Diabetes In Cohort Research Articles

Pattern of Musculoskeletal Manifestation in Patient with Diabetes Mellitus

Background: Diabetic mellitus (DM) both type 1 and type 2 increasing dramatically throughout worldwide. DM involved all the vital organs including musculoskeletal system. Objective: The purpose of study was to find out patterns of musculoskeletal manifestation (MSM) in diabetic patients & to find out a strategy to improve the outcome of the MS complications in patients with Diabetes Mellitus. Material and Methods: This was hospital based observational study conducted on 143 diabetics patients with musculoskeletal manifestations, both men and women (aged e”15- 70 years) visited in outpatient department and hospital admitted patient in a tertiary care of teaching hospital. Patterns were defined by a meticulous history, relevant general and systemic examination & with the aid of musculoskeletal (MS) Function Assessment semi structured Questionnaire. Results: MSM are common among patients with type 2 diabetes Out of 143 patients in our study 103(72.03%) were Male and 40(27.97%) were female, and male –female ratio 2.57:1. The age distribution of study patients was 15 to 70 years. Overall, 72.03.% of patients were among the 40-59 years old and about 20.28% were 60 years and mean age of the patients was 55±5. Above which is statistically significant (P= 0.048). The shoulder involvement as adhesive capsulitis (frozen shoulder) was found among 69(48.25%) on the diabetic cohort and statistically significant (P= <.05) and mostly among the housewife (27.99%) and manual worker like cultivator (13.99%). Degenerative osteoarthritis was commonly associated with MSM with DM than inflammatory arthritis. Conclusion: In our study shows degenerative, non-inflammatory MSM are common among the diabetic patients that leads to significant pain and disability that directly related with poor glycemic control and co-morbidities like stroke and obesity. Early recognition of these complications, and multidisciplinary management between diabetes and rheumatology specialists is necessary to reduce morbidity. EWMCJ Vol. 12, No. 1&2, January-July 2024: 66-69

Aspartate aminotransferase to alanine aminotransferase ratio and short-term prognosis of patients with type 2 diabetes hospitalized for heart failure

IntroductionWe aimed to explore the prognostic value of the aspartate aminotransferase to alanine aminotransferase (AST/ALT) ratio in non-surgical patients with type 2 diabetes hospitalized for heart failure.Material and methodsUsing a large electronic medical record-based cohort of diabetes in China (WECODe), we gathered data on non-surgical hospitalized patients with type 2 diabetes and heart failure from 2011 to 2019. Baseline AST/ALT ratio was calculated. The primary outcomes were all-cause death within 30 days after discharge, composite cardiac events, major acute kidney injury, and major systemic infection. A multivariable Cox proportional regression model was utilized to evaluate the association between the AST/ALT ratio and outcomes.ResultsThis retrospective cohort included 8,073 patients (39.4% women) with type 2 diabetes hospitalized for heart failure. The median age was 71 years. Higher AST/ALT ratio was associated with higher risks of poor endpoints (with per standard deviation increment in AST/ALT ratio, for death within 30 days after discharge: adjusted hazard ratio [HR], 1.35, 95% confidence interval [CI], 1.21 to 1.50; for composite cardiac events: HR, 1.18, 95% CI: 1.06 to 1.31). Compared to patients in the lowest quartile for the AST/ALT ratio, those in the highest quartile have elevated risk of death within 30 days after discharge and major systemic infection (HRs [95% CIs]: 1.61 [1.18 to 2.19] and 1.28 [1.06 to 1.56], respectively). Subgroup analyses and sensitivity analyses confirmed the robustness of the findings.ConclusionsType 2 diabetes patients hospitalized for heart failure with the AST/ALT ratio in the highest quartile face a poor short-term prognosis.

The Contribution of Postprandial Glucose Levels to Hyperglycemia in Type 2 Diabetes Calculated from Continuous Glucose Monitoring Data: Real World Evidence from the DIALECT-2 Cohort.

