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PurposeWe examined the relationship between glycemic control and urinary tract infections in women with type 1 diabetes mellitus.Materials and methodsWomen enrolled in the Epidemiology of Diabetes Interventions and Complications study, the observational followup of the Diabetes Control and Complications Trial, were surveyed to assess the rate of physician diagnosed urinary tract infections in the preceding 12 months. The relationship between glycated hemoglobin levels and number of urinary tract infections in the previous 12 months was assessed using a multivariable Poisson regression model.ResultsA total of 572 women were evaluated at year 17. Mean age was 50.7 ± 7.2 years, mean body mass index was 28.6 ± 5.9 kg/m(2), mean type 1 diabetes duration was 29.8 ± 5.0 years and mean glycated hemoglobin was 8.0% ± 0.9%. Of these women 86 (15.0%) reported at least 1 physician diagnosed urinary tract infection during the last 12 months. Higher glycated hemoglobin levels were significantly associated with number of urinary tract infections such that for every unit increase (1%) in recent glycated hemoglobin level, there was a 21% (p=0.02) increase in urinary tract infection frequency in the previous 12 months after adjusting for race, hysterectomy status, urinary incontinence, sexual activity in the last 12 months, peripheral and autonomic neuropathy, and nephropathy.ConclusionsThe frequency of urinary tract infections increases with poor glycemic control in women with type 1 diabetes. This relationship is independent of other well described predictors of urinary tract infections and suggests that factors directly related to glycemic control may influence the risk of lower urinary tract infections.

We examined whether persistence of epigenetic DNA methylation (DNA-me) alterations at specific loci over two different time points in people with diabetes are associated with metabolic memory, the prolonged beneficial effects of intensive vs. conventional therapy during the Diabetes Control and Complications Trial (DCCT) on the progression of microvascular outcomes in the long-term follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) Study. We compared DNA-me profiles in genomic DNA of whole blood (WB) isolated at EDIC Study baseline from 32 cases (DCCT conventional therapy group subjects showing retinopathy or albuminuria progression by EDIC Study year 10) vs. 31 controls (DCCT intensive therapy group subjects without complication progression by EDIC year 10). DNA-me was also profiled in blood monocytes (Monos) of the same patients obtained during EDIC Study years 16-17. In WB, 153 loci depicted hypomethylation, and 225 depicted hypermethylation, whereas in Monos, 155 hypomethylated loci and 247 hypermethylated loci were found (fold change ≥1.3; P < 0.005; cases vs. controls). Twelve annotated differentially methylated loci were common in both WB and Monos, including thioredoxin-interacting protein (TXNIP), known to be associated with hyperglycemia and related complications. A set of differentially methylated loci depicted similar trends of associations with prior HbA1c in both WB and Monos. In vitro, high glucose induced similar persistent hypomethylation at TXNIP in cultured THP1 Monos. These results show that DNA-me differences during the DCCT persist at certain loci associated with glycemia for several years during the EDIC Study and support an epigenetic explanation for metabolic memory.

Aims To determine the prevalence of the metabolic syndrome in the Sandy Lake Oji-Cree and to examine its interaction with HNF1A in association with impaired glucose tolerance and Type 2 diabetes. Methods Using data collected from the Sandy Lake Health and Diabetes Project (1993–1995), the presence or absence of the metabolic syndrome was determined in 515 Oji-Cree subjects, ≥ 18 years of age. In the original study, fasting plasma analytes were measured, a 75-g oral glucose tolerance test was administered, and subjects were genotyped for HNF1A G319S. Results The unadjusted prevalence of the metabolic syndrome in the Oji-Cree adults was 29.9%. The adjusted odds ratio (OR) and 95% confidence interval for Type 2 diabetes among subjects who carried the HNF1A G319S mutation and had the modified metabolic syndrome (excluding hyperglycaemia) was 20.3 (6.94, 59.6). Adjusted ORs for Type 2 diabetes for subjects with either the HNF1A G319S mutation alone or the modified metabolic syndrome alone were 5.56 (2.85, 10.9) and 4.84 (2.53, 9.27), respectively. The risk of having impaired glucose tolerance was not influenced by the presence of either factor. Conclusions The risk of Type 2 diabetes was similar (approximately five-fold increased) for subjects with either the presence of the modified metabolic syndrome or the private HNF1A G319S mutation. Interestingly, when present in combination, the two independent risk factors appeared to act synergistically to confer an even greater increased risk of Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Abstract In parallel experiments designed to find the genetic determinants of type 2 diabetes in Oji-Cree, we identified several linked chromosomal regions, using genomic scanning, in addition to a private diabetes-associated mutation, namely HNF1A G319S, using candidate gene sequencing. The genome scan did not identify the region harboring HNF1A as being linked with diabetes. Also, the HNF1A mutation, when used directly in sib-pair linkage analysis, was not linked with diabetes. However, HNF1A G319S was very strongly associated with diabetes, predicted the clinical severity of diabetes, and performed well as a diagnostic predictive test for diabetes in the Oji-Cree. Despite the failure of linkage analysis to identify HNF1A as a determinant of type 2 diabetes, we feel justified in interpreting that G319S has a very important pathogenic role in Oji-Cree diabetes, based upon the highly suggestive association studies. The probable etiologic heterogeneity of type 2 diabetes in the Oji-Cree created a situation in which association analysis was much more sensitive to detect a relationship between HNF1A S319 and diabetes than was linkage analysis. The effectiveness of linkage analysis will probably be limited in study samples that have an even greater complexity of genetic background and/or disease etiology. Thus, the absence of linkage does not always mean that a genomic variant is not an important determinant of a complex disease. Furthermore, our experience confirms the value of using several complementary strategies to identify susceptibility genes for a complex disease. [ABSTRACT FROM AUTHOR]

Aims The aim of this study was to compare long-term safety and efficacy of the basal insulin analogue degludec with glargine in insulin-naive subjects with Type 2 diabetes. Methods This open-label trial included a 52-week core period followed by a 52-week extension. Participants were randomized 3:1 to once-daily degludec or glargine, administered with metformin ± dipeptidyl peptidase-4 inhibitors. Basal insulin was titrated to target pre-breakfast plasma glucose 3.9-4.9 mmol/l. Results At end of treatment (104 weeks), mean HbA1c reductions were similar for degludec and glargine; estimated treatment difference between degludec and glargine was 1 mmol/mol (95% CI −1 to 3) [0.07% (95% CI −0.07 to 0.22)], P = 0.339 in the extension trial set (degludec 551, glargine 174), comprising subjects who completed core trial and continued into the extension trial. Overall confirmed hypoglycaemia rates (1.72 vs. 2.05 episodes/patient-year), rates of adverse events possibly or probably related to trial product (0.19 events/patient-year), weight gain (2.7 vs. 2.4 kg) and mean daily insulin doses (0.63 U/kg) were similar between treatments in the safety analysis set (degludec 766, glargine 257) comprising all treated subjects. Rates of nocturnal confirmed hypoglycaemia (0.27 vs. 0.46 episodes/patient-year; P = 0.002) and severe hypoglycaemia (0.006 vs. 0.021 episodes/patient-year, P = 0.023) were significantly lower with degludec for the safety analysis set (analysis based on intention-to-treat full analysis set comprising all randomized subjects). Conclusions In Type 2 diabetes, insulin degludec in combination with oral anti-diabetic drugs, safely and effectively improves long-term glycaemic control, with a significantly lower risk of nocturnal hypoglycaemia as compared with glargine. [ABSTRACT FROM AUTHOR]

