Type 2 Diabetes Mellitus Research Articles

Worldwide prevalence of type 2 diabetes mellitus (T2DM) and obesity has heightened the need to find treatments that control hyperglycemia, together with weight gain and resultant organ damage. Under this arrangement, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as transformative agents. They act through both intra- and extrapancreatic pathways to promote glucose-dependent insulin secretion, lower glucagon concentrations, slow stomach emptying, and control circuits of cerebral appetite. This helps the body regulate blood glucose levels, leading to clinically significant weight loss. In addition to regulating metabolism, strong cardiovascular and renal outcome trial data (including STEP, SELECT, and FLOW) suggest that they can lower the disease burden of serious cardiovascular events and protect kidney functioning. It means they are disease-modifying agents. Other barriers include their high cost, gastrointestinal side effects, injectable formulations, and lack of long-term safety information, although they are an effective intervention for achieving greater use. Recently, novel agents such as oral semaglutide, dual and triple incretin agonists (tirzepatide, retatrutide), and drug-based combinations with sodium-glucose cotransporter-2 (SGLT2) have revolutionized the treatment of the disease and improved its clinical utility. Individualized optimization of treatment using precision medicine, in the form of tailored behavior, with respect to phenotypes and comorbidities, holds promise to enhance outcomes. The combination of glycemic control, long-term weight loss, and organ protection is shifting the approach to cardiac, renal, and other organ health, leveraging the action of GLP-1 receptor agonists.

To identify health utility decrements of injection treatment-related attributes among patients with type 2 diabetes mellitus (T2DM) in China. Health states of four attributes (hypoglycemia, dose frequency, flexibility and injection site reaction) were generated using a vignette-based method. Patients with T2DM were recruited from eight cities in China. The sample was broadly consistent with Chinese T2DM population with regard to age and sex distribution. Respondents completed seven time trade-off (TTO) tasks during face-to-face interviews. The ordinary least square (OLS), fixed effects (FE) and random effects (RE) models were used for TTO data. In subgroup analysis, groups were categorized based on whether injection treatment was currently used, number of medications, needle phobia, duration of injectable treatment and travel frequency. A total of 400 patients (52.75% male, mean [SD] age 50.30 [12.05] years) were included in this study. Severe hypoglycemia had the largest disutility value of all attributes (-0.023, P < 0.001). Three times daily, twice daily and once daily injection (needed to be carried with the patient on short trips) were associated with -0.023 (P < 0.001), -0.018 (P < 0.001) and -0.011 (P = 0.022) disutility values compared with once weekly injection (not required to be carried with the patient on short trips), respectively. The disutility value associated with injection site reaction attribute was -0.013 (P < 0.001). In subgroup analysis, the relative importance of treatment-related attributes was found to depend on patient characteristics. This study provides disutility values associated with several injection treatment-related attributes for Chinese patients with T2DM. Hypoglycemia appears to be the most important attribute, followed by dose frequency, flexibility and injection site reaction.

Type 2 diabetes mellitus (T2DM) frequently coexists with hyperthyroidism (HT), compounding metabolic disturbances. However, the role of specific biomarkers in this comorbid condition remains unclear. This study investigates the clinical significance of serum semaphorin 5A (Sema5A) and insulin-like growth factor-binding protein 3 (IGFBP-3) in patients with T2DM and HT, focusing on their association with glucose metabolism and diagnostic potential. A total of 191 participants were enrolled and divided into 3 groups: T2DM with HT (n = 68), T2DM only (n = 51), and healthy controls (n = 72). Clinical parameters and serum levels of Sema5A, IGFBP-3, fasting plasma glucose, glycated hemoglobin, homeostasis model assessment of insulin resistance (HOMA-IR), and fasting insulin were measured. Pearson correlation, logistic regression, and receiver operating characteristic curve analyses were performed to evaluate associations and diagnostic performance. Serum levels of Sema5A and IGFBP-3 were significantly elevated in the T2DM with HT group compared to other groups (P < .01). Both biomarkers showed positive correlations with fasting plasma glucose, glycated hemoglobin, HOMA-IR, and fasting insulin (P < .001). Multivariate logistic regression identified Sema5A, IGFBP-3, HOMA-IR, and thyroid autoantibodies (thyroid-stimulating hormone receptor antibody and thyroid peroxidase antibody) as independent risk factors. Receiver operating characteristic analysis demonstrated strong diagnostic value for Sema5A (area under the curve = 0.793) and IGFBP-3 (area under the curve = 0.831). Elevated Sema5A and IGFBP-3 levels are closely associated with impaired glucose metabolism in T2DM patients with HT and may serve as promising biomarkers for early diagnosis and clinical assessment of this comorbidity.

