to April 2021. Varenicline, 1 mg, twice daily or matched placebo administered for 12 weeks. Patients in both treatment groups also received smoking cessation counseling. The primary efficacy end point of the study was the continuous abstinence rate (CAR) at weeks 9 to 24. Secondary efficacy end points were the CAR at weeks 9 to 12 and weeks 9 to 52 as well as 7-day point prevalence of abstinence at weeks 12, 24, and 52. A total of 300 patients (mean SD age, 57.4 0.8 years 117 men 78.0% in varenicline group and 119 men 79.3% in placebo group) were randomized to receive varenicline (n 150) or placebo (n 150). The CAR at weeks 9 to 24 was significantly higher for the varenicline than placebo group (24.0% vs 6.0% odds ratio OR, 4.95 95% CI, 2.29-10.70 P < .001). The CARs at weeks 9 to 12 (31.3% vs 7.3% OR, 5.77 95% CI, 2.85-11.66 P < .001) and weeks 9 to 52 (18.7% vs 5.3% OR, 4.07 95% CI, 1.79-9.27 P < .001) as well as the 7-day point prevalence of abstinence at weeks 12, 24, and 52 were also significantly higher for the varenicline vs placebo group. The most frequent adverse events occurring in the varenicline group compared with the placebo group were nausea (41 27.3% vs 17 11.4%), insomnia (29 19.4% vs 19 12.7%), abnormal dreams (19 12.7% vs 5 3.4%), anxiety (17 11.4% vs 11 7.3%), and irritability (14 9.4% vs 8 5.4%). Serious adverse events were infrequent in both groups and not treatment-related. Results of this trial showed that inclusion of varenicline in a smoking cessation program is efficacious in achieving long-term abstinence without serious adverse events. Varenicline should be routinely used in diabetes education programs to help patients with type 2 diabetes stop smoking. ClinicalTrials.gov Identifier NCT01387425.

StatPearls

Diabetes mellitus is taken from the Greek word

StatPearls

Diabetes mellitus is taken from the Greek word