Nonlinear association of triglyceride-glucose body mass index with all-cause mortality in postmenopausal women, a retrospective cohort study: Evidence from the 2001 to 2014 National Health and nutrition examination survey.

BACKGROUND: The triglyceride-glucose body mass index (TyG-BMI) is a novel indicator combining an insulin resistance proxy (TyG index) with adiposity. It remains unclear how TyG-BMI relates to long-term mortality risk in postmenopausal women, a group prone to metabolic changes after menopause. This study investigated the association between TyG-BMI and all-cause mortality, with secondary outcomes of cardiovascular disease (CVD) mortality and cancer mortality, in a nationally representative cohort of US postmenopausal women.

METHODS: We analyzed data from 3844 postmenopausal women (mean age 64.8 ± 10.8 years) in the 2001-2014 National Health and Nutrition Examination Survey (NHANES) who had baseline fasting triglycerides, glucose, and body mass index (BMI) measured. The TyG-BMI index was calculated as ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2] × BMI (kg/m2). Mortality outcomes (all-cause, CVD, and cancer mortality) were ascertained through linkage to National Death Index records, with median follow-up of 119 months (approximately 9.9 years). Cox proportional hazards models were used to estimate hazard ratios (HRs) for mortality per standard deviation (SD) increase in TyG-BMI, adjusting for age, ethnicity, poverty-income ratio, smoking, alcohol use, and total physical activity (MET-min/week). We used restricted cubic splines to assess nonlinearity and a two-piece Cox model to estimate threshold effects, with log-likelihood ratio tests to confirm nonlinear associations. Sensitivity analyses were conducted to test the robustness of findings.

RESULTS: Over follow-up, 1033 participants died (26.9%), including 336 CVD deaths (8.7%) and a similar order of magnitude of cancer deaths. The baseline TyG-BMI averaged 260.7 ± 67.0. We observed a nonlinear (U-shaped) relationship between TyG-BMI and all-cause mortality (P < 0.0001 for nonlinearity). An inflection point was identified at a TyG-BMI of approximately 289. Below this point, higher TyG-BMI was associated with lower mortality risk: for each 1 SD (67.0-unit) increase in TyG-BMI, the adjusted HR for all-cause mortality was 0.77 (95% confidence interval [CI] 0.69-0.86, P < 0.0001). Above the threshold of 289, higher TyG-BMI was associated with higher mortality risk: per SD increase HR = 1.28 (95% CI 1.13-1.46, P = 0.0002). In secondary outcome analyses, TyG-BMI showed a similar nonlinear pattern with CVD mortality (U-shaped association, with low TyG-BMI linked to higher CVD death risk and an increasing hazard at the upper end), although estimates were less precise due to fewer events. By contrast, no significant positive association was observed between TyG-BMI and cancer mortality; if anything, higher TyG-BMI tended to correspond to a slight reduction in cancer mortality risk, although this trend did not reach statistical significance. All results were consistent in sensitivity analyses.

CONCLUSION: In this cohort of US postmenopausal women, TyG-BMI exhibited a U-shaped association with all-cause mortality. Both low and high TyG-BMI values conferred elevated mortality risk, especially from cardiovascular causes, while intermediate TyG-BMI levels were associated with the lowest risk. These findings suggest that maintaining a balanced TyG-BMI, reflecting neither extreme leanness with low metabolic reserves nor excessive insulin-resistant adiposity, might be important for longevity in older women.