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A phenome-wide comparative analysis of genetic discordance between obesity and type 2 diabetes.

Obesity and type 2 diabetes are causally related, yet there is considerable heterogeneity in the consequences of both conditions and the mechanisms of action are poorly defined. Here we show a genetic-driven approach defining two obesity profiles that convey highly concordant and discordant diabetogenic effects. We annotate and then compare association signals for these profiles across clinical and molecular phenotypic layers. Key differences are identified in a wide range of traits, including cardiovascular mortality, fat distribution, liver metabolism, blood pressure, specific lipid fractions and blood levels of proteins involved in extracellular matrix remodelling. We find marginal differences in abundance of Bacteroidetes and Firmicutes bacteria in the gut. Instrumental analyses reveal prominent causal roles for waist-to-hip ratio, blood pressure and cholesterol content of high-density lipoprotein particles in the development of diabetes in obesity. We prioritize 17 genes from the discordant signature that convey protection against type 2 diabetes in obesity, which may represent logical targets for precision medicine approaches.

Ertugliflozin Delays Insulin Initiation and Reduces Insulin Dose Requirements in Patients With Type 2 Diabetes Analyses From VERTIS CV.

VERTIS CV evaluated the cardiovascular safety of ertugliflozin in patients with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD). The aim of these analyses was to assess the insulin requirements of VERTIS CV patients over the trial duration. Patients received ertugliflozin 5 mg, 15 mg, or placebo once daily mean follow-up was 3.5 years. Time to insulin initiation in patients who were insulin naïve at baseline, change in insulin dose in patients receiving baseline insulin, and hypoglycemia incidence in both patient groups were assessed. In VERTIS CV, mean duration of type 2 diabetes was 13.0 years glycated hemoglobin was 8.2%. Among 4348 (53%) insulin-naïve patients, the likelihood of insulin initiation was significantly reduced with ertugliflozin vs placebo (ertugliflozin 5 mg hazard ratio HR 0.70, 95% CI 0.58-0.84 ertugliflozin 15 mg HR 0.64, 95% CI 0.53-0.78). Time to insulin initiation was delayed with ertugliflozin the estimated delay in reaching a 10% cumulative incidence of new insulin initiations vs placebo was 399 days with ertugliflozin 5 mg and 669 days with ertugliflozin 15 mg. Among 3898 (47%) patients receiving baseline insulin, the likelihood of requiring a ≥20% increase in insulin dose was significantly reduced with ertugliflozin vs placebo (ertugliflozin 5 mg HR 0.62, 95% CI 0.52-0.75 ertugliflozin 15 mg HR 0.51, 95% CI 0.41-0.62). The incidence of hypoglycemia events was not increased with ertugliflozin treatment. In VERTIS CV patients, ertugliflozin reduced the likelihood of insulin initiation, delayed the time to insulin initiation by up to ∼1.8 years, and reduced insulin dose requirements vs placebo, without increasing hypoglycemia events.

Activation of PDGF signaling in the adult muscle stem cell niche in patients with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2D) negatively affects muscle mass and function throughout life. Whether adult muscle stem cells contribute to the decrease in muscle health is not clear and insights into the stem cell niche are difficult to obtain. To establish the upstream signalling pathway of microRNA (miR)-501, a marker of activated myogenic progenitor cells, and interrogate this pathway in muscle biopsies from patients with T2D. Analysis of primary muscle cell cultures from mice and 4 normoglycemic humans and muscle biopsies from 7 patients with T2D and 7 normoglycemic controls using gene expression, information on histone methylation, peptide screening and promoter assays. miR-501 shares the promoter of its host gene, the isoform 2 of chloride voltage-gated channel 5 (CLCN5-2), and miR-501 expression increases during muscle cell differentiation. We identify platelet-derived growth factor (PDGF) as upstream regulator of CLCN5-2 and miR-501 via JAKSTAT. Skeletal muscle biopsies from patients with T2D revealed upregulation of PDGF (1.62-fold, p 0.002), CLCN5-2 (2.85-fold, p 0.03), and miR-501 (1.73-fold, p 0.02) compared to normoglycemic controls. In addition, we observed a positive correlation of PDGF and miR-501 in human skeletal muscle (r 0.542, p 0.045, n 14). We conclude that paracrine signaling in the adult muscle stem cells niche is activated in T2D. Expression analysis of the PDGF-miR-501 signaling pathway could represent a powerful tool to classify patients in clinical trials that aim to improve muscle health and glucose homeostasis in diabetic patients.

Usefulness of ICD-10 diagnosis triggers to identify adverse drug events in emergency care.

To assess the usefulness of a tool based on ICD-10 diagnostic codes to identify patients who consult an emergency department for adverse drug events (ADE). Prospective observational study, in which patients discharged from an emergency department during May to August 2022 with a diagnosis coded with one of the 27 ICD-10 diagnoses considered as triggers were included. ADE confirmation was carried out by analyzing drugs prescribed prior to admission, and through a discussion among experts and a phone interview with patients after hospital discharge. 1,143 patients with trigger diagnoses were evaluated, of which 310 (27.1%) corresponded to patients whose emergency visit was attributed to an ADE. A 58.4% of ADE consultations were found with three diagnostic codes K59.0-Constipation (n 87 28.1%), I16.9-Hypertensive Crisis (n 72 23.2%) and I95.1-Orthostatic hypotension (n 22 7.1%). The diagnoses with the highest degree of association with consultations attributed to ADE were E16.2-Hypoglycemia, unspecified (73.7%) and E11.65-Type 2 diabetes mellitus with hyperglycemia (71.4%), while diagnoses D62-Acute posthemorrhagic anemia and I74.3-Embolism and thrombosis of arteries of the lower limbs were not attributed to any case of ADE. The ICD-10 codes associated with trigger diagnoses are a useful tool to identify patients who consult the emergency services with ADE and could be used to apply secondary prevention programs to avoid new consultations to the health care system.

Predictors, Disparities, and Facility-Level Variation SGLT2 Inhibitor Prescription Among US Veterans With CKD.

Sodiumglucose cotransporter 2 (SGLT2) inhibitors are recommended for type 2 diabetes mellitus (T2DM) in patients with chronic kidney disease (CKD) or atherosclerotic cardiovascular disease (ASCVD). We evaluated factors associated with SGLT2 inhibitor prescription, disparities by race and sex, and facility-level variation in prescription patterns. Retrospective cohort. A national sample of US veterans with comorbid T2DM, CKD, and ASCVD with a primary care visit between January 1 and December 31, 2020. Race, sex, and individual Veterans Affairs (VA) location. SGLT2 inhibitor prescription. Multivariable logistic regression assessed associations of race and sex with SGLT2 inhibitor prescription. Facility-level variation in SGLT2i prescription was quantified by median rate ratios (MRR), which express the likelihood that 2 randomly selected facilities differ in their use of SGLT2 inhibitor among similar patients. Of 174,443 patients with CKD, T2DM, and ASCVD, 20,024 (11.5%) were prescribed an SGLT2 inhibitor. Lower odds of SGLT2 inhibitor prescription were seen in Black or African American patients compared with White patients (OR, 0.87 95% CI, 0.83-0.91) and among women compared with men (OR, 0.59 95% CI 0.52-0.67). The adjusted MRR for SGLT2 inhibitor prescription was 1.58 (95% CI 1.48-1.67) in the total cohort, indicating an unexplained 58% variation in treatment between VA facilities, independent of patient and facility characteristics. Facility-level variation was evaluated among Black or African American patients (MRR, 1.55 95% CI 1.41-1.68), White patients (MRR, 1.57 95% CI 1.47-1.66), women (MRR, 1.40 95% CI 1.28-1.51), and men (MRR, 1.57 95% CI 1.48-1.67). Albuminuria was not assessed. Prescription for SGLT2 inhibitors was low among likely eligible patients, with evident disparities by sex and race and between individual VA facilities. Efforts are needed to study and address the reasons for these disparities to improve equitable adoption of these important medications.

Efficacy and safety of imeglimin in type 2 diabetes A systematic review and meta-analysis of randomized placebo-controlled trials.

Imeglimin is a novel new oral compound recently approved for treating type 2 diabetes (T2D) in India. We conducted a systematic review and meta-analysis to evaluate the efficacy of imeglimin in people with T2D in the approved dose of 1000 mg twice daily (BID). We systematically searched the database of PubMed until December 20, 2022, and retrieved all published double-blind, randomized, placebo-controlled trials (RCTs) conducted with imeglimin 1000 mg BID, using appropriate keywords and MeSH terms. A meta-analysis was conducted to study the HbA1c lowering effect of imeglimin 1000 mg BID in people with T2D using the Comprehensive meta-analysis (CMA) software Version 3, Biostat Inc. Englewood, NJ, USA. Of the seven Phase 2 studies and three Phase 3 studies conducted so far, only three published double-blind RCTs have reported the efficacy and safety of imeglimin 1000 mg BID against the placebo. Our meta-analysis using the random-effects model from two monotherapy studies (n 360) showed imeglimin 1000 mg BID reduce HbA1c significantly (Δ -0.9%, 95% Confidence Interval CI, -1.1 to -0.74% P < 0.0001) against the placebo, without any heterogeneity (I This meta-analysis found a significant HbA1c lowering effect of imeglimin in people with T2D with an acceptable tolerability profile. Still, larger and longer studies are needed.

Effect of dates on blood glucose and other metabolic variables A narrative review.

There is a common belief that individuals with type 2 diabetes mellitus (T2DM) must avoid consumption of dates. This article aims to review and discuss the available studies on dates on different variables, specifically blood glucose. A survey of studies related to the influence of consumption of dates on blood glucose, glycosylated hemoglobin, lipid profile, and body weight was conducted between January 2009 and Nov 2022, using various data bases (PubMed, Medline, Google Scholar and Scopus). The glycemic index (GI) of date varieties ranges from 42.8 to 74.6, and glycemic load (GL) 8.5-24. The glycemic indices of various stages of dates are Rutab (semi-ripe), 47.2 Tamer (fully ripe, traditionally sun-dried), 45.3, and Tamer (commercial), 35.5. Glucose tolerance-based studies and cross-sectional studies show no significant changes in glycemic indices or association with glycemic worsening with intake of dates. Few randomized controlled trials (RCT) also showed no change in glycemia and weight in the intervention groups consuming dates. Some data (including one RCT) show that the consumption of dates improve total cholesterol and LDL-C. Available studies show that consumption of dates may not lead to impairment of glycemia in patients with T2DM, however, studies have several limitations like small sample size and short duration. More RCTs pertaining to the GI of different date varieties in different amounts are needed.

Clinical pharmacology of SGLT-2 inhibitors in heart failure.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors constitute a class of oral antiglycemic agents that have emerged as a new therapeutic strategy for heart failure (HF) with reduced ejection fraction (HFrEF) and, potentially, for HF with preserved ejection fraction (HFpEF). Ongoing efforts to clarify the exact mechanisms of action of SGLT2 inhibitors (SGLT2i) reveal that glycosuria and osmotic diuresis, resulting from the blockade of renal receptors, is not the sole pathophysiological mechanism. Nevertheless, the underlying mechanisms, accounting for their cardiovascular beneficial effects which have been clearly demonstrated in clinical trials, remain unclear. The aim of this review is to summarize the primary outcomes of large-scale studies regarding the use of SGLT2i in HF and provide an overview of the potential pathways involved in the SGLT2i-mediated cardioprotection. SGLT2i exhibit favorable pleiotropic effects, which extend beyond their primary indication as pharmaceutical agents intended for glycemic control. Given their unique pathophysiological profile, these agents have revolutionized the management of HF, while in the near future, it is possible that evolving research in the field may unfold further perspectives on their potential use in the treatment of other chronic conditions.

Blood glucose control with different treatment regimens in type 2 diabetes patients hospitalized with COVID-19 infection A retrospective study.

Coronavirus disease (COVID-19) is closely associated with hyperglycemia and a worse prognosis in patients with a previous diagnosis of type 2 diabetes mellitus. A few studies investigated the effects of diabetes treatment regimens in these patients during hospitalization. Here, we evaluate the impact of insulin and non-insulin therapy on glucose control in patients with type 2 diabetes admitted with COVID-19. This is a retrospective study including 359 COVID-19 patients with type 2 diabetes. Patients were divided into 2 groups according to diabetes treatment during hospitalization. The first group included patients treated with insulin only, and the second group patients treated with other antidiabetic agents with or without insulin. Average blood glucose was higher in the insulin-only treatment group (201 ± 66 mgdL vs 180 ± 71 mgdL, P .004), even after excluding mechanically ventilated patients (192 ± 69 vs 169 ± 59 mgdL, P .003). In patients with moderate severity of COVID-19, average blood glucose was also significantly higher in the insulin-only treated group (197 ± 76 vs 168 ± 51 mgdL, P .001). Most patients (80%) in the combination treatment group received metformin. Moderately affected COVID-19 patients with type 2 diabetes could safely be treated with antihyperglycemic medications with or without insulin.

Dietary Factors and All-Cause Mortality in Individuals With Type 2 Diabetes A Systematic Review and Meta-analysis of Prospective Observational Studies.

Type 2 diabetes is a major health concern associated with mortality. Diet may influence the progression of diabetes however, systematic reviews are lacking. This study systematically summarized the evidence on diet and all-cause mortality in individuals with type 2 diabetes. PubMed and Web of Science were searched until June 2022. Prospective observational studies investigating dietary factors in association with all-cause mortality in individuals with type 2 diabetes were selected. We identified 107 studies. Moderate certainty of evidence was found for inverse associations of higher intakes of fish (summary risk ratios per servingweek 0.95 95% CI 0.92, 0.99 n 6 studies), whole grain (per 20 gday 0.84 95% CI 0.71, 0.99 n 2), fiber (per 5 gday 0.86 95% CI 0.81, 0.91 n 3), and n-3 polyunsaturated fatty acids (per 0.1 gday 0.87 95% CI 0.82, 0.92 n 2) and mortality. There was low certainty of evidence for inverse associations of vegetable consumption (per 100 gday 0.88 95% CI 0.82, 0.94 n 2), plant protein (per 10 gday 0.91 95% CI 0.87, 0.96 n 3), and for positive associations of egg consumption (per 10 gday 1.05 95% CI 1.03, 1.08 n 7) and cholesterol intake (per 300 mgday 1.19 95% CI 1.13, 1.26 n 2). For other dietary factors, evidence was uncertain or no association was observed. Higher intake of fish, whole grain, fiber, and n-3 polyunsaturated fatty acids were inversely associated with all-cause mortality in individuals with type 2 diabetes. There is limited evidence for other dietary factors, and, thus, more research is needed.

The National Clinical Care Commission Report to Congress Leveraging Federal Policies and Programs for Population-Level Diabetes Prevention and Control Recommendations From the National Clinical Care Commission.

The etiology of type 2 diabetes is rooted in a myriad of factors and exposures at individual, community, and societal levels, many of which also affect the control of type 1 and type 2 diabetes. Not only do such factors impact risk and treatment at the time of diagnosis but they also can accumulate biologically from preconception, in utero, and across the life course. These factors include inadequate nutritional quality, poor access to physical activity resources, chronic stress (e.g., adverse childhood experiences, racism, and poverty), and exposures to environmental toxins. The National Clinical Care Commission (NCCC) concluded that the diabetes epidemic cannot be treated solely as a biomedical problem but must also be treated as a societal problem that requires an all-of-government approach. The NCCC determined that it is critical to design, leverage, and coordinate federal policies and programs to foster social and environmental conditions that facilitate the prevention and treatment of diabetes. This article reviews the rationale, scientific evidence base, and content of the NCCCs population-wide recommendations that address food systems consumption of water over sugar-sweetened beverages food and beverage labeling marketing and advertising workplace, ambient, and built environments and research. Recommendations relate to specific federal policies, programs, agencies, and departments, including the U.S. Department of Agriculture, the Food and Drug Administration, the Federal Trade Commission, the Department of Housing and Urban Development, the Environmental Protection Agency, and others. These population-level recommendations are transformative. By recommending health-in-all-policies and an equity-based approach to governance, the NCCC Report to Congress has the potential to contribute to meaningful change across the diabetes continuum and beyond. Adopting these recommendations could significantly reduce diabetes incidence, complications, costs, and inequities. Substantial political resolve will be needed to translate recommendations into policy. Engagement by diverse members of the diabetes stakeholder community will be critical to such efforts.

The National Clinical Care Commission Report to Congress Background, Methods, and Foundational Recommendations.

Since the first Federal Commission on Diabetes issued its report in 1975, the diabetes epidemic in the U.S. has accelerated, and efforts to translate advances in diabetes treatment into routine clinical practice have stalled. In 2021, the National Clinical Care Commission (NCCC) delivered a report to Congress that provided recommendations to leverage federal policies and programs to more effectively prevent and treat diabetes and its complications. In the five articles in this series, we present the NCCCs evidence-based recommendations to 1) reduce diabetes-related risks, prevent type 2 diabetes, and avert diabetes complications through changes in federal policies and programs affecting the general population 2) prevent type 2 diabetes in at-risk individuals through targeted lifestyle and medication interventions and 3) improve the treatment of diabetes and its complications to improve the health outcomes of people with diabetes. In this first article, we review the successes and limitations of previous federal efforts to combat diabetes. We then describe the establishment of and charge to the NCCC. We discuss the development of a hybrid conceptual model that guided the NCCCs novel all-of-government approach to address diabetes as both a societal and medical problem. We then review the procedures used by the NCCC to gather information from federal agencies, stakeholders, key informants, and the public and to conduct literature reviews. Finally, we review the NCCCs three foundational recommendations 1) improve the coordination of non-health-related and health-related federal agencies to address the social and environmental conditions that are accelerating the diabetes epidemic 2) ensure that all Americans at risk for and with diabetes have health insurance and access to health care and 3) ensure that all federal policies and programs promote health equity in diabetes.

The National Clinical Care Commission Report to Congress Recommendations to Better Leverage Federal Policies and Programs to Prevent and Control Diabetes.

