title: Contribution of the Nurses' Health Studies to Uncovering Risk Factors for Type 2 Diabetes: Diet, Lifestyle, Biomarkers, and Genetics.
abstract: OBJECTIVE
  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.
authors.affiliation: Sylvia H. Ley, Andres V. Ardisson Korat, Qi Sun, Lu Qi, Walter C. Willett, and Frank B. Hu are with the Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA. Deirdre K. Tobias and JoAnn E. Manson are with the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston. Cuilin Zhang is with Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
authors.forename: Sylvia H
authors.initials: SH
authors.lastname: Ley
authors.affiliation: Sylvia H. Ley, Andres V. Ardisson Korat, Qi Sun, Lu Qi, Walter C. Willett, and Frank B. Hu are with the Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA. Deirdre K. Tobias and JoAnn E. Manson are with the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston. Cuilin Zhang is with Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
authors.forename: Andres V
authors.initials: AV
authors.lastname: Ardisson Korat
authors.affiliation: Sylvia H. Ley, Andres V. Ardisson Korat, Qi Sun, Lu Qi, Walter C. Willett, and Frank B. Hu are with the Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA. Deirdre K. Tobias and JoAnn E. Manson are with the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston. Cuilin Zhang is with Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Sylvia H. Ley, Andres V. Ardisson Korat, Qi Sun, Lu Qi, Walter C. Willett, and Frank B. Hu are with the Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA. Deirdre K. Tobias and JoAnn E. Manson are with the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston. Cuilin Zhang is with Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
authors.forename: Deirdre K
authors.initials: DK
authors.lastname: Tobias
authors.affiliation: Sylvia H. Ley, Andres V. Ardisson Korat, Qi Sun, Lu Qi, Walter C. Willett, and Frank B. Hu are with the Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA. Deirdre K. Tobias and JoAnn E. Manson are with the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston. Cuilin Zhang is with Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
authors.forename: Cuilin
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Sylvia H. Ley, Andres V. Ardisson Korat, Qi Sun, Lu Qi, Walter C. Willett, and Frank B. Hu are with the Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA. Deirdre K. Tobias and JoAnn E. Manson are with the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston. Cuilin Zhang is with Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
authors.forename: Lu
authors.initials: L
authors.lastname: Qi
authors.affiliation: Sylvia H. Ley, Andres V. Ardisson Korat, Qi Sun, Lu Qi, Walter C. Willett, and Frank B. Hu are with the Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA. Deirdre K. Tobias and JoAnn E. Manson are with the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston. Cuilin Zhang is with Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
authors.forename: Walter C
authors.initials: WC
authors.lastname: Willett
authors.affiliation: Sylvia H. Ley, Andres V. Ardisson Korat, Qi Sun, Lu Qi, Walter C. Willett, and Frank B. Hu are with the Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA. Deirdre K. Tobias and JoAnn E. Manson are with the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston. Cuilin Zhang is with Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.affiliation: Sylvia H. Ley, Andres V. Ardisson Korat, Qi Sun, Lu Qi, Walter C. Willett, and Frank B. Hu are with the Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA. Deirdre K. Tobias and JoAnn E. Manson are with the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston. Cuilin Zhang is with Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D004032:Diet; D016021:Epidemiologic Studies; D005260:Female; D006801:Humans; D008019:Life Style; D008137:Longitudinal Studies; D008875:Middle Aged; D009726:Nurses; D011446:Prospective Studies; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D016387:Women's Health
chemical_list: D015415:Biomarkers