Nonlinear association between glycemic markers and incident cardio‑renal‑metabolic multimorbidity: two decades of follow‑up in the Tehran Lipid and Glucose Study
Year: 2025
Type: article
Study design: Observational Study
Abstract: Objective: To investigate the association between glycemic markers and the incidence of cardio-renal-metabolic multimorbidity (CRMM) in initially disease-free individuals. Methods: We used multivariable Cox proportional hazards models to evaluate associations between fasting plasma glucose (FPG), 2-hour post-load glucose (2hPG), serum insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) with incident CRMM, defined as the coexistence of ≥ 2 of cardiovascular disease (CVD) (including coronary heart disease, stroke, or cardiovascular death), type 2 diabetes mellitus (T2DM), and chronic kidney disease (CKD) among individuals initially free of these conditions. Results: During a median follow-up of 15.3 years (IQR: 11.9-16.4), among 5734 participants (3097 women), 340 (5.9 %) developed CRMM. The most frequent combination among those with incident CRMM was CVD and T2DM (49.1 %), followed by CKD and T2DM (19.7 %), CVD and CKD (18.5 %), and all three conditions (12.6 %). Hazard ratios (HRs) of incident CRMM associated with each 1-standard deviation (SD) increase in FPG, 2hPG, insulin (natural log), and HOMA-IR (natural log) were 1.48 (95 % CI: 1.34-1.64), 1.47 (1.32-1.63), 1.10 (0.91 -1.32), and 1.22 (1.01-1.47), respectively. Prediabetes, defined by either ADA or WHO criteria, was significantly associated with increased CRMM risk. Nonlinear threshold analyses indicated that the risk of CRMM increased significantly above an FPG threshold of 90.92 mg/dL and a 2hPG threshold of 109.92 mg/dL. Conclusions: Glycemic levels below the ADA-defined prediabetes thresholds for both FPG and 2hPG were associated with higher risks of CRMM, suggesting that glucose ranges below the current cut-offs conceal considerable risk and may warrant earlier preventive action.
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,900
OpenAlex ID: W4416420273