Abstract
BACKGROUND: Glucose metabolic disorder is associated with the risk of heart failure (HF). Adiposity is a comorbidity that is inextricably linked with abnormal glucose metabolism in older individuals. However, the effect of adiposity on the association between glucose metabolic disorder and HF risk, and the underlying mechanism remain unclear. METHODS: A total of 13,251 participants aged ≥ 60 years from a cohort study were categorized into euglycemia, prediabetes, uncontrolled diabetes, and well-controlled diabetes. Adiposity was assessed using body mass index (BMI), waist-to-hip ratio (WHR), and visceral fat area (VFA). Adiposity-associated metabolic activities were evaluated using adiponectin-to-leptin ratio (ALR), homeostatic model assessment of insulin resistance (HOMA-IR), and triglyceride-glucose index (TyG). The first occurrence of HF served as the outcome during the follow-up period. RESULTS: A total of 1,138 participants developed HF over the course of an average follow-up period of 10.9 years. The rate of incident HF occurrence was higher in prediabetes, uncontrolled diabetes, and well-controlled diabetes participants compared to that in euglycemia participants. However, the high rates were significantly attenuated by BMI, VFA, and WHR. For WHR in particular, the hazard ratio for incident HF was 1.18 (95% confidence interval (CI): 1.03, 1.35, P(adj.)=0.017) in prediabetes, 1.59 (95% CI: 1.34, 1.90, P(adj.)<0.001) in uncontrolled diabetes, and 1.10 (95% CI: 0.85, 1.43, P(adj.)=0.466) in well-controlled diabetes. The population attributable risk percentage for central obesity classified by WHR for incident HF was 30.3% in euglycemia, 50.0% in prediabetes, 48.5% in uncontrolled diabetes, and 54.4% in well-controlled diabetes. Adiposity measures, especially WHR, showed a significant interaction with glucose metabolic disorder in incident HF (all P(adj.)<0.001). ALR was negatively associated and HOMA-IR and TyG were positively associated with BMI, WHR, VFA, and incident HF (all P(adj.)<0.05). ALR, HOMA-IR, and TyG mediated the associations for BMI, WHR and VFA with incident HF (all P(adj).<0.05). CONCLUSIONS: Adiposity attenuated the association of glucose metabolic disorder with incident HF. The results also showed that WHR may be an appropriate indicator for evaluating adiposity in older individuals. Adiposity-associated metabolic activities may have a bridging role in the process of adiposity attenuating the association between glucose metabolic disorder and incident HF. TRIAL REGISTRATION: retrospectively registered number: ChiCTR-EOC-17,013,598.