Traditional glycemic monitoring in type 2 diabetes is limited, whereas continuous glucose monitoring (CGM) offers better insights into glucose fluctuations. This study aimed to determine the correlations and relative contributions of fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels to hyperglycemia. We utilized CGM and recorded carbohydrate intake data from lifestyle diaries of 59 patients enrolled in the Diabetes and Lifestyle Cohort Twente (DIALECT-2). Correlations between FPG and the glucose management indicator (GMI), FPG and Time Above Range (TAR), PPG and GMI, and PPG and TAR were conducted. Daily and mealtime relative contributions of PPG and FPG to glycated hemoglobin (HbA1c) and GMI were determined, considering two ranges: on target (<7.0%, 53 mmol/mol) and not on target (≥7.0%, 53 mmol/mol). Correlations between mealtime PPG and carbohydrate consumption were examined. FPG and PPG correlated with GMI (r = 0.82 and 0.41, respectively, p < 0.05). The relative contribution of PPG in patients with HbA1c, GMI, and TAR values not on target was lower than in patients with HbA1c, GMI, and TAR values on target. When analyzing different mealtimes, patients with target GMI values had a higher PPG (73 ± 21%) than FPG after breakfast (27 ± 21%, p < 0.001). Individuals with elevated GMI levels had lower PPG after lunch (30 ± 20%), dinner (36 ± 23%), and snacks (34 ± 23%) than FPG. PPG after breakfast positively correlated (r = 0.41, p < 0.01) with breakfast carbohydrate intake. Both PPG and FPG contribute to hyperglycemia, with PPG playing a larger role in patients with better glycemic control, especially after breakfast. Targeting PPG may be crucial for optimizing glucose management.

Altered RBC deformability in diabetes: clinical characteristics and RBC pathophysiology

BackgroundReduced red blood cell deformability (RBCD) is associated with diabetic vascular complications, but early pathophysiological RBC changes and predictive demographic and clinical factors in populations with diabetes are unclear. An understanding of early diabetes-specific RBC changes associated with impaired RBCD is essential in investigating mechanisms that predispose to diabetic vascular complications.MethodsWe conducted an outpatient cross-sectional study of participants in a well-controlled diabetes cohort (N81) and nondiabetic controls (N78) at the National Institutes of Health. First, between-group differences in RBCD measures were assessed with shear stress-gradient ektacytometry. Differences in structural RBC parameters were assessed using osmotic gradient ektacytometry and NaCl osmotic fragility. Functional RBC changes were assessed using hemoglobin-oxygen dissociation: p50.ResultsAll shear-stress gradient RBCD measures were significantly altered in the diabetes cohort vs. nondiabetic controls, even after adjustment for confounding covariates (p < 0.001). Adjusted for diabetes-status and demographic factors, significant predictors of reduced RBCD included older age, Black race, male gender, hyperglycemia, and vascular complications (all p < 0.05). Reduced RBCD was also associated with aberrant osmotic-gradient parameters, with a left-shift on osmotic gradient profile indicative of dehydrated RBCs in diabetes. A structure-function relationship was observed with reduced RBCD associated with reduced osmotic fragility (P < 0.001) and increased hemoglobin-oxygen dissociation (P < 0.01).ConclusionsFindings suggest impaired RBCD incurs similar demographic and clinical risk factors as diabetic vascular disease, with early pathophysiological RBC changes indicative of disordered RBC hydration in diabetes. Findings provide strong evidence for disordered oxygen release as a functional consequence of reduced RBCD.Clinical trial number: NCT00071526.

Precisely Engineering a ROS‐Regulatable Decellularized Matrix to Rejuvenate Endogenous Repair for Heart Valve Remodeling in Diabetic Cohort

AbstractThe reconstruction of a heart valve through in situ tissue engineering remains a formidable challenge, particularly for patients with diabetes mellitus, because the pathophysiological alterations associated with diabetes substantially impair the cardiovascular system's intrinsic repair capacity. In this study, reactive oxygen species (ROS) regulation are integrated into the fabrication of pro‐endothelialization interfaces to counteract the adverse repair environment. Specifically, a heparin‐mimicking alginate‐derived glycopeptide and the natural ROS scavenger melanin are modified onto the surface of a decellularized extracellular matrix (dECM). This tailored interface significantly enhances endothelial cell (EC) adhesion while reducing platelet adhesion. The incorporation of melanin effectively suppresses ROS elevation in ECs and macrophages under hyperglycemic conditions. Consequently, this intervention promotes EC rejuvenation by enhancing proliferation, migration, and anti‐apoptotic capabilities, while concurrently attenuating the release of inflammatory and pro‐fibrotic factors by macrophages. The dECM is intravascularly implanted in a diabetic rabbit model after being fabricated into a covered stent, demonstrating favorable remodeling characteristics such as enhanced endothelialization and reduced fibrotic deposition. This scaffold design, specifically tailored to the pathological conditions of diabetes, offers a precise biomaterial strategy for in situ heart valve tissue engineering.