Aim: Studies evaluating the effects of oral antidiabetic drugs (OADs) on beta-cell function in type 2 diabetes mellitus (T2DM) are confounded by an inability to establish the actual baseline degree of beta-cell dysfunction, independent of the deleterious effects of hyperglycaemia (glucotoxicity). Because intensive insulin therapy (IIT) can induce normoglycaemia, we reasoned that short-term IIT could enable evaluation of the beta-cell protective capacity of OADs, free from confounding hyperglycaemia. We applied this strategy to assess the effect of sitagliptin on beta-cell function. Methods: In this pilot study, 37 patients with T2DM of 6.0 + 6.4 years duration and A1c 7.0 + 0.8% on 0–2 OADs were switched to 4–8 weeks of IIT consisting of basal detemir and premeal insulin aspart. Subjects achieving fasting glucose <7.0 mmol/l 1 day after completing IIT ( n = 21) were then randomized to metformin with either sitagliptin ( n = 10) or placebo ( n = 11). Subjects were followed for 48 weeks, with serial assessment of beta-cell function [ratio of AUCCpep to AUCgluc over Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) (AUCCpep/gluc/HOMA-IR)] on 4-h meal tests. Results: During the study, fasting glucagon-like-peptide-1 was higher (p = 0.003) and A1c lower in the sitagliptin arm (p = 0.016). Nevertheless, although beta-cell function improved during the IIT phase, it declined similarly in both arms over time (p = 0.61). By study end, AUCCpep/gluc/HOMA-IR was not significantly different between the placebo and sitagliptin arms (median 71.2 vs 80.4; p = 0.36). Conclusions: Pretreatment IIT can provide a useful strategy for evaluating the beta-cell protective capacity of diabetes interventions. In this pilot study, improved A1c with sitagliptin could not be attributed to a significant effect on preservation of beta-cell function. [ABSTRACT FROM AUTHOR]

Objective:To compare the characteristics and prevalence of the metabolic syndrome (MetS) among Native Indians, Inuit, and non-Aboriginal Canadians.Methods:The study was based on four cross-sectional studies conducted in the late 1980s and early 1990s involving three ethnic groups living in contiguous regions in central Canada: Oji-Cree Indians from several reserves in northern Ontario and Manitoba, Inuit from the Keewatin region of the Northwest Territories, and non-Aboriginal Canadians (predominantly of European heritage) in the province of Manitoba. The MetS was identified among adult subjects according to the National Cholesterol Education Program (NCEP) definition. Prevalence rates were standardized to the 1991 Canadian national population.Results:The age-standardized prevalence of the MetS varied by ethnic group, ranging from as high as 45% among Native Indian women to as low as 8% among Inuit men. Compared with Canadians of European origin, Indians had a worse metabolic profile, while Inuit had a better metabolic profile except for a high rate of abdominal obesity. The NCEP criteria in identifying individuals with the MetS were compared to those of the World Health Organization (WHO) in a subset of subjects with the requisite laboratory data. There was moderate agreement between the NCEP and WHO definitions, with a kappa value of 0.63 (95% confidence interval 0.56–0.70).Conclusions:The results indicate that the MetS is prevalent in diverse ethnic groups in Canada but varies in the pattern of phenotypic expression. Given the diverse nature of these populations, careful consideration should be given to developing culturally appropriate community-based prevention strategies aimed at reducing the frequency of this syndrome.International Journal of Obesity (2006) 30, 669–676. doi:10.1038/sj.ijo.0803179; published online 22 November 2005 [ABSTRACT FROM AUTHOR]

Despite increasingly stringent clinical practice guidelines for glycaemic control, the implementation of recommendations has been disappointing, with over 60% of patients not reaching recommended glycaemic goals. As a result, current management of glycaemia falls significantly short of accepted treatment goals. The Global Partnership for Effective Diabetes Management has identified a number of major barriers that can prevent individuals from achieving their glycaemic targets. This article proposes 10 key practical recommendations to aid healthcare providers in overcoming these barriers and to enable a greater proportion of patients to achieve glycaemic goals. These include advice on targeting the underlying pathophysiology of type 2 diabetes, treating early and effectively with combination therapies, adopting a holistic, multidisciplinary approach and improving patient understanding of type 2 diabetes. Implementation of these recommendations should reduce the risk of diabetes-related complications, improve patient quality of life and impact more effectively on the increasing healthcare cost related to diabetes. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Gestational diabetes mellitus (GDM) identifies a population of young women at high risk of developing type 2 diabetes and thus provides an excellent model for studying early events in the natural history of this disease. Adiponectin, a novel adipocyte-derived protein with insulin-sensitising properties, has been proposed as a factor linking insulin resistance and beta cell dysfunction in the pathogenesis of type 2 diabetes. We conducted the current investigation to determine whether adiponectin is associated with beta cell dysfunction in GDM. Methods: We studied 180 women undergoing OGTT in late pregnancy. Based on the OGTT results, participants were stratified into three groups: (1) NGT (n=93); (2) IGT (n=39); and (3) GDM (n48). First-phase insulin secretion was determined using a validated index previously proposed by Stumvoll. Insulin sensitivity was assessed using the validated OGTT insulin sensitivity index of Matsuda and DeFronzo (ISOGTT). Results: To evaluate beta cell function in relation to ambient insulin sensitivity, an insulin secretion-sensitivity index (ISSI) was derived from the product of the Stumvoll index and the ISOGTT based on the existence of the predicted hyperbolic relationship between these two measures. Mean ISSI was highest in the NGT group (6,731), followed by that in the IGT group (4,976) and then that in the GDM group (3,300) (overall p<0.0001), compatible with the notion of declining beta cell function across these glucose tolerance groups. Importantly, adiponectin was significantly correlated with ISSI (r=0.34, p< 0.000 1), with a stepwise increase in mean ISSI observed per tertile of adiponectin concentration (trend p<0.0001). In multivariate linear regression analysis, ISSI was positively correlated with adiponectin and negatively correlated with GDM, IGT and C-reactive protein (r²=0.54). Conclusions/ interpretation: Adiponectin concentration is an independent correlate of beta cell function in late pregnancy. As such, adiponectin may play a key role in mediating insulin resistance and beta cell dysfunction in the pathogenesis of diabetes. [ABSTRACT FROM AUTHOR]