The National Clinical Care Commission (NCCC) was established by Congress to make recommendations to leverage federal policies and programs to more effectively prevent and treat diabetes and its complications. The NCCC developed a guiding framework that incorporated elements of the Socioecological and Chronic Care Models. It surveyed federal agencies and conducted follow-up meetings with representatives from 10 health-related and 11 non-health-related federal agencies. It held 12 public meetings, solicited public comments, met with numerous interested parties and key informants, and performed comprehensive literature reviews. The final report, transmitted to Congress in January 2022, contained 39 specific recommendations, including 3 foundational recommendations that addressed the necessity of an all-of-government approach to diabetes, health equity, and access to health care. At the general population level, the NCCC recommended that the federal government adopt a health-in-all-policies approach so that the activities of non-health-related federal agencies that address agriculture, food, housing, transportation, commerce, and the environment be coordinated with those of health-related federal agencies to affirmatively address the social and environmental conditions that contribute to diabetes and its complications. For individuals at risk for type 2 diabetes, including those with prediabetes, the NCCC recommended that federal policies and programs be strengthened to increase awareness of prediabetes and the availability of, referral to, and insurance coverage for intensive lifestyle interventions for diabetes prevention and that data be assembled to seek approval of metformin for diabetes prevention. For people with diabetes and its complications, the NCCC recommended that barriers to proven effective treatments for diabetes and its complications be removed, the size and competence of the workforce to treat diabetes and its complications be increased, and new payment models be implemented to support access to lifesaving medications and proven effective treatments for diabetes and its complications. The NCCC also outlined an ambitious research agenda. The NCCC strongly encourages the public to support these recommendations and Congress to take swift action.

The National Clinical Care Commission Report to Congress Summary and Next Steps.

The U.S. is experiencing an epidemic of type 2 diabetes. Socioeconomically disadvantaged and certain racial and ethnic groups experience a disproportionate burden from diabetes and are subject to disparities in treatment and outcomes. The National Clinical Care Commission (NCCC) was charged with making recommendations to leverage federal policies and programs to more effectively prevent and control diabetes and its complications. The NCCC determined that diabetes cannot be addressed simply as a medical problem but must also be addressed as a societal problem requiring social, clinical, and public health policy solutions. As a result, the NCCCs recommendations address policies and programs of both non-health-related and health-related federal agencies. The NCCC report, submitted to the U.S. Congress on 6 January 2022, makes 39 specific recommendations, including three foundational recommendations that non-health-related and health-related federal agencies coordinate their activities to better address diabetes, that all federal agencies and departments ensure that health equity is a guiding principle for their policies and programs that impact diabetes, and that all Americans have access to comprehensive and affordable health care. Specific recommendations are also made to improve general population-wide policies and programs that impact diabetes risk and control, to increase awareness and prevention efforts among those at high risk for type 2 diabetes, and to remove barriers to access to effective treatments for diabetes and its complications. Finally, the NCCC recommends that an Office of National Diabetes Policy be established to coordinate the activities of health-related and non-health-related federal agencies to address diabetes prevention and treatment. The NCCC urges Congress and the Secretary of Health and Human Services to implement these recommendations to protect the health and well-being of the more than 130 million Americans at risk for and living with diabetes.

The National Clinical Care Commission Report to Congress Leveraging Federal Policies and Programs to Prevent Diabetes in People With Prediabetes.

Individuals with an elevated fasting glucose level, elevated glucose level after glucose challenge, or elevated hemoglobin A1c level below the diagnostic threshold for diabetes (collectively termed prediabetes) are at increased risk for type 2 diabetes. More than one-third of U.S. adults have prediabetes but fewer than one in five are aware of the diagnosis. Rigorous scientific research has demonstrated the efficacy of both intensive lifestyle interventions and metformin in delaying or preventing progression from prediabetes to type 2 diabetes. The National Clinical Care Commission (NCCC) was a federal advisory committee charged with evaluating and making recommendations to improve federal programs related to the prevention of diabetes and its complications. In this article, we describe the recommendations of an NCCC subcommittee that focused primarily on prevention of type 2 diabetes in people with prediabetes. These recommendations aim to improve current federal diabetes prevention activities by 1) increasing awareness of and diagnosis of prediabetes on a population basis 2) increasing the availability of, referral to, and insurance coverage for the National Diabetes Prevention Program and the Medicare Diabetes Prevention Program 3) facilitating Food and Drug Administration review and approval of metformin for diabetes prevention and 4) supporting research to enhance the effectiveness of diabetes prevention. Cognizant of the burden of type 1 diabetes, the recommendations also highlight the importance of research to advance our understanding of the etiology of and opportunities for prevention of type 1 diabetes.

Increased intestinal-fatty acid binding protein in obesity-associated type 2 diabetes mellitus.

Obesity is a traditional risk factor for type 2 diabetes mellitus (T2DM). However, recent studies reported that metabolically unhealthy obesity (MUO) exerts a higher risk of developing T2DM than metabolically healthy obesity (MHO) because of its higher state of insulin resistance. This may happen due to metabolic endotoxemia through gut dysbiosis and increased intestinal permeability. Our study aimed to know the association of intestinal permeability using intestinal fatty acid-binding protein (I-FABP) with obesity-related T2DM patients in Indonesia. This was a cross-sectional study that recruited 63 participants with obesity defined using body mass index (BMI) classification for the Asia-Pacific population (BMI ≥25 kgm2). All participants were then grouped into T2DM and non-T2DM based on American Diabetes Association (ADA) diagnostic criteria. The I-FABP levels were measured using the enzyme-linked immunosorbent assay method. The I-FABP level of T2DM group was higher compared to non-T2DM group, namely 2.82 (1.23) ngmL vs. 1.78 (0.81) ngmL (p<0.001 mean difference 1.033 with 95% CI 0.51-1.55). This difference was not attenuated even after adjustment for age. The fitted regression model using linear regression was i-FABP 1.7871.034(DM) (R2 18.20%, standardized ß 0.442, p<0.001). This study underscores the association of intestinal permeability with T2DM in people with obesity and supports the evidence of the potential role of intestinal permeability in the pathogenesis of obesity-related T2DM.

Risk of fracture in adults with type 2 diabetes in Sweden A national cohort study.

Type 2 diabetes mellitus (T2DM) is considered a risk factor for fracture but the evidence regarding the impact of T2DM on fracture risk is conflicting. The objective of the study was to determine if patients with T2DM have increased fracture risk and if T2DM-related risk factors could be identified. In this national cohort study in Sweden, we investigated the risk of fracture in 580,127 T2DM patients, identified through the national diabetes register including from both primary care and hospitals, and an equal number of population-based controls without diabetes matched for age, sex, and county from 2007 to 2017. The mean age at entry was 66.7 years and 43.6% were women. During a median follow-up time of 6.6 (interquartile range (IQR) 3.1 to 9.8) years, patients with T2DM had a marginally but significantly increased risk of major osteoporotic fracture (MOF) (hazard ratio (HR) 1.01 (95% confidence interval CI 1.00 to 1.03)) and hip fracture (HR 1.06 (95% CI 1.04 to 1.08)) compared to controls, associations that were only minimally affected (HR 1.05 (95% CI 1.03 to 1.06) and HR 1.11 (95% CI 1.09 to 1.14), respectively) by multivariable adjustment (age, sex, marital status, and an additional 20 variables related to general morbidity, cardiovascular status, risk of falls, and fracture). In a multivariable-adjusted Cox model, the proportion of the risk for all fracture outcomes (Hellers R2) explained by T2DM was below 0.1%. Among the T2DM patients, important risk factors for fracture were a low BMI (<25 kgm2), long diabetes duration (≥15 years), insulin treatment, and low physical activity. In total, 55% of the T2DM patients had none of these risk factors and a significantly lower fracture risk than their respective controls. The relatively short mean duration of T2DM and lack of bone density data, constitute limitations of the analysis. In this study, we observed only a marginally increased fracture risk in T2DM, a condition that explained less than 0.1% of the fracture risk. Consideration of the herein identified T2DM-related risk factors could be used to stratify T2DM patients according to fracture risk.

Improvements in Glycemic Control and Depressive Symptoms Among Adults With Type 2 Diabetes Retrospective Study.

The prevalence of diabetes remains high, with traditional lifestyle interventions demonstrating limited success in improving diabetes-related outcomes, particularly among individuals with diabetes-related mental health comorbidities. Digital health interventions provide the ability to ease the sustained and rigorous self-management needs associated with diabetes care and treatment. Current interventions though, are plagued by small sample sizes, underpowered pilot studies, and immense heterogeneity in program intervention, duration, and measured outcomes. Therefore, this work aimed to evaluate the effectiveness of a mobile health diabetes management program on measures of glycemic control in a high-risk population with type 2 diabetes (hemoglobin A1c HbA1c ≥8.0%), utilizing a sample of 1128 participants who provided baseline and follow-up data. The sustainability of this change in glycemic control was examined in a subset of participants (n455) at 6 months and 1 year following program enrollment. A secondary analysis examined changes in glycemic control among a subset of participants with self-reported mild-to-moderate depression at baseline. This study utilized a single-arm, retrospective design. Participants were enrolled in the Vida Health Diabetes Management Program. This app-based intervention utilized one-on-one remote sessions with a health coach, registered dietitian nutritionist, andor a certified diabetes care and education specialist and structured lessons and tools related to diabetes management and self-care. Participants provided baseline (-365 to 21 days of program enrollment) as well as follow-up (at least 90 days following program enrollment) HbA1c values. Paired t tests were used to evaluate changes in HbA1c between baseline and follow-up time points. The 8-item Patient Health Questionnaire and the 7-item Generalized Anxiety Disorder Scale were utilized to assess self-reported depressive and anxiety symptoms, respectively. Paired t tests and linear regression modeling accounting for pertinent covariates were used to evaluate changes in mental health symptom acuity and their relationship with changes in glycemic control. We observed a significant decrease in HbA1c of -1.35 points between baseline (mean 9.84, SD 1.64) and follow-up (mean 8.48, SD 1.77 t22.56, P<.001) among this large, high-risk sample. This decrease was sustained up to 1 year following program enrollment. Additionally, a significant relationship between improvements in depressive symptom acuity and improvements in HbA1c was observed (β-0.74, P.03). This study demonstrates clinically meaningful improvements in glycemic control among participants enrolled in the Vida Health Diabetes Management Program. Additionally, this work presents one of the largest studied samples of participants enrolled in a digital health diabetes management program to date.

Prevalence of Undiagnosed Diabetes Identified by a Novel Electronic Medical Record Diabetes Screening Program in an Urban Emergency Department in the US.

This cross-sectional study describes a screening program that was developed to screen for type 2 diabetes in an urban emergency department setting in the US.

Adherence to a Healthy Lifestyle in Association With Microvascular Complications Among Adults With Type 2 Diabetes.

The association between an overall healthy lifestyle and the subsequent risk of microvascular complications among patients with diabetes remains unclear. To examine the association between adherence to a healthy lifestyle before and after diabetes diagnosis and the risk of subsequent microvascular complications among adults with diabetes. This prospective cohort study included incident patients with type 2 diabetes who were free of cardiovascular disease and cancer at the time of diabetes diagnosis and completed the diabetes supplementary questionnaires in the Nurses Health Study (in 2000 and 2005) and the Health Professionals Follow-Up Study (in 2000, 2004, and 2008) in the US. Data were analyzed from April to August 2021. Diet and lifestyle factors before and after diabetes diagnosis were assessed by validated questionnaires. A healthy lifestyle consisted of nonsmoking, having a healthy body weight (a body mass index of ≥18.5 or <25), engaging in moderate-to-vigorous physical activity (≥150 minutes per week), consuming a high-quality diet (top 40th percentile of the Alternative Healthy Eating Index), and moderate alcohol drinking (5-15 gd for women and 5-30 gd for men). Physician-diagnosed microvascular complications including diabetic neuropathy, retinopathy, nephropathy, and foot disorders were self-reported at questionnaire surveys. A total of 7077 patients with type 2 diabetes were included in the cohort (4982 women in NHS and 2095 men in HPFS, mean SD age 61 8.8, 94.2% White). During follow-up, 2878 patients developed microvascular complications. After multivariable adjustment, adherence to a healthy lifestyle before and after diabetes diagnosis were both associated with a lower risk of developing microvascular complications. The relative risk (RR) for participants with 4 or more low-risk lifestyle factors before diabetes diagnosis compared with zero was 0.73 (95% CI, 0.60-0.91) for any microvascular complications, 0.71 (95% CI, 0.54-0.93) for diabetic neuropathy, 0.76 (95% CI, 0.57-1.01) for diabetic retinopathy, 0.42 (95% CI, 0.23-0.79) for diabetic nephropathy, and 0.60 (95% CI, 0.35-1.00) for diabetic foot disorders. Similar results were observed for adherence to a healthy lifestyle after diabetes diagnosis, with an RR of 0.68 (95% CI, 0.55-0.83) for any microvascular complications, 0.67 (95% CI, 0.51-0.88) for diabetic neuropathy, 0.65 (95% CI, 0.48-0.86) for diabetic retinopathy, 0.57 (95% CI, 0.34-0.98) for diabetic nephropathy, and 0.62 (95% CI, 0.37-1.05) for diabetic foot disorders. In addition, greater improvement in lifestyle factors from before to after diabetes diagnosis was also significantly associated with a lower risk of neuropathy or total microvascular complications. Each increment in number of low-risk lifestyle factors was associated with a 6% (RR, 0.94 95% CI, 0.90-0.98) lower risk for any microvascular complications and a 9% (RR, 0.91 95% CI, 0.86-0.96) lower risk for diabetic neuropathy. Consistent results were observed when analyses were stratified by age at diabetes diagnosis, sexcohort, or lifestyle factors before diabetes diagnosis. In this cohort study, adhering to an overall healthy lifestyle was associated with a significantly lower risk of microvascular complications among individuals with diabetes. These findings suggest substantial reduction in the burden of microvascular complications associated with adopting a healthy lifestyle among patients with type 2 diabetes.

Surgical decisions in the setting of zonulopathy.

An 85-year-old man with a history of type 2 diabetes, pseudoexfoliation (PXF) in both eyes, and tamsulosin use was referred for the evaluation of a dense cataract in the right eye and a subluxated intraocular lens (IOL) in the left eye. Unfortunately, his surgery in the left eye was complicated by diffuse zonulopathy. The referring surgeon placed a 3-piece IOL in the sulcus. However, the passively fixated 3-piece IOL moved inferiorly causing monocular diplopia for over a year. Because the patient was pleased with the IOL immediately postoperatively, a refixation procedure was performed in the form of sulcus placement with iris suture fixation in the left eye. Fortunately, the iris-fixated IOL in the left eye has remained well centered and stable without cystoid macular edema (CME) or chronic inflammation for over 8 months. The patient is on no ocular medications and has no family history of glaucoma. He now needs cataract surgery in the right eye and is extremely apprehensive because of his difficult course in the left eye. The corrected distance visual acuity is 2070 in the right eye and 2025 in the left eye. Intraocular pressures (IOPs) measure 20 mm Hg in the right eye and 14 mm Hg in the left eye by Goldmann tonometry. Pachymetry is 536 µm in the right eye and 543 µm in the left eye. Pupils are round with minimal reactivity and without a relative afferent pupillary defect. Extraocular motility is normal in both eyes, and confrontation visual fields is full in both eyes. Gonioscopy reveals an angle open to the pigmented trabecular meshwork (PTM) in the right eye and the ciliary body in the left eye with 1 PTM and without peripheral anterior synechia in both eyes. The retinal nerve fiber layer and macular optical coherence tomography are normal in both eyes. On slitlamp examination, pertinent findings include pseudoexfoliative changes at the pupillary margin with poor dilation of 3.5 mm in both eyes the anterior chamber (AC) is shallow but adequate in the right eye and deep and quiet with rare pigmented cells in the left eye. There is a 5 nuclear sclerotic cataract with pseudoexfoliative changes on the anterior capsule and no obvious phacodonesis in the right eye and a 3-piece posterior chamber IOL in the sulcus fixated to the iris with 10-0 polypropylene sutures at 6 and 12 oclock without pseudophacodonesis in the left eye. Dilated fundus examination reveals a cup-to-disc ratio of 0.4 with healthy neuroretinal rims in both eyes, posterior vitreous detachments in both eyes, and no evidence of diabetic retinopathy in both eyes. All other findings are unremarkable. How would you counsel this patient regarding his risk factors for surgery in the right eye What surgical maneuvers would you use to remove the cataract safely How would you stabilize the IOL if the capsule bag becomes compromised due to zonulopathy

Sleep Medication Use in Adults Aged 18 and Over United States, 2020.

Sleep medications are a common treatment option for insomnia (1). Insufficient sleep is associated with many negative mental and physical health outcomes, including type 2 diabetes, heart disease, obesity, depression, and an increased risk of injury (2). The prevalence of sleep difficulties and use of sleep medication has differed between men and women (3-5). This report uses 2020 National Health Interview Survey (NHIS) data to describe the percentage of men and women who used medication for sleep, defined here as taking any medication to help fall or stay asleep most days or every day in the past 30 days, by selected sociodemographic characteristics.

Diabetes-Related Quality of Life Learning From Individuals Making Lifestyle Changes to Improve Type 2 Diabetes Control.

The purpose of this study was to explore how treatment adherence and lifestyle changes required for glycemic control in type 2 diabetes (T2D) are related to quality of life (QoL) among predominantly ethnic minority and socioeconomically disadvantaged adults engaged in making changes to improve T2D self-management. Adults with T2D in New York City were recruited for the parent study based on recent A1C (≥7.5%) and randomly assigned to 1 of 2 arms, receiving educational materials and additional self-management support calls, respectively. Substudy participants were recruited from both arms after study completion. Participants (N 50 62% Spanish speaking) were interviewed by phone using a semistructured guide and were asked to define QoL and share ways that T2D, treatment, self-management, and study participation influenced their QoL. Interviews were analyzed using thematic analysis. QoL was described as a multidimensional health-related construct with detracting and enhancing factors related to T2D. Detracting factors included financial strain, symptom progression and burden, perceived necessity to change cultural and lifestyle traditions, and dietary and medical limitations. Enhancing factors included social support, diabetes education, health behavior change, sociocultural connection. QoL for diverse and socioeconomically disadvantaged adults with T2D is multifaceted and includes aspects of health, independence, social support, culture, and lifestyle, which may not be captured by existing QoL measures. Findings may inform the development of a novel QoL measure for T2D.

Sex differences in the complications, care and clinical outcomes of patients with type 2 diabetes in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL).