Extracellular vesicles (EVs) miRNAs play pivotal roles in metabolic disorders. This study aimed to describe the plasma EV miRNA profiling of type 2 diabetes mellitus (T2DM) and evaluate the association between differentially expressed miRNAs and T2DM. The subjects were from the Henan Rural Cohort. The miRNA profiling plasma EVs were quantified by the next-generation sequencing of RNA in the discovery sets to identify differentially expressed miRNAs. The association between differentially expressed miR-3120-5p and T2DM was validated in 75 pairs of newly diagnosed T2DM and controls using the logistic regression and generalized linear model. In vitro experiments were performed in HepG2 cells to explore the mRNA and protein expression levels of glucose-related transcription factors and glucose consumption with transfecting miR-3120-5p mimic or inhibitor. In the discovery set, the first phase identified 73 upregulated and 44 downregulated miRNAs, followed by 41 upregulated and 23 downregulated miRNAs in the second phase. miR-3120-5p showed upregulate in the two phases. In the validation set, miR-3120-5p level in plasma EVs was positively associated with the risk of T2DM (OR: 1.22, 95%CI: 1.05, 1.44). In vitro experiments demonstrated that glucose consumption was reduced in HepG2 cells overexpressing miR-3120-5p compared to mimic negative controls, and that expression of the glucose uptake factor GLUT2 protein was also decreased. The plasma EV miR-3120-5p was associated with T2DM in the rural populations with limited resources and might contribute to the pathological process by directly or indirectly inhibiting hepatocyte GLUT2 expression and glucose consumption.

This study aims to investigate the clinical baseline characteristics and HbA1c variability in elderly patients with mild cognitive impairment (MCI) associated with type 2 diabetes mellitus (T2DM), as well as the synergistic relationship between these factors and dementia progression.A total of 186 elderly patients with T2DM with MCI were enrolled and stratified into 94 with normolipidemia and 92 with dyslipidemia. The patients' demographics, baseline characteristics, lipid levels, baseline HbA1c, and Montreal cognitive assessment scale scores were recorded. Patients were followed up for at least 36 months, with a maximum follow-up period of 48 months.Patients in the dyslipidemia group had a longer duration of DM and had significantly higher total cholesterol, triglycerides, and low-density lipoprotein cholesterol than those in the normolipidemia group. Thirty-five patients progressed to dementia, with 25% (23/92) in the dyslipidemia group compared to 12.77% (12/94) in the normolipidemia group. Patients in the dyslipidemia group had significantly higher HbA1c variability than those in the normolipidemia group. Furthermore, the group progressing to dementia exhibited advanced age, prolonged DM duration, shorter years of education, and abnormal lipid levels, as well as greater HbA1c variability. Dyslipidemia under the association with the glycemic variability profile (HbA1c variability ≥ 10.49%) was also strongly associated with the degree of MCI in patients with dementia. Multivariable logistic regression confirmed that both dyslipidemia (OR = 2.05, P = 0.015) and high HbA1c variability (OR = 3.56, P = 0.010) were independent risk factors, with a significant interaction between them (OR = 3.15, P = 0.046).Dyslipidemia and glycemic variability are not only correlates of cognitive decline in patients with T2DM, but may also act synergistically to accelerate the process of MCI to dementia. The stratification by lipid status effectively identifies patient subgroups at differential risk, highlighting the combined impact of these metabolic factors.

While glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is) are established for cardiorenal benefits in type 2 diabetes mellitus (T2DM), prior meta-analyses have not fully integrated cross-class comparisons or net benefit analyses with updated cardiovascular outcome trials (CVOTs). We conducted a systematic review and meta-analysis of 17 CVOTs (N = 132,038; GLP-1RA: N = 73,263; SGLT-2i: N = 58,775) using PubMed and Cochrane CENTRAL. We uniquely synthesized major adverse cardiovascular events (MACE), hospitalization for heart failure (hHF), renal composites, and safety outcomes (e.g., retinopathy, genitourinary infections) with random-effects models for hazard ratios (HRs) and relative risks (RRs). Innovative graphical syntheses (tornado/scatter plots, risk curves) and net benefit calculations (absolute risk reductions [ARRs] minus absolute excess risks [AERs]) were employed. Risk of bias (RoB 2) and GRADE certainty were assessed. Both classes reduced MACE (HR 0.87, 95% CI 0.84-0.90; p = 0.73 for class difference). SGLT-2is were superior for hHF (HR 0.69 vs. 0.88, p < 0.0001) and renal outcomes (HR 0.68 vs. 0.79, p = 0.026). GLP-1RAs increased retinopathy (RR 1.18, AER + 6.5/1000); SGLT-2is increased genitourinary infections (RR 3.34, AER + 19.9/1000) and DKA (RR 2.67, AER + 1.2/1000). Amputation signals attenuated post-sensitivity analysis. Net benefits favored GLP-1RAs for MACE (+ 2.5/1000). For SGLT-2is, base-case estimates using genital-mycotic infections as the sentinel harm were marginal (hHF: - 4.9/1000; renal: - 1.9/1000), whereas sensitivity scenarios with alternative harms (e.g., volume depletion, amputation, DKA) yielded positive net benefits. GRADE certainty was high for efficacy, moderate for harms. Our innovative integration of updated CVOTs, cross-class comparisons, and graphical risk-benefit tools refines therapeutic decision-making, highlighting tailored T2DM management based on patient-specific cardiorenal risks. PROSPERO (CRD420251146788).

An endoscopically placed duodenal-jejunal bypass liner (DJBL) may provide a safe adjunctive therapy for those with poorly controlled type 2 diabetes mellitus (T2DM) and obesity. While some endoscopic therapies have been shown to improve glycemic indices secondary to weight loss, small bowel interventions may have direct metabolic effects. A meta-analysis of observational studies demonstrated reduction in HbA1c by 1.3% at one year following DJBL in patients with T2DM and obesity. This was a multicenter, double-blind, randomized, sham-controlled trial comparing DJBL to sham procedure with medical management and lifestyle modification. Primary endpoints included mean difference in changes in HbA1c at 12 months between arms, and device-related serious adverse events (SAEs). Secondary endpoints included percent total weight loss (%TWL) and subjects achieving HbA1c≤7% and TWL≥5% at 12 months. 320 subjects were randomized to DJBL (n=212) and sham (n=108). Baseline HbA1c and BMI were 8.79±0.92% and 38.45±5.75kg/m2. On modified intent-to-treat analysis, change in HbA1c at 12 months was -1.10±1.45% and -0.28±1.54% for DJBL and sham groups, respectively (P=0.0004). Rate of device-related SAEs was 9.4% including intolerance (3.7%), hemorrhage (2.8%) and hepatic abscess (2.3% stopping study early). At 12 months, DJBL group experienced greater weight loss compared to sham (7.7±9.6% TWL and 2.1±5.4% TWL, respectively; P<0.0001), with significantly more patients achieving HbA1c ≤ 7% (28.3% vs. 9.4%; P<0.0003) and TWL ≥ 5% (60.4% vs. 21.3%; P<0.0001). DJBL met primary glycemic control efficacy and primary safety endpoints, while providing clinically significant weight loss, and comorbidity improvement.