Objective: Little is known about the relation of physical activity and physical fitness to insulin resistance and glucose intolerance in isolated subarctic Native Canadian populations. The purpose of this effort was to examine the relation between activity and fitness and obesity and glucose concentrations in such a unique population.Research Design and Methods: This study describes 530 men and women from the community of Sandy Lake, Ontario, located in the boreal forest region of central Canada. Fasting blood glucose and insulin concentrations were determined after an overnight fast. Past year physical activity levels were assessed using a modified version of an interviewer-administered questionnaire. Maximal oxygen uptake, a measure of cardiovascular fitness, was estimated using a submaximal step test.Results: Total (leisure and occupational) physical activity and physical fitness were significantly associated with fasting insulin concentrations after adjusting for age, BMI or percent body fat, waist circumference, and fasting glucose concentration in men but not in women. The relations between physical activity, fitness, and fasting glucose concentrations were not as strong or as consistent as they were when fasting insulin concentration was the dependent variable.Conclusions: In this isolated Native Canadian community, both physical activity and fitness were independently associated with fasting insulin concentrations, suggesting a beneficial role of physical activity/fitness on insulin sensitivity that is separate from any influence of activity on body composition. The fact that this relation was found in men but not in women is most likely explained by issues related to the measurement of activity and fitness in this study and the fact that the women in this population appear to be less active than the men. [ABSTRACT FROM AUTHOR]

Aims To report preliminary data on baseline serum calcitonin concentrations and associated clinical characteristics in a global population with type 2 diabetes before liraglutide or placebo randomization. Methods The ongoing LEADER trial has enrolled 9340 people with type 2 diabetes and at high risk of cardiovascular disease at 410 centres worldwide. People with baseline serum calcitonin ≤50 ng/l were randomized to liraglutide once daily or placebo and will be followed for up to 5 years. Serum calcitonin was measured at baseline and will be measured annually thereafter. An independent committee of thyroid experts will oversee calcitonin monitoring throughout the trial and will review all calcitonin concentrations ≥20 ng/l. Results The mean age of participants was 64.3 ± 7.2 years, 64.3% were men, and mean the body mass index was 32.5 ± 6.3 kg/m2. The median (interquartile range) baseline serum calcitonin values were 3.9 (1.0 to >7.6) ng/l in men and 1.0 (1.0 to >1) ng/l in women. Serum calcitonin was >10 ng/l in 14.6% of men and in 0.96% of women. In sex-specific multivariable linear analysis of covariance models, a reduced glomerular filtration rate ( GFR) was associated with higher serum calcitonin concentrations that were statistically significant. A 20 ml/min/1.73 m2 decrease in estimated GFR ( eGFR) was associated with a 14% increase in serum calcitonin in women and an 11% increase in men. Conclusions In the LEADER population, the prevalence of elevated serum calcitonin concentrations at baseline was high, and there was an inverse association between eGFR and serum calcitonin concentrations. [ABSTRACT FROM AUTHOR]

The article discusses the consensus approach to the management of hyperglycemia in the non-pregnant adult to help guide health care providers in choosing the most appropriate interventions for their patients type 2 diabetes from the American Diabetes Association and the European Association for the Study of Diabetes. The different medications include metformin, sulfonylureas, glinides, insulin, thiazolidinediones, and glucagon-like peptide 1 agonists.

Background: Sodium-glucose transport protein 2 inhibitors (SGLT2i) have been widely used to treat patients with type 2 diabetes mellitus (T2DM) and have demonstrated protective effects against certain cardiovascular diseases. However, no clinical research has been conducted to explore the relationship between SGLT2i and the risk of aortic aneurysm (AA). Methods: We extracted and analyzed the data of 4964 patients with T2DM from the First Affiliated Hospital of Zhengzhou University during July 2017 to January 2023. Multivariate Cox models, interaction analysis and Kaplan–Meier curves were performed to approximate the associations of SGLT2i therapy on the risk of AA. A sensitivity analysis was performed to test the robustness of results. Mediation analyses explored the roles of inflammatory (neutrophils, lymphocytes, C-reactive protein and alkaline phosphatase) and oxidative stress (gamma glutamyl transferase, total bilirubin, and uric acid) markers in the associations between SGLT2i and AA. Results: A total of 1942 SGLT2 inhibitor (SGLT2i) users (39.12%) and 3022 non-SGLT2 inhibitor (NonSGLT2i) users were included in final analysis. After full adjustment for potential risk factors, SGLT2i patients were associated with a lower risk of aortic aneurysm (HR, 95% CI 0.91, 0.89–0.98, p = 0.001). Dapagliflozin showed the greatest difference for reduction of aortic aneurysm incidence (HR, 95% CI 0.84, 0.80–0.95, p = 0.011). Subgroup analysis indicated that use of SGLT2i lower the risk of aortic aneurysm in some subgroups of T2DM patients. The sensitivity analysis demonstrated the robustness of the results. CRP, lymphocytes, neutrophils, and uric acid were significantly associated with both SGLT2i and AA, with mediation proportions of 13.35%, 8.83%, 9.67% and 31.17%, respectively. Conclusions: Our study suggested that patients using SGLT2i may have a lower risk of aortic aneurysm, and this effect could potentially be mediated by inflammation and oxidative stress. Further mechanistic and prospective studies are required to verify this association. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is one of the fastest growing diseases in terms of global incidence and seriously affects cognitive function. The incidence rate of cognitive dysfunction is up to 13% in diabetes patients aged 65–74 years and reaches 24% in those aged >75 years. The mechanisms and treatments of cognitive dysfunction associated with diabetes mellitus are complicated and varied. Previous studies suggest that hyperglycemia mainly contributes to cognitive dysfunction through mechanisms involving inflammation, autophagy, the microbial-gut-brain axis, brain-derived neurotrophic factors, and insulin resistance. Antidiabetic drugs such as metformin, liraglutide, and empagliflozin and other drugs such as fingolimod and melatonin can alleviate diabetes-induced cognitive dysfunction. Self-management, intermittent fasting, and repetitive transverse magnetic stimulation can also ameliorate cognitive impairment. In this review, we discuss the mechanisms linking diabetes mellitus with cognitive dysfunction and propose a potential treatment for cognitive decline associated with diabetes mellitus. [ABSTRACT FROM AUTHOR]

Diabetes, a chronic condition affecting millions worldwide, necessitates early intervention to prevent severe complications. While accurately predicting diabetes onset or progression remains challenging due to complex and imbalanced datasets, recent advancements in machine learning offer potential solutions. Traditional prediction models, often limited by default parameters, have been superseded by more sophisticated approaches. Leveraging Bayesian optimization to fine-tune XGBoost, researchers can harness the power of complex data analysis to improve predictive accuracy. By identifying key factors influencing diabetes risk, personalized prevention strategies can be developed, ultimately enhancing patient outcomes. Successful implementation requires meticulous data management, stringent ethical considerations, and seamless integration into healthcare systems. This study focused on optimizing the hyperparameters of an XGBoost ensemble machine learning model using Bayesian optimization. Compared to grid search XGBoost (accuracy: 97.24%, F1-score: 95.72%, MCC: 81.02%), the XGBoost with Bayesian optimization achieved slightly improved performance (accuracy: 97.26%, F1-score: 95.72%, MCC:81.18%). Although the improvements observed in this study are modest, the optimized XGBoost model with Bayesian optimization represents a promising step towards revolutionizing diabetes prevention and treatment. This approach holds significant potential to improve outcomes for individuals at risk of developing diabetes. [ABSTRACT FROM AUTHOR]