To examine sex differences in the characteristics and outcomes in participants with type 2 diabetes (T2D), with or without cardiovascular disease (CVD), randomized to once-weekly exenatide (EQW) or placebo in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL). Baseline characteristics were summarized and compared by sex. Cox proportional hazards regression models were used for clinical outcomes, including the primary composite outcome of cardiovascular (CV) death, non-fatal myocardial infarction or non-fatal stroke (MACE3). Models including sex-by-treatment interaction were used to evaluate differences in effects of EQW. Overall, 5603 women and 9149 men were followed for a median of 3.2 years. Women were younger (mean 61.4 vs. 62.2 years, P < .001) and had a shorter duration of diabetes (mean 12.9 vs. 13.2 years, P .039) and less coronary artery disease (35.2% vs. 61.0%, P < .001) than men, but also a less favourable metabolic risk profile and lower use of cardioprotective medications. MACE3 occurred in 9.1% of women and 13.5% of men, corresponding to 2.82 versus 4.40 events100 participant-years (adjusted hazard ratio 0.80, 95% CI 0.70-0.93, P .003). There was no difference in MACE3 with EQW compared with placebo, or evidence of heterogeneity of treatment effect by sex. This analysis of a large population of individuals with T2D, with or without established CVD, identified between-sex differences in clinical characteristics and care. Despite having worse management of CV risk factors, women had significantly lower rates of important CV events not attributable to the effects of study treatment.

Safety and tolerability of semaglutide across the SUSTAIN and PIONEER phase IIIa clinical trial programmes.

Glucagon-like peptide-1 receptor agonists improve glycaemic control some are now available as oral and subcutaneous formulations, and some have indications for reducing cardiovascular risk. The expanded scope for these therapies warrants comprehensive safety evaluations. We report the safetytolerability of subcutaneous and oral semaglutide from the SUSTAIN and PIONEER clinical trial programmes, respectively. Adverse events (AEs) from 16 randomized placebo- or active-controlled phase IIIa trials in patients with type 2 diabetes (n11,159) including once-weekly subcutaneous semaglutide (n3150 SUSTAIN trials) or once-daily oral semaglutide (n4116 PIONEER trials) were analysed. Data pools were analysed for each programme, with separate analyses of cardiovascular outcomes trials (CVOTs n6480). In the phase IIIa pools, gastrointestinal disorders were reported in 41.9%39.1% of patients with subcutaneousoral semaglutide, respectively (most prevalent during initiationescalation) versus 22.0%24.8% with comparators. Rates of kidney disorders, acute pancreatitis, malignant neoplasms, hypoglycaemia, diabetic retinopathy, heart failure and other cardiovascular events were similar for semaglutide versus comparators. Cholelithiasis incidence was higher with subcutaneous and oral semaglutide versus placebo. Diabetic retinopathy incidence was higher with subcutaneous semaglutide versus placebo in SUSTAIN 6. Small pulse rate increases occurred with both formulations there was no increased rate of arrhythmias. Fatal AE incidence was similar between semaglutide and comparators. Versus placebo, CVOTs demonstrated reduced risk of major adverse cardiovascular events with subcutaneous semaglutide and non-inferiority criteria were met with oral semaglutide. The most common AEs with semaglutide were gastrointestinal disorders, which decreased with continued therapy. These comprehensive safetytolerability data may better inform patient selection and guidance in care. This article is protected by copyright. All rights reserved.

Incident and recurrent hypoglycaemia with linagliptin and glimepiride over a median of 6 years in the CAROLINA cardiovascular outcome trial.

The CAROLINA trial established non-inferiority of linagliptin versus glimepiride for major adverse cardiovascular events in patients with relatively early type 2 diabetes at increased cardiovascular risk. In pre-specified and post-hoc analyses, we investigated treatment effects on total hypoglycaemic burden in CAROLINA. Patients were randomized and treated with 5 mg linagliptin (n 3014) or 1-4 mg glimepiride (n 3000) once daily added to standard care. Hypoglycaemia captured from investigator-reported adverse events was analysed with Poisson and negative binomial regressions for the first and total (first plus recurrent) events, respectively. The influence of insulin initiation and glycated haemoglobin (HbA1c) change on the treatment effect for hypoglycaemia was also explored. Over 6.3 years median follow-up, average HbA1c over time did not differ between linagliptin versus glimepiride (weighted mean difference 95% confidence interval 0.00%, -0.05, 0.05), nor did insulin initiation (18.6% vs. 19.2% of patients, respectively), whereas body weight was lower with linagliptin (-1.54 kg, -1.80, -1.28). Hypoglycaemia frequency was lower with linagliptin across all hypoglycaemia categories, including severe episodes. Rate ratios (95% confidence interval) for first and total events for investigator-reported hypoglycaemia were 0.21 (0.19-0.24) and 0.12 (0.10-0.14), respectively, with 8.7 first and 60.8 total estimated events prevented100 patient-years with linagliptin versus glimepiride. These differences occurred during night-time and daytime, and in subgroup analyses of total events. Treatment differences in hypoglycaemia were neither impacted by HbA1c changes nor insulin initiation. Across the severity spectrum, linagliptin substantially reduced the hypoglycaemic burden versus glimepiride in patients with relatively early type 2 diabetes at increased cardiovascular risk.

Long-term impact of weight loss for people with overweight but not obesity, and with type 2 diabetes 10-year outcomes of a randomized trial of gastric band surgery.

Randomized trials reporting 5-year outcomes have shown bariatric surgery to induce diabetes remission and improve cardiovascular risk. However, the longer-term effects of surgery are uncertain, with only one randomized trial reporting 10-year diabetes outcomes in people with obesity. We aimed to compare 10-year diabetes outcomes of people who are overweight but not obese, randomly assigned to receive either multidisciplinary diabetes care, or multidisciplinary diabetes care combined with gastric band (GB) surgery. Between 2009 and 2011, 51 adults were randomized. After 5 years, they were discharged to receive community care and reassessed after 10 years. The primary outcome was diabetes remission, defined as glycated haemoglobin (HbA1c) <6.5% (48 mmolmol) without glucose-lowering medication. Forty-one participants (20 medical and 21 GB) completed the 10-year assessment. The median (Q1, Q3) weight loss in the GB group was 9.8 (6.7, 16.3)% at 10 years compared with 5.6 (3.4, 7.6)% in the medical group (median difference 4.2% p .008). Diabetes remission occurred in five GB participants and no medical participants (relative risk 0.76, 95% CI 0.55-0.93, p .048). GB participants used fewer glucose-lowering medications at 10 years but HbA1c, fasting glucose, calculated cardiovascular risk, quality-of-life and incident diabetes complications did not differ significantly between the groups. When compared with medical care, GB surgery achieved greater weight loss and modestly increased the likelihood of diabetes remission. However, it did not improve HbA1c, cardiovascular risk or quality of life.

Cardiovascular outcomes trial data from EMPA-REG OUTCOME, CAROLINA, and CARMELINA assessment of a novel staging system for type 2 diabetes.

The Diabetes Staging System (DSS), a novel disease staging system similar to those used in oncology and designed to improve physicianpatient communication and diabetes management, was applied to three large type 2 diabetes (T2D) cardiovascular (CV) outcome trials to assess if increasing DSS stage was associated with higher rates of all-cause mortality (ACM) andor CV death. DSS uses discrete CV events (none to ≥3 stage 1 to 4), end-stage kidney disease (stage 5) and microvascular complications (none to 3 A to D) to determine disease stage in individuals with T2D. The DSS stage for patients from CAROLINA, EMPA-REG OUTCOME, and CARMELINA trials was determined. Incidence rates for ACMCV death were calculated across DSS stages and Cox regression analyses performed. Risk for ACM or CV death increased with increasing DSS stage 1 to 5 (p for trend <0.0001) in all trials. In CAROLINA, risk for ACM and CV death increased with increasing number of microvascular complications (A to D) (both p for trend <0.0001), similar in CARMELINA (p for trend 0.0020 and 0.0005, respectively). In EMPA-REG OUTCOME, having all three microvascular complications (stage D) versus none increased risk for ACM and CV death (p0.0015 and 0.0010, respectively). Applying the DSS across T2D clinical trial populations with different CV risk revealed significantly increased risk for ACM and CV death with higher DSS stage. The DSS may benefit from assessment in other T2D populations and with evaluation of the impact of additional outcomes, such as heart failure. This article is protected by copyright. All rights reserved.

Meta-analysis of head-to-head clinical trials comparing incretin-based glucose-lowering medications and basal insulin An update including recently developed glucagon-like peptide-1 (GLP-1) receptor agonists and the glucose-dependent insulinotropic polypeptideGLP-1 receptor co-agonist tirzepatide.

To assess comparative efficacy, safety and tolerability of injectable incretin-based glucose-lowering medications (IBGLMs) versus basal insulin treatment in patients with type 2 diabetes. We performed an updated meta-analysis of randomized clinical trials of head-to-head comparisons of IBGLMs (short- and long-acting glucagon-like peptide-1 GLP-1 receptor agonists GLP-1RAs and glucose-dependent insulinotropic polypeptide GIPGLP-1 receptor co-agonist tirzepatide) versus basal insulin using a PubMed database search (April 2022). The primary endpoint was difference in reduction of glycated haemoglobin (HbA In all, 20 studies, representing 47 study arms and 11 843 patients, were eligible. Compared with basal insulin, IGBLMs lowered HbA Recently introduced, highly effective IBGLMs were superior to basal insulin treatment, reinforcing the recommendation that IBGLMs should be considered as the first injectable treatment for most patients with type 2 diabetes.

The Effect of the Interaction between Abnormal Body Mass Index and Hypertension on the Risk of Type 2 Diabetes.

Many patients with type 2 diabetes have an abnormal body mass index (BMI) and hypertension together, but few studies on the interaction of the two on the risk of T2DM are reported. We aim to explore the effect of the interaction between abnormal BMI and hypertension on the risk of type 2 diabetes mellitus (T2DM) in Uyghur residents. Based on the physical examination data of 27,4819 Uygur residents in Moyu County, a logistic regression model was used to analyze the correlation between BMI abnormality, hypertension, and T2DM disease, and then, the effect of their interaction on the risk of T2DM was evaluated by an additive model and a multiplicative model. The results showed that the detectable rate of T2DM was 5.58%, the proportion of abnormal BMI was 59.49%, and the proportion of hypertension was 25.14%. The risk of T2DM in people with an abnormal BMI and hypertension was higher than that in people with a normal weight and without hypertension, and the difference was statistically significant ( The interaction between abnormal BMI and hypertension can increase the risk of T2DM, and improving BMI and controlling blood pressure within the normal range can effectively reduce the risk of T2DM.

Application and trend of bioluminescence imaging in metabolic syndrome research.

Bioluminescence imaging is a non-invasive technology used to visualize physiological processes in animals and is useful for studying the dynamics of metabolic syndrome. Metabolic syndrome is a broad spectrum of diseases which are rapidly increasing in prevalence, and is closely associated with obesity, type 2 diabetes, nonalcoholic fatty liver disease, and circadian rhythm disorder. To better serve metabolic syndrome research, researchers have established a variety of animal models expressing luciferase, while also committing to finding more suitable luciferase promoters and developing more efficient luciferase-luciferin systems. In this review, we systematically summarize the applications of different models for bioluminescence imaging in the study of metabolic syndrome.

Evaluation of altered brain activity in type 2 diabetes using various indices of brain function A resting-state functional magnetic resonance imaging study.

Type 2 diabetes mellitus (T2DM) has been identified as a risk factor that increases the rate of cognitive decline. Previous studies showed that patients with T2DM had brain function alterations based on a single index of resting-state functional magnetic resonance imaging (rs-fMRI). The present study aimed to explore spontaneous brain activity in patients with T2DM by comparing various rs-fMRI indices, and to determine the relationship between these changes and cognitive dysfunction. A total of 52 patients with T2DM and age- and sex-matched control participants were included in this study. The amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and voxel-mirrored homotopic connectivity (VMHC) values were calculated to represent the status of spontaneous neural activity. The Montreal Cognitive Assessment (MoCA) was used for the rapid evaluation of cognition in all subjects. Pearson correlation and mediation analyses were conducted to investigate the relationship between rs-fMRI indices and clinical parameters such as fasting glucose, disease duration, and MoCA. Patients with T2DM had alterations of concordant spontaneous brain activity in brain areas including the bilateral cerebellum posterior lobe, the left inferior temporal gyrus (ITG.L), the parahippocampal gyrus, and the left supplementary motor area (SMA.L). The indices were significantly correlated to each other in most of the detected brain areas. Positive correlations were observed between fasting glucose and neural activity in the surrounding areas of the left insula and the inferior frontal gyrus. MoCA scores were negatively correlated with the ReHo values extracted from the left anterior occipital lobe and the superior cerebellar cortex and were positively correlated with VMHC values extracted from the left caudate and the precentral gyrus (PreCG). No significant mediation effect of abnormal brain activity was found in the relationship between clinical parameters and MoCA scores. The current study demonstrated the functional concordance of abnormal brain activities in patients with T2DM by comparing ALFF, ReHo, and VMHC measurements. Widespread abnormalities mainly involved in motor and sensory processing functions may provide insight into examining T2DM-related neurological pathophysiology.

Relation Between HbA1c and Lipid Profile Among Prediabetics, Diabetics, and Non-diabetics A Hospital-Based Cross-Sectional Analysis.

An unusually high blood glucose level is a hallmark of diabetes mellitus, with an imbalance between insulin levels and insulin sensitivity leading to an insulin functional deficit. Since it serves as both a risk indicator and a gauge of long-term glycemic control, the HbA1c concentration is a crucial component of standard diabetes treatment. The use of the HbA1c concentration in the diagnosis of diabetes is expanding as the tests accuracy increases. Dyslipidemic profiles can appear before type 2 diabetes manifests itself and are independent risk factors for the disease. Additionally, dyslipidemia, especially in diabetics, might affect pancreatic beta-cell survival and activity. This study was undertaken with the aim to find out any correlation between HbA1c and lipid profile among diabetics, prediabetics, and non-diabetics. A total of 1,000 individuals with age 18-60 years were included in the study (non-diabetics 186, prediabetics 238, diabetics 576). HbA1c was estimated by capillary electrophoresis and a lipid profile was done using a fully automatic chemistry analyzer. Diabetes was found to be significantly associated with dyslipidemia. In diabetics, a statistically significant increase in the level of triglyceride and very low-density lipoprotein (VLDL) was seen as compared to prediabetics. Diabetic women were found to be significantly more dyslipidemic as compared to diabetic males. The mean HbA1c among diabetics was found to be 8.3. In hyperglycemia-induced dyslipidemia, raised triglyceride and VLDL were the most common findings, and combined lipid abnormalities were more commonly seen as compared to a single abnormality in the lipid profile. Patients with poor glycemic control more commonly develop dyslipidemia, which may be a reason for an increased incidence of cardiovascular catastrophes in such patients.

Extracellular vesicles regulate the transmission of insulin resistance and redefine noncommunicable diseases.

Noncommunicable diseases (NCDs), such as diabetes and related neurological disorders, are considered to not be directly transmissible from one person to another. However, NCDs may be transmissible

Effects of electroacupuncture on bladder dysfunction and the expression of PACAP38 in a diabetic rat model.

Changes in the structure, perfusion, and function of the hippocampus in type 2 diabetes mellitus.

This study aims to explore the changes in the structure, perfusion, and function of the bilateral hippocampus in type 2 diabetes mellitus (T2DM) applying multimodal MRI methods, hoping to provide reliable neuroimaging evidence for the diagnosis of hippocampus-related brain injury in T2DM. We recruited 30 T2DM patients and 45 healthy controls (HCs), on which we performed 3D T1-weighted images, resting-state functional MRI (rs-fMRI), arterial spin labeling (ASL) sequences, and a series of cognitive tests. Then, we compared the differences of two groups in the cerebral blood flow (CBF) value, amplitude of low-frequency fluctuation (ALFF) value, fractional ALFF (fALFF) value, coherence-based regional homogeneity (Cohe-ReHo) value, and degree centrality (DC) values of the bilateral hippocampus. In the T2DM group, the bilateral hippocampal volumes and the CBF value of the right hippocampus were lower than those in the HCs, while the ALFF value, fALFF value, and Cohe-ReHo value of the bilateral hippocampus were higher than those in the HCs. Correlation analysis showed that fasting blood glucose (FBG) was negatively correlated with the residuals of left hippocampal volume ( This study indicated that the volume and perfusion of the hippocampus are decreased in T2DM patients that related to chronic hyperglycemia. Local spontaneous neural activity and coordination are increased in the hippocampus of T2DM patients, possibly as an adaptive compensation for cognitive decline.

The association between a genetic variant in the

Clearance of triglyceride-rich lipoproteins (TRLs) is mediated by several receptors, including heparan sulfate proteoglycans (HSPGs). Sulfate glucosamine-6-O-endosulfatase-2 is a gene related to the regulation of HSPG. A variant in this gene, rs2281279, has been shown to be associated with triglycerides and insulin resistance. To determine the relationship between rs2281279, metabolic parameters and vascular events, and type 2 diabetes mellitus (T2DM) in patients at high cardiovascular risk and whether Patients ( There was no relationship between imputed rs2281279 genotype and triglycerides, non-high-density lipoprotein (HDL)-cholesterol, insulin and quantitative insulin sensitivity check index. During a median follow-up of 11.8 (IQR, 9.3-15.5) years, 1026 cardiovascular events and 320 limb events occurred. The presence of the G allele in rs2281279 did not affect the risk of vascular events hazard ratio (HR), 1.03 95% confidence interval (CI), 0.94-1.14 or limb events (HR, 0.92 95% CI, 0.77-1.10). The presence of the G allele in rs2281279 did not affect the risk of T2DM (HR, 1.09 95% CI, 0.94-1.27). The presence of the minor G allele of rs2281279 was associated with a beneficial risk profile in ε2ε2 patients, but not in ε3ε3 patients. Imputed rs2281279 genotype is not associated with metabolic parameters and does not increase the risk of vascular events or T2DM in patients at high risk for cardiovascular disease.

THE INCREASED PLASMA LEVELS OF INTERMEDIN IN PATIENTS WITH TYPE 2 DIABETES MELLITUS.

