The additive effect of the triglyceride-glucose index and estimated glucose disposal rate on long-term mortality among individuals with and without diabetes: a population-based study

Abstract

Background: The triglyceride-glucose (TyG) index and estimated glucose disposal rate (eGDR), which are calculated using different parameters, are widely used as markers of insulin resistance and are associated with cardiovascular diseases and prognosis. However, whether they have an additive effect on the risk of mortality remains unclear. This study aimed to explore whether the combined assessment of the TyG index and eGDR improved the prediction of long-term mortality in individuals with and without diabetes.

Methods: In this cross-sectional and cohort study, data were derived from the National Health and Nutrition Examination Survey (NHANES) 2001-2018, and death record information was obtained from the National Death Index. The associations of the TyG index and eGDR with all-cause and cardiovascular mortality were determined by multivariate Cox regression analysis and restricted cubic splines.

Results: Among the 17,787 individuals included in the analysis, there were 1946 (10.9%) all-cause deaths and 649 (3.6%) cardiovascular deaths during a median follow-up of 8.92 years. In individuals with diabetes, the restricted cubic spline curves for the associations of the TyG index and eGDR with mortality followed a J-shape and an L-shape, respectively. The risk of mortality significantly increased after the TyG index was > 9.04 (all-cause mortality) or > 9.30 (cardiovascular mortality), and after eGDR was < 4 mg/kg/min (both all-cause and cardiovascular mortality). In individuals without diabetes, the association between eGDR and mortality followed a negative linear relationship. However, there was no association between the TyG index and mortality. Compared with individuals in the low TyG and high eGDR group, those in the high TyG and low eGDR group (TyG > 9.04 and eGDR < 4) showed the highest risk for all-cause mortality (hazard ratio [HR] = 1.592, 95% confidence interval [CI] 1.284-1.975) and cardiovascular mortality (HR = 1.683, 95% CI 1.179-2.400) in the overall population. Similar results were observed in individuals with and without diabetes.

Conclusions: There was a potential additive effect of the TyG index and eGDR on the risk of long-term mortality in individuals with and without diabetes, which provided additional information for prognostic prediction and contributed to improving risk stratification.

Keywords: Estimated glucose disposal rate; Insulin resistance; Mortality; NHANES; Triglyceride-glucose index.

Fig. 1

Flow chart of participant recruitment and screening. Abbreviations: eGDR, estimated glucose disposal rate; NHANES, National Health and Nutrition Examination Survey; TyG, triglyceride-glucose; ULN, upper limit of normal

Fig. 2

Receiver operating characteristic curves of the insulin resistance indices for (A) all-cause mortality and (B) cardiovascular mortality. Abbreviations: eGDR, estimated glucose disposal rate; HOMA-IR, homeostatic model assessment of insulin resistance; TyG, triglyceride-glucose; TyG-BMI, triglyceride glucose-body mass index; TyG-WC, triglyceride glucose-waist circumference; TyG-WHtR, triglyceride glucose-waist to height ratio

Fig. 3

Kaplan-Meier survival curves showing associations of the TyG index (A and B) and eGDR (C and D) with long-term mortality. Abbreviations: eGDR, estimated glucose disposal rate; TyG, triglyceride-glucose

Fig. 4

Dose-response relationship between the TyG index and mortality in the (A and D) overall population, (B and E) individuals without diabetes, and (C and F) individuals with diabetes according to multivariable-adjusted restricted cubic spline analysis. Adjusted for Model 2 in the Cox regression analysis. Abbreviations: CI, confidence interval; HR, hazard ratio; TyG, triglyceride-glucose

Fig. 5

Dose-response relationship between eGDR and mortality in the (A and D) overall population, (B and E) individuals without diabetes, and (C and F) individuals with diabetes according to multivariable-adjusted restricted cubic spline analysis. Adjusted for Model 2 in the Cox regression analysis. Abbreviations: CI, confidence interval; eGDR, estimated glucose disposal rate; HR, hazard ratio

Fig. 6

Association between the combination of the TyG index and eGDR and long-term mortality in the (A and D) overall population, (B and E) individuals without diabetes, and (C and F) individuals with diabetes. Adjusted for Model 2 in the Cox regression analysis. Abbreviations: CI, confidence interval; eGDR, estimated glucose disposal rate; HR, hazard ratio; TyG, triglyceride-glucose