Background: The combination of cardiovascular disease and diabetes is a highly prevalent condition in the United Arab Emirates. Development and dissemination of evidence-based regional recommendations for optimal screening, treatment and referrals of people with diabetes and high cardiovascular risk is an important priority. Consensus panel: An expert panel of diabetologists, endocrinologists and cardiologists from the Emirates Cardiac Society and Emirates Diabetes and Endocrine Society as well as different entities in the UAE, discussed and reviewed evidence and also a consensus report from the American Diabetes Association to formulate contextualized recommendations that could be applied for optimal management of cardiovascular risk in people with diabetes in the UAE. Consensus findings: The combination of heart failure and other cardiovascular risks is a highly prevalent finding among people with diabetes in the United Arab Emirates. The causal inter-relationships between diabetes and heart failure are multifactorial and regular assessments of symptoms and steps for mitigation of risk factors are an important priority. The universal definition and classification of heart failure provides a useful framework for recommending optimal screening, treatment, and referral strategies to diabetic individuals at various stages of the cardiovascular continuum. Routine measurement (at least yearly) of natriuretic peptides and high-sensitivity troponins can help identify patients requiring cardiac imaging referrals. However, recommending routine measurements of natriuretic peptides and/or high-sensitivity troponins to all diabetic individuals must balance clinical judgment and cost implications. While SGLT2i must be an important part of the standard of care, insulin, GLP1 receptor agonists and/or metformin can be useful for additional glycemic control. Conclusion: The consensus panel hopes that the recommendations presented herein can offer guidance for optimal screening, treatment and referral of people with a concomitance of diabetes and high cardiovascular risk in the United Arab Emirates. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging global health concern, and it is not only the keystone precursor of eventual liver-related morbidity, but it also places patients at considerably higher cardiovascular risk, which is still a leading cause of death in these patients. The most important common underlying pathophysiological mechanisms in these diseases are primarily related to insulin resistance, chronic inflammation and oxidative stress. The presence of MASLD with cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) elevates the risk for poor outcomes, thus this review highlights a method to the therapeutic approaches. Given the intertwined nature of MASLD, T2DM, and CVD, there is an urgent need for therapeutic strategies that address all three conditions. Although lifestyle changes are important as treatment, medication plays a crucial role in managing hyperglycemia, enhancing liver function and lowering cardiovascular risk. The onset and progression of MASLD should be addressed through a multifaceted therapeutic approach, targeting inflammatory, immune, metabolic, oxidative stress, hormonal and gutaxis pathways, alongside the treatment strategies for T2DM. In this review, we discuss the effects of antidiabetic drugs with an impact on both liver outcomes and cardiovascular risk in patients affected by MASLD, T2DM and CDV. [ABSTRACT FROM AUTHOR]

Background: Diabetes is an increasingly important public health problem due to its socioeconomic impact, high morbidity, and mortality. Although there is evidence of increasing diabetes-related deaths over the last ten years, little is known about the population level predictors of diabetes-related mortality risks (DRMR) in Florida. Identifying these predictors is important for guiding control programs geared at reducing the diabetes burden and improving population health. Therefore, the objective of this study was to identify geographic disparities and predictors of county-level DRMR in Florida. Methods: The 2019 mortality data for the state of Florida were obtained from the Florida Department of Health. The 10th International Classification of Disease codes E10-E14 were used to identify diabetes-related deaths which were then aggregated to the county-level. County-level DRMR were computed and presented as number of deaths per 100,000 persons. Geographic distribution of DRMR were displayed in choropleth maps and ordinary least squares (OLS) regression model was used to identify county-level predictors of DRMR. Results: There was a total 6,078 diabetes-related deaths in Florida during the study time period. County-level DRMR ranged from 9.6 to 75.6 per 100,000 persons. High mortality risks were observed in the northern, central, and southcentral parts of the state. Relatively higher mortality risks were identified in rural counties compared to their urban counterparts. Significantly high county-level DRMR were observed in counties with high percentages of the population that were: 65 year and older (p < 0.001), current smokers (p = 0.032), and insufficiently physically active (p = 0.036). Additionally, percentage of households without vehicles (p = 0.022) and percentage of population with diabetes (p < 0.001) were significant predictors of DRMR. Conclusion: Geographic disparities of DRMR exist in Florida, with high risks being observed in northern, central, and southcentral counties of the state. The study identified county-level predictors of these identified DRMR disparities in Florida. The findings are useful in guiding health professionals to better target intervention efforts. [ABSTRACT FROM AUTHOR]

Background: The complications of diabetes mellitus (DM) have incapacitated many patients, especially in poor-income countries. DM is an endocrine disease but its far-reaching complications arise from cardiovascular derangements. The cardiovascular complications usually stem from endothelial dysfunction, which culminates in atherosclerosis. Progressively, atherosclerosis results in microvascular and macrovascular complications. Materials and Methods: Literature searches were carried out in Google, PubMed, and MEDLINE using the following keywords: DM, endothelial dysfunction, biomarkers, anti-diabetic drugs, C-reactive protein (CRP), and intercellular adhesion molecule. Original articles, systematic reviews, and meta-analytic articles were reviewed, and important findings were incorporated into this review. Summary: The review aims to evaluate mechanisms responsible for endothelial dysfunction in diabetes. Endothelial dysfunction may arise from one or a combination of these molecular mechanisms: (i) decreased nitric oxide synthesis, (ii) activation of protein kinase C and reactive oxygen species generation, (iii) activity of advanced glycation endproducts, (iv) activation of tumor necrosis factor-alpha, and (iv) defective insulin signaling and so on. The biomarkers of endothelial dysfunction were also explored and they include CRP, intracellular adhesion molecule-1, vascular cell adhesion molecule-1, microalbuminuria, asymmetric dimethylarginine, Toll-like receptors, and others. The review also evaluated the effectiveness of anti-diabetic medications in modulating the biomarkers of endothelial dysfunction in diabetic patients. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a chronic non-communicable disease with an increasing prevalence in Latin America and worldwide, impacting various social and economic areas. It causes numerous complications for those affected. Current treatments for diabetes include oral hypoglycemic drugs, which can lead to adverse effects and health complications. Other natural alternatives for DM treatment have been studied as adjunct therapies that could reduce or eliminate the need for antidiabetic medications. Several natural supplements may offer an alternative way to improve the quality of life for patients with DM, and they may have other nutraceutical applications. Due to their phenolic compound content, some leguminous substances have been proposed as these alternatives. Phenolic compounds, with their high antioxidant activity, have shown promising potential in insulin synthesis, secretion, and the functionality of the endocrine pancreas. This review provides valuable information on various leguminous plants with anti-diabetic properties, including antioxidant, hypoglycemic, anti-fat-induced damage, and anti-apoptotic properties in vitro and in vivo, attributed to the high content of phenolic compounds in their seeds. Natural products with antidiabetic and pharmacological treatment potential improve diabetes management by offering more effective and complementary alternatives. To integrate these herbal remedies into modern medicine, further research on phenolic compound type, doses, efficacy, and safety in the human population is needed. [ABSTRACT FROM AUTHOR]