Intermedin (IMD) is the member of calcitonin gene-related peptide family, and tightly associated with type 2 diabetes mellitus (T2DM). The change of plasma IMD levels in T2DM is still unknown. We aimed to investigate the plasma levels of IMD in patients with T2DM. Fortyone patients with T2DM who were hospitalized in the endocrinology department of Civil Aviation General Hospital from January 2012 to June 2015 were enrolled, and 44 volunteers were selected as the control group. Plasma level of IMD was detected by ELISA. Diagnostic value of IMD was analyzed by area under the receiver operating characteristic (ROC) curve (AUC). The plasma level of IMD in T2DM group was higher than that in the healthy control group, whereas smoking or cardiovascular complications did no influence the IMD levels. IMD levels were correlated with BMI, DBP, triglyceride, uric acid, urea nitrogen, fasting and 2 hours postprandial blood glucose, and HbA1C. The greatest value of AUC for IMD was only 58.73%. Although plasma levels of IMD were increased in patients with T2DM, the very low diagnostic value of IMD for T2DM might not be used for the disease diagnosis.

Do patients with type 2 diabetes have impaired hip bone microstructure A study using 3D modeling of hip dual-energy X-ray absorptiometry.

Patients with type 2 diabetes (T2DM) have more risk of bone fractures. However, areal bone mineral density (aBMD) by conventional dual-energy x-ray absorptiometry (DXA) is not useful for identifying this risk. This study aims to evaluate 3D-DXA parameters determining the cortical and trabecular compartments in patients with T2DM compared to non-diabetic subjects and to identify their determinants. Case-control study in 111 T2DM patients (65.4 ± 7.6 years old) and 134 non-diabetic controls (64.7 ± 8.6-year-old). DXA, 3D-DXA modelling Mean-adjusted values showed higher aBMD (5.4%-7.7%, ES 0.33-0.53) and 3D-DXA parameters (4.1%-10.3%, ES 0.42-0.68) in the T2DM group compared with the control group. However, TBS was lower in the T2DM group compared to the control group (-14.7%, ES 1.18). In addition, sex (β 0.272 to 0.316) and body mass index (BMI) (β 0.236 to 0.455) were the most consistent and positive predictors of aBMD (p ≤ 0.01). BMI and P1NP were negative predictors of TBS (β -0.530 and -0.254, respectively, p ≤ 0.01), while CTX was a positive one (β 0.226, p0.02). Finally, BMI was consistently the strongest positive predictor of 3D-DXA parameters (β 0.240 to 0.442, p<0.05). Patients with T2DM present higher bone mass measured both by conventional DXA and 3D-DXA, suggesting that 3D-DXA technology is not capable of identifying alterations in bone structure in this population. Moreover, BMI was the most consistent determinant in all bone outcomes.

Stratified glucose-lowering response to vildagliptin and pioglitazone by obesity and hypertriglyceridemia in a randomized crossover trial.

Understanding which group of patients with type 2 diabetes will have the most glucose lowering response to certain medications (which target different aspects of glucose metabolism) is the first step in precision medicine. We hypothesized that people with type 2 diabetes who generally have high insulin resistance, such as people of MāoriPacific ethnicity, and those with obesity andor hypertriglyceridemia (OHTG), would have greater glucose-lowering by pioglitazone (an insulin sensitizer) versus vildagliptin (an insulin secretagogue). A randomised, open-label, two-period crossover trial was conducted in New Zealand. Adults with type 2 diabetes, HbA1c>58mmolmol (>7.5%), received 16 weeks of either pioglitazone (30mg) or vildagliptin (50mg) daily, then switched to the other medication over for another 16 weeks of treatment. Differences in HbA1c were tested for interaction with ethnicity or OHTG, controlling for baseline HbA1c using linear mixed models. Secondary outcomes included weight, blood pressure, side-effects and diabetes treatment satisfaction. 346 participants were randomised (55% MāoriPacific) between February 2019 to March 2020. HbA1c after pioglitazone was lower than after vildagliptin (mean difference -4.9mmolmol 0.5% 95% CI -6.3, -3.5 p<0.0001). Primary intention-to-treat analysis showed no significant interaction effect by MāoriPacific vs other ethnicity (1.5mmolmol 0.1%, 95% CI -0.8, 3.7), and per-protocol analysis (-1.2mmolmol 0.1%, 95% CI -4.1, 1.7). An interaction effect (-4.7mmolmol 0.5%, 95% CI -8.1, -1.4) was found by OHTG status. Both treatments generated similar treatment satisfaction scores, although there was greater weight gain and greater improvement in lipids and liver enzymes after pioglitazone than vildagliptin. Comparative glucose-lowering by pioglitazone and vildagliptin is not different between MāoriPacific people compared with other New Zealand ethnic groups. Presence of OHTG predicts greater glucose lowering by pioglitazone than vildagliptin. www.anzctr.org.au, identifier (ACTRN12618001907235).

Exploring novel targets of sitagliptin for type 2 diabetes mellitus Network pharmacology, molecular docking, molecular dynamics simulation, and SPR approaches.

Diabetes has become a serious global public health problem. With the increasing prevalence of type 2 diabetes mellitus (T2DM), the incidence of complications of T2DM is also on the rise. Sitagliptin, as a targeted drug of DPP4, has good therapeutic effect for T2DM. It is well known that sitagliptin can specifically inhibit the activity of DPP4 to promote insulin secretion, inhibit islet β cell apoptosis and reduce blood glucose levels, while other pharmacological mechanisms are still unclear, such as improving insulin resistance, anti-inflammatory, anti-oxidative stress, and anti-fibrosis. The aim of this study was to explore novel targets and potential signaling pathways of sitagliptin for T2DM. Firstly, network pharmacology was applied to find the novel target most closely related to DPP4. Semi-flexible molecular docking was performed to confirm the binding ability between sitagliptin and the novel target, and molecular dynamics simulation (MD) was carried to verify the stability of the complex formed by sitagliptin and the novel target. Furthermore, surface-plasmon resonance (SPR) was used to explored the affinity and kinetic characteristics of sitagliptin with the novel target. Finally, the molecular mechanism of sitagliptin for T2DM was predicted by the enrichment analysis of GO function and KEGG pathway. In this study, we found the cell surface receptor-angiotensin-converting enzyme 2 (ACE2) most closely related to DPP4. Then, we confirmed that sitagliptin had strong binding ability with ACE2 from a static perspective, and the stability of sitagliptin-ACE2 complex had better stability and longer binding time than BAR708-ACE2 in simulated aqueous solution within 50 ns. Significantly, we have demonstrated a strong affinity between sitagliptin and ACE2 on SPR biosensor, and their kinetic characteristics were fast bindingfast dissociation. The guiding significance of clinical administration low dose can reach saturation, but repeated administration was needed. Finally, there was certain relationship between COVID-19 and T2DM, and ACE2Ang-(1-7)Mas receptor (MasR) axis may be the important pathway of sitagliptin targeting ACE2 for T2DM. This study used different methods to prove that ACE2 may be another novel target of sitagliptin for T2DM, which extended the application of ACE2 in improving diabetes mellitus.

The relationship between sugar-sweetened beverages, sleep disorders, and diabesity.

Diabetes and obesity in adults are global issues. Obesity and type 2 diabetes mellitus (T2DM) are increasingly categorized under the umbrella term diabesity. Health risk factors (HRFs), which include altering sleep habits and reducing sugar-sweetened beverages (SSBs) consumption, have emerged as relatively novel and crucial strategies for preventing and treating diabetes. We aimed to explore 1) whether SSBs could affect diabesity in Chinas community 2) whether HRFs could moderate this relationship and 3) whether a three-way interaction exists between HRFs, SSBs, and diabesity. On December 10, 2018, we investigated diabetes complications in four cities in Anhui Province and obtained basic and lifestyle information using a detailed questionnaire. The primary exposure was SSBs and outcomes were body mass index (BMI) and waist circumference (WC), while glycated hemoglobin (HbA1c) and sleep patterns (including duration and disorders) were considered moderators. Overall, 1920 participants were enrolled, and those who did not complete the questionnaire were excluded. Finally, this study included 1765 participants, with a response rate of 92.0%. The mean age was (57.10 ± 10.0) years. Patients with lower educational levels were more likely to have a lower prevalence of WC ( SSBs positively correlated with patterns dose-dependently. Moreover, SSBs could also be associated with sleep patterns, and blood glucose levels were correlated with diabesity. A three-way interaction effect was discovered between SSBs, sleep patterns, blood glucose levels, and patterns. Therefore, understanding the diabesity caused by SSBs and other HRFs can help prevent its occurrence.

Effect of sodium-glucose cotransporter protein-2 inhibitors on left ventricular hypertrophy in patients with type 2 diabetes A systematic review and meta-analysis.

This systematic review and meta-analysis was performed to compare the effect of sodium-glucose cotransporter protein-2 inhibitors (SGLT-2i) and placebo on left ventricular hypertrophy (LVH) in patients with type 2 diabetes. Randomized controlled trials (RCTs) comparing the LVH parameters of SGLT-2i to placebo in patients with type 2 diabetes were included. Our primary outcomes were the changes in left ventricular mass (LVM) and left ventricular mass index (LVMI) from baseline to the study endpoint. Secondary outcomes were the changes in left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and the ratio of early mitral inflow velocity to atrial inflow velocity (EA). Summary odds ratios were estimated using a fixed-effect or random-effect model. A total of 11 articles were included. Data were extracted from 11 original studies matching our inclusion criteria. In our meta-analysis, there were significant improvement in LVM (SMD -0.23, 95% CI -0.44 to -0.02, This meta-analysis confirmed the beneficial effects of SGLT-2i on reversal of left ventricular remodeling. The LVH regression was more pronounced in studies of type 2 diabetes patients receiving SGLT-2i than placebo.

Structural homology between 11 beta-hydroxysteroid dehydrogenase and

Metabolic syndrome is considered the precursor of type 2 diabetes mellitus. Tuberculosis is a leading infection that constitutes a global threat remaining a major cause of morbi-mortality in developing countries. People with type 2 diabetes mellitus are more likely to suffer from infection with

Diagnosis and Treatment of Water-Contaminated Severe Legionella Pneumonia with Digestive Symptoms as the First Symptom A Case Report and Review of the Literature.

Although Legionella is not the most common pathogen of community-acquired pneumonia, the epidemiological distribution of pneumonia pathogens has changed in recent years, with a gradual increase in some rare pathogens. For example, pneumonia that occurs after water source contamination is mostly caused by Legionella infection. This paper reports the diagnosis and treatment process of a patient after Legionella infection, who had misdiagnosis at the beginning, rapidly progressed to severe disease and combined with fungal infection. This article focuses on the timely and effective treatment of rapidly progressing Legionella pneumonia, in anticipation of a better understanding of the diagnosis and treatment of the disease. Here, we report a case of legionella infection with the nausea, vomiting as the first symptoms accompanied by weakness, chills, dizziness, abdominal discomfort in a 75-year-old female. The patient had a history of type 2 diabetes for 30 years, diabetic peripheral neuropathy for more than 20 years, arterial hypertension for 10 years, bone hyperplasia for more than 5 years, resection of right-sided thyroid cystadenoma in 1990. The patient had firstly been diagnosed with cholecystitis and gallbladder neck stones, diet abstinence, metronidazole, cefoperazone sulbactam, and rehydration were given. The patient responded poorly to these empiric treatments. The patient was given moxifloxacin in combination with azithromycin after the onset of respiratory symptoms, but the condition continued to deteriorate, and tigecycline was subsequently added. After the mechanical ventilation and the treatment plan adjusting, she improved significantly. Immunocompromised patient combined with underlying diseases are more susceptible to infection in an environment contaminated with Legionella, and the rapid onset and atypical respiratory symptoms make it easy to misdiagnose the disease, thus delaying treatment and leading to further deterioration. Timely diagnosis, early mechanical ventilation and rational drug administration were fundamental to treat Legionella pneumonia.

Simiao Wan and its ingredients alleviate type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a metabolic disease. Simiao Wan (SMW) is a commonly used clinical drug for hyperuricemia treatment. SMW has been confirmed to improve insulin resistance and is expected to be a novel hypoglycemic agent. However, the hypoglycemic bioactive ingredients and mechanisms of action of SMW are unclear. To explore the hypoglycemic effects and reveal the mechanisms of SMW and bioactive ingredients (SMW-BI). The hypoglycemic effects of SMW and SMW-BI were verified in a mouse model of T2DM induced by streptozotocin (STZ) and a high-fat and high-sugar diet (HFSD). Network pharmacology was used to predict the mechanisms of SMW and SMW-BI. Histological analysis and real-time quantitative polymerase chain reaction (RT-qPCR) verified network pharmacology results. RT-qPCR results were further verified by immunofluorescence (IFC) and molecular docking. The correlation between proteins and biochemical indicators was analyzed by Spearmans correlation. Chlorogenic acid, phellodendrine, magnoflorine, jateorhizine, palmatine, berberine, and atractydin were identified as SMW-BI. After 8 weeks of treatment, SMW and SMW-BI decreased the levels of fasting blood glucose (FBG), total cholesterol (TC), triacylglycerols (TG) and low-density lipoprotein cholesterol (LDL-C), increased the level of high-density lipoprotein cholesterol (HDL-C), alleviated weight loss, and increased serum insulin levels in T2DM mice. In addition, SMW and SMW-BI improved hepatocyte morphology in T2DM mice, decreased the number of adipocytes, and increased liver glycogen. Network pharmacological analysis indicated that SMW and SMW-BI may exert hypoglycemic by regulating insulin receptor substrate 1 (IRS1)RAC-beta serinethreonine-protein kinase (AKT2)forkhead box protein O1 (FOXO1)glucose transporter type 2 (GLUT2) signaling. Moreover, correlation analysis showed that SMW and SMW-BI were associated with activation of IRS1, AKT2, and GLUT2, and inhibiting FOXO1. RT-qPCR revealed that SMW and SMW-BI could increase levels of IRS1, AKT2, and GLUT2 in the livers of T2DM mice and lower the level of FOXO1. Furthermore, immunofluorescence analysis showed that FOXO1 expression in the livers of T2DM mice decreased after oral administration of SMW and SMW-BI. Furthermore, molecular docking showed that SMW-BI could bind directly to IRS1 and AKT2. SMW and SMW-BI are potential hypoglycemic drugs that alleviate T2DM by regulating IRS1AKT2FOXO1 signaling. Our study provides a research idea for screening the bioactive ingredients in traditional Chinese medicine (TCM).

Evaluation of the Combination of Metformin and Rapamycin in an MPP

Metformin (MET) and rapamycin (RAPA) have been reported to protect against neurodegeneration in cellular and animal models of Parkinsons disease (PD). MET, which is a first-line drug for type 2 diabetes, and RAPA are known as mTORC1 inhibitors. MET also acts as an AMPK activator, which leads to the inhibition of mTORC1 activity. mTORC1 is a downstream target of Akt signaling. Inactivation of AktmTORC1 and its downstream S6K1 can promote autophagy, a process involved in PD pathogenesis. Based on their mechanisms and potential benefits, we evaluated the potential protective effect of pretreatment with combinations of MET and RAPA in a 1-methyl-4-phenylpyridinium ion (MPP

High Cost Leads Some Americans with Diabetes to Ration Insulin.

Younger people are more likely to skip or skimp on doses.

miR-132-3p and KLF7 as novel regulators of aortic stiffening-associated EndMT in type 2 diabetes mellitus.

The prevalence of diabetes mellitus has risen considerably and currently affects more than 422 million people worldwide. Cardiovascular diseases including myocardial infarction and heart failure represent the major cause of death in type 2 diabetes (T2D). Diabetes patients exhibit accelerated aortic stiffening which is an independent predictor of cardiovascular disease and mortality. We recently showed that aortic stiffness precedes hypertension in a mouse model of diabetes (dbdb mice), making aortic stiffness an early contributor to cardiovascular disease development. Elucidating how aortic stiffening develops is a pressing need in order to halt the pathophysiological process at an early time point. To assess EndMT occurrence, we performed co-immunofluorescence staining of an endothelial marker (CD31) with mesenchymal markers (α-SMAS100A4) in aortic sections from dbdb mice. Moreover, we performed qRT-PCR to analyze mRNA expression of EndMT transcription factors in aortic sections of dbdb mice and diabetic patients. To identify the underlying mechanism by which EndMT contributes to aortic stiffening, we used aortas from dbdb mice and diabetic patients in combination with high glucose-treated human umbilical vein endothelial cells (HUVECs) as an in vitro model of diabetes-associated EndMT. We demonstrate robust CD31α-SMA and CD31S100A4 co-localization in aortic sections of dbdb mice which was almost absent in control mice. Moreover, we demonstrate a significant upregulation of EndMT transcription factors in aortic sections of dbdb mice and diabetic patients. As underlying regulator, we identified miR-132-3p as the most significantly downregulated miR in the micronome of dbdb mice and high glucose-treated HUVECs. Indeed, miR-132-3p was also significantly downregulated in aortic tissue from diabetic patients. We identified Kruppel-like factor 7 (KLF7) as a target of miR-132-3p and show a significant upregulation of KLF7 in aortic sections of dbdb mice and diabetic patients as well as in high glucose-treated HUVECs. We further demonstrate that miR-132-3p overexpression and KLF7 downregulation ameliorates EndMT in high glucose-treated HUVECs. We demonstrate for the first time that EndMT contributes to aortic stiffening in T2D. We identified miR-132-3p and KLF7 as novel EndMT regulators in this context. Altogether, this gives us new insights in the development of aortic stiffening in T2D.

Hemoglobin A1c in type 2 diabetes mellitus patients with preserved ejection fraction is an independent predictor of left ventricular myocardial deformation and tissue abnormalities.

