Low BMI predicts mortality in T2DM older adults: cholesterol parameters demonstrate negative mediation

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). 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. 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). 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.

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Journal
Diabetology & Metabolic Syndrome
Published
2026-03-03
DOI
https://doi.org/10.1186/s13098-026-02118-y
Primary Topic
Cardiovascular Function and Risk Factors
Type
article
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article

Low BMI predicts mortality in T2DM older adults: cholesterol parameters demonstrate negative mediation

Huiting Yu, Hongfei Mo, Shuyue Sun, Qinghua Yan et al.
Diabetology & Metabolic Syndrome
Cardiovascular Function and Risk Factors
article

Low BMI predicts mortality in T2DM older adults: cholesterol parameters demonstrate negative mediation

Huiting Yu, Hongfei Mo, Shuyue Sun, Qinghua Yan, Minna Cheng, Yining Wang, Qinping Yang, Yan Shi, Fan Wang
article en

Abstract

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). 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. 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). 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.

Diabetology & Metabolic Syndrome
Fudan University (CN), Shanghai Municipal Center For Disease Control Prevention (CN)
Openalex Percentile: Top 42%
Cardiovascular Function and Risk Factors
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