The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC. [ABSTRACT FROM AUTHOR]

The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC. [ABSTRACT FROM AUTHOR]

The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC. [ABSTRACT FROM AUTHOR]

The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC. [ABSTRACT FROM AUTHOR]

The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC. [ABSTRACT FROM AUTHOR]

The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC. [ABSTRACT FROM AUTHOR]

The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC. [ABSTRACT FROM AUTHOR]

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as important agents for the treatment of type 2 diabetes mellitus (T2DM). SGLT2 inhibitors have been associated with improved cardiovascular outcomes, not only through their immediate hemodynamic effects—such as glycosuria and (at least temporary) increased natriuresis—but also due to their multifaceted impact on metabolism. Recently, studies have also focused on the effects of SGLT2 inhibitors on adipose tissue. Aside from the well-documented effects on human adiposity, SGLT2i have shown, both in vitro and in murine models, the ability to reduce fat mass, upregulate genes related to browning of white adipose tissue, influence adipocyte size and fatty acid oxidation, and improve oxidative stress and overall metabolic health. In humans, even though data are still limited, recent evidence seems to confirm that the SGLT2i effects observed in cardiovascular outcome trials could be partially explained by their impact on adipose tissue. This review aims to clarify the impact of SGLT2i on adipose tissue, highlighting their role in metabolic health and their potential to transform treatment strategies for T2DM beyond glucose metabolism. [ABSTRACT FROM AUTHOR]

Over the past decades, the global prevalence of Type 2 diabetes mellitus (T2D) and impaired glucose tolerance (IGT) has been increasing at an epidemic rate, yet the exact cause remains unknown. It is widely accepted that glucose metabolism can be impaired by circadian rhythms and sleep disturbances. Concurrently, exposures to light at night have been closely linked to circadian and sleep disturbances. However, there is no direct experiment on primates to demonstrate the precise extent of how serious light pollution impairs glucose metabolism, whether people will eventually become accustomed to this environment, and whether the pollution has synergistic impairing effects with aging and weight on glucose metabolism. To quantitatively address these questions, 137 cynomolgus were exposed to three distinct nocturnal light intensities for consecutive 10 months. Monthly glucose metabolism assessments were conducted. Data pertaining to the mortality rate of preexisting diabetes, incidence of light‐induced diabetes and IGT, and alterations in insulin secretion were collected and analyzed. The results show that nocturnal light (1) caused premature deaths in individuals with preexisting diabetes; (2) intensity‐dependently induced diabetes and IGT in previous healthy monkeys; (3) intensity‐dependently reduced melatonin secretion; (4) had a synergistic impairing effect on glucose metabolism with aging and weight; and (5) although monkeys would eventually adapt to the environment, the disrupted glucose metabolism would not fully recover in most individuals. In conclusion, nocturnal light is associated with the global high prevalence of T2D and IGT. The harmful effects of light pollution on glucose metabolism are synergistic with age and weight. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a progressive condition that affects more than 10% of the population worldwide, accounting for more than 843 million (M) individuals. The prevalence of CKD (844 M patients) is higher than that of diabetes mellitus (422 M patients), cancer (42 M patients), and HIV (37 M patients), but people are often less aware of it. Global expert groups predict reductions in the nephrology workforce in the next decade, with a declining interest in nephrology careers. Over time, KDIGO guidelines have also focused on topics related to the prevention or management of CKD patients in real-life settings. On these premises, a new educational program with international experts in the field of nephrology took place from November 2022 until March 2023 in Milan, Italy. This multinational masterclass provided an educational platform providing unbiased education on diagnosis and treatment by sharing the most recent research data on CKD and comorbidities, therefore creating a snowball effect to increase the implementation of best practices worldwide, using examples from 'real-life' patient outcomes. This paper provides an overview of the International Nephrology Masterclass (INM) concept, summarizing the key lectures and discussions, and giving an outline of future key developments. [ABSTRACT FROM AUTHOR]

Peripheral neuropathy (PN) significantly impacts the quality of life, causing substantial morbidity and increased mortality, as well as escalating healthcare costs. While PN can have various causes, the most common form, diabetic peripheral neuropathy, poses considerable risks for potential complications. Diabetic peripheral neuropathy (DPN) affects over 50% of people with prediabetes and diabetes. Despite its prevalence, a global gap in diagnosis and management exists, exacerbated by the COVID-19 pandemic. This expert consensus was formulated through a comprehensive evaluation by a panel of experts, informed by a focused literature review, aiming to establish a clinically robust approach to diagnosing and managing pre- and diabetic PN with the early utilization of neurotropic B vitamins. This document offers a consensus perspective on the existing challenges in diagnosing and managing PN, focusing on DPN. The expert panel proposes measures to address this underdiagnosed burden, highlighting the importance of early intervention through innovative screening methods, integrated care approaches, and therapeutic strategies. The document advocates for increased awareness, targeted campaigns, and proactive care strategies to bridge gaps in the patient care of individuals with diabetes, emphasizing the importance of early detection and timely management to improve overall health outcomes. Specific recommendations include incorporating simplified questionnaires and innovative screening methods into routine care, prioritizing neurotropic B vitamin supplementation, optimizing glucagon-like peptide 1 (GLP-1) receptor agonist treatments, and adopting a holistic approach to neuropathy management. The consensus underscores the urgent need to address the underdiagnosis and undertreatment of PN, offering practical measures to enhance early detection and improve health outcomes for individuals with DPN. [ABSTRACT FROM AUTHOR]

Introduction and objective: Diabetes represents one of the most significant healthcare challenges of the 21st century. The disease is frequently asymptomatic, with patients often remaining undiagnosed for extended periods and failing to seek assistance from healthcare professionals. A sedentary lifestyle, excessive caloric intake, and a lack of physical activity contribute to the development of obesity, which in turn leads to carbohydrate metabolism disorders. In this study, we will examine the relationship between diabetes and obesity, and discuss the drug semaglutide, which is used to treat type 2 diabetes and also promotes weight loss. Review methods: Review and summary of research studies available in open-source format on Google Scholar, PubMed. Abbreviated description of the state of knowledge: Numerous clinical studies have demonstrated the efficacy of semaglutide in improving lipid profiles and promoting weight loss. This effect is believed to be mediated by the drug's ability to slow gastric emptying. It is evident that semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, exerts a beneficial effect on carbohydrate parameters and helps to delay the occurrence of complications associated with diabetes. Summary: A review of clinical reports and conducted studies indicates that semaglutide has the potential to enhance parameters that directly or indirectly impact the quality of life of patients with diabetes. However, the utilisation of the aforementioned pharmaceutical is associated with adverse effects, which may impede patient-physician collaboration and potentially precipitate the development of new health complications in patients. One of the effects of semaglutide treatment is a reduction in appetite, which contributes to weight loss. This property of the drug makes it suitable for use in patients with excessive body weight. [ABSTRACT FROM AUTHOR]