Importance of the Hemoglobin Glycation Index for Risk of Cardiovascular and Microvascular Complications and Mortality in Individuals with Type 2 Diabetes.

This study investigated the prognostic importance of the hemoglobin glycation index (HGI) for macrovascular and microvascular outcomes, mortality, and hypoglycemia occurrence in a type 2 diabetes cohort and compared it to glycated hemoglobin (HbA1c). Baseline and mean first-year HGI and HbA1c, and the variability thereof, were assessed in 687 individuals with type 2 diabetes (median follow-up, 10.6 years). Multivariable Cox regression was conducted to evaluate the associations of HGI and HbA1c parameters with macrovascular (total and major cardiovascular events) and microvascular outcomes (microalbuminuria, advanced renal failure, retinopathy, and peripheral neuropathy), mortality (all-cause and cardiovascular), and moderate/severe hypoglycemia occurrence. During follow-up, there were 215 total cardiovascular events (176 major) and 269 all-cause deaths (131 cardiovascular). Microalbuminuria developed in 126 patients, renal failure in 104, retinopathy in 161, and neuropathy in 177. There were 90 hypoglycemia episodes. Both HGI and HbA1c predicted all adverse outcomes, except microalbuminuria and hypoglycemia. Their adjusted risks were roughly equivalent for all outcomes. For example, the adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), estimated for 1 standard deviation increments, of mean first-year HGI were 1.23 (1.05 to 1.44), 1.20 (1.03 to 1.38), 1.36 (1.11 to 1.67), 1.28 (1.09 to 1.67), and 1.29 (1.09 to 1.54), respectively, for cardiovascular events, all-cause mortality, renal failure, retinopathy, and neuropathy; whereas the respective HRs (95% CIs) of mean HbA1c were 1.31 (1.12 to 1.53), 1.28 (1.11 to 1.48), 1.36 (1.11 to 1.67), 1.33 (1.14 to 1.55), and 1.29 (1.09 to 1.53). HGI was no better than HbA1c as a predictor of adverse outcomes in individuals with type 2 diabetes, and its clinical use cannot be currently advised.

Associations between weight self-stigma and healthy diet and physical activity among adults with type 2 diabetes:Cross-sectional results from the second Diabetes MILES - Australia (MILES-2) study.

To examine associations between weight self-stigma and healthy diet or physical activity, and potential moderating effects of self-esteem, diabetes self-efficacy, and diabetes social support, among adults with type 2 diabetes. Diabetes MILES-2 data were used, an Australian cross-sectional online survey. Participants with type 2 diabetes who considered themselves overweight, and reported concern about weight management (N = 726; 48% insulin-treated), completed the Weight Self-Stigma Questionnaire (WSSQ; total score and subscales: self-devaluation, fear of enacted stigma), measures of diabetes self-care (diet, exercise), and hypothesised psychosocial moderators (self-esteem, diabetes self-efficacy, and diabetes social support). Adjusted linear regression tested associations and interaction effects, separately by insulin treatment status. Greater weight self-stigma (WSSQ total) was associated with less optimal dietary self-care (both groups: β = -0.3), and with a lower level of exercise (non-insulin only: β = -0.2; all p < 0.001). All hypothesised moderators were negatively associated with weight self-stigma (range r = -0.2 to r = -0.5). Positive associations were identified between the hypothesised moderators and self-care behaviours (strongest between diet and diabetes self-efficacy, r = > 0.5). No significant interaction effects were observed. This study provides novel evidence of negative associations between weight self-stigma and self-care behaviours among adults with type 2 diabetes. Weight self-stigma is a demonstrated barrier to self-care behaviours in type 2 diabetes cohorts. Acknowledgement and strategies to address weight self-stigma are needed in clinical care and health programmes.

Intravitreal Dexamethasone Implant in Anti-Vascular Endothelial Growth Factor Pretreated Diabetic Macular Edema-A Swiss Cohort Study.