Early detection of subclinical myocardial dysfunction in patients with type 2 diabetes mellitus (T2DM) is essential for preventing heart failure. This study aims to search for predictors of left ventricular (LV) myocardial deformation and tissue abnormalities in T2DM patients with preserved ejection fraction by using CMR T1 mapping and feature tracking. 70 patients and 44 sex- and age-matched controls (Cs) were recruited and underwent CMR examination to obtain LV myocardial extracellular volume fraction (ECV) and global longitudinal strain (GLS). The patients were subdivided into three groups, including 19 normotensive T2DM patients (G1), 19 hypertensive T2DM patients (G2) and 32 hypertensive patients (HT). The baseline biochemical indices were collected before CMR examination. LV ECV in T2DM patients was significantly higher than that in Cs (30.75 ± 3.65% vs. 26.33 ± 2.81% p < 0.05). LV GLS in T2DM patients reduced compared with that in Cs (-16.51 ± 2.53% vs. -19.66 ± 3.21%, p < 0.001). In the subgroup analysis, ECV in G2 increased compared with that in G1 (31.92 ± 3.05% vs. 29.59 ± 3.90%, p 0.032) and that in HT, too (31.92 ± 3.05% vs. 29.22 ± 6.58%, p 0.042). GLS in G2 significantly reduced compared with that in G1 (-15.75 ± 2.29% vs. -17.27 ± 2.57%, p < 0.05) and in HT, too (-15.75 ± 2.29% vs. -17.54 ± 3.097%, p < 0.05). In T2DM group, including both G1 and G2, hemoglobin A1c (HbA1c) can independently forecast the increase in ECV (β 0.274, p 0.001) and decrease in GLS (β 0.383, p 0.018). T2DM patients with preserved ejection fraction show increased ECV but deteriorated GLS, which may be exacerbated by hypertension of these patients. Hemoglobin A1c is an index that can independently predict T2DM patients LV myocardial deformation and tissue abnormalities.

The influence of different glucose tolerance on QTc interval a population-based study.

Corrected QT (QTc) interval has been reported to be associated with type 2 diabetes. This study aimed to explore the relationship between different glucose tolerance and QTc intervals among middle-aged and older Chinese individuals. We conducted a cross-sectional analysis that included 9898 subjects (3194 men and 6704 women) in a Chinese population. Glucose tolerance was studied during the oral glucose tolerance test (OGTT). Insulin, blood pressure, hemoglobin A1c (HbA1c), serum lipids, hepatic transaminases and waist-to-hip ratio were assessed. The QTc interval was derived from ECG recordings, and the subjects were stratified based on different glucose tolerance. QTc interval levels were increased significantly in the subjects with abnormal glucose metabolism compared with the normal glucose regulation group. Multiple regression analyses showed that the QTc interval was significantly associated with fasting plasma glucose, 2-h OGTT plasma glucose and HbA1c. The odds ratio of prolonged QTc was 1.396 for impaired glucose regulation (IFG)impaired fasting glucose (IGT) (95% CI 0.126-1.730), and 1.342 for type 2 diabetes (95% CI 0.142-1.577) after all potential confounders were adjusted. Impaired glucose tolerance (IGR) and diabetes are associated with prolonged QTc intervals among middle-aged and older Chinese individuals. Abnormal glucose regulation can be used to monitor the QTc interval in the population.

Liver fibrosis is closely related to metabolic factors in metabolic associated fatty liver disease with hepatitis B virus infection.

This case-control study aimed to identify the clinical characteristics and explore the risk factors for liver fibrosis in metabolic associated fatty liver disease (MAFLD) patients with hepatitis B virus (HBV) infection. The patients were grouped into MAFLD HBV and MAFLD (without HBV infection). Propensity score matching (PSM) was used to match baseline features between the groups. We included 401 patients with biopsy-proven MAFLD, 179 of whom had HBV infection. A total of 83 pairs were successfully matched via PSM, and steatosis scores and ballooning in the MAFLD HBV group were lower than those in the MAFLD group, while the inflammation scores and liver fibrosis stages were higher. After adjusted for confounding factors, HBV infection was associated with a higher risk of significant liver fibrosis in patients with MAFLD odds ratio (OR) 3.140, P 0.003. Overall, 43.58% (78179) of patients in the MAFLD HBV group had significant liver fibrosis. Further multivariate regression analysis, hypertension (OR 2.640 P 0.031), type 2 diabetes (OR 4.939 P 0.035), and elevated glutamyl-transferase levels (OR 3.980 P 0.001) were risk factors for liver fibrosis in the MAFLD HBV group. This suggests metabolic rather than viral factors are more closely associated with liver fibrosis in MAFLD patients with HBV infection.

Application of isoindole fluorophore formation for determination of linagliptin in the sole and co-formulated tablets Application for plasma assay and content uniformity testing.

Linagliptin is a new medicament belonging to dipeptidyl peptidase-4 enzyme inhibitors group. The mentioned medication is used to cure type 2 diabetes and is taken orally as a monotherapy or in a co-formulation with metformin. or empagliflozin. Herein, a novel, straightforward, and cost-effective method for linagliptin assay was developed with a workable use of an isoindole derivative. The primary amine moiety present in linagliptin enables its condensation with o-phthalaldehyde to form a fluorescent product in the presence of a sulfhydryl group-containing compound (2-mercaptoethanol) 0.01 % VV. The isoindole fluorophore yield was monitored at (λ

Environmental endocrine disruptor Bisphenol A induces metabolic derailment and obesity via upregulating IL-17A in adipocytes.

Bisphenol A (BPA), a ubiquitous environmental endocrine disruptor, has been extensively demonstrated to be associated with metabolic disorders, including obesity and type 2 diabetes mellitus. However, the underlying mechanism underpinning the environmental etiology of chronic metabolic disorders has not been sufficiently elucidated. This study is designed to explore the toxicological pathogenesis of chronic inflammation in BPA exposure during obesity. We investigated the role of IL-17A in the association of BPA exposure and obesity from human cross-sectional study to animal models, including genetically modified IL-17A Here, our work started from case-control observation that BPA exposure was significantly associated with risk of obesity (odds ratio 4.72, 95%CI 3.18 - 11.18, P < 0.01), metabolic disorder and levels of interleukin-17A (IL-17A) in human adipose (estimated changes β 0.46, 95%CI 0.15 - 1.01, P < 0.01) with bariatric surgery. Animal model fed with high-fat diet (HFD) confirmed that BPA exposure aggravated body weight gain and insulin resistance, concurrent with much heightened inflammatory responses in the adipose tissue including increase in IL-17A and macrophage polarization towards M1 stage. Genetically modified IL-17A ablated mice (IL-17A This research paradigm from human to animal provides strong evidence for the elucidation of IL-17A moderating inflammation and insulin resistance in obesity. Such findings reiterate the obesogenic role of environmental endocrine disruptor BPA in metabolic disorders and unveils the potential toxicological mechanisms underpinning such effect.

The Metabolic Health Index Identifies Patients That Will Benefit From Metabolic Surgery.

Metabolic syndrome is a modern worlds major health hazard related to comorbidities like type 2 diabetes and cardiovascular disease. Bariatric surgery is well known to lower this health risk in patients with obesity. There is a need for an objective measure to assess the intended reduction in health hazard and indirectly the eligibility for bariatric surgery. The Metabolic Health Index (MHI) quantitatively summarizes the cumulative impact of the metabolic syndrome on health status on a scale from 1 to 6. This study describes the use of the MHI as a supportive tool in the decision for and outcome assessment of bariatric surgery. The general usability of the MHI was tested by extending its application to patient data of five other bariatric centers in the Netherlands. Retrospective laboratory and national bariatric quality registry data of 11,501 patients were collected. The quantification of (improvement in) metabolic health burden as measured by the MHI was independent of the dataset that was used to derive the MHI model. Patients with MHI > 2.8 prior to surgery improved significantly more in MHI 12 mo after surgery compared to patients with MHI ≤ 2.8 (1.1 compared to 0.4 MHI points, respectively P < 0.001). The MHI is robust between centers and is suitable for general use in clinical decision-making. As changes in MHI over time reflect metabolic health alterations, it is suitable as an outcome measure of surgery. An MHI cut-off value of 2.8 helps to predict the likelihood of significant improvement after surgery, independent of body mass index and known metabolic comorbidities.

Insulin resistance and lipid levels in the middle-aged offspring of parents with severe mental illness.

Type 2 diabetes and dyslipidemias co-occur frequently with severe mental illnesses (SMI). However, less is known about serum insulin and lipid levels and prevalence of Insulin Resistance (IR) in offspring with familial risk for SMI. The Northern Finland Birth Cohort 1966 consists of 12,068 mothers, 11,068 fathers, and 12,231 children from the two northernmost provinces in Finland. At age 46 they participated in clinical examination including measurements of glucose, lipids, and IR and answered a questionnaire including information about their nutrition and physical activity. The information on parental SMI was obtained from the Hospital Discharge Register. Parents with SMI were those who had been treated in hospital for any psychiatric disorder during 1969-1982 (ICD-8 codes 290-315). The final study group included 334 (7.3 %) offspring who had a parent with SMI and 4249 (92.7 %) offspring in the comparison group. We did not find increased risk for disturbances in lipid levels, insulin levels, or IR levels between the study group (offspring of either parent with SMI) compared with the comparison group. All offspring, especially female offspring of either parent with SMI, had an increased risk for higher glucose levels and waist circumference. The results remained the same after excluding offspring with SMI. Our findings suggest that offspring of parents with SMI, especially female offspring, have partly increased risk for disturbances in cardiometabolic risk factors. Disturbances in glucose metabolism may have an effect via familial risk of severe mental illness.

Effect of glucagon-like peptide-1 receptor agonists on glycemic control, and weight reduction in adults A multivariate meta-analysis.

To explore the effect of glucagon-like peptide-1 receptor agonist (GLP-1 RAs) on glycemic control and weight reduction in adults. Databases were searched from August 2021 to March 2022. Data were analyzed using mean difference (MD) values with 95% confidence intervals (CIs). Both random-and fixed-effect models were employed. Heterogeneity was explored using pre-specified subgroup analyses and meta-regression. Structural equation modeling fitting was used for the multivariate meta-analysis. A total of 31 double-blind randomized controlled trials with 22,948 participants were included in the meta-analysis. The MD and 95% CI of the pooled GLP1-RA-induced change in the glycated hemoglobin level was -0.78% (-0.97%, -0.60%) in the random-effects model and -0.45% (-0.47%, -0.44%) in the fixed-effect model, with a high heterogeneity (I2 97%). The pooled body weight reduction was -4.05 kg (-5.02 kg, -3.09 kg) in the random-effects model and -2.04 kg (-2.16 kg, -1.92 kg) in the fixed-effect model (I2 98%). The standardized pooled correlation coefficient between HbA1c levels and body weight was -0.42. A negative correlation between glycemic control and weight reduction was obtained. Long-acting GLP-1 RAs significantly reduced the glycated hemoglobin level and body weight in adults.

Site-Specific Fracture Incidence Rates Among Patients With Type 1 Diabetes, Type 2 Diabetes or Without Diabetes in Denmark (1997-2017).

To investigate trends in incidence rates (IRs) at various fracture sites for patients with type 1 diabetes and type 2 diabetes compared with patients without diabetes in Denmark in 1997-2017. Patients aged ≥18 years with a vertebral, hip, humerus, forearm, foot, or ankle fracture between 1997 and 2017 were identified from Danish hospital discharge data. IRs per 10,000 person-years were calculated over the study period. Median IRs for the first (1997-2001) and the last (2013-2017) 5 years were compared. We used Poisson models to estimate age-adjusted IR ratios (IRRs) of fractures among patients with type 1 and type 2 diabetes versus patients without diabetes. Except for foot fractures, fracture IRs were higher in patients with type 1 or type 2 diabetes compared with patients without diabetes. Hip fracture IRs declined between the first and last 5 years by 35.2%, 47.0%, and 23.4% among patients with type 1, type 2, and without diabetes, respectively. By contrast, vertebral fracture IRs increased 14.8%, 18.5%, 38.9%, respectively. While age-adjusted IRRs remained elevated in patients with type 1 diabetes compared with patients without diabetes, IRRs in patients with type 2 diabetes converged with those observed in patients without diabetes. Unadjusted fracture rates are higher in patients with diabetes but have decreased between 1997 and 2017 except for vertebral fractures, which increased in all groups. Fracture rates change after age adjustment.

A novel non-invasive model for the prediction of advanced liver fibrosis in chronic hepatitis B patients with NAFLD.

There are still lack of non-invasive models to evaluate liver fibrosis in chronic hepatitis B (CHB) patients with nonalcoholic fatty liver disease (NAFLD). We aimed to establish a predictive model for advanced fibrosis in these patients. A total of 504 treatment-naive CHB patients with NAFLD who underwent liver biopsy were enrolled and randomly divided into a training set (n 336) and a validation set (n 168). Receiver operating characteristic (ROC) curve was used to compare predicting accuracy for the different models. One hundred fifty-six patients (31.0%) had advanced fibrosis. In the training set, platelet, prothrombin time, type 2 diabetes, HBeAg positivity and globulin were significantly associated with advanced fibrosis by multivariable analysis. A predictive model namely PPDHG for advanced fibrosis was developed based on these parameters. The areas under the ROC curve (AUROC) of PPDHG with an optimal cut-off value of -0.980 in predicting advanced fibrosis was 0.817 (95% confidence interval 0.772 to 0.862), with a sensitivity of 81.82% and a specificity of 66.81%. The predicting accuracy of PPDHG for advanced fibrosis was significantly superior to AST to platelet ratio index (APRI), fibrosis-4 score (FIB-4) and NAFLD fibrosis score (NFS). Further analysis revealed that the AUROC of PPDHG remained significantly higher than FIB-4 and NFS indexes, while it was comparable with APRI for predicting advanced fibrosis in the validation set. PPDHG had a better predicting performance than established models for advanced fibrosis in CHB patients with NAFLD. The application of PPDHG can reduce the necessary for liver biopsy in these patients.

Impact of Heart Failure History at Baseline on Cardiovascular Effects of GLP-1 Receptor Agonists in Type 2 Diabetes a Meta-analysis.

Effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in type-2 diabetes mellitus (T2DM) with or without prior heart failure (HF) have been inconsistent across cardiovascular outcome trials. This study aimed to investigate the impact of HF history at baseline on cardiovascular effects of GLP-1 RAs in T2DM. PubMed, Embase, Web of Science, and clinical trial registries were searched for randomized controlled trials (RCTs) or post hoc analyses (≥ 24 weeks) reporting HF hospitalizations andor cardiovascular death (HHFCVD), major adverse cardiovascular events (MACE) comprising of cardiovascular death, myocardial infarction, and stroke in adults with T2DM with or without HF history (PROSPEROCRD42022367633). Hazard ratios (HRs) in GLP-1RAs versus placebo arms were pooled together using the generic inverse variance method in fixed-effects model. Subgroup analysis was performed. We identified 5 eligible studies, pooling data retrieved from six RCTs and 48,489 individuals with T2DM. On pooled analysis, GLP1RA treatment versus placebo significantly reduced risk of HHFCVD in only T2DM without HF history (HR 0.84 95%CI, 0.77-0.91 I GLP-1RAs consistently prevented HF hospitalizations and MACE in T2DM regardless of baseline HF history, whereas significant attenuation of benefits on composite HHFCV death were observed in those with HF history.

Economic burden of excessive sedentary behaviour in Canada.

To estimate health care and health-related productivity costs associated with excessive sedentary behaviour (> 8 hday and > 9 hday) in Canadian adults. Three pieces of information were used to estimate costs (1) the pooled relative risk estimates of adverse health outcomes consistently shown to be associated with excessive sedentary behaviour, gathered from meta-analyses of prospective cohort studies (2) the prevalence of excessive sedentary behaviour in Canadian men and women, obtained using waist-worn accelerometry in a nationally representative sample of adults (Canadian Health Measures Survey 2018-2019) and (3) the direct (health care) and indirect (lost productivity due to premature mortality) costs of the adverse health outcomes, selected using the Economic Burden of Illness in Canada 2010 data. The 2010 costs were then adjusted to 2021 costs to account for inflation, population growth, and higher average earnings. A Monte Carlo simulation was conducted to account for uncertainty in the model. The total costs of excessive sedentary behaviour in Canada were $2.2 billion (8 hday cut-point) and $1.8 billion (9 hday cut-point) in 2021, representing 1.6% and 1.3% of the overall burden of illness costs, respectively. The two most expensive chronic diseases attributable to excessive sedentary behaviour were cardiovascular disease and type 2 diabetes. A 10% decrease in excessive sedentary behaviour (from 87.7% to 77.7%) would save an estimated $219 million per year in costs. Excessive sedentary behaviour significantly contributes to the economic burden of illness in Canada. There is a need for evidence-based and cost-effective strategies that reduce excessive sedentary behaviour in the population. RéSUMé OBJECTIF Estimer le coût des soins de santé et le coût de productivité lié à la santé associés au comportement sédentaire excessif (> 8 heuresjour et > 9 heuresjour) chez les Canadiennes et les Canadiens adultes. MéTHODE Trois informations ont servi à estimer ces coûts 1) les estimations combinées du risque relatif des résultats sanitaires indésirables uniformément associés au comportement sédentaire excessif, collectées à partir de méta-analyses d’études prospectives de cohortes 2) la prévalence du comportement sédentaire excessif chez les Canadiennes et les Canadiens, obtenue à l’aide d’un accéléromètre porté à la taille par un échantillon représentatif national d’adultes (Enquête canadienne sur les mesures de la santé 2018-2019) et 3) les coûts directs (soins de santé) et indirects (perte de productivité due à la mortalité prématurée) des résultats sanitaires indésirables sélectionnés, d’après les données du Fardeau économique de la maladie au Canada de 2010. Les coûts de 2010 ont ensuite été ajustés aux coûts de 2021 pour tenir compte de l’inflation, de la croissance démographique et de la hausse moyenne des revenus. Nous avons effectué une simulation de Monte-Carlo pour tenir compte de l’incertitude du modèle. RéSULTATS Les coûts totaux du comportement sédentaire excessif au Canada étaient de 2,2 milliards de dollars (point de coupure de 8 heuresjour) et de 1,8 milliard de dollars (point de coupure de 9 heuresjour) en 2021, ce qui représente 1,6 % et 1,3 % du fardeau global des coûts des maladies, respectivement. Les deux maladies chroniques les plus chères imputables au comportement sédentaire excessif étaient les maladies cardiovasculaires et le diabète de type 2. Une baisse de 10 % du comportement sédentaire excessif (de 87,7 % à 77,7 %) économiserait environ 219 millions de dollars de coûts par année. CONCLUSION Le comportement sédentaire excessif contribue de façon significative au fardeau économique de la maladie au Canada. Il nous faut des stratégies fondées sur les preuves et efficaces par rapport au coût pour réduire le comportement sédentaire excessif dans la population.

Mobile health technologies, social justice and population-based vulnerabilities A public health ethics perspective on mHealth using the example of type 2 diabetes mellitus.

