title: Prospective association of fatty acids in the de novo lipogenesis pathway with risk of type 2 diabetes: the Cardiovascular Health Study.
abstract: BACKGROUND
  Experimental evidence suggests that hepatic de novo lipogenesis (DNL) affects insulin homeostasis via synthesis of saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs). Few prospective studies have used fatty acid biomarkers to assess associations with type 2 diabetes.
  
  
  OBJECTIVE
  We investigated associations of major circulating SFAs [palmitic acid (16:0) and stearic acid (18:0)] and MUFA [oleic acid (18:1n-9)] in the DNL pathway with metabolic risk factors and incident diabetes in community-based older U.S. adults in the Cardiovascular Health Study. We secondarily assessed other DNL fatty acid biomarkers [myristic acid (14:0), palmitoleic acid (16:1n-7), 7-hexadecenoic acid (16:1n-9), and vaccenic acid (18:1n-7)] and estimated dietary SFAs and MUFAs.
  
  
  METHODS
  In 3004 participants free of diabetes, plasma phospholipid fatty acids were measured in 1992, and incident diabetes was identified by medication use and blood glucose. Usual diets were assessed by using repeated food-frequency questionnaires. Multivariable linear and Cox regression were used to assess associations with metabolic risk factors and incident diabetes, respectively.
  
  
  RESULTS
  At baseline, circulating palmitic acid and stearic acid were positively associated with adiposity, triglycerides, inflammation biomarkers, and insulin resistance (P-trend < 0.01 each), whereas oleic acid showed generally beneficial associations (P-trend < 0.001 each). During 30,763 person-years, 297 incident diabetes cases occurred. With adjustment for demographics and lifestyle, palmitic acid (extreme-quintile HR: 1.89; 95% CI: 1.27, 2.83; P-trend = 0.001) and stearic acid (HR: 1.62; 95% CI: 1.09, 2.41; P-trend = 0.006) were associated with higher diabetes risk, whereas oleic acid was not significantly associated. In secondary analyses, vaccenic acid was inversely associated with diabetes (HR: 0.56; 95% CI: 0.38, 0.83; P-trend = 0.005). Other fatty acid biomarkers and estimated dietary SFAs or MUFAs were not significantly associated with incident diabetes.
  
  
  CONCLUSIONS
  In this large prospective cohort, circulating palmitic acid and stearic acid were associated with higher diabetes risk, and vaccenic acid was associated with lower diabetes risk. These results indicate a need for additional investigation of biological mechanisms linking specific fatty acids in the DNL pathway to the pathogenesis of diabetes.
authors.affiliation: From the Department of Epidemiology, Harvard School of Public Health, Boston, MA (WM, QW, and DM); the Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (DM); the Divisions of Aging (LD) and Cardiovascular Medicine and Channing Division of Network Medicine (DM), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; the Boston Veterans Affairs Healthcare System, Boston, MA (LD); the Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA (KJM); The George Institute for Global Health, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia (JHYW); the Cardiovascular Health Research Unit, Departments of Medicine (RNL and DSS), Epidemiology (DSS), and Biostatistics (MLB), and the Collaborative Health Studies Coordinating Center (JAD), University of Washington, Seattle, WA; the Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (XS); the Department of Internal Medicine, University of New Mexico, Albuquerque, NM (IBK); and the Department of Medicine, Albert Einstein College of Medicine, Bronx, NY (JRK).
authors.forename: Wenjie
authors.initials: W
authors.lastname: Ma
authors.affiliation: From the Department of Epidemiology, Harvard School of Public Health, Boston, MA (WM, QW, and DM); the Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (DM); the Divisions of Aging (LD) and Cardiovascular Medicine and Channing Division of Network Medicine (DM), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; the Boston Veterans Affairs Healthcare System, Boston, MA (LD); the Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA (KJM); The George Institute for Global Health, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia (JHYW); the Cardiovascular Health Research Unit, Departments of Medicine (RNL and DSS), Epidemiology (DSS), and Biostatistics (MLB), and the Collaborative Health Studies Coordinating Center (JAD), University of Washington, Seattle, WA; the Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (XS); the Department of Internal Medicine, University of New Mexico, Albuquerque, NM (IBK); and the Department of Medicine, Albert Einstein College of Medicine, Bronx, NY (JRK).
authors.forename: Jason H Y
authors.initials: JH
authors.lastname: Wu
authors.affiliation: From the Department of Epidemiology, Harvard School of Public Health, Boston, MA (WM, QW, and DM); the Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (DM); the Divisions of Aging (LD) and Cardiovascular Medicine and Channing Division of Network Medicine (DM), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; the Boston Veterans Affairs Healthcare System, Boston, MA (LD); the Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA (KJM); The George Institute for Global Health, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia (JHYW); the Cardiovascular Health Research Unit, Departments of Medicine (RNL and DSS), Epidemiology (DSS), and Biostatistics (MLB), and the Collaborative Health Studies Coordinating Center (JAD), University of Washington, Seattle, WA; the Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (XS); the Department of Internal Medicine, University of New Mexico, Albuquerque, NM (IBK); and the Department of Medicine, Albert Einstein College of Medicine, Bronx, NY (JRK).