Diabetic macular edema (DME) is a significant cause of visual impairment, often treated with anti-vascular endothelial growth factor (anti-VEGF) agents. However, some patients do not respond adequately to this treatment. This study aims to evaluate the contribution of the intravitreal dexamethasone (DEX) implant as a second-line treatment in DME patients with insufficient response to anti-VEGF therapy or with high treatment burden. This retrospective multicenter cohort study was conducted across seven clinical sites in Switzerland. The study included eyes with active DME that had been pretreated with anti-VEGF for at least six months before receiving DEX therapy. Data were extracted from electronic patient records, focusing on best-corrected visual acuity (BCVA), central subfield thickness (CST), and injection frequency. A total of 95 eyes from 89 patients (38.8% females, mean age 65.6 ± 9.1 years, follow-up time 80.6 ± 38.5 [13.5-166.7] months) were analyzed. Prior to the first DEX implant, eyes had undergone an average of 16.0 ± 13.3 anti-VEGF injections over 32.5 ± 22.4 months. Post-DEX treatment, 22.1% of eyes received DEX monotherapy, 44.2% received a combination of DEX and anti-VEGF, 25.3% continued with anti-VEGF monotherapy, and 8.4% received no further treatment. The number of anti-VEGF injections decreased significantly from 6.4 ± 3.1 in the year before DEX to 1.6 ± 2.4 in the year after DEX (p < 0.001). BCVA remained stable (0.4 ± 0.3 logMAR at baseline, 0.4 ± 0.5 logMAR at 24 months, p = 0.2), while CST improved from 477.7 ± 141.0 to 320.4 ± 125.5 μm (p < 0.001), and the presence of retinal fluid decreased from 98.0% to 61.1% (p = 0.021). During follow-up, 26.3% of eyes required glaucoma medication, 4.2% underwent glaucoma surgery, and 1.1% needed cataract surgery. In real-world clinical settings, the addition of DEX to anti-VEGF therapy in DME patients significantly reduces treatment burden and retinal fluid while maintaining visual function. Treatment decisions should balance anatomical and functional outcomes, considering individual patient needs.

Development and validation of nomograms for predicting cardiovascular disease risk in patients with prediabetes and diabetes

This study aimed to develop and validate distinct nomogram models for assessing CVD risk in individuals with prediabetes and diabetes. In a cross-sectional study design, we examined data from 2294 prediabetes and 1037 diabetics who participated in the National Health and Nutrition Examination Survey, which was conducted in the United States of America between 2007 and 2018. The dataset was randomly divided into training and validation cohorts at a ratio of 0.75–0.25. The Boruta feature selection method was used in the training cohort to identify optimal predictors for CVD diagnosis. A web-based dynamic nomogram was developed using the selected features, which were validated in the validation cohort. The Hosmer–Lemeshow test was performed to assess the nomogram's stability and performance. Receiver operating characteristics and calibration curves were used to assess the effectiveness of the nomogram. The clinical applicability of the nomogram was evaluated using decision curve analysis and clinical impact curves. In the prediabetes cohort, the CVD risk prediction nomogram included nine risk factors: age, smoking status, platelet/lymphocyte ratio, platelet count, white blood cell count, red cell distribution width, lactate dehydrogenase level, sleep disorder, and hypertension. In the diabetes cohort, the CVD risk prediction nomogram included eleven risk factors: age, material status, smoking status, systemic inflammatory response index, neutrophil-to-lymphocyte ratio, red cell distribution width, lactate dehydrogenase, high-density lipoprotein cholesterol, sleep disorder, hypertension, and physical activity. The nomogram models developed in this study have good predictive and discriminant utility for predicting CVD risk in patients with prediabetes and diabetes.

Toward Reliable Symptom Coding in Electronic Health Records for Symptom Assessment and Research: Identification and Categorization of International Classification of Diseases, Ninth Revision, Clinical Modification Symptom Codes.

