Cardiovascular diabetology. Endocrinology reports最新文献

BACKGROUND: Obesity and type 2 diabetes are the primary drivers of atherosclerotic cardiovascular disease (ASCVD), the leading cause of death worldwide. Injectable GLP-1 receptor agonists reduce major adverse cardiovascular events. Yet for many individuals, injection hesitancy remains a significant barrier to long-term adherence. Orforglipron is a novel once-daily oral non-peptide GLP-1 receptor agonist designed to provide comprehensive cardiometabolic risk reduction. METHODS: PRISMA-compliant systematic review and meta-analysis (PROSPERO CRD420251229397) of placebo-controlled phase 2 and phase 3 trials of orforglipron. Random-effects models were used to pool mean differences (MD) and risk ratios (RR) with 95% confidence intervals. RESULTS: Across four large trials, orforglipron produced dose-dependent, clinically meaningful improvements in major modifiable cardiovascular risk factor compared with placebo: body weight − 6.08% (95% CI − 7.68 to − 4.47; up to − 9.31% at higher doses), HbA1c − 0.85% (95% CI − 1.53 to − 0.18; up to − 1.36%), systolic blood pressure − 4.32 mmHg (95% CI − 5.61 to − 3.03; up to − 5.78 mmHg at 45 mg), LDL-cholesterol − 4.14% (95% CI − 6.38 to − 1.91), triglycerides − 10.90% (95% CI − 14.36 to − 7.43), VLDL-cholesterol − 10.81% (95% CI − 14.10 to − 7.51), and HDL-cholesterol + 3.31% (95% CI + 1.66 to + 4.97). Notably, heterogeneity was very low to absent (I² = 0%) for systolic blood pressure and all lipid outcomes. Gastrointestinal side effects were common but typical of the GLP-1 class (nausea RR 5.22, vomiting RR 3.24, eructation RR 6.80). CONCLUSION: Orforglipron provides highly consistent reductions across the full spectrum of ASCVD risk factors, with effect sizes on lipids and blood pressure comparable to those linked to MACE reduction in trials of injectable GLP-1 receptor agonists. As a novel small-molecule GLP-1 agonist in its class, Orforglipron offers a transformative option for comprehensive cardiometabolic risk reduction and ASCVD prevention in patients with obesity and type 2 diabetes.

Treating hypertension in diabetic patients with antihypertensive medications should be done with careful consideration because these medications may interfere with macro- and microvascular complications of diabetes, such as myocardial infarction, stroke, and diabetic nephropathy. Some medications also come with cardio- and reno-protective effects along with lowering blood pressure. This narrative review focuses on major antihypertensive drug classes and their efficacy, safety, and metabolic impacts in type 1 and type 2 diabetes mellitus. We found that most classes of drugs, such as ACEIs (Angiotensin-Converting Enzyme Inhibitors), ARBs (Angiotensin II-Receptor Blockers), and thiazide diuretics, exert cardio- and renoprotective effects but also come with their own set of side effects, including dry cough, hyperkalemia, and hypokalemia, respectively. Beta blockers are used when patients have underlying conditions such as a previous heart attack or angina, but with caution, as they can cause masking of hypoglycemia. This review also discusses emerging therapies such as SGLT2 (Sodium-Glucose CoTransporter-2) inhibitors. Hence, all these drugs can offer additional benefits in addition to lowering blood pressure if chosen properly and tailored to suit the patient’s overall health needs.

Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM), driven largely by atherogenic dyslipidaemia. Conventional lipid parameters such as total and low-density lipoprotein cholesterol (LDL-C) do not adequately reflect the complex lipid disturbances that characterize T2DM. Composite lipid-based indices offer inexpensive and integrative measures of cardiovascular risk, but their predictive utility in African populations remains poorly characterized. This study investigated the association between multiple atherogenic indices and 10-year estimated CVD risk in Nigerian adults with T2DM.

Methods: In this analytical cross-sectional study, 197 adults with T2DM aged 40-74 years without established CVD were included in the final analysis from an endocrinology clinic in Makurdi, Nigeria. Sociodemographic, clinical, and fasting lipid data were collected. Ten-year CVD risk was estimated using the World Health Organization (WHO) risk prediction laboratory-based chart for Western sub-Saharan Africa. Several atherogenic indices were derived, and a series of hierarchical multiple regression analyses was used to determine their comparative incremental predictive value beyond traditional risk factors like age, systolic blood pressure, diabetes duration, anti-lipid therapy, and anti-hypertensive therapy. Receiver operating characteristic (ROC) analysis assessed their discriminatory performance for elevated CVD risk (≥ 10%).

