title: Trans-palmitoleic acid, metabolic risk factors, and new-onset diabetes in U.S. adults: a cohort study.
abstract: BACKGROUND
  Palmitoleic acid (cis-16:1n-7), which is produced by endogenous fat synthesis, has been linked to both beneficial and deleterious metabolic effects, potentially confounded by diverse determinants and tissue sources of endogenous production. Trans-palmitoleate (trans-16:1n-7) represents a distinctly exogenous source of 16:1n-7, unconfounded by endogenous synthesis or its determinants, that may be uniquely informative.
  
  
  OBJECTIVE
  To investigate whether circulating trans-palmitoleate is independently related to lower metabolic risk and incident type 2 diabetes.
  
  
  METHODS
  Prospective cohort study from 1992 to 2006.
  
  
  METHODS
  Four U.S. communities.
  
  
  METHODS
  3736 adults in the Cardiovascular Health Study.
  
  
  METHODS
  Anthropometric characteristics and levels of plasma phospholipid fatty acids, blood lipids, inflammatory markers, and glucose-insulin measured at baseline in 1992 and dietary habits measured 3 years earlier. Multivariate-adjusted models were used to investigate how demographic, clinical, and lifestyle factors independently related to plasma phospholipid trans-palmitoleate; how trans-palmitoleate related to major metabolic risk factors; and how trans-palmitoleate related to new-onset diabetes (304 incident cases). Findings were validated for metabolic risk factors in an independent cohort of 327 women.
  
  
  RESULTS
  In multivariate analyses, whole-fat dairy consumption was most strongly associated with higher trans-palmitoleate levels. Higher trans-palmitoleate levels were associated with slightly lower adiposity and, independently, with higher high-density lipoprotein cholesterol levels (1.9% across quintiles; P = 0.040), lower triglyceride levels (-19.0%; P < 0.001), a lower total cholesterol-HDL cholesterol ratio (-4.7%; P < 0.001), lower C-reactive protein levels (-13.8%; P = 0.05), and lower insulin resistance (-16.7%, P < 0.001). Trans-palmitoleate was also associated with a substantially lower incidence of diabetes, with multivariate hazard ratios of 0.41 (95% CI, 0.27 to 0.64) and 0.38 (CI, 0.24 to 0.62) in quintiles 4 and 5 versus quintile 1 (P for trend < 0.001). Findings were independent of estimated dairy consumption or other fatty acid dairy biomarkers. Protective associations with metabolic risk factors were confirmed in the validation cohort.
  
  
  CONCLUSIONS
  Results could be affected by measurement error or residual confounding.
  
  
  CONCLUSIONS
  Circulating trans-palmitoleate is associated with lower insulin resistance, presence of atherogenic dyslipidemia, and incident diabetes. Our findings may explain previously observed metabolic benefits of dairy consumption and support the need for detailed further experimental and clinical investigation.
  
  
  BACKGROUND
  National Heart, Lung, and Blood Institute and National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, and Harvard School of Public Health, Boston, Massachusetts 02115, USA. dmozaffa@hsph.harvard.edu
authors.forename: Dariush
authors.initials: D
authors.lastname: Mozaffarian
authors.forename: Haiming
authors.initials: H
authors.lastname: Cao
authors.forename: Irena B
authors.initials: IB
authors.lastname: King
authors.forename: Rozenn N
authors.initials: RN
authors.lastname: Lemaitre
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Song
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.forename: Gökhan S
authors.initials: GS
authors.lastname: Hotamisligil
mesh_terms: D050154:Adiposity; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003611:Dairy Products; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology*; D005229:Fatty Acids, Monounsaturated / Q000097:blood*; D005247:Feeding Behavior; D005260:Female; D006801:Humans; D015994:Incidence; D007333:Insulin Resistance; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D014481:United States / Q000453:epidemiology
chemical_list: D008076:Cholesterol, HDL; D005229:Fatty Acids, Monounsaturated; D014280:Triglycerides; C008757:palmitoleic acid; D002097:C-Reactive Protein; D002784:Cholesterol