This study compares the effectiveness of sleeve gastrectomy (SG) and one-anastomosis gastric bypass (OAGB) on the predicted 10-year atherosclerotic cardiovascular disease (ASCVD) risk and identifies key factors influencing postoperative (post-op) changes in ASCVD risk. This prospective cohort study assessed the 10-year ASCVD risk in patients undergoing SG or OAGB between 2013 and 2023 using the ACC/AHA ASCVD Risk Estimator. In addition to the baseline assessment, the risk score was evaluated at 6, 12, 24, 36, and 48 months post-op. Longitudinal analysis tracked changes in ASCVD risk, and regression models identified individual and combined factors influencing these changes. The analysis enrolled 1397 individuals (mean age 50.1 years, 87.9% female), including 952 SG and 445 OAGB participants. Following adjustments, the 10-year ASCVD risk significantly reduced post-op with no observed differences between the surgical groups. Positive associations with risk reduction were found for baseline risk, total cholesterol (TC), type 2 diabetes mellitus (T2DM), triglycerides (TG), systolic blood pressure (SBP), fasting plasma glucose (FPG), and estimated glomerular filtration rate (eGFR). In contrast, age, triglyceride-glucose (TyG) index, hemoglobin A1c (HbA1c), male sex, smoking, and high-density lipoprotein cholesterol (HDL-C) demonstrated negative associations with ASCVD risk reduction. Metabolic and bariatric surgery significantly reduced the 10-year ASCVD risk, with comparable outcomes between SG and OAGB. Key determinants influencing the 10-year ASCVD risk reduction included baseline risk score, age, TC, T2DM, TyG index, TG, HbA1c, SBP, sex, FPG, smoking, HDL-C, and eGFR.

When we consider the treatment of polycystic ovary syndrome (PCOS), one of our treatment options is metformin, which reduces free testosterone levels in PCOS patients. We were interested to know what happens to the free testosterone levels of male type 2 diabetes mellitus (T2DM) patients when we use metformin. The effect of metformin on testosterone level, fertility, and sexual activity in males has been issues of interest to researchers. This study was conducted to observe the effect of metformin on free testosterone levels in male T2DM patients. One hundred fifty male patients (mean age, 40-46 years; SD, 1.2), newly diagnosed with T2DM and drug-naïve, were enrolled. Initially, the baseline-free testosterone level was measured. Then, 75 of them were given metformin, and 75 of them were treated with other antidiabetics. After treatment for 30 days, the free testosterone level was measured again. In both groups, the mean value of free testosterone change in 1 month was calculated. Then, a comparison between the mean change in the 2 groups was done. Baseline-free testosterone of metformin (mean = 7.9, SD = 2.2) and non-metformin (mean = 8.1, SD = 1.9) groups were compared, and no significant difference was seen between them (P = .264). After 30 days of treatment, there was an increased level of free testosterone in both groups (mean metformin = 9.75, non-metformin = 10.77). But. free testosterone rise in non-metformin group(M = 2.63,SD = 1.07) was significantly higher (mean difference = .80,95% CI) than metformin group (M = 1.82,SD = .99,t = 4.76, P < .001). Metformin is inferior to other antidiabetic medications in raising free testosterone levels. Larger multicenter studies are further warranted.

The aim of this study is to compare the mid- and long-term results after laparoscopic sleeve gastrectomy (LSG) according to the distance of the first staple from the pylorus. This study is a retrospective analysis of prospectively collected data of patients who underwent LSG. While the distance of the first staple from the pylorus was 2-3cm in group A, the distance of the first staple to the pylorus was 5-6cm in group B. Laboratory parameters, comorbidity resolution, anthropometric measurements, and complications were documented at the end of the first, third, and fifth postoperative years. Of the total 376 patients, 127 were excluded for various reasons, 102 patients were lost to follow-up, and 147 patients were included in the final analysis. Upon examining the follow-up data at the 1st, 3rd, and 5th years, a statistically significant difference was observed between the groups in terms of total weight loss (TWL%), excess body mass index loss (EBMIL%), and recurrent weight gain (RWG)%, with group A showing an advantage. The majority of the patients requiring conversional metabolic and bariatric surgery (MBS) were in group B, and the difference was significant (p = 0.017). The distance of the first staple from the pylorus may significantly influence the outcomes related to RWG%, TWL%, and type 2 diabetes mellitus (T2DM) resolution in the medium-long-term. Furthermore, additional research is needed to determine the optimal positioning for enhanced patient results.

