Higher Dietary Insulinemic Potential Linked to Risk of All-Cause Mortality

Senior woman wearing mask infected by coronavirus on hospital bed receiving medicine by drip. Close-up fingers of the senior patient ´s hand while she is sleeping. Horizontal photo
Investigators studied whether diets higher in insulinemic potential were associated with a greater risk of cardiovascular disease, cancer, and overall mortality.

A diet with higher insulinemic potential is strongly associated with an increased risk of all-cause, cardiovascular disease (CVD), and cancer-related mortality, researchers reported in Diabetes Care.

The prospective study included 63,464 women from the Nurses’ Health Study who aged 30-55 years and 42,880 men from the Health Professionals Follow-up Study who were aged 40-75 years. The year 1986 was used as a baseline for both cohorts.

The investigators assessed the participants’ diet using validated semiquantitative food frequency questionnaires (FFQs) administered every 4 years, and evaluated the insulinemic potential of diet using a food-based empirical dietary index for hyperinsulinemia (EDIH), a weighted dietary pattern score that maximally predicts plasma C-peptide concentrations.

Participants who were in the highest EDIH quintile had a higher body mass index and lower physical activity levels in general, and were more likely to have a family history of diabetes. They also reported lower consumption of dietary fiber, alcohol, and coffee, and a higher intake of red and processed meat.

During 30 years of follow-up (2,792,550 person-years), 38,329 deaths were recorded in the 2 cohorts. Age-adjusted and multivariable-adjusted analyses demonstrated a consistently positive association between EDIH and mortality risk.

The pooled multivariable-adjusted hazard ratios (HRs) (95% CIs) for participants in the highest quintile of EDIH compared with those in the lowest quintile were 1.33 (95% CI, 1.29, 1.38; P-trend < .001) for all-cause mortality, 1.37 (95% CI, 1.27, 1.46; P-trend < .001) for CVD mortality, and 1.20 (95% CI, 1.13, 1.28; P-trend < .001) for cancer mortality.

Participants who had the highest EDIH score increase (quintile 5) had a significantly higher risk of all-cause mortality (HR 1.13; 95% CI, 1.09; 1.18; P-trend < .001) and CVD mortality (HR 1.10; 95% CI, 1.01, 1.21; P-trend = .006), compared with those whose EDIH scores were more stable (quintile 3).

For the joint association of scores at initial assessment and 8 years later,  participants with the largest increase in EDIH (low to high) had a 20% higher risk of all-cause mortality (HR 1.20; 95% CI, 1.12, 1.28) and 28% higher risk of CVD mortality (HR 1.28; 95% CI, 1.12, 1.47), compared with participants who had consistently low EDIH scores.

Similar associations were observed between changes in EDIH scores for 12- and 16-year periods and subsequent mortality risk.

Among several study limitations, dietary assessment was based on the self-reported questionnaire. Additionally, the study participants were health professionals and mostly White. Also, the analyses did not address the potential variability in mortality risk associated with insulin resistance, and the potential for reverse causation could not be ruled out.

“Adopting a diet with low insulinemic potential might be an effective approach to improve overall health,” the researchers concluded. “Dietary recommendations emphasizing the importance of avoiding high insulinemic dietary patterns as one of the important components of a healthy diet could be considered for the primary prevention of premature death.”


Wan Y, Tabung FK, Lee DH, Fung TT, Willett WC, Giovannucci EL. Dietary insulinemic potential and risk of total and cause-specific mortality in the nurses’ health study and the health professionals follow-up study. Diabetes Care. Published online November 29, 2021. doi:10.2337/dc21-1530