肥胖会改变心力衰竭风险与老年人葡萄糖代谢紊乱之间的关联：一项基于社区的前瞻性队列研究。

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=0.017) in prediabetes, 1.59 (95% CI: 1.34, 1.90, P<0.001) in uncontrolled diabetes, and 1.10 (95% CI: 0.85, 1.43, P=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<0.001). ALR was negatively associated and HOMA-IR and TyG were positively associated with BMI, WHR, VFA, and incident HF (all P<0.05). ALR, HOMA-IR, and TyG mediated the associations for BMI, WHR and VFA with incident HF (all P.<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.

背景：葡萄糖代谢紊乱与心力衰竭（HF）的风险相关。肥胖是一种与老年人异常葡萄糖代谢密切相关的合并症。然而，肥胖对葡萄糖代谢紊乱与 HF 风险之间关联的影响，以及潜在机制仍不清楚。

方法：本研究共纳入了 13251 名年龄≥60 岁的队列研究参与者，他们被分为血糖正常、糖尿病前期、未控制糖尿病和控制良好的糖尿病。采用体重指数（BMI）、腰臀比（WHR）和内脏脂肪面积（VFA）来评估肥胖。采用脂联素与瘦素比值（ALR）、稳态模型评估的胰岛素抵抗指数（HOMA-IR）和甘油三酯-葡萄糖指数（TyG）评估与脂肪相关的代谢活性。HF 的首次发生作为随访期间的结局。

结果：在平均 10.9 年的随访期间，共有 1138 名参与者发生 HF。与血糖正常组相比，糖尿病前期、未控制糖尿病和控制良好的糖尿病组发生 HF 的发生率更高。然而，BMI、VFA 和 WHR 显著降低了这种高风险。特别是对于 WHR，糖尿病前期的 HF 发生率的危险比为 1.18（95%置信区间（CI）：1.03，1.35，P=0.017），未控制糖尿病为 1.59（95%CI：1.34，1.90，P<0.001），控制良好的糖尿病为 1.10（95%CI：0.85，1.43，P=0.466）。WHR 分类的中心性肥胖对 HF 的人群归因风险百分比在血糖正常组为 30.3%，糖尿病前期组为 50.0%，未控制糖尿病组为 48.5%，控制良好的糖尿病组为 54.4%。肥胖指标，尤其是 WHR，在 HF 的发生中与葡萄糖代谢紊乱有显著的交互作用（均 P<0.001）。ALR 与 BMI、WHR、VFA 和 HF 的发生呈负相关，HOMA-IR 和 TyG 与 BMI、WHR、VFA 和 HF 的发生呈正相关（均 P<0.05）。ALR、HOMA-IR 和 TyG 介导了 BMI、WHR 和 VFA 与 HF 发生之间的关联（均 P<0.05）。

结论：肥胖减轻了葡萄糖代谢紊乱与 HF 发生之间的关联。结果还表明，WHR 可能是评估老年人肥胖的一个合适指标。与脂肪相关的代谢活性可能在肥胖减轻葡萄糖代谢紊乱与 HF 发生之间的关联过程中发挥桥梁作用。

试验注册：回顾性注册编号：ChiCTR-EOC-17.013598。