Results: Traditional risk factors accounted for 72.4% of the variance in estimated 10-year CVD risk. Non-high-density lipoprotein cholesterol (non-HDL-C) demonstrated the strongest incremental predictive value, explaining an additional 6.2% of the variance (ΔR² = 0.062, p < 0.001). Other cholesterol-based ratios (CRI-II, CRI-I) added minor, significant value, but triglyceride-centric indices like the Atherogenic Index of Plasma (AIP) did not. However, none of the indices alone demonstrated significant discriminative power in ROC analysis.

Conclusions: In this study population, non-HDL-C significantly enhances the prediction of 10-year CVD risk beyond conventional factors, outperforming other cholesterol-based ratios. Triglyceride-centric indices, including AIP, offered no significant incremental value. Therefore, incorporating this low-cost index into existing risk assessment frameworks could strengthen early identification of high-risk individuals in resource-limited settings.

Clinical trial number: Not Applicable.

Background: Benign prostate hyperplasia (BPH) is a non-cancerous enlargement of both glandular and epithelial tissue of the prostate. The disease affects a significant portion of older ages, particularly those above 40 years old. It is thought that in addition to age, there is a contribution of metabolic syndrome (Mets) to the pathogenesis of BPH. There is scanty of study regarding to association of MetS with BPH, So this study is primarily intended to assess the association of MetS with BPH among patients attending Jimma University Medical Center (JUMC).

Methods and materials: A hospital-based cross-sectional study design was employed among 158 BPH patients attending JUMC, the subjects were selected consecutively, and all socio-demographic variables were collected by trained nurses after informed consent was obtained. Biochemical data were collected by laboratory technologists. Before analysis, daily quality control was checked. The collected data were entered into epi-data 4.6.0.6 checked, cleaned, and exported into SPSS version 26 for analysis. All descriptive variables were shown using tables, figures, and charts. After checking all assumptions of logistic regression, analysis was conducted at a significant value of 0.05.

Results: Our study found that the overall prevalence of metabolic syndrome among BPH patients was 38.6% (0.31,0.46). Among the components, low HDL comprises a high proportion following high blood glucose, elevated TG, and hyperglycemia respectively. Regarding factors associated with enlargement of the prostate, fasting blood glucose, obesity, and low HDL were significantly associated with large prostate volume (enlargement of the prostate).

Conclusion: According to our study, components of metabolic syndrome are the predictor variables for the enlargement of the prostate gland highlighting the importance of early diagnosis and treatment to alleviate further complications.

BACKGROUND: Individuals with schizophrenia suffer from reduced life expectancy, primarily due to obesity-related metabolic disorders and cardiovascular disease (CVD). The presence of cardiac autonomic neuropathy (CAN) may contribute to CVD, but CAN is reversible, and it may improve following weight loss. Semaglutide, a GLP-1 receptor agonist (GLP-1RA), induces weight loss and improves cardio-metabolic risk factors. Therefore, this study evaluated the impact of semaglutide on CAN in individuals with schizophrenia. METHODS: We conducted a double-blind, randomized, placebo-controlled trial with 154 adults (18–60 years, BMI ≥27 kg/m2) who were receiving treatment with second-generation antipsychotics (SGAs) for schizophrenia and prediabetes (HbA1c: 39–47 mmol/mol). Participants were randomized (1:1) to receive once-weekly semaglutide or placebo (titrated to 1.0 mg or maximally tolerated dose) for 30 weeks. RESULTS: A total of 141 participants completed the trial (semaglutide: 74; placebo: 67). CAN prevalence was high (84%), with 50% of the participants showing definite CAN. CAN prevalence increased with obesity: the risk of having definite CAN increased significantly from BMI 30–35 kg/m2 and to BMI > 35 kg/m2 (p < 0.001). Clozapine treatment was associated with CAN (p < 0.001). Semaglutide treatment for 30 weeks reduced BMI by 2.86 kg/m2 but did not alter CAN levels (p = 0.516). No significant changes were observed in the placebo group. INTERPRETATION: CAN is highly prevalent in patients with schizophrenia, and CAN correlates with BMI and clozapine treatment. Although semaglutide reduced BMI, CAN remained unchanged, despite its relationship with BMI. Thus, longer periods with semaglutide treatment may be required before CAN improves. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05193578.

