Diets with Higher Insulinemic Potential Are Associated with Increased Risk of Overall and Cardiovascular Disease-specific Mortality.

Hyperinsulinemia and insulin resistance have been proposed to be associated with mortality risk, and diet can modulate insulin response. However, whether dietary patterns with high insulinemic potential are associated with mortality remains unknown. We prospectively examined the associations between hyperinsulinemic diets and the risk of total and cause-specific mortality in a large nationally representative population. Dietary factors were assessed by 24-hour recalls. Two empirical dietary indices for hyperinsulinemia (EDIH) and insulin resistance (EDIR) were developed to identify food groups most predictive of biomarkers for hyperinsulinemia (C-peptide and insulin) and insulin resistance (homeostatic model assessment for insulin resistance), respectively. Deaths from date of the first dietary interview until December 31, 2015 were identified by the National Death Index. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression models. During a median follow-up of 7.8 years, 4,904 deaths were documented among 40,074 participants. For EDIH, the multivariable-adjusted HRs (comparing extreme quintiles) were 1.20 (95% CI: 1.09-1.32, P-trend<0.001) for overall mortality, and 1.41 (95% CI: 1.15-1.74, P-trend=0.002) for cardiovascular disease (CVD) mortality. Similar associations were observed for EDIR with HRs of 1.18 (95% CI: 1.07-1.29, P-trend<0.001) for total and 1.35 (95% CI: 1.09-1.67, P-trend=0.005) for CVD mortality. After further adjustments for body mass index and diabetes, these positive associations were somewhat attenuated, but most remained statistically significant. Our findings suggested that diets with higher insulinemic potential are associated with increased risk of overall and CVD-specific mortality. Strategies to avoid hyperinsulinemic dietary patterns may potentially promote health and longevity.