Association of Triglyceride Glucose-Related Indices with Diabetic Foot Ulcer and Mortality: Evidence from NHANES 1999–2004

BackgroundTriglyceride glucose (TyG) related indices are cost-effective and reliable markers for the assessment of insulin resistance. Diabetic foot ulcer (DFU) is a serious complication of diabetes mellitus, causing a huge social burden worldwide. However, research on the relationship between TyG-related indices and DFU remains limited. In this study, we aimed to assess the associations between TyG-related indices with DFU prevalence and all-cause mortality, with a focus on DFU-specific mortality.MethodsThis cross-sectional study included 1118 participants from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004. Three TyG-related indices were identified in the subjects: TyG-waist circumference (TyG-WC), TyG-waist height ratio (TyG-WHtR), and TyG-body mass index (TyG-BMI). Weighted multivariable logistic regression was applied to assess the relationship between TyG-related indices and DFU. We employed Cox proportional hazards models and Kaplan-Meier survival analysis to evaluate the association between TyG-related indices and all-cause mortality over a median follow-up of <b>14.8 years</b>. Additionally, restricted cubic splines (RCS) modeling, subgroup analyses, and receiver operating characteristic (ROC) curves were conducted to enhance the accuracy and interpretability of the results.ResultsIn the study, a total of 1118 U.S. participants (age≥18) with diabetes were included, among whom 91 (8.14%) had DFU. A significant positive correlation was found between TyG-related indices and DFU in fully adjusted model [odds ratios (ORs) for Q3 versus Q1; TyG-WC: 5.85(95%CI: 2.45,13.97); TyG-WHtR: 4.16(95%CI: 1.45,11.95); TyG-BMI: 6.94(95%CI: 2.56,18.78), <i>p</i> for trend <0.05]. Similar trends were observed for all-cause mortality [HRs for Q3 versus Q1; TyG-WC: 1.29 (95%CI: 1.08,1.56); TyG-WHtR: 1.64 (95%CI: 1.17,2.31); TyG-BMI: 1.40 (95%CI: 1.02,1.91), <i>p</i> for trend <0.05]. Additionally, TyG-WHtR and TyG-BMI showed a non-linear relationship with DFU after adjusting all three models and the ROC curve indicated that TyG-WC had the highest predictive accuracy (AUC=0.656). In DFU participants, higher TyG-WC and TyG-WHtR (per 1-SD) were independently associated with all-cause mortality, whereas TyG-BMI was not; no significant TyG-related index × DFU interaction was observed in the overall cohort (all p for interaction > 0.05).ConclusionsElevated TyG-related indices, particularly TyG-WC, are independently associated with increased risk of DFU and all-cause mortality, suggesting that they can be cost-effective and reliable markers for identifying high-risk DFU in diabetic individuals.LimitationsDiabetes and DFU were self-reported, and detailed DFU wound characteristics and DFU-related comorbidities were unavailable in NHANES.