Mobile health technologies (mHealth) promote the trend towards personal responsibility and self-management. By using the example of type 2 diabetes mellitus (T2DM), the article aims to deepen the discussion on mHealth, personal responsibility and justice-which has so far only been rudimentary-from a public health ethical perspective. It shows that in the field of T2DM, mHealth can on the one hand improve social health justice, but on the other hand can also exacerbate social health injustices. From a justice-focused, public health ethical perspective on T2DM mHealth, it is necessary to better understand whether and how vulnerable population groups are considered in mHealth development and implementation, how these groups experience the use of the technology, what social-epidemiological impacts the increasing use of mHealth can have, which health inequalities in the area of T2DM are unfair, to what extent personal responsibility should be placed in the hands of the users, and where the limits of personal responsibility lie. Considering social diversity and the social determinants of health is an ongoing process and must permeate all phases of mHealth development and implementation. Mobile Gesundheitstechnologien (mHealth) fördern den Trend hin zu Eigenverantwortung und Selbstmanagement. Ziel des Beitrags ist es, am Beispiel von Diabetes mellitus Typ 2 (T2DM) die Diskussion zu mHealth, Eigenverantwortung und Gerechtigkeit – welche es bisher nur in Ansätzen gibt – aus einer Public-Health-ethischen Perspektive zu vertiefen. Dabei zeigt sich, dass mHealth im Bereich T2DM soziale Gesundheitsgerechtigkeit einerseits verbessern, andererseits aber auch soziale Gesundheitsungerechtigkeiten verschärfen kann. Aus einer gerechtigkeitsfokussierten, Public-Health-ethischen Perspektive auf T2DM-mHealth ist es notwendig, besser zu verstehen, ob und wie vulnerable Bevölkerungsgruppen bei mHealth-Entwicklung und -Einsatz mitbedacht werden, wie sie die Nutzung der Technologie erleben, welche sozialepidemiologischen Auswirkungen der zunehmende Einsatz von mHealth haben kann, welche gesundheitlichen Ungleichheiten im Bereich T2DM ungerecht sind, inwieweit die Eigenverantwortung in die Hände der Nutzenden gelegt werden soll und wo die Grenzen der Eigenverantwortung liegen. Die Berücksichtigung der sozialen Diversität und der sozialen Determinanten von Gesundheit ist ein stetiger Prozess und muss alle Phasen der Entwicklung und des Einsatzes von mHealth durchziehen.

How dietary amino acids and high protein diets influence insulin secretion.

Glucose homeostasis is the maintenance and regulation of blood glucose concentration within a tight physiological range, essential for the functioning of most tissues and organs. This is primarily achieved by pancreatic secretion of insulin and glucagon. Deficient pancreatic endocrine function, coupled with or without peripheral insulin resistance leads to prolonged hyperglycemia with chronic impairment of glucose homeostasis, most commonly seen in diabetes mellitus. High protein diets (HPDs) are thought to modulate glucose homeostasis through various metabolic pathways. Insulin secretion can be directly modulated by the amino acid products of protein digestion, which activate nutrient receptors and nutrient transporters expressed by the endocrine pancreas. Insulin secretion can also be modulated indirectly, through incretin release from enteroendocrine cells, and via vagal neuronal pathways. Additionally, glucose homeostasis can be promoted by the satiating effects of anorectic hormones released following HPD consumption. This review summarizes the insulinotropic mechanisms by which amino acids and HPDs may influence glucose homeostasis, with a particular focus on their applicability in the management of Type 2 diabetes mellitus.

Transcatheter Aortic Valve Replacement for Severe Aortic Valve Stenosis Do Patients Experience Better Quality of Life Regardless of Gradient

Aortic valve replacement improves survival for patients with low-gradient aortic valve stenosis, but there is a paucity of data on postoperative quality of life for this population. In a single-center retrospective analysis of 304 patients with severe aortic valve stenosis who underwent transcatheter aortic valve replacement, patients were divided into 4 groups based on mean pressure gradient, left ventricular ejection fraction, and stroke volume index. Using the Kansas City Cardiomyopathy Questionnaire-12, quality of life was assessed immediately before and 1 month after transcatheter aortic valve replacement. Most patients in the low-flow, low-gradient group were men this group had higher relative rates of cardiovascular disease and type 2 diabetes than the paradoxical low-flow, low-gradient group the normal-flow, low-gradient group and the high-gradient group. All-cause mortality did not differ significantly among the groups at 1 month after surgery, and all groups experienced a significant improvement in quality-of-life scores after surgery. The mean improvement was 27 points in the low-flow, low-gradient group, 25 points in the paradoxical low-flow, low-gradient group, 30 points in the normal-flow, low-gradient group, and 30 points in the high-gradient group (all P < .001). Quality of life improves significantly across all subgroups of aortic valve stenosis after trans-catheter aortic valve replacement, regardless of flow characteristics or aortic valve gradients.

Association of dietary intake with body mass index and glycemic profile among newly diagnosed patients with type 2 diabetes mellitus.

Dietary intake plays an important role in determining body mass index (BMI) and glycemic profile in patients with type 2 diabetes mellitus (T2DM). Our aim was to describe habitual dietary intake and its associations with BMI and glycemic profile in a cohort of patients with newly diagnosed T2DM in Sri Lanka. A cross-sectional study was carried out among 158 patients with newly diagnosed T2DM in Galle, Sri Lanka. Data on demographic, lifestyle, and family history of diabetes mellitus, and clinical measures were collected. The dietary information was collected using a 24-h dietary recall. Among the total number of study subjects, only 12.0%, 5.7% and 1.3% met the recommended daily consumption value of protein, fat, and fiber, respectively, whereas 99.4% of subjects had taken carbohydrates that exceeded the recommended consumption. There was a positive association between carbohydrate intake and BMI (0.004, 0.002, p .048) and carbohydrate intake and glycated hemoglobin (HbA The diet of the majority of newly diagnosed T2DM patients in this cohort consisted of a higher carbohydrate intake than the recommended level. However, they did not meet the recommended daily intake of protein, fat, and fiber. Both carbohydrate and fat intake were significantly and positively associated with BMI and HbA

Network meta-analysis of glucose-lowering drug treatment regimens with the potential risk of hypoglycemia in patients with type 2 diabetes mellitus in terms of glycemic control and severe hypoglycemia.

Insulin and its secretagogues are essential for some patients with type 2 diabetes (T2D) to maintain good glycemic control (GC), but severe hypoglycemia (SH) is a concern. This network meta-analysis aimed to find optimal glucose-lowering drug treatment regimens in terms of GC and SH in T2D patients. MEDLINE and EMBASE were used to identify trials that compared two or more treatments including insulins andor sulfonylurea or glinides and that examined both GC and SH. Treatment hierarchy was expressed as the surface under the cumulative ranking curve (SUCRA) probabilities. We identified 137 eligible trials comprising 42 treatments. The use of insulins and non-insulin glucose-lowering agents except for sulfonylurea or glinide had a higher SUCRA than insulins only for hemoglobin A1c (A1C) (p 0.01) changes and achievement of A1C < 7.0% (p 0.02) or A1C ≤ 6.5% (p 0.002). The use of sulfonylurea or glinide and other non-insulin glucose-lowering agents resulted in a lower SUCRA for SH than insulins only when trials were analyzed for A1C change (p 0.06) and achievement of A1C < 7.0% (p 0.004) or A1C ≤ 6.5% (p 0.004). Cluster analysis indicated that premixed insulin plus glucagon-like peptide-1 receptor agonist (Mix-ins GLP1) belonged to the high-efficacy category for GC and glinide plus thiazolidinedione (glinide TZD) belonged to the relatively high-efficacy category for GC among several high-safety categories regarding SH. In T2D patients, clinicians should consider appropriate combinations of non-insulin glucose-lowering agents (especially glinide TZD) for reducing SH risk before switching to insulin therapies. If switching, they should be willing to add non-insulin glucose-lowering agents (especially, Mix-ins GLP1) to insulins to further improve GC.

Expression of urinary exosomal miRNA-615-3p and miRNA-3147 in diabetic kidney disease and their association with inflammation and fibrosis.

Diabetic kidney disease (DKD) is one of the most common chronic complications of type 2 diabetes mellitus (T2DM), and it is particularly important to identify a high-quality method for evaluating disease progression. Urinary exosomes contain microRNA that might promise early diagnostic and monitoring markers of DKD. The present study aimed to identify novel exosome-related markers associated with inflammation and fibrosis to assess the progression of DKD. Exosomes were extracted from the urine of 83 participants to determine the expression levels of miRNA-615-3p and miRNA-3147 in 20 healthy people, 21 patients with T2DM and 42 patients with DKD, as determined by RT-qPCR. The circulating expression level of TGF-β1 was detected by ELISA. Serum Cystatin C was measured by a latex-enhanced immunoturbidimetric method. The correlation analyses were performed for all clinical and laboratory parameters. The expression level of urinary exosomal miRNA-615-3p in DKD patients was significantly higher than that in the control group and the T2DM group by RT-qPCR. The expression of miRNA-3147 showed an upward trend in the three groups of subjects, but it was not statistically significant. The urinary exosomal miRNA-615-3p was positively correlated with serum Cystatin C, plasma TGF-β1, creatinine, BUN, PCR and 24-h urine protein, and negatively correlated with eGFR and albumin. The diagnostic efficacy of urinary exosomal miRNA-615-3p combined with the ACR was higher than that of ACR alone. Urinary exosomal miRNA-615-3p may be used as a novel biomarker for evaluating the progression of DKD, and may be involved in the process of inflammation and fibrosis in DKD. The combined diagnosis of urinary exosomal miRNA-615-3p and ACR may be used as more stable and sensitive diagnostic criteria for DKD.

Long-Term Visit-to-Visit Glycemic Variability as a Predictor of Major Adverse Limb and Cardiovascular Events in Patients With Diabetes.

Background Peripheral arterial disease (PAD) is a severe complication in patients with type 2 diabetes. Glycemic variability (GV) is associated with increased risks of developing microvascular and macrovascular diseases. However, few studies have focused on the association between GV and PAD. Methods and Results This cohort study used a database maintained by the National Taiwan University Hospital, a tertiary medical center in Taiwan. For each individual, GV parameters were calculated, including fasting glucose coefficient of variability (FGCV) and hemoglobin A1c variability score (HVS). Multivariate Cox regression models were constructed to estimate the relationships between GV parameters and composite scores for major adverse limb events (MALEs) and major adverse cardiovascular events (MACEs). Between 2014 and 2019, a total of 45 436 adult patients with prevalent type 2 diabetes were enrolled for analysis, and GV was assessed during a median follow-up of 64.4 months. The average number of visits and time periods were 13.38 and 157.87 days for the HVS group and 14.27 and 146.59 days for the FGCV group, respectively. The incidence rates for cardiac mortality, PAD, and critical limb ischemia (CLI) were 5.38, 20.11, and 2.41 per 1000 person-years in the FGCV group and 5.35, 20.32, and 2.50 per 1000 person-years in HVS group, respectively. In the Cox regression model with full adjustment, the highest FGCV quartile was associated with significantly increased risks of MALEs (hazard ratio HR, 1.57 95% CI, 1.40-1.76

High Plasma Levels of Soluble Lectin-like Oxidized Low-Density Lipoprotein Receptor-1 Are Associated With Inflammation and Cardiometabolic Risk Profiles in Pediatric Overweight and Obesity.

Background Lectin-like oxidized low-density lipoprotein (ox-LDL) receptor-1 is a scavenger receptor for oxidized low-density lipoprotein. In adults, higher soluble lectin-like ox-LDL receptor-1 (sLOX-1) levels are associated with cardiovascular disease, type 2 diabetes, and obesity, but a similar link in pediatric overweightobesity remains uncertain. Methods and Results Analyses were based on the cross-sectional HOLBAEK Study, including 4- to 19-year-olds from an obesity clinic group with body mass index >90th percentile (n1815) and from a population-based group (n2039). Fasting plasma levels of sLOX-1 and inflammatory markers were quantified, cardiometabolic risk profiles were assessed, and linear and logistic regression analyses were performed. Pubertalpostpubertal children and adolescents from the obesity clinic group exhibited higher sLOX-1 levels compared with the population (

A study of hormonal and anthropometric parameters in polycystic ovarian syndrome.

Polycystic Ovarian Syndrome (PCOS) is an endocrinopathy with a complex metabolic disorder. PCOS is characterized by reproductive hormonal imbalances leading to the clinical presentation of hyperandrogenism and infertility. PCOS is also showing an increased prevalence of several other conditions such as obesity, dyslipidemia, hypertension, metabolic syndrome and type 2 diabetes mellitus (DM2) when compared with women without PCOS. The principal symptoms in patients with PCOS are irregular menstruation, acne, and excessive amounts of androgenic hormones. The Rotterdam PCOS consensus workshop has given specific criteria to establish PCOS diagnosis only after exclusion of other known disorders. Obesity is a common finding of women with PCOS, but it is not part of the diagnostic criteria. PCOS has metabolic characteristics that include prominent defects in insulin action and beta-cell function, defects that confer a substantially increased risk for obesity and type 2 diabetes mellitus. PCOS women have an increased level of luteinizing hormone (LH) and a decreased level of follicle-stimulating hormone (FSH), which leads to disorders in the regulation of the menstrual cycle. The values of LH and FSH are dependent on the day of the menstrual cycle in which the hormones are measured. Obesity also has an influence on these values. The objective of this study was to compare the hormonal and anthropometric parameters in women with PCOS and healthy control group. This study was carried out in the Department of Pathology, Dr. D Y Patil Medical College and Research Centre, Pune, Maharashtra. Fifty female patients aged 16-40 years diagnosed with PCOS by known criteria were included in the study and compared with 50 healthy control group females. Elevated levels of thyroid-stimulating hormone, LH, FSH, and prolactin along with increased body mass index and waist-to-hip ratio were predictors of PCOS and the early metabolic abnormalities.

Brain stem auditory evoked potentials in type 2 diabetes mellitus patients at varying frequencies.

As per the World Health Organization, in 2005, more than 180 million people had diabetes worldwide. This figure will be more than double by 2030. Neuropathy is common and late complication of diabetes mellitus (DM). Sensory neural hearing loss which is severe at higher frequencies has been reported in Type 2 DM patients. Auditory nerve tract damage increases the latency and reduces the amplitude of the response. Evoked potential recordings evaluate the neural pathways in the central nervous system. Brainstem auditory evoked potentials (BAEP) localize anatomic structures using different waves and detect acoustic and central neuropathy (CN). Hence, brainstem evoked response of audiometry (BERA) is used widely in clinical set up. 1. To record BERA waves in normal subjects with normal blood sugar levels (hemoglobin A To study the BERA parameters with the normal subjects with blood sugar subjects and compare them with Type 2 DM patients. n 30, Type 2 DM patients between the age of 35-50 years of either sex were chosen from the Diabetic Clinic of GMC, Aurangabad, Maharashtra. HbA Unpaired Students t-test. Mean ± Standard deviation of the absolute latency and interpeak latency of BERA waves at 2, 4, and 6 KHz at 80 dB in Type 2 DM patients were delayed and found to be significant as compared to control group. The above study explains that if BAEP is recorded at higher frequencies like 6 KHz and at 80 dB, CN involvement can be detected earlier in diabetic patients. Hence, it is recommended to carry out BERA in diabetic patients at least once in a year.

Shoulder capsulitis What relation with diabetes mellitus in a moroccan population

Shoulder capsulitis (SC) is a common musculoskeletal complication in patients with diabetes. It can be particularly disabling. It is often overlooked by clinicians. The aim of this study is to evaluate the prevalence of retractile capsulitis and to identify the risk factors in a population of Moroccan diabetic patients. We realised a cross-sectional study including patients with diabetes mellitus (DM). We recorded the demographic and diabetic characteristics of our patients. SC and vascular complications were assessed by clinical and para-clinical investigations. The prevalence of SC was calculated. The factors associated with SC were evaluated by suitable statistical tests. Three hundred and Sixty-five patients were included 84.9% had Type 2 DM (T2DM). The mean age of the participants was 52.6 ± 13.6. Shoulder capsulitis was present in 12.6% of patients. In statistical analysis, age >50 years (P 0.001), T2DM (P 0.03), duration of progression >10 years (P 0.03), dyslipidemia (P 0.013) and macrovascular complications (P 0.009) were associated with an increased frequency of SC. This study shows that the prevalence of SC is higher in diabetic patients. Therefore, inclusion of this pathology in the global management of the diabetic patient is necessary.

Gastrointestinal disorders potentially associated with Semaglutide an analysis from the Eudravigilance Database.

Semaglutide is a Glucagon-like peptide-1 receptor agonist used in the second-line treatment of poorly controlled type 2 diabetes and can be used in monotherapy or associated with other oral antidiabetics or even insulin, increasing the effectiveness of the treatment. This work aims to analyze the profile of adverse drug reactions reported for semaglutide in Eudravigilance. Data on Individual Cases Safety Reports were obtained from the database of the centralized European spontaneous reporting system Eudravigilance by accessing www.adrreports.eu. (1 December 2021). It is possible to observe a high prevalence of gastrointestinal disorders (N 3502, 53.2%). The most severe reported cases were primarily gastrointestinal disorders, metabolic, and nutritional disorders, eye disorders, renal and urinary disorders and cardiac disorders, with an evident higher prevalence of adverse gastrointestinal events both in oral and injectable dosage form (N 133, 50.0% vs N 588, 47.2%, respectively). Through a comparative analysis, semaglutide had a greater number of reported gastrointestinal adverse events compared to sitagliptin and empaglifozin (p < 0.00001). Semaglutide has a good safety profile, however the definition of subgroups within the type 2 diabetes population who are particularly prone to develop serious adverse event when treated with GLP-1 RAs is crucial.

Obesity among Latinx people in the United States A review.

Obesity is a serious, chronic disease that is associated with a range of adiposity-based comorbidities, including cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver disease. In the United States, obesity is a public health crisis, affecting more than 40% of the population. Obesity disproportionately affects Latinx people, who have a higher prevalence of obesity and related comorbidities (such as cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver disease) compared with the general population. Many factors, including genetic predisposition, environmental factors, traditional calorie-dense Latinx diets, family dynamics, and differences in socioeconomic status, contribute to the increased prevalence and complexity of treating obesity in the Latinx population. Additionally, significant heterogeneity within the Latinx population and disparities in health care access and utilization between Latinx people and the general population add to the challenge of obesity management. Culturally tailored interventions have been successful for managing obesity and related comorbidities in Latinx people. Antiobesity medications and bariatric surgery are also important options for obesity treatment in Latinx people. As highlighted in this review, when managing obesity in the Latinx population, it is critical to consider the impact of genetic, dietary, cultural, and socioeconomic factors, in order to implement an individualized treatment strategy.

