論文丨低BMI可預測老年2型糖尿病患者的死亡率：膽固醇參數呈現負向中介作用

論文發表

近日，由我院王帆教授（共同通訊作者）、公共衛生學院博士研究生莫鴻飛（共同第一作者），以及上海市疾病預防控制中心程旻娜主任（共同通訊作者）、楊沁平醫師（共同第一作者）等專家合作完成的論文“Low BMI predicts mortality in T2DM older adults: cholesterol parameters demonstrate negative mediation”發表于期刊《Diabetology & Metabolic Syndrome》（JCR Q2）。該期刊是糖尿病與內分泌代謝領域專業期刊，聚焦糖尿病及其并發癥的流行病學、臨床管理及基礎研究，涵蓋脂代謝、肥胖與慢性病預后等方向。本研究成果體現了王帆教授團隊在社區糖尿病管理及體重相關代謝異常方面的積極探索。

本研究基于上海市糖尿病管理隊列中372,559名老年2型糖尿病（T2DM）患者，系統探討了低身體質量指數（BMI＜22 kg/m2）與全因死亡風險的關聯，并量化了總膽固醇（TC）、高密度脂蛋白膽固醇（HDL-C）、低密度脂蛋白膽固醇（LDL-C）在該關聯中的中介作用。研究發現，低BMI顯著增加老年T2DM患者的全因死亡風險（HR=1.10）；TC和LDL-C與死亡風險呈U型非線性關系，HDL-C呈L型關系，最佳閾值分別為5.03 mmol/L、0.98 mmol/L和3.39 mmol/L。更重要的是，TC、HDL-C、LDL-C均呈現負向中介作用（即“遮掩效應”），其中HDL-C的負向中介效應最強（中介比例為?111.99%），提示低BMI相關的HDL-C下降可能部分解釋了低BMI與死亡風險之間的關聯。該成果首次揭示了膽固醇參數在老年T2DM患者低BMI與死亡風險關聯中的復雜間接作用，尤其是HDL-C的核心遮掩角色，為臨床實踐中關注低體重老年糖尿病患者的血脂代謝紊亂（特別是HDL-C偏低）提供了新的科學依據，對優化個體化體重與血脂管理策略具有重要臨床與公共衛生意義。

作者/Authors

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

摘要/Abstract

目的本研究旨在探討低身體質量指數（BMI＜22 kg/m2）及核心血脂指標與老年2型糖尿病（T2DM）患者全因死亡風險的關聯，并評估總膽固醇（TC）、甘油三酯（TG）、高密度脂蛋白膽固醇（HDL-C）和低密度脂蛋白膽固醇（LDL-C）在其中的中介作用。

方法研究數據來源于上海市疾病預防控制中心（SCDC）糖尿病管理隊列，共納入372,559名年齡≥60歲的T2DM患者，按BMI＜22 kg/m2進行分層分析。采用線性回歸分析低BMI與血脂指標的關聯，采用Cox回歸評估低BMI及血脂指標與死亡風險的關系。使用限制性立方樣條（RCS）模型評估非線性趨勢，并采用貝葉斯中介模型量化中介效應。

結果與低BMI組相比，非低BMI組的全因死亡風險顯著更高（HR = 1.10，95% CI：1.06～1.13）。在血脂指標中，TC、HDL-C和LDL?C與死亡風險呈非線性關聯（TC和LDL-C呈U型，HDL-C呈L型），其最佳閾值分別為5.03 mmol/L、0.98 mmol/L和3.39 mmol/L。中介分析顯示，TC（中介比例PE = -16.68%）、HDL-C（PE = -111.99%）和LDL-C（PE = -4.12%）均表現出顯著的負向中介作用，其中HDL-C的遮掩效應最強（βACME = 1.44，95% CI：1.33～1.56）。

結論低BMI與老年T2DM患者死亡風險增加獨立相關。膽固醇指標，尤其是HDL-C，可能通過負向中介作用部分解釋這一關聯。該發現提示臨床應更多關注低體重老年T2DM患者的脂代謝紊亂問題。

ObjectiveThe 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).

MethodsData 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.

ResultsThe 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).

ConclusionLow 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.

關鍵詞/Key Words

全因死亡率；膽固醇；低身體質量指數；脂質參數；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)

全文鏈接/Link

https://link.springer.com/article/10.1186/s13098-026-02118-y

來源｜Diabetology & Metabolic Syndrome