Background: The current review aims to present the beneficial effects of SGLT2 inhibitors (dapagliflozin and empagliflozin) on several hemodynamic parameters such as blood pressure, filtration pressure at the level of the glomerular capillaries, and the improvement of the preload and afterload of heart muscle. In order to stop chronic kidney disease (CKD) from progressing, SGLT2 inhibitors have become an important disease-modifying treatment. Materials and methods: Recent clinical studies have shown the success of these drugs in treating heart failure, reducing the risk of cardiovascular events, hospitalization, and mortality. Results: The hemodynamic effects of SGLT2 inhibitors include a diuretic effect, due to reduced sodium reabsorption. Also, at this level, numerous studies have confirmed the beneficial effect of dapagliflozin in patients with chronic kidney disease, associated with a 44% reduced risk of progression in this pathology. SGLT2 inhibitors are associated with a reduction in blood pressure and weight loss, because of their diuretic effect, especially empagliflozin, which can explain the beneficial effects in patients with heart failure. In addition, mainly empagliflozin reduces stiffness and arterial resistance. Conclusions: Although the exact mechanism of action is unknown, SGLT2 inhibitors reduce the interstitial volume by blocking the tubular reabsorption of glucose. This leads to reduced blood pressure and enhanced endothelial function. Consequently, there have been improvements in hospitalization and fatality rates. Because of their beneficial effects, these medications have been guidelines for managing heart failure and chronic kidney disease. [ABSTRACT FROM AUTHOR]

Background: Sodium–glucose cotransporter-2 inhibitors (SGLT2Is) have demonstrated effects beyond glucose-lowering, leading to their approval for treating chronic heart failure (HF) in Japan. This study examines prescription trends for SGLT2Is in patients with diabetes versus those without diabetes, focusing on their backgrounds and HF treatment status of patients without diabetes who received SGLT2I after an HF diagnosis. Methods: Using data from DeSC Healthcare Inc., we analyzed patients aged 65 and above who received their first SGLT2I prescription between October 2014 and February 2023. Patients were classified into SGLT2I-treated diabetic and non-diabetic groups. We analyzed the annual prescription trends and compared the characteristics of both groups who started SGLT2I between 2022 and 2023. Additionally, we assessed the timing of SGLT2I initiation and the use of concomitant HF treatment in patients without diabetes after HF diagnosis. Results: The proportion of patients without diabetes receiving their first SGLT2I prescription has increased since 2021. Patients without diabetes receiving SGLT2Is were older, likely owing to aging-related diseases. In patients without a confirmed diabetes diagnosis, SGLT2I was most frequently initiated at the time of HF diagnosis. Mineralocorticoid receptor antagonists (MRAs) are the most common concomitant HF medications. The increase in SGLT2I prescriptions for patients without diabetes receiving SGLT2I since 2021, particularly in older individuals, suggests that SGLT2I is being initiated either at the time of HF diagnosis or in a stepwise manner. Conclusion: In Japan, MRA is commonly used as a concomitant medication in patients without diabetes receiving SGLT2I. [ABSTRACT FROM AUTHOR]

Background: Sodium–glucose co-transporter 2 (SGLT-2) inhibitors, initially designed for type 2 diabetes, promote glucose excretion and lower blood glucose. Newer analogs like empagliflozin and dapagliflozin improve cardiovascular outcomes through mechanisms other than glycemic control, including blood pressure reduction and anti-inflammatory effects. Given the high cardiovascular risk present in diabetes, our study aims to emphasize the cardioprotective benefits of SGLT-2 inhibitors as a preventive therapy for heart failure (HF) in high-risk T2DM patients. Methods: Using data from 2542 patients identified by the ICD-10 E11 code from 2016 to 2020, this longitudinal study excluded those with E10 codes or those undergoing insulin treatment to focus on non-insulin-dependent T2DM. a multiple logistic regression model assessed HF incidence while adjusting for demographics and HbA1c. Results: SGLT-2 inhibitor use significantly lowered the odds of heart failure events (OR = 0.55, 95% CI: 0.31–0.99, p = 0.046), with a significant difference by gender (OR = 0.45, 95% CI: 0.28–0.71, p = 0.001) and eGFR (OR = 0.98, 95% CI: 0.97–0.99, p = 0.004). Conclusions: The real-world data highlight SGLT-2 inhibitors as promising for HF prevention and broader cardiometabolic health in T2DM, with potential value in managing complex comorbid profiles. [ABSTRACT FROM AUTHOR]

A glycaemic control identical with the normal has been achieved in unrestrained totally depancreatised dogs using a portable open-loop insulin delivery system. The device consisted of a battery power pack with a flow-rate controller, an insulin reservoir and a peristaltic pump from which pulses of insulin were delivered every 90 seconds into the inferior vena cava through an exteriorised indwelling catheter. Insulin was infused at the basal rate of 0.45±0.03 mUkg min (Mean±s.e.m.) in the postabsorptive state resulting in peripheral IRI and plasma glucose levels of 12±1 μU ml and 86±7 mg dl. In the postprandial period the infusion rate was enhanced sevenfold to the rate of 3.16±0.21 mU kgmin for 7h and then reduced to 1.05±0.07 mU kg min for an additional 2.25 h. A weight-maintaining constant diet was provided and the resulting glycaemic profiles were similar to age, sex and weight-matched healthy controls. Fasting peripheral insulin levels in the infused diabetic dogs were not significantly different from non-diabetic controls (10±1μUml). However, in the postprandial period of enhanced delivery, insulin levels in the diabetic dogs were 3.1 times higher than the controls. With the compound square waveforms of preprogrammed insulin infusion found appropriate in this study unaccountable low or high plasma glucose levels did not occur but hyperinsulinism accompanied the glycaemic normalisation following a mixed meal. [ABSTRACT FROM AUTHOR]

We examined the relationship between usual patterns of food intake, fattiness of food preparation and consumption, and diabetes and obesity status in a Native Canadian reserve in northwestern Ontario. Patterns of intake were estimated using a 34-item food frequency instrument. Scales and scores were developed using factor analysis procedures and were tested for reliability using coefficient alpha. Impaired glucose tolerance (IGT) and diabetes status was determined by administering a 75-g glucose tolerance test. A number of the food groups appear to have a protective effect in regard to IGT and diabetes, including vegetables [odds ratio (OR) = 0.41, confidence interval (CI) = 0.18-0.91], breakfast foods (OR = 0.41, CI = 0.18-0. 93) and hot meal foods (OR = 0.29, CI = 0.11-0.78). Most of these foods are relatively high in fiber and low in fat. High consumption of junk foods and the bread and butter group was associated with substantial increases in risk for diabetes (OR = 2.40, CI = 1.13-5. 10; OR = 2.22, CI = 1.22-4.41, respectively). These foods tend to be high in simple sugars, low in fiber and high in fat. More fatty methods of food preparation are also associated with increased risk for diabetes in this population (OR = 2.58, CI = 1.11-6.02). This information has been incorporated into an ongoing community-based diabetes prevention program in the community. [ABSTRACT FROM AUTHOR]

Presents a study which determined the absorption of subcutaneous human insulin in patients with Type I diabetes mellitus. Comparison between the absorption of human insulin and animal insulin; Characteristics of human insulin in the control of post-prandial glycemic response; Use of glucose-oxidase method in biochemical analysis.