Obesity among Asian American people in the United States A review.

Standard measures of obesity, i.e., body weight and BMI, suggest that Asian American people have a lower obesity prevalence than other racial groups in the United States. However, Asian American people face a unique challenge in their pattern of adiposity with central obesity, which raises the risk for multiple comorbidities, such as type 2 diabetes, metabolic syndrome, and cardiovascular disease, at a lower BMI compared with other populations. Several organizations recommend lower BMI cutoffs for obesity in Asian people (BMI ≥25.0 or ≥27.5 kgm

Shift patterns, physical exercise, and Type 2 diabetes mellitus (T2DM) a prospective cohort study in China.

To examine the relationships between different shift patterns and Type 2 diabetes mellitus (T2DM) risk, and determine whether physical exercise reduced the incidence of T2DM in shift workers in the oil industry. Baseline data were collected from participants in May 2013 who were then followed for 4 years in a prospective cohort study. The cohort initially consisted of 3,002 workers and ultimately included 2,827 people. Baseline and follow-up questionnaires were sent to participants every 2 years (in May 2015 and May 2017) to update medical and lifestyle information during the follow-up period. The risk of T2DM among two shift workers relative risk (RR) 3.442, 95% CI 1.904-6.799), three shift workers (RR 2.534, 95% CI 1.484-4.571), and four shift workers (RR 4.230, 95% CI 2.680-7.518) was higher than that among day workers. An increasing trend was observed with respect to T2DM risk, with the lowest risk in three shift workers, moderate risk in two shift workers, and highest risk in four shift workers. In the interactive analysis between shift work and physical exercise, taking part in mild physical exercise increased the risk of T2DM for workers. Four shift workers who took part in mild physical exercise had an increased risk of T2DM. The relative excess risk due to interaction (RERI) was 33.769 (0.398-67.140). The attributable proportion due to interaction API (%) was 0.704 (0.529-0.880). The synergy index (SI) was 3.563 (1.900-6.683). Shift work is significantly correlated with increased incidence of T2DM. Risk of T2DM is lowest risk in three shift workers, moderate in two shift workers, and highest in four shift workers. Shift workers who participated in moderate and severe physical exercise had reduced risk of developing T2DM. This study investigated the role of different shift patterns and physical exercise on type 2 diabetes mellitus (T2DM) risk factors of shift workers. We hypothesized that shift patterns would be correlated with the incidence of type 2 diabetes and that physical exercise would reduce the risk of type 2 diabetes. We studied 2,827 workers using a cohort study design following for 4 years. The study sample consisted of 1,249 fixed-day-shift workers, 650 three-shift workers, 297 two-shift workers, and 631 four-shift workers. We found that compared with fixed day shift workers, alternating shift workers were at an increased risk for developing T2DM. And moderate and severe physical exercise reduced the risk of T2DM in shift workers. We concluded that physical exercise is associated with decreased type 2 diabetes risk in shift workers, particularly when physical exercise is moderate and severe. The findings of the current study may assist enterprise management departments in developing diabetes interventions among shift workers.

Clinical Evidence and Proposed Mechanisms for Cardiovascular and Kidney Benefits from Sodium-Glucose Co-transporter-2 Inhibitors.

The number of people living with type 2 diabetes (T2D) and its complications worldwide is increasing at an alarming rate. Fortunately, our understanding of the benefits of glucose-lowering agents from the sodium-glucose co-transporter-2 (SGLT2) inhibitor and glucagon-like peptide-1 (GLP-1) receptor agonist classes on cardiovascular and kidney outcomes is advancing this means we now have new options to mitigate the risks of these complications in patients with T2D. The SGLT2 inhibitors have consistently demonstrated benefits on atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD) and heart failure (HF) events in dedicated outcome trials. Large guidelines groups now recommend SGLT2 inhibitors as a standard of care in patients with T2D and comorbid ASCVD, CKD and or HF. Evolving evidence additionally indicates kidney and HF benefits of SGLT2 inhibitors in populations without diabetes. These agents likely provide heart and kidney benefits through multiple mechanisms, as their impact on heart and kidney outcomes cannot be fully explained by their direct metabolic effects. On-going work to elucidate the beneficial mechanisms at play with SGLT2 inhibitors will help further optimize these life-saving therapies in patients with and without T2D.

Malnutrition among patients with Type-2 Diabetes Mellitus.

The present study aims to evaluate the nutritional status of diabetic patients using Subjective Global Assessment (SGA) tool. A prospective cross-sectional study was conducted at Endocrine and Medicine Department of Lady Reading Hospital from September 2019 to March 2020. A total of 359 patients diagnosed with Type-2 Diabetes Mellitus (T2DM) were included in the study. The malnutrition status was assessed using SGA, and clinical parameters including albumin and total leukocyte count (TLC). We have observed mild to moderate malnutrition among 48.2% patients, and severe malnutrition in 10.6% patients as per the SGA scoring. Among the factors associated with nutritional status were BMI (p<0.01), and presence of CAD (DM complication) (p0.015). As per the correlation analysis, BMI had a significant negative correlation with nutritional status (r-0.351 p<0.01). It is concluded from the study results that there is a high prevalence of malnutrition among the enrolled diabetic patients.

Recreational nitrous oxide induced subacute combined degeneration of the spinal cord A case report.

Nitrous oxide is a gas frequently used in the medicaldental field for anesthesia and analgesic purposes and in the food industry as a spray propellant or foaming agent. Overexposure can lead to subacute combined degeneration (SACD) of the spinal cord through the mechanism of vitamin B12 deficiency. Because this drug is easily accessible, relatively inexpensive, and legal to possess, it has potential to be abused for recreational purposes. The number of published cases of nitrous oxide abuse has been increasing since 2010. Large-scale and long-term use of nitrous oxide have been found to cause nerve damage from vitamin B12 deficiency, thromboembolic phenomenon from elevated homocysteine levels, and even death from hypoxia. A 44-year-old male patient with past medical history of recently diagnosed type 2 diabetes, on Metformin, presented for 1 month of worsening bilateral upper and lower extremity weakness. On initial physical examination, he demonstrated pertinent abnormal findings of 25 hand strength bilaterally, 45 strength in his left upper extremity and right lower extremity, impaired coordination, ataxic gait, rigidity, and decreased but symmetrical reflexes. He reported using 50-100 canisters of nitrous oxide per day to obtain a feeling of relaxation and euphoria. Blood work revealed vitamin B12 deficiency, and abnormalities were seen on MRI. He was treated with 1000 μg of intramuscular vitamin B12 every other day for 3 doses, followed by 500 μg oral cyanocobalamin daily. He demonstrated a great amount of improvement in his neuropathy during his stay. However, he was still dependent in basic transfers, activities of daily living, and mobility and was discharged to acute rehabilitation. Vitamin B12 deficiency can lead to subacute combined degeneration, which presents with sensory deficits, weakness, ataxia, spasticity, and gait abnormalities. Treatment for SACD should be aggressive and rapid to prevent irreversible neurological deficits. Amid an opioid epidemic, practitioners can easily overlook the use of nitrous oxide and patients may consider this drug to be relatively harmless. This case demonstrates the importance of thorough history taking, patient education, and early recognition and treatment of vitamin B12 deficiency and the deleterious effects that may result without intervention.

Effects of co-ingesting glucose and whey protein on blood glucose, plasma insulin and glucagon concentrations, and gastric emptying, in older men with and without type 2 diabetes.

Co-ingestion of dietary protein with, or before, carbohydrate may be a useful strategy to reduce postprandial hyperglycaemia in younger and older men without type 2 diabetes (T2D), but its effect in older people with T2D is not known. Blood glucose, plasma insulin and glucagon concentrations were measured for 180 min following a drink containing either 30 g glucose (G, 120 kcal), 30 g whey protein (P, 120 kcal), 30 g glucose plus 30 g whey protein (GP, 240 kcal), or control (2 kcal) in older men with T2D (n 10, 77 ± 1 years 31 ± 1.7 kgm GP vs. G (i) markedly reduced the increase in blood glucose concentrations (P < 0.001) and (ii) had a synergistic effect on the increase in insulin concentrations (P < 0.001), in men both with and without T2D. Glucose concentrations were higher in men with, when compared to without, T2D whereas insulin and glucagon concentrations were largely unaffected by the presence of T2D. Gastric emptying was faster in men with than without T2D. We conclude that the ability of whey protein to reduce carbohydrate-induced, postprandial hyperglycaemia is retained in older men with, when compared to without, T2D and that whey protein supplementation may be a useful strategy in the prevention and management of T2D in older people. This article is protected by copyright. All rights reserved.

Relationship of liver fat content with systemic metabolism and chronic complications in patients with type 2 diabetes mellitus.

This study investigated the correlation of liver fat content (LFC) with metabolic characteristics and its association with chronic complications in type 2 diabetes mellitus (T2DM) patients. Eighty-one prospectively enrolled T2DM patients were divided into non-alcoholic fatty liver disease (NAFLD) group and the non-NAFLD group according to the presence of NAFL complications. LFC was determined by MRI IDEAL-IQ Sequence, and patients were divided into 4 groups according to LFC by quartile method. Basic information, metabolic indexes, and occurrence of chronic complications in different groups were analyzed and compared. BMI, SBP, DBP, TG, ALT, AST, GGT, UA, HbA1c, FCP, 2 h CP, HOMA-IR, and HOMA-IS in the NAFLD group were significantly higher than the non-NAFLD group (P < 0.05). The incidences of chronic complications in the NAFLD group were higher than in the non-NAFLD group but not statistically significant (P > 0.05). BMI, SBP, DBP, TC, TG, ALT, AST, FCP, 2 h CP, HOMA-IR, and HOMA-IS showed significant differences between the patients with different LFC, and these indexes were significantly higher in patients with higher LFC than those with lower LFC (P < 0.05). Moreover, diabetes duration, TC, HOMA-IR, and LFC were the risk factors for ASCVD complications, while diabetes duration, TG, and LDL-C were risk factors for DN complications. Also, diabetes duration and SBP were risk factors for both DR and DPN complications in T2DM patients (P < 0.05). LFC is positively correlated with the severity of the systemic metabolic disorder and chronic complications in T2DM patients.

Pre-hyperglycemia immune cell trafficking underlies subclinical diabetic cataractogenesis.

This work elucidates the first cellular and molecular causes of cataractogenesis. Current paradigm presupposes elevated blood glucose as a prerequisite in diabetic cataractogenesis. Novel evidence in our model of diabetic cataract challenges this notion and introduces immune cell migration to the lens and epithelial-mesenchymal transformation (EMT) of lens epithelial cells (LECs) as underlying causes. Paucity of suitable animal models has hampered mechanistic studies of diabetic cataract, as most studies were traditionally carried out in acutely induced hyperglycemic animals. We introduced diabetic cataract in the Nile grass rat (NGR) that spontaneously develops type 2 diabetes (T2D) and showed its closeness to the human condition. Specialized stereo microscopy with dual bright-field illumination revealed novel hyperreflective dot-like microlesions in the inner cortical regions of the lens. To study immune cell migration to the lens, we developed a unique in situ microscopy technique of the inner eye globe in combination with immunohistochemistry. Contrary to the existing paradigm, in about half of the animals, the newly introduced hyper reflective dot-like microlesions preceded hyperglycemia. Even though the animals were normoglycemic, we found significant changes in their oral glucose tolerance test (OGTT), indicative of the prediabetic stage. The microlesions were accompanied with significant immune cell migration from the ciliary bodies to the lens, as revealed in our novel in situ microscopy technique. Immune cells adhered to the lens surface, some traversed the lens capsule, and colocalized with apoptotic nuclei of the lens epithelial cells (LECs). Extracellular degradations, amorphous material accumulations, and changes in E-cadherin expressions showed epithelial-mesenchymal transformation (EMT) in LECs. Subsequently, lens fiber disintegration and cataract progression extended into cortical, posterior, and anterior subcapsular cataracts. Our results establish a novel role for immune cells in LEC transformation and death. The fact that cataract formation precedes hyperglycemia challenges the prevailing paradigm that glucose initiates or is necessary for initiation of the pathogenesis. Novel evidence shows that molecular and cellular complications of diabetes start during the prediabetic state. These results have foreseeable ramifications for early diagnosis, prevention and development of new treatment strategies in patients with diabetes.

The real-world safety profile of sodium-glucose co-transporter-2 inhibitors among older adults (≥ 75 years) a retrospective, pharmacovigilance study.

As indications for sodium-glucose co-transporter-2 inhibitors (SGLT2i) are expanding, a growing number of older adults have become candidates for treatment. We studied the safety profile of SGLT2i among older adults. A retrospective, pharmacovigilance study of the FDAs global database of safety reports. To assess reporting of pre-specified adverse events following SGLT2i among adults (< 75 years) and older adults (≥ 75), we performed a disproportionality analysis using the sex-adjusted reporting odds ratio (adj.ROR). We identified safety reports of 129,795 patients who received non-insulin anti-diabetic drugs (NIAD), including 24,253 who were treated with SGLT2i (median age 60 IQR 51-68 years, 2,339 9.6% aged ≥ 75 years). Compared to other NIAD, SGLT2i were significantly associated with amputations (adj.ROR 355.1 95%CI 258.8 - 487.3 vs adj.ROR 250.2 79.3 - 789.5), Fournier gangrene (adj.ROR 45.0 34.5 - 58.8 vs adj.ROR 88.0 27.0 - 286.6), diabetic ketoacidosis (adj.ROR 32.3 30.0 - 34.8 vs adj.ROR 23.3 19.2 - 28.3), genitourinary infections (adj.ROR 10.3 9.4 - 11.2 vs adj.ROR 8.6 7.2 - 10.3), nocturia (adj.ROR 5.5 3.7 - 8.2 vs adj.ROR 6.7 2.8 - 15.7), dehydration (adj.ROR 2.5 2.3 - 2.8 vs adj.ROR 2.6 2.1 - 3.3), and fractures (adj.ROR 1.7 1.4 - 2.1 vs adj.ROR 1.5 1.02 - 2.1) in both adults and older adults, respectively. None of these safety signals was significantly greater in older adults (P In this global post-marketing study, none of the adverse events was reported more frequently among older adults. Our findings provide reassurance regarding SGLT2i treatment in older adults, although careful monitoring is warranted.

The worsening effect of anemia on left ventricular function and global strain in type 2 diabetes mellitus patients a 3.0 T CMR feature tracking study.

To explore the additive effects of anemia on left ventricular (LV) global strains in patients with type 2 diabetes mellitus (T2DM) with or without anemia via cardiac magnetic resonance (CMR) feature tracking technology. 236 T2DM patients with or without anemia and 67 controls who underwent CMR examination were retrospectively enrolled. LV function parameters, LV global radial peak strain (GRPS), longitudinal peak strain (GLPS), and circumferential peak strain (GCPS) were used to analyze the function and global strain of the heart. One-way analysis of variance and the chi-square test were used for intergroup analysis. Multivariable linear regression analysis was performed for the two T2DM groups to explore factors associated with LV global strains. The T2DM group with anemia was oldest and had a lowest hemoglobin (Hb) concentration, lowest estimated glomerular filtration rate, highest LV end-systolic volume index, highest end-diastolic volume index and highest LV mass index than the control group and T2DM without anemia group (all P ≤ 0.001). Besides, The LV global peak strains in all three directions worsened successively from the control group to the T2DM without anemia group to the T2DM with anemia group (all p < 0.001). Among all clinical indices, the decrease in Hb was independently associated with the worsening in GRPS (β 0.237, p 0.001), GCPS (β 0.326, p < 0.001), and GLPS (β 0.265, p < 0.001). Anemia has additive deleterious effects on LV function and LV global strains in patients with T2DM. Regular detection and early intervention of anemia might be beneficial for T2DM patients.

The antidiabetic drug metformin aids bacteria in hijacking vitamin B12 from the environment through RcdA.

Years of use of the antidiabetic drug metformin has long been associated with the risk of vitamin B12 (B12) deficiency in type 2 diabetes (T2D) patients, although the underlying mechanisms are unclear. Accumulating evidence has shown that metformin may exert beneficial effects by altering the metabolism of the gut microbiota, but whether it induces human B12 deficiency via modulation of bacterial activity remains poorly understood. Here, we show that both metformin and the other biguanide drug phenformin markedly elevate the accumulation of B12 in E. coli. By functional and genomic analysis, we demonstrate that both biguanides can significantly increase the expression of B12 transporter genes, and depletions of vital ones, such as tonB, nearly completely abolish the drugs effect on bacterial B12 accumulation. Via high-throughput screens in E. coli and C. elegans, we reveal that the TetR-type transcription factor RcdA is required for biguanide-mediated promotion of B12 accumulation and the expressions of B12 transporter genes in bacteria. Together, our study unveils that the antidiabetic drug metformin helps bacteria gather B12 from the environment by increasing the expressions of B12 transporter genes in an RcdA-dependent manner, which may theoretically reduce the B12 supply to T2D patients taking the drug over time.

Novel loci for hyperglycemia identified by QTL mapping of longitudinal phenotypes and congenic analysis.

We previously reported that four hyperglycemia loci are located on three chromosomes in the Nagoya-Shibata-Yasuda (NSY) mouse model, commonly used to study type 2 diabetes. However, we did not search for hyperglycemia loci across all chromosomes. In this study, we performed quantitative trait loci (QTLs) mapping of longitudinal phenotypes from crosses between NSY (hyperglycemic) and C3H (normoglycemic) mice. We identified four new QTLs for hyperglycemia, namely Nidd5nsy, Nidd6nsy, Nidd1c3h, and Nidd2c3h, on Chromosome 1, 4, 10, and 13, respectively. These QTLs were associated with hyperglycemia in young mice and had attenuated effects in older mice. Nidd5nsy and Nidd6nsy were hyperglycemic with NSY alleles, and Nidd1c3h and Nidd2c3h were hyperglycemic with C3H alleles. We further bred Nidd5nsy congenic mice and demonstrated that Nidd5nsy has a strong effect on hyperglycemia when young, accompanied by insulin resistance and visceral fat accumulation. These results showed that the effects of individual QTLs strengthened or weakened with age, and that the sum of the effects of QTLs captured the age-related deterioration of glucose tolerance in individuals. Our results support the importance of longitudinal phenotypes in the genetic analysis of polygenic traits and have implications for the genetic basis and pathogenesis of type 2 diabetes in humans.

