Contribution of the Nurses' Health Studies to Uncovering Risk Factors for Type 2 Diabetes: Diet, Lifestyle, Biomarkers, and Genetics

Abstract

Objectives: To review the contribution of the Nurses' Health Study (NHS) and the NHS II to addressing hypotheses regarding risk factors for type 2 diabetes.

Methods: We carried out a narrative review of 1976 to 2016 NHS and NHS II publications.

Results: The NHS and NHS II have uncovered important roles in type 2 diabetes for individual nutrients, foods, dietary patterns, and physical activity independent of excess body weight. Up to 90% of type 2 diabetes cases are potentially preventable if individuals follow a healthy diet and lifestyle. The NHS investigations have also identified novel biomarkers for diabetes, including adipokines, inflammatory cytokines, nutrition metabolites, and environmental pollutants, offering new insights into the pathophysiology of the disease. Global collaborative efforts have uncovered many common genetic variants associated with type 2 diabetes and improved our understanding of gene-environment interactions. Continued efforts to identify epigenetic, metagenomic, and metabolomic risk factors for type 2 diabetes have the potential to reveal new pathways and improve prediction and prevention.

Conclusions: Over the past several decades, the NHS and NHS II have made major contributions to public health recommendations and strategies designed to reduce the global burden of diabetes.

FIGURE 1—

Multivariate Relative Risks for Type 2 Diabetes According to Ascending Quintiles of Intake of (a) Cereal Fiber, (b) the Ratio of Polyunsaturated-Fat Intake to Saturated-Fat Intake, (c) Intake of Trans Fat, and (d) Glycemic Load: Nurses’ Health Study, United States, 1980–1996 Note. Whiskers indicate 95% confidence intervals. Each of the relative risks was adjusted for the other 3 dietary variables and for age, time, the presence or absence of a family history of diabetes, menopausal status, use or nonuse of postmenopausal hormone therapy, smoking status, body mass index, weekly frequency of moderate to vigorous exercise, and daily alcohol consumption. Source. Adapted with permission from Hu et al.

FIGURE 2—

Relative Risks for Type 2 Diabetes According to Frequency of Sugar-Sweetened Beverage Consumption: Nurses’ Health Study II, United States, 1991–1999 Note. Whiskers indicate 95% confidence intervals. The sample size was n = 91 249 women. Relative risks were adjusted for age, alcohol intake, physical activity, family history of diabetes, smoking, menopausal hormone use, oral contraceptive use, intake of cereal fiber, magnesium, trans fat, and ratio of polyunsaturated to saturated fat. Source. Adapted with permission from Schulze et al.

FIGURE 3—

Percent Changes in Risk of Developing Type 2 Diabetes Associated With TV Viewing, Other Sedentary Behaviors, and Walking: Nurses’ Health Study, United States, 1992–1998 Note. Data were adjusted for age, smoking, alcohol consumption, family history of diabetes, and dietary covariates. All sedentary behavior variables were included simultaneously in the model. Other sitting includes reading, eating meals, and time spent sitting at a desk. Source. Adapted with permission from Hu et al.