Background: Insulin response to diet might predict the risk of mortality; however, the evidence is limited. We prospectively evaluated the link between the dietary hyperinsulinemia index (DHI) and dietary insulin resistance index (DIRI) with all-cause and cause-specific (cardiovascular disease [CVD] and cancer) mortality.Methods: The National Health and Nutrition Examination Survey (1999-2010) database was used. Vital status through December 31, 2011, was ascertained. Stepwise linear regression models consisted of 39 macro/micronutrients applied, and fasting plasma C-peptide for the DHI and triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C) for the DIRI were used. Adjusted Cox regression (followed by propensity score matching) was performed to determine the hazard ratios (HRs) and 95% confidence interval (95% CIs).Results: Overall, 22,246 participants were included (mean age = 47.8 years; 48.9% men). There was a significant increasing risk of mortality across the quartiles of DHI, i.e., participants with a highest score of DHI (Q4) had a greater risk of all-cause (HR: 1.21, 95% CI: 1.17-1.26), CVD (HR: 1.17, 95% CI: 1.07-1.29), and cancer (HR: 1.15, 95% CI: 1.08-1.23) mortality compared with the first quartile (Q1; p < 0.001 for all comparisons). Similarly, participants in the highest DIRI quartile (Q4) had 23% and 31% higher risk of all-cause and CVD mortality, respectively, compared with Q1, while the association between cancer mortality and DIRI was non-significant (HR: 0.88, 95% CI: 0.35-2.61).Conclusions: These findings highlight, for the first time, the detrimental role (association) of insulinemia and insulin resistance potential of diet on all-cause and cause-specific mortality. Our findings support the role of C-peptide and TG/HDL-C ratio as cost-effective and practical biomarkers in clinical settings. These results need to be confirmed to establish their implications.
Keywords: C-peptide; Hyperinsulinemia; cancer; cardiovascular disease; dietary hyperinsulinemia index; dietary insulin resistance index; high-density lipoprotein; insulin resistance; mortality; triglyceride.