To date, symptom documentation has mostly relied on clinical notes in electronic health records or patient-reported outcomes using disease-specific symptom inventories. To provide a common and precise language for symptom recording, assessment, and research, a comprehensive list of symptom codes is needed. The International Classification of Diseases, Ninth Revision or its clinical modification ( International Classification of Diseases, Ninth Revision, Clinical Modification ) has a range of codes designated for symptoms, but it does not contain codes for all possible symptoms, and not all codes in that range are symptom related. This study aimed to identify and categorize the first list of International Classification of Diseases, Ninth Revision, Clinical Modification symptom codes for a general population and demonstrate their use to characterize symptoms of patients with type 2 diabetes mellitus in the Cerner database. A list of potential symptom codes was automatically extracted from the Unified Medical Language System Metathesaurus. Two clinical experts in symptom science and diabetes manually reviewed this list to identify and categorize codes as symptoms. A total of 1888 International Classification of Diseases, Ninth Revision, Clinical Modification symptom codes were identified and categorized into 65 categories. The symptom characterization using the newly obtained symptom codes and categories was found to be more reasonable than that using the previous symptom codes and categories on the same Cerner diabetes cohort.

Identifying subtypes of type 2 diabetes mellitus based on real-world electronic medical record data in China

AimsTo replicate the European subtypes of type 2 diabetes mellitus (T2DM) in the Chinese diabetes population and investigate the risk of complications in different subtypes. MethodsA diabetes cohort using real-world patient data was constructed, and clustering was employed to subgroup the T2DM patients. Kaplan–Meier analysis and the Cox models were used to analyze the association between diabetes subtypes and the risk of complications. ResultsA total of 2,652 T2DM patients with complete clustering data were extracted. Among them, 466 (17.57 %) were classified as severe insulin-deficient diabetes (SIDD), 502 (18.93 %) as severe insulin-resistant diabetes (SIRD), 672 (25.34 %) as mild obesity-related diabetes (MOD), and 1,012 (38.16 %) as mild age-related diabetes (MARD). The risk of chronic kidney disease (CKD) and diabetic retinopathy (DR) were different in the four subtypes. Compared with MARD, SIRD had a higher risk of CKD (HR 2.40 [1.16, 4.96]), and SIDD had a higher risk of DR (HR 2.16 [1.11, 4.20]). The risk of stroke and coronary events had no difference. ConclusionsThe European T2DM subtypes can be replicated in the Chinese diabetes population. The risk of CKD and DR varied among different subtypes, indicating that proper interventions can be taken to prevent specific complications in different subtypes.

Rate and risk factors of kidney function decline among South Asians with type 2 diabetes: analysis of the CARRS Trial

IntroductionPeople with diabetes are at risk of developing chronic kidney disease. However, limited data are available to quantify their risk of kidney function decline in South Asia. This study evaluates...

Multiple urinary peptides are associated with hypertension: a link to molecular pathophysiology.

Hypertension is a common condition worldwide; however, its underlying mechanisms remain largely unknown. This study aimed to identify urinary peptides associated with hypertension to further explore the relevant molecular pathophysiology. Peptidome data from 2876 individuals without end-organ damage were retrieved from the Human Urinary Proteome Database, belonging to general population (discovery) or type 2 diabetic (validation) cohorts. Participants were divided based on systolic blood pressure (SBP) and diastolic BP (DBP) into hypertensive (SBP ≥140 mmHg and/or DBP ≥90 mmHg) and normotensive (SBP <120 mmHg and DBP <80 mmHg, without antihypertensive treatment) groups. Differences in peptide abundance between the two groups were confirmed using an external cohort ( n = 420) of participants without end-organ damage, matched for age, BMI, eGFR, sex, and the presence of diabetes. Furthermore, the association of the peptides with BP as a continuous variable was investigated. The findings were compared with peptide biomarkers of chronic diseases and bioinformatic analyses were conducted to highlight the underlying molecular mechanisms. Between hypertensive and normotensive individuals, 96 (mostly COL1A1 and COL3A1) peptides were found to be significantly different in both the discovery (adjusted) and validation (nominal significance) cohorts, with consistent regulation. Of these, 83 were consistently regulated in the matched cohort. A weak, yet significant, association between their abundance and standardized BP was also observed. Hypertension is associated with an altered urinary peptide profile with evident differential regulation of collagen-derived peptides. Peptides related to vascular calcification and sodium regulation were also affected. Whether these modifications reflect the pathophysiology of hypertension and/or early subclinical organ damage requires further investigation.

Data-driven Cluster Analysis Reveals Increased Risk for Severe Insulin-Deficient Diabetes in Black/African Americans.

