Dual Roles of HbA1c Variability and Body Composition for Cardiovascular Risk: A Cohort Study of 8224 Adults With Type 2 Diabetes Mellitus

BACKGROUND: Glycaemic variability and body composition are emerging predictors of cardiovascular disease (CVD) in patients with Type 2 diabetes mellitus (T2DM); however, their combined impact remains unclear. We investigated the association among HbA1c variability, body composition parameters and cardiovascular outcomes in adults with T2DM. METHODS: This retrospective cohort study analysed electronic health records from a university hospital (2011-2020), including 8224 adults (mean age 58.3 years, 50.1% women) with T2DM and no history of CVD. HbA1c variability score (HVS) was defined as the percentage of successive measurements differing by ≥ 0.5% (5.5 mmol/mol). Body composition was assessed by bioimpedance analysis. The primary outcome was incident CVD (ischemic heart disease, heart failure, atrial fibrillation, stroke, myocardial infarction). RESULTS: During median follow-up of 4.0 years, patients with high HVS (third tertile) showed significantly increased CVD risk compared to low HVS (first tertile) (adjusted hazard ratio [aHR] 1.70 [95% CI 1.13-2.40]; p < 0.010). HbA1c variability demonstrated superior cardiovascular risk prediction over fasting and postprandial glucose variability. Individuals with high HVS had significantly higher systolic blood pressure (122.72 ± 14.96 vs. 120.53 ± 14.52 mmHg, p = 0.017), HbA1c (7.72% ± 1.75% vs. 7.02% ± 1.09%, p < 0.001) and lower skeletal muscle mass (24.60 ± 5.73 vs. 25.85 ± 7.84 kg, p < 0.001). Higher appendicular skeletal muscle mass was protective against CVD (aHR 0.75 [95% CI 0.63-0.88]), while increased total fat percentage elevated CVD risk (aHR 1.10 [95% CI 1.03-1.20]). HVS correlated positively with changes in total fat percentage (β = 0.439, p < 0.001) and negatively with changes in relative appendicular skeletal muscle mass (β = -0.258, p < 0.001). In multivariate analysis, significant contributors to increased CVD risk included high HVS (aHR 1.65, p = 0.011), elevated average HbA1c (aHR 1.09, p = 0.016) and age over 65 years (aHR 1.61, p = 0.035). CONCLUSIONS: HbA1c variability and body composition independently predicted cardiovascular outcomes in patients with T2DM. Higher HbA1c variability increased CVD risk by 70%, while higher appendicular muscle mass reduced risk by 25%, and higher total fat percentage increased risk by 10%. Incorporating these parameters into risk stratification models could enhance cardiovascular risk prediction and guide preventive strategies for diabetes management.