Dietary Insulinemic Potential and Risk of Total and Cause-Specific Mortality in the Nurses’ Health Study and the Health Professionals Follow-up Study

Yi Wan, Fred K. Tabung, Dong Hoon Lee, Teresa T. Fung, Walter C. Willett, Edward L. Giovannucci

Research output: Contribution to journalArticlepeer-review


OBJECTIVE Insulin response is related to overall health. Diet modulates insulin response. We investigated whether insulinemic potential of diet is associated with risk of all-cause and cause-specific mortality. RESEARCH DESIGN AND METHODS We prospectively followed 63,464 women from the Nurses’ Health Study (1986–2016) and 42,880 men from the Health Professionals Follow-up Study (1986–2016). Diet was assessed by food frequency questionnaires every 4 years. The insulinemic potential of diet was evaluated using a food-based empirical dietary index for hyperinsulinemia (EDIH), which was predefined based on predict-ing circulating C-peptide concentrations. RESULTS During 2,792,550 person-years of follow-up, 38,329 deaths occurred. In the pooled multivariable-adjusted analyses, a higher dietary insulinemic potential was associated with an increased risk of mortality from all-cause (hazard ratio [HR] comparing extreme quintiles: 1.33; 95% CI 1.29, 1.38; P-trend <0.001), cardiovascular disease (CVD) (HR 1.37; 95% CI 1.27, 1.46; P-trend <0.001), and can-cers (HR 1.20; 95% CI 1.13, 1.28; P-trend <0.001). These associations were independent of BMI and remained significant after further adjustment for other well-known dietary indices. Furthermore, compared with participants whose EDIH scores were stable over an 8-year period, those with the greatest increases had a higher subsequent risk of all-cause (HR 1.13; 95% CI 1.09, 1.18; P-trend <0.001) and CVD (HR 1.10; 95% CI 1.01, 1.21; P-trend 5 0.006) mortality. CONCLUSIONS Higher insulinemic potential of diet was associated with increased risk of all-cause, CVD, and cancer mortality. Adopting a diet with low insulinemic potential might be an effective approach to improve overall health and prevent premature death.

Original languageEnglish
Pages (from-to)451-459
Number of pages9
JournalDiabetes Care
Issue number2
Publication statusPublished - 2022 Feb

Bibliographical note

Funding Information:
Acknowledgments. The authors would like to thank the participants and staff of the Nurses’ Health Study and Health Professionals Follow-up Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, and WY. The authors assume full responsibility for analyses and interpretation of these data. Funding. This work was supported by grants from the National Institutes of Health (UM1 CA186107, P01 CA87969, and U01 CA167552), and Friends of FACES.

Publisher Copyright:
© 2022, American Diabetes Association Inc. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialised Nursing


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