Sex-specific Differences in the Association Between Leg Fat and Diabetes Risk: The Mediating Role of Visceral Adipose Tissue
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 542
- 试验地点
- 1
- 主要终点
- Prevalence of diabetes in relation to lower extremity fat
研究概览
简要总结
This study investigates the association between LFP, VAT and T2DM using DXA in 542 adults. We apply penalized regression, generalized additive models (GAM), and causal mediation analysis to explore whether higher LFP reduces diabetes risk and whether this effect is mediated by VAT. Sex-specific analyses further clarify the biological differences in adipose distribution. The findings aim to improve understanding of fat distribution and metabolic health.
详细描述
T2DM is a major public health concern, and growing evidence suggests that not all body fat confers equal metabolic risk. Beyond total adiposity, the regional distribution of fat strongly influences insulin resistance and diabetes development. VAT is metabolically detrimental, promoting inflammation and lipotoxicity, whereas lower-body subcutaneous fat, particularly in the legs and gluteofemoral region, may exert protective metabolic effects by serving as a "safe storage" depot for excess lipids. However, the causal mechanisms underlying these associations remain incompletely understood, and whether the protective role of LFP differs by sex remains unclear.
This study aims to elucidate the metabolic and causal pathways linking LFP, VAT, and diabetes risk in adults. Using DXA for precise body composition assessment, the study evaluates the associations between LFP, VAT, and T2DM prevalence, with a focus on sex-specific effects. A total of 542 adult participants will be analyzed, including both men and women with and without T2DM. Clinical, biochemical, and anthropometric data will be collected concurrently.
The analytic framework integrates multiple complementary approaches:
- Penalized regression models (LASSO, ridge, elastic net) will identify the most predictive adiposity components for T2DM while minimizing collinearity.
- GAMs will examine potential nonlinear relationships between LFP, VAT, and diabetes risk, separately for male and female.
- Causal mediation analysis will quantify the extent to which VAT mediates the relationship between LFP and diabetes, providing mechanistic insight into adipose redistribution pathways.
- Inverse-probability-of-treatment weighting (IPTW) will strengthen causal inference by balancing covariates across LFP strata.
- Two-sample Mendelian randomization (MR) will further test the causal effect of genetically predicted LFP on T2DM risk using summary-level genome-wide association data.
We hypothesize that higher LFP will be associated with lower diabetes risk and that this protective effect will be partially mediated by reduced VAT accumulation, particularly in females.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults (≥18 years old)
- •Available DXA measurement of fat distribution
- •Complete fasting glucose or diabetes diagnosis record
排除标准
- •Missing key variables (fat distribution, diabetes status)
- •Severe systemic disease interfering with data integrity
- •Implausible or inconsistent records
结局指标
主要结局
Prevalence of diabetes in relation to lower extremity fat
时间窗: Baseline
T2DM will be defined according to standard diagnostic criteria (fasting plasma glucose ≥ 7.0 mmol/L and/or HbA1c ≥ 6.5%, or a physician diagnosis). The primary outcome is the association between LFP and diabetes status, estimated using multivariable logistic regression and causal mediation analysis.
次要结局
- Mediating Effect of VAT(baseline)
- Sex-specific Differences in the LFP-T2D Association(Baseline)
研究者
Xuan Song
Associated physician
Qianfoshan Hospital