Background: Admission dysglycemia is linked to adverse outcomes after ST-elevation myocardial infarction (STEMI); however, its relationship with early recovery of left ventricular (LV) function after primary percutaneous coronary intervention (PPCI), particularly when using stress-adjusted indices, remains uncertain in South Asian settings.

Objective: To evaluate whether admission glycemia (glucose and hemoglobin A1c [HbA1c]) and relative indices (stress hyperglycemia ratio [SHR] and glycemic gap) are independently associated with early improvement in LV ejection fraction (LVEF) and whether these associations persist at 30-90 days and align with early major adverse cardiovascular events (MACE).

Methods: A retrospective cohort of 600 consecutive STEMI patients undergoing PPCI (January 2023-December 2024) was stratified a priori into good, intermediate, or poor glycemic control. The primary outcome was follow-up LVEF within 7 days, modeled by analysis of covariance (ANCOVA) with baseline LVEF and clinical/angiographic covariates (heteroscedasticity-robust HC3 standard error). Sensitivity analyses included two-time-point mixed-effects models, continuous SHR/glycemic gap specifications (with splines), a non-diabetic subset, and adjustment for echocardiography timing.

Results: Early LVEF gains were greater with good control than with intermediate or poor control (mean change, 4.13% [SD, 4.78] vs. 2.15% (SD, 5.12) and 1.01% [5.45]; p < 0.001). In adjusted analyses, follow-up LVEF was lower in intermediate vs good by -2.42% points (95% CI, -3.38 to -1.46) and in poor vs good by -3.74% points (95% CI, -4.76 to -2.71) (both p < 0.001). Accordingly, early recovery declined stepwise with worsening admission glycemia, and the gradient persisted at 30 and 90 days in parallel with higher MACE across the strata. Accordingly, early recovery declined stepwise with worsening admission glycemia, and the gradient persisted at 30 and 90 days in parallel with higher MACE across the strata.

Conclusions: Admission dysglycemia, including stress-adjusted indices, was associated with attenuated early LVEF recovery after PPCI, with signals persisting through 90 days and aligning with early MACE. In practice, routine HbA1c-anchored stress-adjusted profiling at presentation may refine risk stratification and support protocolized inpatient glucose management.

BACKGROUND: Novel triglyceride-glucose-related(TyG-related) indices have garnered increasing interest as predictors of cardiometabolic risk. However, their prospective associations with the incidence of hypertension among middle-aged and elderly adults are insufficiently characterized. METHODS: We analysed 4,541 participants aged 45 years or older, with no history of hypertension at baseline, from the China Health and Retirement Longitudinal Study (CHARLS). Cox proportional hazards regression and restricted cubic spline (RCS) regression analyses were applied to assess the associations between the novel TyG-related indices and incident hypertension. Time-dependent ROC curves were used to assess the predictive discriminatory ability of the model at different time points over time. We used the NRI and IDI to evaluate the improvement in risk prediction capability of TyG-related indices compared to the TyG index alone and BMI. The robustness of the study findings was examined, to some extent, through subgroup and sensitivity analyses. RESULTS: In the longitudinal analysis, 1,484 participants (32.7%) experienced an new-onset hypertension. In fully adjusted models, each 1-SD increase in TyG–BRI, TyG–ABSI, TyG–WWI, and TyG–CVAI was associated with hypertension hazards of 1.21 (95% CI, 1.14–1.28), 1.09 (1.03–1.16), 1.12 (1.05–1.19), and 1.21 (1.18–1.28), respectively. RCS analysis revealed a significant positive linear association between TyG-related indices and the risk of incident hypertension. The time-dependent ROC curves demonstrated that TyG-BRI and TyG-CVAI consistently exhibited higher AUC values over time compared with TyG-ABSI and TyG-WWI, indicating better discriminatory performance, although the Delong test suggested that these differences were not statistically significant in most cases. TyG-BRI and TyG-CVAI demonstrated better predictive performance compared to the TyG index and base model, as evidenced by higher improvements in both NRI and IDI across multiple follow-up periods. The findings were consistent across multiple subgroup and sensitivity analyses. CONCLUSION: All four TyG-related indices were significantly associated with the risk of incident hypertension among middle-aged and older Chinese adults, emphasizing the need to increase attention to these indices to enhance hypertension detection and prevention in this population.