In recent years, coinciding with the increasing incidence of type 2 diabetes mellitus (T2DM) in children and adolescents, the global prevalence of diabetic kidney disease (DKD) and end-stage renal disease (ESRD) are rising year on year. In contrast, the mortality and morbidity due to cardiovascular disease (CVD) and stroke in people with diabetes have been declining. The precise cause of the disparate vascular outcomes in diabetes remains unexplored.To elucidate the relationship, we conducted a retrospective cohort study on the UK Biobank data. In our study, the exposure variables were the age of diabetes and hypertension diagnosis, while the outcome variables were ESRD, myocardial infarction, angina, and stroke.Univariable and multivariable logistic regression models were fitted to assess odds ratios (ORs) and 95% confidence intervals (CIs). Model performance was evaluated using the receiver operating characteristic (ROC) curve. Sensitivity analyses were conducted on participants who developed diabetes before and after the age of 20years and with and without female participants. Univariable logistic regression showed that compared to those diagnosed after the age of 60, the odds of ESRD for those diagnosed at ages < 20, 20-40, and 41-60years were 5.26 (3.00 - 9.40), 7.78 (4.81 - 13.16) and 2.33 (1.50 - 3.84), respectively. Myocardial infarction and stroke did not have a statistically significant relationship with younger age of diabetes diagnosis. In those with a dual diagnosis of diabetes and hypertension, irrespective of the age of diabetes diagnosis, the age of hypertension diagnosis at age < 20, 20-40, and 41-60years, compared to those who developed it after the age of 60years, had a greater risk of ESRD, 2.20 (1.58 - 3.11), 5.03 (3.79 - 6.81), and 1.53 (1.16 - 2.06), respectively. After adjusting for sex and albuminuria, multivariable logistic regression model 1 showed that compared to those who developed diabetes above the age of 60, those who developed it < 20, 20-40 and 41-60 had a higher risk of ESRD, 4.71 (2.47 - 9.28), 4.67 (2.63 - 8.78), and 1.94 (1.16 - 3.49), respectively. Likewise, in model 2, when the duration of diabetes was used as the explanatory variable, each year of increased duration of diabetes increased the odds of ESRD by 2%, with an odds ratio of 1.02 (1.01-1.03). Younger onset of hypertension but not diabetes increased the odds of myocardial infarction (MI). There was no statistically significant relationship between the age of diabetes, and hypertension diagnoses with angina and stroke. Model performance was excellent, with over 80% of the data points falling below the area under the curve. Sensitivity analyses showed young-onset diabetes as a significant determinant of ESRD. Young-onset and longer-duration of diabetes increase the risk of ESRD. For those with diabetes and hypertension, a younger onset of hypertension but not diabetes may also increase the risk of MI.

The global rise in type 2 diabetes mellitus (T2DM) underscores the importance of early prevention in primary care. This study examined how changes in glucose tolerance and the presence of neuropsychiatric disorders relate to cardiovascular outcomes (CVO) and mortality. In a 10-year longitudinal study, 1,069 general practice patients (mean age 62.9 years; 51% male) underwent standard 2-hour glucose tolerance tests (GTT). Data on lifestyle, cardiovascular risk factors, comorbidities, and neuropsychiatric diagnoses (MINI Interview) were collected. The difference between baseline and follow-up GTT values (GTTdiff) was analyzed in relation to cardiovascular events and mortality. Patients who died had significantly higher GTTdiff (mean 1.37 mmol/L) compared to those with CVO (0.95 mmol/L) or without events (0.81 mmol/L; p = .002). Kaplan-Meier analysis showed shorter survival in patients with Major Depressive Episode (MDE) and GTTdiff > 3 mmol/L (7.43 years) versus those without MDE (8.76 years). Greater glucose variability and comorbid depression are associated with increased cardiovascular mortality. Interventions targeting both glucose control and mental health may improve outcomes in non-diabetic primary care populations.

Introduction Type 1 diabetes mellitus (T1DM) is increasing globally and represents a significant public health concern. Periodontitis affects about 11% of the global population, particularly in its severe forms, and is 1.5 to 2 times more prevalent in individuals with poorly controlled T1DM. Both conditions are multifactorial, chronic, and inflammatory, sharing a bidirectional relationship: T1DM accelerates the onset and progression of periodontitis, while periodontal inflammation worsens glycemic control. Methods This observational case-control study included adults with T1DM and metabolically healthy controls, stratified by periodontal status: healthy, gingivitis, or periodontitis. Cytokine profiles were assessed in both saliva and gingival crevicular fluid (GCF) to characterize the oral immune response. Results Significant associations were observed between T1DM and both the extent and severity of periodontal disease. T1DM patients with gingivitis exhibited increased bleeding on probing (BOP) and probing pocket depth (PPD), with BOP remaining significantly elevated in those with periodontitis. GCF analysis revealed a dysregulated immune profile in T1DM patients, characterized by elevated IL-1 β , IL-6, IL-8 and IL-17A, and reduced levels of IL-2, IL-4, IL-12p70 and IP-10. The salivary cytokine profile generally mirrored GCF findings, with higher IL-6 and IL-8 concentrations and strong correlations with key pro-inflammatory cytokines. Discussion Salivary IL-8 emerged as the most promising biomarker for distinguishing periodontal status in T1DM patients. Overall, these findings highlight the clinical potential of salivary immune profiling as a non-invasive tool for monitoring periodontal inflammation and assessing disease activity in individuals with T1DM.

