Hongfei Mo1,2†, Qinping Yang3†, Yining Wang2, Qinghua Yan3, Shuyue Sun1,2, Huiting Yu4, Yan Shi3, Fan Wang1* and Minna Cheng3*

¹Fudan Development Institute, Fudan University, Shanghai, People's Republic of China

²School of Public Health, Fudan University, Shanghai, People's Republic of China

³Institute for Chronic Non-Communicable Diseases Control, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, People's Republic of China

⁴Department of Vital Statistics, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, People's Republic of China

†Hongfei Mo and Qinping Yang contributed equally

*Correspondence to Fan Wang and Minna Cheng

目的 本研究旨在探讨低身体质量指数（BMI＜22 kg/m²）及核心血脂指标与老年2型糖尿病（T2DM）患者全因死亡风险的关联，并评估总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）和低密度脂蛋白胆固醇（LDL-C）在其中的中介作用。

方法 研究数据来源于上海市疾病预防控制中心（SCDC）糖尿病管理队列，共纳入372,559名年龄≥60岁的T2DM患者，按BMI＜22 kg/m²进行分层分析。采用线性回归分析低BMI与血脂指标的关联，采用Cox回归评估低BMI及血脂指标与死亡风险的关系。使用限制性立方样条（RCS）模型评估非线性趋势，并采用贝叶斯中介模型量化中介效应。

结果 与低BMI组相比，非低BMI组的全因死亡风险显著更高（HR = 1.10，95% CI：1.06～1.13）。在血脂指标中，TC、HDL-C和LDL‑C与死亡风险呈非线性关联（TC和LDL-C呈U型，HDL-C呈L型），其最佳阈值分别为5.03 mmol/L、0.98 mmol/L和3.39 mmol/L。中介分析显示，TC（中介比例PE = -16.68%）、HDL-C（PE = -111.99%）和LDL-C（PE = -4.12%）均表现出显著的负向中介作用，其中HDL-C的遮掩效应最强（βACME = 1.44，95% CI：1.33～1.56）。

结论 低BMI与老年T2DM患者死亡风险增加独立相关。胆固醇指标，尤其是HDL-C，可能通过负向中介作用部分解释这一关联。该发现提示临床应更多关注低体重老年T2DM患者的脂代谢紊乱问题。

Objective The present study aims to investigate the association of low body mass index (BMI < 22 kg/m2) and core lipid parameters on all-cause mortality among older adults with type 2 diabetes mellitus (T2DM), and to assess the mediating roles of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C).

Methods Data were analyzed from 372,559 T2DM participants aged ≥ 60 years, obtained from the Shanghai Center for Disease Control and Prevention (SCDC) diabetes management cohort, stratified by BMI < 22 kg/m2. Associations between low BMI and lipid parameters were examined using linear regression, associations of low BMI and lipid parameters with mortality risk were assessed via Cox regression. Restricted cubic spline (RCS) models were used to evaluate nonlinear trends, and Bayesian mediation models quantified the mediating effects.

Results The low BMI group had a significantly higher risk of all-cause mortality compared to the non-low BMI group (HR = 1.10, 95% CI: 1.06 ~ 1.13). Among the lipid parameters, TC, HDL-C, and LDL-C were nonlinearly associated with mortality risk (U-shaped for TC and LDL-C, L-shaped for HDL-C), with optimal thresholds identified at 5.03 mmol/L, 0.98 mmol/L, and 3.39 mmol/L, respectively. Mediation analysis demonstrated significant negative mediation for TC (proportion mediated, PE = –16.68%), HDL-C (PE = –111.99%), and LDL-C (PE = –4.12%), with HDL-C showing the strongest masking effect (βACME = 1.44, 95% CI: 1.33 ~ 1.56).

Conclusion Low BMI is independently associated with an increased risk of mortality in T2DM older adults. Cholesterol parameters, particularly HDL-C, may explain part of this association through negative mediation. These findings suggest the need for clinical attention to lipid metabolic disturbances among underweight older adults.

全因死亡率；胆固醇；低身体质量指数；脂质参数；中介分析；老年人；2型糖尿病

All-cause mortality, Cholesterol, Low BMI, Lipid parameters, Mediation analysis, Older adults, Type 2 diabetes mellitus (T2DM)

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