Background: Among diabetes mellitus (DM) patients, stress hyperglycemia ratio (SHR) is a strong predictor of short- and long-term prognosis, and adverse cardiovascular events. However, whether SHR is associated with increased risk of presence and severity of chronic kidney (CKD) disease remains undetermined. Methods: Patients with DM from the National Health and Nutrition Examination Survey (NHANES) database (1999–2020) were included and divided into 5 groups according to their SHR level (quintile 1 to 5). Study outcomes were CKD, advanced CKD (ACKD), and CKD severity. Logistic regression and restricted cubic spline (RCS) were used to assess the association between the SHR and outcomes. Results: Totally, 6,119 patients were included. After adjustment, compared to patients with SHR in quintile 3 (as reference), the risk of CKD is 1.50 (P<0.001) for quintile 1, 1.23 (P=0.140) for quintile 2, 1.95 (P<0.001) for quintile 4, and 1.79 (P<0.001) for quintile 5. For the risk of ACKD, the OR is 1.46 (P=0.410) for quintile 1, 1.07 (P=0.890) for quintile 2, 3.28 (P=0.030) for quintile 4, and 3.89 (P=0.002) for quintile 5. For the CKD severity, the OR is 1.46 (P<0.001) for quintile 1, 1.20 (P=0.163) for quintile 2, 1.84 (P<0.001) for quintile 4, and 1.83 (P<0.001) for quintile 5. RCS analysis also showed a U-shaped association between SHR and outcomes (All P for nonlinearity<0.05). Conclusion: Our study demonstrated that too low or too high SHR level is significantly associated with adverse renal outcomes in patients with DM. [ABSTRACT FROM AUTHOR]

Background: Progressive deterioration of ß-cell function is a characteristic of type 2 diabetes mellitus (T2DM). We aimed to investigate the relative contributions of clinical factors to ß-cell function in T2DM. Methods: In a T2DM cohort of 470 adults (disease duration 0 to 41 years), ß-cell function was estimated using insulinogenic index (IGI), disposition index (DI), oral disposition index (DIO), and homeostasis model assessment of ß-cell function (HOMA-B) derived from a 75 g oral glucose tolerance test (OGTT). The relative contributions of age, sex, disease duration, body mass index, glycosylated hemoglobin (HbA1c) levels (at the time of the OGTT), area under the curve of HbA1c over time (HbA1c AUC), coefficient of variation in HbA1c (HbA1c CV), and antidiabetic agents use were compared by standardized regression coefficients. Longitudinal analyses of these indices were also performed. Results: IGI, DI, DIO, and HOMA-B declined over time (P<0.001 for all). Notably, HbA1c was the most significant factor affecting IGI, DI, DIO, and HOMA-B in the multivariable regression analysis. Compared with HbA1c =9%, DI was 1.9-, 2.5-, 3.7-, and 5.5-fold higher in HbA1c of 8%-<9%, 7%-<8%, 6%-<7%, and <6%, respectively, after adjusting for confounding factors (P<0.001). Conversely, ß-cell function was not affected by the type or duration of antidiabetic agents, HbA1c AUC, or HbA1c CV. The trajectories of the IGI, DI, DIO, and HOMA-B mirrored those of HbA1c. Conclusion: ß-Cell function declines over time; however, it is flexible, being largely affected by recent glycemia in T2DM. [ABSTRACT FROM AUTHOR]

Background/Aim: In several studies, Sodiumglucose co-transporter-2 inhibitors (SGLT2i) have been reported to increase hemoglobin (Hb) levels. In a study in which Hb levels were compared between patients who received SGLT2i and dipeptidyl peptidase-4 inhibitors, some patients exhibited increased Hb levels (>1.0 g/dl), whereas some exhibited unchanged Hb levels. Notably, several factors may influence the Hb-increasing effect of SGLT2i. This study aimed to analyze the factors influencing the Hb-increasing effect of SGLT2i. Patients and Methods: Type 2 diabetes patients were divided into three groups: SGLT2i (SGLT2i only group, n=36), those receiving a combination of SGLT2i and angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) (SGLT2i+ACEi/ARBs group, n=32), and those not receiving these drugs (control group, n=49). We retrospectively analyzed Hb changes in these groups. Kaplan-Meier curves compared Hb changes from SGLT2i initiation to day 63, with an Hb increase defined as ≥0.5 g/dl. In addition, sex, age, ACEi/ARBs, estimated glomerular filtration rate, and hematocrit levels were analyzed using Cox proportional hazards as factors influencing Hb-increasing events. Results: Hb-increasing event rates were 61%, 41%, and 20% in the SGLT2i only, SGLT2i+ACEi/ARBs, and control groups, respectively. The Kaplan-Meier curves showed significantly higher Hbincreasing event rates in the SGLT2i only group than in the control and SGLT2i+ACEi/ARBs groups. In the Cox proportional hazards model, ACEi/ARBs use was associated with a 39% reduction in the incidence of Hb-increasing events. Conclusion: SGLT2i exhibit a Hb-increasing effect, which may be reduced by ACEi/ARBs. [ABSTRACT FROM AUTHOR]

The pancreatic islet vasculature comprises microvascular endothelial cells surrounded by mural cells (pericytes). Both cell types support the islet by providing (1) a conduit for delivery and exchange of nutrients and hormones; (2) paracrine signals and extracellular matrix (ECM) components that support islet development, architecture, and endocrine function; and (3) a barrier against inflammation and immune cell infiltration. In type 2 diabetes, the islet vasculature becomes inflamed, showing loss of endothelial cells, detachment, and/or trans-differentiation of pericytes, vessel dilation, and excessive ECM deposition. While most work to date has focused either on endothelial cells or pericytes in isolation, it is very likely that the interaction between these cell types and disruption of that interaction in diabetes are critically important. In fact, dissociation of pericytes from endothelial cells is an early, key feature of microvascular disease in multiple tissues/disease states. Moreover, in beta-cell replacement therapy, co-transplantation with microvessels versus endothelial cells alone is substantially more effective in improving survival and function of the transplanted cells. Ongoing studies, including characterization of islet vascular cell signatures, will aid in the identification of new therapeutic targets aimed at improving islet function and benefiting people living with all forms of diabetes. [ABSTRACT FROM AUTHOR]

