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Prospective association of fatty acids in the de novo lipogenesis pathway with risk of type 2 diabetes: the Cardiovascular Health Study.
Wednesday,2015-03-04 14:26 America/Los_Angeles — zdrager
| Title | Prospective association of fatty acids in the de novo lipogenesis pathway with risk of type 2 diabetes: the Cardiovascular Health Study. |
| Publication Type | Journal Article |
| Year of Publication | 2015 |
| Authors | Ma, W, H Y Wu, J, Wang, Q, Lemaitre, RN, Mukamal, KJ, Djoussé, L, King, IB, Song, X, Biggs, ML, Delaney, JA, Kizer, JR, Siscovick, DS, Mozaffarian, D |
| Journal | Am J Clin Nutr |
| Volume | 101 |
| Issue | 1 |
| Pagination | 153-63 |
| Date Published | 2015 Jan |
| ISSN | 1938-3207 |
| Keywords | Aged, Biomarkers, Cohort Studies, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Female, Follow-Up Studies, Humans, Incidence, Lipogenesis, Liver, Male, Palmitic Acid, Phospholipids, Prevalence, Proportional Hazards Models, Risk Factors, Stearic Acids, United States, Up-Regulation |
| Abstract | <p><b>BACKGROUND: </b>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.</p><p><b>OBJECTIVES: </b>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.</p><p><b>DESIGN: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.</p> |
| DOI | 10.3945/ajcn.114.092601 |
| Alternate Journal | Am. J. Clin. Nutr. |
| PubMed ID | 25527759 |
| PubMed Central ID | PMC4266885 |
| Grant List | 2R01-HL-085710 / HL / NHLBI NIH HHS / United States AG023629 / AG / NIA NIH HHS / United States HHSN268200800007C / / PHS HHS / United States HHSN268201200036C / / PHS HHS / United States HL080295 / HL / NHLBI NIH HHS / United States N01 HC55222 / HC / NHLBI NIH HHS / United States N01HC85079 / HC / NHLBI NIH HHS / United States N01HC85080 / HC / NHLBI NIH HHS / United States N01HC85081 / HC / NHLBI NIH HHS / United States N01HC85082 / HC / NHLBI NIH HHS / United States N01HC85083 / HC / NHLBI NIH HHS / United States N01HC85086 / HC / NHLBI NIH HHS / United States R01 HL085710 / HL / NHLBI NIH HHS / United States R01-HL-085710 / HL / NHLBI NIH HHS / United States R01-HL-094555 / HL / NHLBI NIH HHS / United States |