authors.forename: Qianyi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: From the Department of Epidemiology, Harvard School of Public Health, Boston, MA (WM, QW, and DM); the Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (DM); the Divisions of Aging (LD) and Cardiovascular Medicine and Channing Division of Network Medicine (DM), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; the Boston Veterans Affairs Healthcare System, Boston, MA (LD); the Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA (KJM); The George Institute for Global Health, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia (JHYW); the Cardiovascular Health Research Unit, Departments of Medicine (RNL and DSS), Epidemiology (DSS), and Biostatistics (MLB), and the Collaborative Health Studies Coordinating Center (JAD), University of Washington, Seattle, WA; the Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (XS); the Department of Internal Medicine, University of New Mexico, Albuquerque, NM (IBK); and the Department of Medicine, Albert Einstein College of Medicine, Bronx, NY (JRK).
authors.forename: Rozenn N
authors.initials: RN
authors.lastname: Lemaitre
authors.affiliation: From the Department of Epidemiology, Harvard School of Public Health, Boston, MA (WM, QW, and DM); the Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (DM); the Divisions of Aging (LD) and Cardiovascular Medicine and Channing Division of Network Medicine (DM), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; the Boston Veterans Affairs Healthcare System, Boston, MA (LD); the Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA (KJM); The George Institute for Global Health, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia (JHYW); the Cardiovascular Health Research Unit, Departments of Medicine (RNL and DSS), Epidemiology (DSS), and Biostatistics (MLB), and the Collaborative Health Studies Coordinating Center (JAD), University of Washington, Seattle, WA; the Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (XS); the Department of Internal Medicine, University of New Mexico, Albuquerque, NM (IBK); and the Department of Medicine, Albert Einstein College of Medicine, Bronx, NY (JRK).
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Mukamal
authors.affiliation: From the Department of Epidemiology, Harvard School of Public Health, Boston, MA (WM, QW, and DM); the Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (DM); the Divisions of Aging (LD) and Cardiovascular Medicine and Channing Division of Network Medicine (DM), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; the Boston Veterans Affairs Healthcare System, Boston, MA (LD); the Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA (KJM); The George Institute for Global Health, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia (JHYW); the Cardiovascular Health Research Unit, Departments of Medicine (RNL and DSS), Epidemiology (DSS), and Biostatistics (MLB), and the Collaborative Health Studies Coordinating Center (JAD), University of Washington, Seattle, WA; the Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (XS); the Department of Internal Medicine, University of New Mexico, Albuquerque, NM (IBK); and the Department of Medicine, Albert Einstein College of Medicine, Bronx, NY (JRK).
authors.forename: Luc
authors.initials: L
authors.lastname: Djoussé
authors.affiliation: From the Department of Epidemiology, Harvard School of Public Health, Boston, MA (WM, QW, and DM); the Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (DM); the Divisions of Aging (LD) and Cardiovascular Medicine and Channing Division of Network Medicine (DM), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; the Boston Veterans Affairs Healthcare System, Boston, MA (LD); the Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA (KJM); The George Institute for Global Health, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia (JHYW); the Cardiovascular Health Research Unit, Departments of Medicine (RNL and DSS), Epidemiology (DSS), and Biostatistics (MLB), and the Collaborative Health Studies Coordinating Center (JAD), University of Washington, Seattle, WA; the Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (XS); the Department of Internal Medicine, University of New Mexico, Albuquerque, NM (IBK); and the Department of Medicine, Albert Einstein College of Medicine, Bronx, NY (JRK).
authors.forename: Irena B
authors.initials: IB
authors.lastname: King
authors.affiliation: From the Department of Epidemiology, Harvard School of Public Health, Boston, MA (WM, QW, and DM); the Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (DM); the Divisions of Aging (LD) and Cardiovascular Medicine and Channing Division of Network Medicine (DM), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; the Boston Veterans Affairs Healthcare System, Boston, MA (LD); the Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA (KJM); The George Institute for Global Health, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia (JHYW); the Cardiovascular Health Research Unit, Departments of Medicine (RNL and DSS), Epidemiology (DSS), and Biostatistics (MLB), and the Collaborative Health Studies Coordinating Center (JAD), University of Washington, Seattle, WA; the Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (XS); the Department of Internal Medicine, University of New Mexico, Albuquerque, NM (IBK); and the Department of Medicine, Albert Einstein College of Medicine, Bronx, NY (JRK).