Statins are foundational therapies in cardiometabolic disease prevention, yet their clinical utility is could be limited by muscle-related adverse effects whose molecular origins have remained incompletely understood. In a landmark structural study, atorvastatin is shown to bind directly to skeletal muscle RyR1 in a unique triplet configuration, sequentially destabilizing the closed channel and promoting pathological Ca²⁺ leak. This work provides the first atomic-level explanation for statin-induced myopathy and reveals why individuals with RyR1 gain-of-function variants—already known to be overrepresented among statin-intolerant patients—are particularly vulnerable to muscle toxicity. For endocrinology, these findings are especially significant: statins remain central interventions in dyslipidemia, diabetes, obesity, and metabolic syndrome, and intolerance disproportionately affects individuals with high cardiometabolic burden. By establishing a receptor-mediated mechanism of statin myotoxicity, this study opens the door to genotype-informed statin prescribing, rational engineering of “RyR1-silent” lipid-lowering agents, and improved long-term adherence in patients with endocrine and metabolic disorders. These findings represent a major advance at the interface of metabolism, muscle physiology, and precision pharmacology, with the potential to reshape clinical practice across the endocrine continuum.

BACKGROUND AND AIM: Type 2 diabetes mellitus (T2D) is associated with a high risk of cardiovascular complications, including carotid atherosclerosis (CAS). This study aimed to investigate the link between CAS and T2D by identifying novel risk factors and examining the relationship between autonomic dysfunction (via heart rate variability, HRV) and systemic inflammation. METHODS: We conducted a retrospective observational study of 232 T2D patients, categorized into three groups based on carotid ultrasound: normal arteries (n = 47), intima-media thickening (n = 49), and carotid plaques (n = 136). Differences in clinical and inflammatory markers across groups were analyzed. Independent risk factors for CAS were identified using multivariate logistic regression, and a predictive model was developed and evaluated by Receiver Operating Characteristic (ROC) curve analysis. To infer causality, a bidirectional two-sample Mendelian randomization (MR) analysis was performed using summary-level data from large-scale genome-wide association studies (GWAS). RESULTS: Significant differences were observed in age, insulin usage, and inflammatory markers (NLR, PLR, LMR) among the groups (all p < 0.05). Logistic regression identified age, SDNN (a measure of HRV), LMR, and hs-CRP as independent risk factors for CAS. The combined model integrating hs-CRP, SDNN, and LMR demonstrated exceptional predictive accuracy for CAS (AUC = 0.941; 95% CI: 0.912–0.969). MR analysis provided genetic evidence supporting a causal relationship between genetically predicted HRV reduction and increased carotid intima-media thickness. CONCLUSION: Our findings underscore the critical interplay between autonomic dysfunction and inflammation in the development of CAS in T2D. The proposed integrative model shows high potential for risk stratification. Future large-scale multicenter studies are warranted to validate these findings and elucidate the underlying mechanisms.

BACKGROUND: Diabetes is an independent risk factor for ischemic stroke. This study was undertaken to determine whether hemodynamic cerebral ischemia (HCI), which increases stroke severity, is more frequent in diabetic patients. METHODS: Between 01/01/1990 and 30/06/2019, we revascularized 4117 carotid bifurcations in 3745 patients (2687 men and 1058 women; mean age: 71 (range: 28–97) years; 940 (25.1%) diabetics and 2805 (74.9%) nondiabetics). HCI was diagnosed clinically, under regional anesthesia, when a shunt needed to be inserted. All data were included in a prospective database. RESULTS: The HCI rate during carotid-clamping, requiring shunt placement, was 11.0% (114/1034) for diabetics and 7.1% (219/3083) for nondiabetics (odds ratio,1.62 [95% CI, 1.27–2.05]; P < 0.0001). CONCLUSIONS: Diabetes was associated with increased HCI risk in our patients with carotid stenosis. This HCI-associated excess risk might explain, in part, stroke severity and heightened carotid surgical risk in diabetics.