Type 2 diabetes mellitus (T2DM) and depression are significant global health problems. In particular, approximately 26–30 % of people with diabetes suffer from depression of varying severity, and T2DM doubles the risk of developing depression. The latter can be caused by behavioral factors, including unbalanced eating habits, obesity, physical inactivity, social instability, substance abuse, and sleep disturbances. Insulin resistance (IR), one of the leading signs of T2DM, has different forms specific to certain tissues. In particular, peripheral IR is manifested by reduced glucose uptake by skeletal muscles and adipose tissue due to defects in insulin receptor function and signaling pathways. IR of brain cells is associated with changes in insulin signaling in neurons and glial cells, with neurodegenerative processes, which links it to both cognitive decline and mood disorders. There are several hypotheses regarding common risk factors, such as the psychological impact of managing a chronic disease, potentially shared genetic predisposition, or pathophysiological disorders. The latter include dysregulation of the hypothalamic-pituitary-adrenal axis, activation of chronic low-grade inflammation, changes in the autonomic nervous system, dysfunction of the sympathoadrenal system, dysregulation of insulin signaling and neurotransmission, activation of oxidative stress processes and mitochondrial dysfunction, disturbance of intestinal microbiota homeostasis and dysfunction of the gut-brain axis, dysfunction of brain-derived neurotrophic factor, changes in synaptic plasticity of neurons, and disruption of autophagy. At the same time, it is reported that the relationship between T2DM and an increased risk of developing depressive symptoms is partly explained by increased levels of biomarkers of microvascular dysfunction, neurodegeneration, advanced glycation end products, and arterial stiffness. However, a significant impact of chronic low-grade inflammation processes has not been identified. The review aimed to examine the current state of research on the relationship between IR, depression, and T2DM, and to identify new trends and directions for future research. The search was conducted in Scopus, ScienceDirect (from Elsevier), and PubMed, including MEDLINE databases. The keywords used were “insulin resistance”, “depression”, “type 2 diabetes”, and “brain-derived neurotrophic factor”. A manual search for the bibliography of publications was used to identify research results that could not be found during the online search.

Correlation Between Body Mass Index and Self-Reported Voice Handicap in Patients with Diabetes Mellitus Type II.

Urinary albumin excretion is an established marker of cardiovascular (CV) risk in people with type 2 diabetes mellitus (T2DM). However, its prognostic significance within the normoalbuminuric range (< 30mg/g) remains uncertain, particularly regarding sex-specific differences. This study examined whether urinary albumin-to-creatinine ratio (UACR; KDIGO A1 range) is associated with coronary artery disease (CAD) severity and 6-year major adverse cardiovascular events (MACE) in women and in men with T2DM and preserved kidney function (eGFR > 60 mL/min/1.73m², UACR < 30mg/g), treating sex differences as a co-primary objective. We conducted a retrospective cohort study involving adults with T2DM who underwent diagnostic coronary angiography. Baseline associations between log-transformed UACR, CAD severity, CV risk factors, and inflammatory markers were evaluated using multivariable linear regression. MACE (defined as non-fatal myocardial infarction or unstable angina requiring urgent revascularization, stroke, or CV death) were recorded during 6-year of follow-up. Cox proportional hazards models, adjusted for age, sex, hypertension, smoking, BMI, lipid profile, hs-CRP, and ACEI/ARB use, were used to assess UACR-MACE associations. We included 420 adults (180 women, 42.9%) with a mean of age 65.3 ± 10.7 years and a median UACR 7.56mg/g (IQR 4.12-15.5). Significant CAD was present in 310 participants (73.8%), and 78 experienced MACE during follow-up (35.5%). Higher UACR was independently associated with greater coronary stenosis (adjusted R² = 0.090, p < 0.001). Kaplan-Meier analysis showed a significantly higher incidence of MACE in the highest UACR tertile (log-rank p = 0.039). In multivariable Cox models adjusted for age, sex, hypertension, smoking, lipid profile, hs-CRP, SSI, and ACEI/ARB use, higher log-UACR independently predicted MACE (adjusted HR 1.67, 95% CI 1.35-2.10; p < 0.01). In sex-stratified Cox models, higher log-UACR predicted MACE in both sexes and remained independently associated in multivariable analyses (adjusted HR 1.67, 95% CI 1.35-2.10; p < 0.01). Associations were directionally stronger in women, who showed higher cumulative event rates across UACR tertiles, although the formal UACR × sex interaction did not reach statistical significance. Within the normoalbuminuric range, UACR is associated with greater CAD burden and higher 6-year MACE risk, with sex-specific differences. These findings suggest potential sex-related variation in the prognostic value of high-normal albuminuria, particularly among women, warranting validation in larger and more diverse cohorts.