Background: Transcription factor 7-like 2 (TCF7L2) variants seem to affect diabetes susceptibility through β-cell dysfunction, underlying basis of which has been considered to be β-cell dedifferentiation rather than apoptotic β-cell death. The Extracellular regulated protein kinases/Mitogen-activated protein kinase signaling pathway (ERK/MAPK signaling pathway) has been confirmed to be significantly associated with multiple cellular process, including cellular dedifferentiation. However, the effects of TCF7L2 on β-cell function and ERK/MAPK signaling pathway are poorly understood. Objectives: This study aimed to elucidate the regulation of TCF7L2 in β-cell function and ERK/MAPK signaling pathway, which further participate in glucose metabolism and diabetes progression. Methods: After transfection of TCF7L2 siRNA and lenti-TCF7L2 plasmids, the activation of ERK/MAPK signaling and β-cell dedifferentiation were evaluated respectively. Six week-old male db / db mice were randomly grouped and fed a normal or high-fat diet, and then pancreatic level of TCF7L2 protein were measured respectively when the mice were fed to 8, 12, and 16 weeks of age. Furthermore, the contributions of TCF7L2 to ERK/MAPK signaling and glucose metabolism were investigated in a β-cell-specific TCF7L2 deletion mice model (TCF7L2β−/−). Results: The results demonstrated that impaired TCF7L2 induces β-cell dedifferentiation and decreases insulin secretion of MIN6 cells via ERK/MAPK signaling pathway. Consistently, decreased pancreatic TCF7L2 protein in parallel with reduced functional β-cells were observed in db / db mice after weeks of normal or high-fat diet. However, the differences between were only significant when the mice were fed to 12 weeks of age. After weeks of high-fat diet feeding, impaired glucose tolerance and increased activation of ERK/MAPK signaling were simultaneously observed in TCF7L2β−/− mice. Conclusion: The study indicate that the induction of β-cell dedifferentiation mediated by ERK/MAPK signaling pathway might be an essential component of TCF7L2 variants in the development of diabetes. Plain Language Summary: Inhibitory effect of TCF7L2 on pancreatic β-cell dedifferentiation via ERK/MAPK signaling pathway in diabetes Transcription factor 7-like 2 (TCF7L2) variants seem to affect diabetes susceptibility through β-cell dysfunction, underlying basis of which has been considered to be β-cell dedifferentiation rather than apoptotic β-cell death. Nowadays, how TCF7L2 participates in β-cell dedifferentiation and how pancreatic TCF7L2 protein changes during diabetes progression are poorly understood. The Extracellular regulated protein kinases/Mitogen-activated protein kinase signaling pathway (ERK/MAPK signaling pathway) has been confirmed to be significantly associated with multiple cellular process, including cellular dedifferentiation. Here, we demonstrated that impaired TCF7L2 induces β-cell dedifferentiation and decreases insulin secretion of MIN6 cells via ERK/MAPK signaling pathway. Consistently, declined pancreatic TCF7L2 protein in parallel with reduced mature β-cells were observed in db / db mice after weeks of normal or high-fat diet feeding. Furthermore, the role of TCF7L2 in dedifferentiation and glucose homeostasis were validated in mice with β cell-specific TCF7L2 deletion (TCF7L2β−/−). In conclusion, the study indicate that the induction of β-cell dedifferentiation mediated by ERK/MAPK signaling pathway might be an essential component of TCF7L2 variants in the development of diabetes. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic Kidney Disease (DKD) is the main cause of end-stage renal disease in the developed world. The current treatment of the DKD with reninangiotensin system (RAS) blockade does not totally halt the progression to end stage kidney disease. Currently, several drugs have shown to delay DKD progression such as sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like-1 receptor agonists (GLP-1RA). We hypothesized that by combining several drugs that prevent DKD progression on top of RAS blockade a synergistic effect would be achieved in terms of cardiorenal protection. In the present study, we analysed if the combination of a RAS blocker (ramipril) with a SGLT2i (empagliflozin) and/or GLP-1RA (semaglutide) in a type 2 diabetic mouse model could have add-on effects in kidney and heart protection. Methods: Male and female uninephrectomized type 2 diabetic db/db mice were treated with empagliflozin and/or semaglutide on top of ramipril during 8 weeks. During the study body weight, water and food intake were weekly monitored, glycaemia biweekly and albuminuria and glomerular filtration rate (GFR) before and after the treatment. At the end of the experiment, kidney and heart were isolated for histological and gene expression studies as well as for intrarenal RAS state assessment. Results: Semaglutide combined with ramipril and/or empagliflozin significantly decreased albuminuria but only when combined with both compounds, semaglutide further decreased blood glucose, glomerular hyperfiltration in male mice and glomerular mesangial matrix expansion. In kidney, only the triple treatment with empagliflozin, semaglutide and ramipril reduced the expression of the proinflammatory and profibrotic genes ccl2 and TGFß1. In addition, the combination of empagliflozin and semaglutide on top of RAS blockade was superior in decreasing cardiomyocyte hypertrophy and heart fibrosis in db/db mice. Discussion: Our results suggest that the combination of SGLT2i with GLP-1RA is superior in cardiorenal protection in DKD than the drugs administered alone on top of RAS blockade. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) and cancer share common risk factors including obesity, inflammation, hyperglycemia, and hyperinsulinemia. High insulin levels activate the PI3K/Akt/mTOR signaling pathway promoting cancer cell growth, survival, proliferation, metastasis, and anti-apoptosis. The inhibition of the PI3K/Akt/mTOR signaling pathway for cancer remains a promising therapy; however, drug resistance poses a major problem in clinical settings resulting in limited efficacy of agents; thus, combination treatments with therapeutic inhibitors may solve the resistance to such agents. Understanding the metabolic link between diabetes and cancer can assist in improving the therapeutic strategies used for the management of cancer patients with diabetes and vice versa. This review provides an overview of shared molecular mechanisms between diabetes and cancer as well as discusses established and emerging therapeutic anti-cancer agents targeting the PI3K/Akt/mTOR pathway in cancer management. [ABSTRACT FROM AUTHOR]

Background Type 2 diabetes mellitus (T2DM) may be a long-term sequela of infection with Mycobacterium tuberculosis (Mtb) by mechanisms that remain to be fully explained. We evaluated the association between Mtb sensitization and T2DM and, via mediation analysis, the extent to which it is mediated by insulin resistance and/or β-cell failure. Methods Adults were assessed for T2DM by fasting plasma glucose, 2-hour oral glucose tolerance testing, and hemoglobin A1c; β-cell dysfunction and insulin resistance by homoeostasis model assessment 2; and Mtb sensitization by tuberculin skin testing. Associations between Mtb sensitization and T2DM were modeled with probit regression and decomposed into indirect effects of β-cell dysfunction and insulin resistance. Analyses were adjusted for sociodemographic, behavioral, and clinical characteristics. Results We included 1843 adults. Individuals with Mtb sensitization were older than those without Mtb (median [IQR], 54 [39–64] vs 47 [33–62] years). As compared with being uninfected, Mtb sensitization was associated with T2DM (adjusted absolute risk difference, 9.34% [95% CI, 2.38%–15.0%]; P <.001) and increased insulin resistance (adjusted median difference, 0.16 [95% CI,.03–.29]; P =.014) but not β-cell dysfunction (adjusted median difference, −3.1 [95% CI, −10.4 to 4.3]; P =.42). In mediation analyses, insulin resistance mediated 18.3% (95% CI, 3.29%–36.0%; P =.020) of the total effect of the association between Mtb sensitization and T2DM. Conclusions Definitive prospective studies examining incident T2DM following tuberculosis are warranted. Notwithstanding, our findings suggest that exposure to Mtb may be a novel risk factor for T2DM, likely driven by an increase in insulin resistance. [ABSTRACT FROM AUTHOR]