Diabetes is a heterogenic disease and distinct clusters have emerged, but the implications for diverse populations have remained understudied. Apply cluster analysis to a diverse diabetes cohort in the U.S. Deep South. Retrospective hierarchical cluster analysis of electronic health records from 89,875 patients diagnosed with diabetes between January 1, 2010, and December 31, 2019, at the Kirklin Clinic of the University of Alabama at Birmingham, an ambulatory referral center. Adult patients with ICD diabetes codes were selected based on available data for 6 established clustering parameters (GAD-autoantibody; HbA1c; BMI; Diagnosis age; HOMA2-B; HOMA2-IR); ∼42% were Black/African American. Diabetes subtypes and their associated characteristics in a diverse adult population based on clustering analysis. We hypothesized that racial background would affect the distribution of subtypes. Outcome and hypothesis were formulated prior to data collection. Diabetes cluster distribution was significantly different in Black/African Americans compared to Whites (P<0.001). Black/African Americans were more likely to have severe insulin deficient diabetes (SIDD) (OR 1.83, CI 1.36-2.45, P<0.001), associated with more serious metabolic perturbations and a higher risk for complications (OR 1.42, 95% CI 1.06-1.90, P=0.020). Surprisingly, Black/African Americans specifically had more severe impairment of beta cell function (HOMA2-B, C-peptide) (P<0.001), while not being more obese or insulin resistant. Racial background greatly influences diabetes cluster distribution and Black/African Americans are more frequently and more severely affected by SIDD. This may further help explain the disparity in outcomes and have implications for treatment choice.

Pre-gestational diabetes mellitus, gestational diabetes mellitus, and its association with the MTHFR C677T polymorphism.

Gestational diabetes mellitus (GDM) is a common condition during pregnancy and is associated with an increased risk of pre-eclampsia. The methylenetetrahydrofolate reductase (MTHFR) gene plays a crucial role in folate metabolism and has been implicated in GDM. To investigate the relationship between the MTHFR C677T gene polymorphism and the conditions of GDM and gestational prediabetes in pregnant women. A case-control study was conducted in 114 pregnant women with GDM and 96 pregnant women without GDM, from the first trimester to the prenatal examination at Can Tho Obstetrics Hospital. The pregnant women underwent a 1-hour (G1) and 2-hour (G2) oral glucose tolerance test (OGTT) and genetic polymorphism analysis based on real-time PCR technique. In pregnant women with GDM, weight, concentrations of G0, G1, G2, and folic acid were higher than those in the non-GDM group, with P < .05. When analyzing the subgroup without gestational diabetes, we found that the rate of prediabetes was 16.6% (16/96 pregnant women). In this group, blood glucose levels at 1 hour and 2 hours during the OGTT were higher compared to the normal glucose group (P < .05). A 2-hour post-OGTT glucose level of 7.78 mmol/L had a sensitivity of 93.8%, a specificity of 100%, and an area under the curve of 0.987 for diagnosing gestational prediabetes (P < .001). However, there were no statistically significant differences in the CC, CT, and TT polymorphisms of the MTHFR C677T gene among pregnant women with or without pre-gestational and GDM. Both fasting blood glucose and 2-hour glucose concentrations during the OGTT, as well as folic acid concentrations, were higher in both the pre-gestational and GDM groups compared to the non-gestational diabetes cohort. However, the analysis of MTHFR C677T polymorphisms revealed no statistically significant differences among the groups, highlighting the necessity for more extensive investigations to gain deeper insights into this relationship.

Examining the Impact of Ertugliflozin on Cardiovascular Outcomes in Patients with Diabetes and Metabolic Syndrome: A Systematic Review of Clinical Trials.