Diabetic retinopathy (DR) is a leading cause of vision loss in individuals with type 2 diabetes mellitus (T2DM) and is influenced by genetic factors. We investigated the association between the erythropoietin (EPO) gene polymorphism (rs1617640 C > T/G) and DR risk in a Punjabi Pakistani cohort of adults with T2DM. In a case-control design, 573 T2DM patients (294 with DR, 279 controls without retinopathy, CDR) were genotyped by ARMS-PCR. The protective CC genotype was significantly more frequent in controls (96.77%) than in cases (30.61%) and was associated with markedly reduced DR risk (OR = 68; 95% CI 33.468-138.162; p < 0.001). Conversely, the GG and TT genotypes were absent in controls but present in DR patients (27.55% and 21.43%, respectively) and were strongly associated with increased DR risk (p < 0.001). Allele-level analysis mirrored genotype findings: the C allele predominated in controls (98.39%) but was significantly less frequent in cases (39%), while G and T alleles were enriched among DR patients (p < 0.001). Together, genotype- and allele-based results indicate that the rs1617640 C variant is protective against DR in this Punjabi T2DM population, whereas G and T variants increase DR susceptibility.

In Diabetes Mellitus (DM), a metabolic disorder characterized by elevated blood glucose due to impaired insulin action, platelet function is dysregulated and contributes to the pathological progression of the disease. In type 2 diabetes mellitus (T2DM), hyperglycemia, insulin resistance, oxidative stress, and inflammation impair endothelial function and platelet regulation, promoting a prothrombotic state. Platelet hyperreactivity is associated with T2DM cardiovascular complications, a leading cause of mortality in patients. Antiplatelet therapies often prove ineffective for a subset of T2DM patients due to aspirin resistance, necessitating alternative therapeutic strategies. Resveratrol, a natural polyphenol, is a potential therapeutic agent for T2DM, including inhibition of platelet aggregation. One of the pleiotropic actions of resveratrol is to modulate the FoF1-ATP synthase rotational catalysis. Platelet chemical energy demand during the activation phase is achieved through oxidative phosphorylation. Both mitochondrial and extra-mitochondrial oxidative phosphorylation drive aerobic energy production in activated platelets, utilizing fatty acids and glucose, respectively. Hyperglycemia can cause an overwork of the oxidative phosphorylation, producing oxidative stress. Targeting FoF1-ATP synthase with resveratrol may reduce platelet hyperreactivity in aspirin-resistant cases. This paper reviews the implications of resveratrol ability to inhibit platelet FoF1-ATP synthase on its potential as a novel alternative or synergistic antiplatelet strategy for aspirin-resistant T2DM patients.