Bariatric surgery in a patient with cystic fibrosis and diabetes A case report.

Cystic fibrosis (CF) is incurable and chronic, causing severe multisystemic damage and long-term complications. The most prominent extrapulmonary long-term complication is CF-related diabetes, which is the most reported form of diabetes in individuals with cystic fibrosis. Here we present the first case of an individual with cystic fibrosis who developed type 2 diabetes due to obesity rather than CF-related diabetes. The type 2 diabetes went into remission due to extreme weight loss after gastric bypass surgery. To our knowledge, this case is also the first report describing the effect of bariatric surgery in a patient with CF. This case demonstrates that patients with CF may present with type 2 diabetes instead of CF-related diabetes. Differential diagnosis of these two types of diabetes is essential for optimal treatment and quality of life.

The association between plasma zinc concentrations and markers of glucose metabolism in adults in Cameroon.

An abnormal Zn status has been suggested to play a role in the pathogenesis of type 2 diabetes. However, epidemiological studies of the relationship between plasma Zn concentrations and diabetes are sparse and inconclusive. We aimed to investigate the association between plasma Zn concentrations and glycaemic markers (fasting glucose, 2-h glucose and homeostatic model assessment of insulin resistance) in rural and urban Cameroon. We studied 596 healthy adults (63·3 % women) aged 25-55 years in a population-based cross-sectional study. The mean plasma Zn concentration was 13·7 ± 2·7 µmolL overall, with higher levels in men (14·4 ± 2·9 µmoll) than in women (13·2 ± 2·6 µmoll),

Interactions between structure and function of resistant glucans for alleviating type 2 diabetes mellitus (T2DM) and its complications in mice.

Resistant glucan, a functional dietary fiber, has been shown to alleviate type 2 diabetes mellitus (T2DM) and its complications in clinical studies. However, the interactions between the special structure of resistant glucan and the metabolism-related pathways in T2DM have not yet been systematically studied. This study identified the structural differences between resistant glucans prepared by new and old methods. Oral gavage with two resistant glucans in T2DM mice, led to significant improvements in glucose and lipid metabolism as measured by related indicators (including gut microbiota, fecal metabolites, and physiological and biochemical indexes). According to these results, in addition to van der Waals forces, micelle formation, and hydrogen bonding, the branching structures of resistant glucans produced more hydroxyl, carbonyl, and keto groups that linked cholesterols, cholesterol esters, and low-density lipoprotein intermediates. Moreover, after lipid clearing, the metabolic environment was more conducive to the proliferation of specific gut microbiota (including Phascolarctobacterium, Prevotella, Butyricicoccus, Weissella, and Anaerostipes) with decreasing abundance ratios of Firmicutes and Bacteroides. This facilitated the synthesis of high-density lipoprotein, conversion of cholesterol into coprostanol, and production of short-chain fatty acids and bile acids. Our findings provide a foundation for comprehensive investigation of the structure of resistant glucan in the promotion and prevention of T2DM.

Molecular mechanism of insulin aggregation in the presence of a cationic surfactant.

Protein aggregation and amyloid fibrillation are connected with neurodegenerative disorders. Insulin, a small molecular weight protein related to type II diabetes, has been shown to self-assemble to form protein aggregates. In this work, we investigated the effects of cetyltrimethylammonium bromide (CTAB) of insulin on the in vitro aggregation process at pH 7.4 and 2.0. The aggregation tendency of insulin was measured using a variety of biophysical approaches, including turbidity measurements, light scattering, far UV-CD, ThT dye binding, and transmission electron microscopy. The turbidity results demonstrated that at pH 7.4, a low concentration of CTAB (30-180 μM) causes insulin aggregation but at higer concentration (>180 μM) aggregation was not seen. However, at pH 2.0, both low as well as high concentrations of CTAB were unable to promote insulin aggregation. The ThT dye binding and far-UV CD data suggest that aggregation induced by CTAB is not having an ordered structure. Insulin treated with higher concentrations (>180 μM) of CTAB, the insulin gained a secondary structure. The possible cause of inducing aggregation in insulin is electrostatic and hydrophobic interaction because insulin contains a net negative charge at pH 7.4 and no aggregation at pH 2.0 due to electrostatic repulsion.

All-cause mortality after hypoglycemic and hyperglycemic emergencies among U.S. adults with diabetes, 2011-2020.

Estimated all-cause mortality within 30-days of hypoglycemic emergencies is 0.8 % in adults with type 1 diabetes and 1.7 % with type 2 diabetes and within 30-days of hyperglycemic emergencies, it is 1.2 % with type 1 diabetes and 2.8 % with type 2 diabetes. These rates changed little between 2011 and 2020.

Glucometabolic perturbations in type 2 diabetes mellitus and coronavirus disease 2019 causes, consequences, and how to counter them using novel antidiabetic drugs.

The growing amount of evidence suggests the existence of a bidirectional relation between coronavirus disease 2019 (COVID-19) and type 2 diabetes mellitus (T2DM), as these two conditions are worsening each other, causing a significant healthcare and socioeconomic burden. The alterations in innate and adaptive cellular immunity, adipose tissue, alveolar, and endothelial dysfunction, hypercoagulation, propensity to an increased viral load, and chronic diabetic complications are all associated with glucometabolic perturbations characteristic for T2DM patients, and predispose them to severe forms and mortality of COVID-19. On the other hand, severe acute respiratory syndrome coronavirus 2 infection negatively impacts glucose homeostasis due to its effects on insulin sensitivity and β-cell function, further aggravating the preexisting glucometabolic perturbations in individuals with T2DM. Thus, we are in the urgent need for the most effective ways of countering these glucometabolic disturbances occurring during the acute COVID-19 illness in T2DM patients. The novel classes of antidiabetic medications (dipeptidyl peptidase 4 inhibitors (DPP-4is), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose co-transporter-2 inhibitors (SGLT-2is) are considered as candidate drugs for this purpose. The aim of this review article was to summarize current knowledge regarding the glucometabolic disturbances during acute COVID-19 illness in T2DM patients and the potential ways to tackle those using novel antidiabetic medications. Recent observational data suggest that preadmission use of GLP-1 RAs and SGLT-2is are associated with a decreased, while the preadmission use of DPP-4is is associated with an increased in-hospital mortality of T2DM patients with COVID-19. Although these results provide further evidence for the widespread use of these two classes of medications in the COVID-19 era, dedicated randomized controlled trials analyzing the effects of in-hospital use of novel antidiabetic agents in T2DM patients with COVID-19 are needed.

Loci for insulin processing and secretion provide insight into type 2 diabetes risk.

Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10

Quantifying the Relationship Between Physical Activity Energy Expenditure and Incident Type 2 Diabetes A Prospective Cohort Study of Device-Measured Activity in 90,096 Adults.

To investigate the association between accelerometer-derived physical activity energy expenditure (PAEE) and incident type 2 diabetes (T2D) in a cohort of middle-aged adults and within subgroups. Data were from 90,096 UK Biobank participants without prevalent diabetes (mean 62 years of age 57% women) who wore a wrist accelerometer for 7 days. PAEE was derived from wrist acceleration using a population-specific method validated against doubly labeled water. Logistic regressions were used to assess associations between PAEE, its underlying intensity, and incident T2D, ascertained using hospital episode and mortality data up to November 2020. Models were progressively adjusted for demographic, lifestyle factors, and BMI. The association between PAEE and T2D was approximately linear (n 2,018 events). We observed 19% (95% CI 17-21) lower odds of T2D per 5 kJ · kg-1 · d-1 in PAEE without adjustment for BMI and 11% (9-13) with BMI adjustment. The association was stronger in men than women and weaker in those with obesity and higher genetic susceptibility to obesity. There was no evidence of effect modification by genetic susceptibility to T2D or insulin resistance. For a given level of PAEE, odds of T2D were lower among those engaging in more moderate-to-vigorous activity. There was a strong linear relationship between PAEE and incident T2D. A difference in PAEE equivalent to an additional daily 20-min brisk walk was associated with 19% lower odds of T2D. The association was broadly similar across population subgroups, supporting physical activity for diabetes prevention in the whole population.

Mobile Health Apps for the Control and Self-management of Type 2 Diabetes Mellitus Qualitative Study on Users Acceptability and Acceptance.

Mobile health apps are promising tools to help patients with type 2 diabetes mellitus (T2DM) improve their health status and thereby achieve diabetes control and self-management. Although there is a wide array of mobile health apps for T2DM available at present, apps are not yet integrated into routine diabetes care. Acceptability and acceptance among patients with T2DM is a major challenge and prerequisite for the successful implementation of apps in diabetes care. This study provides an in-depth understanding of the perceptions of patients with T2DM before use (acceptability) and after use (acceptance) regarding 4 different mobile health apps for diabetes control and self-management. A descriptive qualitative research design was used in this study. Participants could choose 1 of the 4 selected apps for diabetes control and self-management (ie, Clear.bio in combination with FreeStyle Libre, mySugr, MiGuide, and Selfcare). The selection was based on a systematic analysis of the criteria for (functional) requirements regarding monitoring, data collection, provision of information, coaching, privacy, and security. To explore acceptability, 25 semistructured in-depth interviews were conducted with patients with T2DM before use. This was followed by 4 focus groups to discuss the acceptance after use. The study had a citizen science approach, that is, patients with T2DM collaborated with researchers as coresearchers. All coresearchers actively participated in the preparation of the study, data collection, and data analysis. Data were collected between April and September 2021. Thematic analysis was conducted using a deductive approach using AtlasTi9. In total, 25 coresearchers with T2DM participated in this study. Of them, 12 coresearchers tested Clear, 5 MiGuide, 4 mySugr, and 4 Selfcare. All coresearchers participated in semistructured interviews, and 18 of them attended focus groups. Personal health was the main driver of app use. Most coresearchers were convinced that a healthy lifestyle would improve blood glucose levels. Although most coresearchers did not expect that they need to put much effort into using the apps, the additional effort to familiarize themselves with the app use was experienced as quite high. None of the coresearchers had a health care professional who provided suggestions on using the apps. Reimbursement from insurance companies and the acceptance of apps for diabetes control and self-management by the health care system were mentioned as important facilitating conditions. The research showed that mobile health apps provide support for diabetes control and self-management in patients with T2DM. Integrating app use in care as usual and guidelines for health care professionals are recommended. Future research is needed on how to increase the implementation of mobile health apps in current care pathways. In addition, health care professionals need to improve their digital skills, and lifelong learning is recommended.

Potential cost savings in the United States from a reduction in sensor-detected severe hypoglycemia among users of the InPen smart insulin pen system.

Impact of Type D Personality, Role Strain, and Diabetes Distress on Depression in Women With Type 2 Diabetes A Cross-Sectional Study.

Women with diabetes face a significantly elevated risk of developing depression. Clarifying the factors associated with depression is critical to designing more timely interventions for this vulnerable population. This study was developed to examine the impact of Type D personality, diabetes-care-related role strain, and diabetes-related distress on depression in women with Type 2 diabetes. A cross-sectional design was used. Convenience sampling was used to recruit 298 women aged 20-64 years who had been diagnosed with Type 2 diabetes for over 6 months from three outpatient endocrine clinics in Taiwan. Demographic and disease characteristics and Type D personality (negative affectivity and social inhibition), diabetes-care-related role strain, and diabetes-related distress and depression status information were collected using self-reported questionnaires and medical records. The important factors of influence on depression were examined using hierarchical multiple regression. On the basis of the results of the hierarchical multiple regression analysis, age, negative affectivity, diabetes-care-related role strain, and diabetes-related distress were identified as significantly associated with depression, with negative affectivity explaining most (43.4%) of the variance in depression, followed by diabetes-care-related role strain and diabetes-related distress, which respectively explained 3% and 2.5% of the variance. The negative affectivity associated with the Type D personality was shown to be more significantly associated with depression than diabetes-related psychosocial factors such as diabetes-related distress and diabetes-care-related role strain. Timely assessment of negative affectivity and the provision of brief mindfulness intervention to reduce negative affectivity may be useful in preventing depression in women with Type 2 diabetes, whereas addressing diabetes-related distress and diabetes-care-related role strain should not be neglected when providing comprehensive depression-preventing interventions to young women with diabetes.

A novel combination of sitagliptin and melatonin ameliorates T2D manifestations studies on experimental diabetic models.

Type 2 diabetes (T2D) is an endocrine disorder characterized by hyperglycemia, insulin resistance, dysregulated glucose and lipid metabolism, reduced pancreatic β-cell function and mass, and a reduced incretin effect. Circadian rhythm disruption is associated with increased T2D risk. We have investigated the therapeutic potential of a combination of melatonin (M) and sitagliptin (S), a dipeptidyl peptidase IV (DPP-IV) inhibitor, in the amelioration of T2D manifestations in high-fat diet (HFD) induced T2D mouse model and also on β-cell proliferation under gluco-lipotoxicity stress in vitro. For in vivo study, mice were fed with HFD for 25 weeks to induce T2D and were treated with monotherapies and S M for four weeks. For the in vitro study, primary mouse islets were exposed to normal glucose and high glucose palmitate to induce gluco-lipotoxic stress. Our results suggest that monotherapies and S M improve metabolic parameters and glyco-lipid metabolism in the liver and adipose tissue, respectively, and improve mitochondrial function in the skeletal muscle. Moreover, it increases peripheral insulin sensitivity. Our in vitro and in vivo studies suggest that β-cell mass was preserved in all the drug-treated groups. The combination treatment is superior to monotherapies in the management of T2D.

Chaperonin counteracts diet-induced non-alcoholic fatty liver disease by aiding sirtuin 3 in the control of fatty acid oxidation.

The mitochondrial chaperonin heat shock protein (HSP) 60 is indispensable in protein folding and the mitochondrial stress response however, its role in nutrient metabolism remains uncertain. This study investigated the role of HSP60 in diet-induced non-alcoholic fatty liver disease (NAFLD). We studied human biopsies from individuals with NAFLD, murine high-fat-diet (HFD a diet with 60% energy from fat)-induced obesity (DIO), transgenic (Tg) mice overexpressing Hsp60 (Hsp60-Tg), and human HepG2 cells transfected with HSP60 cDNA or with HSP60 siRNA. Histomorphometry was used to assess hepatic steatosis, biochemistry kits were used to measure insulin resistance and glucose tolerance, and an automated home cage phenotyping system was used to assess energy expenditure. Body fat was assessed using MRI. Macrophage infiltration, the lipid oxidation marker 4-hydroxy-2-nonenal (4-HNE) and the oxidative damage marker 8-hydroxy-2-deoxyguanosine (8-OHdG) were detected using immunohistochemistry. Intracellular lipid droplets were evaluated by Nile red staining. Expression of HSP60, and markers of lipogenesis and fatty acid oxidation were quantified using RT-PCR and immunoblotting. Investigations were analysed using the two-way ANOVA test. Decreased HSP60 expression correlated with severe steatosis in human NAFLD biopsies and murine DIO. Hsp60-Tg mice developed less body fat, had reduced serum triglyceride levels, lower levels of insulin resistance and higher serum adiponectin levels than wild-type mice upon HFD feeding. Respiratory quotient profile indicated that fat in Hsp60-Tg mice may be metabolised to meet energy demands. Hsp60-Tg mice showed amelioration of HFD-mediated hepatic steatosis, M1M2 macrophage dysregulation, and 4-HNE and 8-OHdG overproduction. Forced HSP60 expression reduced the mitochondrial unfolded protein response, while preserving mitochondrial respiratory complex activity and enhancing fatty acid oxidation. Furthermore, HSP60 knockdown enhanced intracellular lipid formation and loss of sirtuin 3 (SIRT3) signalling in HepG2 cells upon incubation with palmitic acid (PA). Forced HSP60 expression improved SIRT3 signalling and repressed PA-mediated intracellular lipid formation. SIRT3 inhibition compromised HSP60-induced promotion of AMP-activated protein kinase (AMPK) phosphorylation and peroxisome proliferator-activated receptor α (PPARα levels), while also decreasing levels of fatty acid oxidation markers. Mitochondrial HSP60 promotes fatty acid oxidation while repressing mitochondrial stress and inflammation to ameliorate the development of NAFLD by preserving SIRT3 signalling. This study reveals the hepatoprotective effects of HSP60 and indicates that HSP60 could play a fundamental role in the development of therapeutics for NAFLD or type 2 diabetes.

Therapeutic inertia related to the injectable glucagon-like peptide-1 receptor agonists dulaglutide and semaglutide in patients with type 2 diabetes in UK primary care.

To determine the extent of therapeutic inertia related to the weekly injectable glucagon-like peptide-1 receptor agonists dulaglutide and semaglutide in patients with type 2 diabetes (T2D) in the United Kingdom. Adults with T2D who received their first primary care prescription of dulaglutide or semaglutide between January and July 2019 were identified from the UK Clinical Practice Research Datalink GOLD primary care database. Doses prescribed, glycated haemoglobin (HbA1c), body mass index (BMI) and concomitant T2D medications were assessed at first prescription and at 3, 6 and 9 months. Of the patients prescribed dulaglutide (N 748 mean SD age 59.0 11.2 years) and semaglutide (N 437 mean SD age 58.4 10.6 years), 93.0% and 89.0%, respectively, had an HbA1c level ≥7.5% (≥58.46 mmolmol), and 56.4% and 54.9%, respectively, had an HbA1c level ≥9.0% (≥74.86 mmolmol), at first prescription. At 6 to 9 months, 75.0% of those on dulaglutide 0.75 mg and 57.6% of those on semaglutide 0.25 mg or 0.5 mg had an HbA1c level ≥7.5% (≥58.46 mmolmol). At 9 months, 21.9% of the dulaglutide cohort were on the suboptimal dose of 0.75 mg, and 46.1% of the semaglutide cohort were on the suboptimal doses of 0.25 mg or 0.5 mg. Multiple examples of therapeutic inertia were identified, including first prescription at HbA1c levels considerably above target and failure to escalate to optimal doses even with evidence of suboptimal metabolic control. A substantial proportion of patients therefore did not achieve optimal HbA1c targets.