Cardiovascular diseases (CVDs) constitute a significant cause of morbidity and mortality globally, particularly among individuals with type 2 diabetes mellitus (T2DM). Ertugliflozin, a Sodium-Glucose Co-transporter-2 (SGLT2) inhibitor, is hypothesized to confer cardiovascular protection; however, long-term follow-up studies are necessary to support the hypothesis. This systematic review was conducted to evaluate the cardiovascular effects of ertugliflozin in diabetic versus non-diabetic cohorts, focusing on major adverse cardiovascular events (MACEs), hospitalizations for heart failure, and cardiovascular mortality. Adhering to PRISMA guidelines, the review encompassed studies indexed in PubMed, Scopus, and Web of Science up to March 2024. Eligibility was restricted to studies involving T2DM patients undergoing ertugliflozin treatment with reported outcomes relevant to cardiovascular health. Out of 767 initially identified articles, 6 met the inclusion criteria. Data concerning hazard ratios (HR) and confidence intervals (CI) were extracted to compare the effects of ertugliflozin with those of a placebo or other standard therapies. The collective sample size across these studies was 8246 participants. Ertugliflozin was associated with a significant reduction in hospitalizations for heart failure relative to a placebo (HR 0.70, 95% CI 0.54-0.90, p < 0.05). Furthermore, when combined with metformin, ertugliflozin potentially reduced MACEs (HR 0.92, 95% CI 0.79-1.07), although this finding did not reach statistical significance. Importantly, for patients with pre-existing heart failure, ertugliflozin significantly decreased the exacerbations of heart failure (HR 0.53, 95% CI 0.33-0.84, p < 0.01). Overall, ertugliflozin markedly reduces hospitalizations due to heart failure in T2DM patients and may improve additional cardiovascular outcomes. These results endorse the integration of ertugliflozin into therapeutic protocols for T2DM patients at elevated cardiovascular risk and substantiate its efficacy among SGLT2 inhibitors. Continued investigations are recommended to delineate its long-term cardiovascular benefits in diverse patient populations, including the potential impact on arrhythmias.

Lipid Levels and Risk of Diabetic Polyneuropathy in 2 Danish Type 2 Diabetes Cohorts.

Reduction of blood lipids may aid in preventing diabetic polyneuropathy (DPN), but evidence remains conflicting. We investigated the association between lipid parameters and DPN risk in individuals with type 2 diabetes mellitus (T2DM). We conducted a population-based cohort study of individuals with newly diagnosed T2DM and a cross-sectional study using a clinically recruited T2DM cohort. Triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and non-HDL cholesterol were measured in routine diabetes care. Each lipid parameter was categorized according to the latest cutoffs in clinical guidelines on dyslipidemia. DPN was assessed with validated hospital diagnosis codes in the population-based cohort and with the Michigan Neuropathy Screening Instrument questionnaire in the clinical cohort. We calculated hazard ratios (HRs) using Cox regression and prevalence ratios (PRs) using Poisson regression. We included 61,853 individuals in the population-based cohort (median age 63 [quartiles 54-72] years) and 4,823 in the clinical cohort (median age 65 [quartiles 57-72] years). The incidence rate of hospital-diagnosed DPN in the population-based cohort was 3.6 per 1000 person-years during a median follow-up of 7.3 years. Achieving guideline targets for HDL, LDL, and non-HDL cholesterol showed no association with DPN risk. By contrast, adjusted HRs (95% CI) for DPN were 1.02 (0.89-1.18) for triglyceride levels between 150 and 204 mg/dL (1.7-2.3 mmol/L) and 1.28 (1.13-1.45) for levels >204 mg/dL (2.3 mmol/L). In the clinical cohort with a DPN prevalence of 18%, DPN associated strongly with triglycerides >204 mg/dL (2.3 mmol/L) with an adjusted PR (95% CI) of 1.40 (1.21-1.62). The prevalence of DPN was modestly elevated for individuals with HDL cholesterol <39 mg/dL (1.0/1.3 mmol/L) in men and <50 mg/dL (1.3 mmol/L) in women (PR 1.13 [0.99-1.28]) and for individuals with non-HDL cholesterol >131 mg/dL (3.4 mmol/L) (PR 1.27 [1.05-1.52]). In both cohorts, spline models showed an increasing risk of DPN starting from triglyceride levels >124 mg/dL (1.4 mmol/L). All results were similar among statin users. High triglyceride levels are a strong DPN risk factor. Future intervention studies shall determine whether triglyceride reduction is more important for DPN prevention than reduction of other lipids.

Metformin use and survival in people with ovarian cancer: A population-based cohort study from British Columbia, Canada