Objective Glycated hemoglobin (HbA1c) variability is a crucial indicator for evaluating the stability of long-term glycemic control in patients with diabetes mellitus. This study aimed to clarify the association between HbA1c variability and the risk of incident cardiovascular disease (CVD) and mortality in patients with type 2 diabetes mellitus (T2DM) through a systematic review, thereby providing evidence-based support for the early prevention of adverse cardiovascular events in T2DM patients. Methods We systematically searched the PubMed, Web of Science, The Cochrane Library, and Embase databases for studies on the association between HbA1c variability and cardiovascular outcomes in patients with T2DM, published from the establishment of each database up to August 5, 2025. Cardiovascular outcomes included the incidence of CVD and CVD-related mortality. Two researchers independently conducted literature screening, data extraction, and risk of bias assessment. Meta-analysis was performed using Review Manager 5.3 software, with hazard ratio (HR) or odds ratio (OR) as the effect size. Results A total of 31 cohort studies were included, covering 545,956 participants from 13 countries and regions. The results of the meta-analysis showed that a higher coefficient of variation (CV) of HbA1c was significantly associated with an increased risk of cardiovascular events (HR = 1.32, 95% CI: 1.18–1.49, P &amp;lt; 0.00001; OR = 1.39, 95% CI: 1.22–1.57, P &amp;lt; 0.00001), and also significantly elevated the risk of mortality (HR = 1.35, 95% CI: 1.16–1.57, P &amp;lt; 0.00001). The standard deviation (SD) of HbA1c was also significantly correlated with a higher risk of cardiovascular events (HR = 1.27, 95% CI: 1.17–1.38, P &amp;lt; 0.00001; OR = 1.30, 95% CI: 1.07–1.57, P = 0.008) and a significant increase in mortality risk (HR = 1.27, 95% CI: 1.17–1.37, P&amp;lt;0.00001). The hemoglobin glycation index (HGI) was significantly associated with the risk of cardiovascular events in terms of HR (HR = 1.36, 95% CI: 1.14–1.62, P = 0.0006), but no statistical significance was observed in terms of OR (OR = 1.47, 95% CI: 0.98–2.20, P = 0.06). In contrast, the HbA1c variability score (HVS) showed no significant association with either the risk of cardiovascular events (HR = 1.31, 95% CI: 0.97–1.78, P = 0.08) or mortality risk (HR = 1.00, 95% CI: 0.76–1.31, P = 1.00). Conclusions HbA1c variability is positively associated with the risk of adverse cardiovascular events in patients with T2DM. Among the indicators of HbA1c variability, the coefficient of variation (CV), standard deviation (SD), and hemoglobin glycation index (HGI) can serve as significant predictors for the risk of cardiovascular disease (CVD) occurrence and mortality. However, the HbA1c variability score (HVS) did not show significant predictive value in this study. Systematic Review Registration https://www.crd.york.ac.uk/prospero/ , identifier CRD420251132972.

The AI-CVD initiative aims to maximize the value of coronary artery calcium (CAC) scans for cardiometabolic risk prediction by extracting opportunistic screening information. We investigated whether artificial intelligence (AI)-derived measures from CAC scans are associated with new-onset Type 2 diabetes mellitus (T2DM) in adults without obesity or hyperglycemia. Baseline CAC scans and up to 23 years of follow-up data were analyzed for participants without obesity (body mass index < 30kg/m²) and hyperglycemia (fasting plasma glucose < 100mg/dL) from the Multi-Ethnic Study of Atherosclerosis (MESA). AI-derived measures included liver attenuation index (LAI), subcutaneous fat index (SFI), total visceral fat index (TVFI), epicardial fat index (EFI), skeletal muscle index, and skeletal muscle mean density. Cox regression models compared highest vs. lowest quartiles of each AI-derived metric for T2DM risk. Multivariable models assessed adjusted predictive value using Wald chi-squared statistics. Subgroup analyses stratified participants by demographic and clinical factors. During a median follow-up of 19.7 years among 2,993 participants (baseline mean age 61.9 ± 10.5 years, 53% women), 257 participants (8.6%) developed T2DM. Key predictors included LAI (HR: 3.13, 95% CI: 2.15-4.55), SFI (HR: 2.85, 95% CI: 1.93-4.21), TVFI (HR: 2.49, 95% CI: 1.72-3.60), and EFI (HR: 1.59, 95% CI: 1.09-2.32). LAI remained the most robust predictor after adjusting for all metrics (Wald χ² = 38.24). Subgroup analyses confirmed LAI's consistent predictive performance. AI-derived adiposity measures from CAC scans-especially liver fat-can identify adults without obesity or hyperglycemia at elevated risk for developing T2DM. These findings underscore the potential of AI-enabled opportunistic screening during CAC imaging to support early T2DM risk stratification in individuals not captured by current clinical guidelines.