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Song
authors.affiliation: From the Department of Epidemiology, Harvard School of Public Health, Boston, MA (WM, QW, and DM); the Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (DM); the Divisions of Aging (LD) and Cardiovascular Medicine and Channing Division of Network Medicine (DM), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; the Boston Veterans Affairs Healthcare System, Boston, MA (LD); the Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA (KJM); The George Institute for Global Health, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia (JHYW); the Cardiovascular Health Research Unit, Departments of Medicine (RNL and DSS), Epidemiology (DSS), and Biostatistics (MLB), and the Collaborative Health Studies Coordinating Center (JAD), University of Washington, Seattle, WA; the Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (XS); the Department of Internal Medicine, University of New Mexico, Albuquerque, NM (IBK); and the Department of Medicine, Albert Einstein College of Medicine, Bronx, NY (JRK).
authors.forename: Mary L
authors.initials: ML
authors.lastname: Biggs
authors.affiliation: From the Department of Epidemiology, Harvard School of Public Health, Boston, MA (WM, QW, and DM); the Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (DM); the Divisions of Aging (LD) and Cardiovascular Medicine and Channing Division of Network Medicine (DM), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; the Boston Veterans Affairs Healthcare System, Boston, MA (LD); the Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA (KJM); The George Institute for Global Health, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia (JHYW); the Cardiovascular Health Research Unit, Departments of Medicine (RNL and DSS), Epidemiology (DSS), and Biostatistics (MLB), and the Collaborative Health Studies Coordinating Center (JAD), University of Washington, Seattle, WA; the Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (XS); the Department of Internal Medicine, University of New Mexico, Albuquerque, NM (IBK); and the Department of Medicine, Albert Einstein College of Medicine, Bronx, NY (JRK).
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Delaney
authors.affiliation: From the Department of Epidemiology, Harvard School of Public Health, Boston, MA (WM, QW, and DM); the Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (DM); the Divisions of Aging (LD) and Cardiovascular Medicine and Channing Division of Network Medicine (DM), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; the Boston Veterans Affairs Healthcare System, Boston, MA (LD); the Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA (KJM); The George Institute for Global Health, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia (JHYW); the Cardiovascular Health Research Unit, Departments of Medicine (RNL and DSS), Epidemiology (DSS), and Biostatistics (MLB), and the Collaborative Health Studies Coordinating Center (JAD), University of Washington, Seattle, WA; the Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (XS); the Department of Internal Medicine, University of New Mexico, Albuquerque, NM (IBK); and the Department of Medicine, Albert Einstein College of Medicine, Bronx, NY (JRK).
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Kizer
authors.affiliation: From the Department of Epidemiology, Harvard School of Public Health, Boston, MA (WM, QW, and DM); the Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (DM); the Divisions of Aging (LD) and Cardiovascular Medicine and Channing Division of Network Medicine (DM), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; the Boston Veterans Affairs Healthcare System, Boston, MA (LD); the Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA (KJM); The George Institute for Global Health, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia (JHYW); the Cardiovascular Health Research Unit, Departments of Medicine (RNL and DSS), Epidemiology (DSS), and Biostatistics (MLB), and the Collaborative Health Studies Coordinating Center (JAD), University of Washington, Seattle, WA; the Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (XS); the Department of Internal Medicine, University of New Mexico, Albuquerque, NM (IBK); and the Department of Medicine, Albert Einstein College of Medicine, Bronx, NY (JRK).
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.affiliation: From the Department of Epidemiology, Harvard School of Public Health, Boston, MA (WM, QW, and DM); the Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (DM); the Divisions of Aging (LD) and Cardiovascular Medicine and Channing Division of Network Medicine (DM), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; the Boston Veterans Affairs Healthcare System, Boston, MA (LD); the Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA (KJM); The George Institute for Global Health, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia (JHYW); the Cardiovascular Health Research Unit, Departments of Medicine (RNL and DSS), Epidemiology (DSS), and Biostatistics (MLB), and the Collaborative Health Studies Coordinating Center (JAD), University of Washington, Seattle, WA; the Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (XS); the Department of Internal Medicine, University of New Mexico, Albuquerque, NM (IBK); and the Department of Medicine, Albert Einstein College of Medicine, Bronx, NY (JRK).
authors.forename: Dariush
authors.initials: D
authors.lastname: Mozaffarian
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D050155:Lipogenesis; D008099:Liver / Q000378:metabolism*; D008297:Male; D019308:Palmitic Acid / Q000097:blood* / Q000378:metabolism; D010743:Phospholipids / Q000097:blood* / Q000378:metabolism; D015995:Prevalence; D016016:Proportional Hazards Models; D012307:Risk Factors; D013229:Stearic Acids / Q000097:blood* / Q000378:metabolism; D014481:United States / Q000453:epidemiology; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D010743:Phospholipids; D013229:Stearic Acids; D019308:Palmitic Acid; C031183:stearic acid
keywords: biomarker; diabetes mellitus; diet; fatty acids; metabolism