ObjectivesThere is an active debate regarding whether metformin use improves survival in people with ovarian cancer. We examined this issue using methods designed to avoid immortal time bias—as bias that occurs when participants in a study cannot experience the outcome for a certain portion of the study time. MethodsWe used time-dependent analyses to study the association between metformin use for all 4,951 patients diagnosed with ovarian cancer in 1997 through 2018 in the province of British Columbia, Canada. Cox proportional hazards models were run to estimate the association between metformin and survival in the full cohort of ovarian cancer patients and among a cohort restricted to patients with diabetes. ResultsMetformin use was associated with a 17 % better ovarian cancer survival in the full cohort (adjusted hazard ratio (aHR) = 0.83 (95 %CI 0.67, 1.02)), and a 16 % better ovarian cancer survival for serous cancers patient's cohort (aHR = 0.84 (95 %CI 0.66, 1.07)), although both were not significant. However, a statistically significant protective effect was observed when restricting to the diabetic cohort (aHR = 0.71 (95 %CI 0.54–0.91)), which was also seen among serous cancers (aHR = 0.73 (95 %CI 0.54–0.98)). ConclusionMetformin use was associated with improved ovarian cancer survival. The lack of statistical significance in the full cohort may reflect that diabetes is associated with reduced cancer survival, and thus diabetes itself may offset the benefit of metformin when examining the full cohort. Future research should examine metformin use among non-diabetic ovarian cancer patients.

Surgical Management of Complex Ankle Fractures in Patients with Diabetes: A National Retrospective Multicentre Study.

Objectives: Patients with ankle fractures associated with diabetes experience more complications following standard open reduction-internal fixation (ORIF) than those without diabetes. Augmented fixation strategies, namely extended ORIF and hindfoot nails (HFNs), may offer better results and early weightbearing in this group. The aim of this study was to define the population of patients with diabetes undergoing primary fixation for ankle fractures. Secondarily, we aimed to assess the utilisation of standard and augmented strategies and the effect of these choices on surgical outcomes, including early post-operative weightbearing and surgical complications. Methods: A national multicentre retrospective cohort study was conducted between January and June 2019 in 56 centres (10 major trauma centres and 46 trauma units) in the United Kingdom; 1360 patients with specifically defined complex ankle fractures were enrolled. The patients' demographics, fixation choices and surgical and functional outcomes were recorded. Statistical analysis was performed to compare high-risk patients with and without diabetes. Results: There were 316 patients in the diabetes cohort with a mean age of 63.9 yrs (vs. 49.3 yrs. in the non-diabetes cohort), and a greater frailty score > 4 (24% vs. 14% (non-diabetes cohort) (p < 0.03)); 7.5% had documented neuropathy. In the diabetes cohort, 79.7% underwent standard ORIF, 7.1% extended ORIF and 10.2% an HFN, compared to 87.7%, 3.0% and 10.3% in the non-diabetes cohort. Surgical wound complications after standard-ORIF were higher in the diabetes cohort (15.1% vs. 8.7%) (p < 0.02), but patients with diabetes who underwent augmented techniques showed little difference in surgical outcomes/complications compared to non-diabetes patients, even though early-weightbearing rates were greater than for standard-ORIF. Conclusions: Ankle fractures in diabetes occur in older, frailer patients, whilst lower-than-expected neuropathy rates suggest a need for improved assessment. Augmented surgical techniques may allow earlier weightbearing without increasing complications, in keeping with modern guidelines in ankle fracture management.

Dyslipidemia and hyperglycemia induce overexpression of Syndecan-3 in erythrocytes and modulate erythrocyte adhesion.

Erythrocytes are important vascular components that play vital roles in maintaining vascular homeostasis, in addition to carrying oxygen. Previously, we reported that the changes in the internal milieu (e.g. hyperglycemia or hypercholesterolemia) increase erythrocyte adhesion to various extracellular matrix components, potentially through altering glycosaminoglycans (GAGs). In this study, we have investigated the expression of syndecan (Sdc) family members that could be involved in mediating cytoadherence under conditions of dyslipidemia and hyperglycemia. Among the Sdc family members analysed, we found significant overexpression of Sdc-3 in erythrocyte membranes harvested from high-fat-fed control and diabetic animals. Animal studies revealed a positive correlation between Sdc-3 expression, blood sugar levels and erythrocyte adhesion. In the human study, diabetic cohorts with body mass index >24.9 showed significantly increased expression of Sdc-3. Interestingly, blocking the Sdc-3 moiety with an anti-Sdc-3 antibody revealed that the core protein might not be directly involved in erythrocyte adhesion to fibronectin despite the GAGs bringing about adhesion. Lastly, Nano liquid chromatography-mass spectrometry/MS verified the presence of Sdc-3 in erythrocyte membranes. In conclusion, the high-fat diet and diabetes modulated Sdc-3 expression in the erythrocyte membrane, which may alter its adhesive properties and promote vascular complications.