Aims Although allopurinol is used for urate-lowering therapy, its effect on myocardial infarction risk remains unclear. This study assessed the association between allopurinol use and myocardial infarction in adults with gout. Methods A systematic review and meta-analysis was conducted following PROSPERO registration (CRD420261305257). PubMed, Scopus, and Web of Science were searched from inception to January 2026. Observational studies of adults with confirmed gout that reported adjusted hazard ratios (HRs) for myocardial infarction and separately identifiable allopurinol exposure were included. Pooled estimates were calculated using an inverse-variance random-effects model with the Paule–Mandel estimator. Robustness was assessed through leave-one-out, active-comparator, and Hartung–Knapp sensitivity analyses. Results Four retrospective cohort studies met the revised eligibility criteria. In the primary random-effects analysis, allopurinol use was associated with a lower risk of myocardial infarction (HR 0.84; 95% CI 0.76–0.94; I 2 = 0%). However, the association was not statistically significant after excluding the study contributing the greatest weight (HR 1.04; 95% CI 0.79–1.36), when restricted to active comparators (HR 1.04; 95% CI 0.79–1.36), or using the Hartung–Knapp adjustment (HR 0.84; 95% CI 0.71–1.00). Conclusion Allopurinol therapy was associated with a modest but significant reduction in myocardial infarction risk in adults with gout.
Background The impact of Antidiabetic Agents on COPD Exacerbations remains uncertain. We conducted a comprehensive review to evaluate the impact Antidiabetic Agents on COPD Exacerbations in patients with T2DM. Methods We searched PubMed, Embase, and Web of Science from inception to January 15, 2026 for observational studies involving adults with T2DM and COPD. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects models, treatments were ranked using the Surface Under the Cumulative Ranking Curve (SUCRA), and study quality was assessed using the Newcastle–Ottawa Scale. Results Thirteen studies comprising 755,206 participants were included. Compared with sulfonylureas, SGLT-2 inhibitors were associated with the lowest risk of overall COPD exacerbations (RR 0.71, 95% CI 0.66–0.77), followed by GLP-1 receptor agonists (RR 0.77, 95% CI 0.71–0.84). Metformin demonstrated a near-neutral association (RR 0.89, 95% CI 0.79–1.00), whereas DPP-4 inhibitors (RR 1.05, 95% CI 0.97–1.13) and meglitinides (RR 1.13, 95% CI 0.93–1.36) showed no evidence of benefit. Similar findings were observed for severe exacerbations, with SGLT-2 inhibitors and GLP-1 receptor agonists demonstrating the strongest associations. Conclusions SGLT-2 inhibitors and GLP-1 receptor agonists were associated with a lower risk of COPD exacerbations than sulfonylureas, whereas metformin showed a near-neutral association and DPP-4 inhibitors and meglitinides showed no clear benefit.
BackgroundHeart failure (HF) is closely associated with abnormalities in glucose metabolism, which substantially influence clinical outcomes. The hemoglobin glycation index (HGI), reflecting the discrepancy between observed and predicted glycated hemoglobin, has emerged as a marker of interindividual variation in glycation beyond conventional HbA1c. However, the prognostic significance of HGI in hospitalized patients with HF remains unclear.MethodsIn this retrospective cohort study, we analyzed data from the MIMIC-IV database and included 3,470 adult patients hospitalized with HF. HGI was calculated as the difference between measured HbA1c and predicted HbA1c derived from fasting plasma glucose, and participants were categorized into quartiles. The primary outcome was 365-day all-cause mortality, and the secondary outcome was 30-day all-cause mortality. Kaplan-Meier survival analysis, restricted cubic spline modeling, multivariable Cox regression, and subgroup analyses were performed to evaluate the association between HGI and mortality.ResultsAmong the 3,470 included patients, 837 (24.1%) died within 365 days after discharge. Restricted cubic spline analysis demonstrated a predominantly L-shaped association between HGI and both 30-day and 365-day all-cause mortality, with excess mortality risk mainly concentrated at low HGI values. In multivariable Cox models, compared with the lowest quartile, higher HGI quartiles were associated with significantly lower risks of both short-term and long-term mortality, supporting the particular vulnerability of patients with extremely low HGI. Subgroup analyses generally supported the robustness of these findings, although a significant interaction with diabetes status was observed for 365-day mortality.ConclusionsHGI was independently associated with short-term and long-term all-cause mortality in hospitalized patients with HF, with a predominantly L-shaped pattern observed. Excess mortality risk was mainly concentrated at low HGI values. HGI may serve as a simple and accessible marker for risk stratification in this population.
Background Type 2 diabetes mellitus (T2DM) involves alterations in lipid metabolism beyond conventional cholesterol profiles. We examined whether specific plasma lipidomic signatures are related to pericoronary adipose tissue (PCAT) inflammation and coronary artery disease (CAD) burden. Methods This cross-sectional analysis included 176 T2DM participants from the GADA study. PCAT inflammation was measured by the fat attenuation index (FAI), CAD burden by Gensini/SYNTAX scores and plasma lipid species by targeted LC-MS. Multivariable regression were used to identify lipid species associated with FAI and CAD burden. For lipid species linked to both, mediation analyses were performed. Results We quantified 660 lipid molecular species across 20 classes. Five species were associated with FAI: sphingomyelin (SM) (34:4), phosphatidylcholines (PC) (16:0/20:4), Lysophosphatidylethanolamine (LPE) (18:1), LPE (20:4), and LPE (18:2). The three LPE species remained independently associated with both Gensini and SYNTAX scores after adjustment for clinical risk factors, conventional lipid measures, triglycerides, and hsCRP. Mediation analyses indicated that FAI accounted for part of the associations between these LPE species and CAD burden. Conclusions In T2DM patients, circulating LPE (18:1), LPE (20:4), and LPE (18:2) were associated with both PCAT inflammation and CAD burden. These findings point to altered LPE metabolism as a lipid-inflammatory signature linked to residual atherosclerotic burden beyond conventional lipid and glycemic measures.
Depression is a clinically important comorbidity in people living with diabetes, yet biological pathways linking these conditions remain unclear. Chronic inflammation has been proposed as one mechanism connecting metabolic dysfunction with depressive symptoms. This scoping review examined knowledge on inflammation and depression/depressive symptoms in adults with diabetes, with attention to differences by diabetes type and sex. Thirty-seven studies met inclusion criteria, predominantly observational and focused on type 2 diabetes. Inflammatory markers were more frequently associated with depressive symptoms in type 2 diabetes than in type 1. CRP/hs-CRP was the most commonly studied biomarker and was often positively associated with depressive symptoms, while composite immune-metabolic indices reflected depressive symptom burden across studies. In contrast, findings for individual cytokines, including IL-6 and TNF-α, were heterogenous and appeared dependent on adiposity, metabolic health, or vascular comorbidity. Evidence in type 1 diabetes was less uniform, with studies suggesting involvement of vascular, lipid-associated, or non-classical inflammatory pathways. Sex appeared to modify inflammation and depression associations, although patterns varied across biomarkers and study populations. Overall, the literature suggests that inflammation is relevant to depression in diabetes, particularly in type 2, but that this relationship is heterogeneous and shaped by diabetes type, sex, adiposity, and vascular burden.
