Prospective association of fatty acids in the de novo lipogenesis pathway with risk of type 2 diabetes: The Cardiovascular Health Study

Ma Wenjie, Jason H Y Wu, Qianyi Wang, Rozenn N. Lemaitre, Kenneth J. Mukamal, Luc Djoussé, Irena B. King, Xiaoling Song, Mary L. Biggs, Joseph A. Delaney, Jorge Kizer, David S. Siscovick, Dariush Mozaffarian

Research output: Contribution to journalArticle

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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. Objectives: 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. Design: 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. This trial was registered at clinicaltrials.gov as NCT00005133.

Original languageEnglish (US)
Pages (from-to)153-163
Number of pages11
JournalAmerican Journal of Clinical Nutrition
Volume101
Issue number1
DOIs
StatePublished - Jan 1 2015

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Lipogenesis
Type 2 Diabetes Mellitus
Fatty Acids
Monounsaturated Fatty Acids
Health
Palmitic Acid
Oleic Acid
Biomarkers
Adiposity
Myristic Acid
Metabolic Networks and Pathways
Insulin Resistance
Blood Glucose
Life Style
Linear Models
Phospholipids
Triglycerides
Homeostasis
Demography
Prospective Studies

Keywords

  • Biomarker
  • Diabetes mellitus
  • Diet
  • Fatty acids
  • Metabolism

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Prospective association of fatty acids in the de novo lipogenesis pathway with risk of type 2 diabetes : The Cardiovascular Health Study. / Wenjie, Ma; Wu, Jason H Y; Wang, Qianyi; Lemaitre, Rozenn N.; Mukamal, Kenneth J.; Djoussé, Luc; King, Irena B.; Song, Xiaoling; Biggs, Mary L.; Delaney, Joseph A.; Kizer, Jorge; Siscovick, David S.; Mozaffarian, Dariush.

In: American Journal of Clinical Nutrition, Vol. 101, No. 1, 01.01.2015, p. 153-163.

Research output: Contribution to journalArticle

Wenjie, M, Wu, JHY, Wang, Q, Lemaitre, RN, Mukamal, KJ, Djoussé, L, King, IB, Song, X, Biggs, ML, Delaney, JA, Kizer, J, Siscovick, DS & Mozaffarian, D 2015, 'Prospective association of fatty acids in the de novo lipogenesis pathway with risk of type 2 diabetes: The Cardiovascular Health Study', American Journal of Clinical Nutrition, vol. 101, no. 1, pp. 153-163. https://doi.org/10.3945/ajcn.114.092601
Wenjie, Ma ; Wu, Jason H Y ; Wang, Qianyi ; Lemaitre, Rozenn N. ; Mukamal, Kenneth J. ; Djoussé, Luc ; King, Irena B. ; Song, Xiaoling ; Biggs, Mary L. ; Delaney, Joseph A. ; Kizer, Jorge ; Siscovick, David S. ; Mozaffarian, Dariush. / Prospective association of fatty acids in the de novo lipogenesis pathway with risk of type 2 diabetes : The Cardiovascular Health Study. In: American Journal of Clinical Nutrition. 2015 ; Vol. 101, No. 1. pp. 153-163.
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T1 - Prospective association of fatty acids in the de novo lipogenesis pathway with risk of type 2 diabetes

T2 - The Cardiovascular Health Study

AU - Wenjie, Ma

AU - Wu, Jason H Y

AU - Wang, Qianyi

AU - Lemaitre, Rozenn N.

AU - Mukamal, Kenneth J.

AU - Djoussé, Luc

AU - King, Irena B.

AU - Song, Xiaoling

AU - Biggs, Mary L.

AU - Delaney, Joseph A.

AU - Kizer, Jorge

AU - Siscovick, David S.

AU - Mozaffarian, Dariush

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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. Objectives: 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. Design: 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. This trial was registered at clinicaltrials.gov as NCT00005133.

AB - 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. Objectives: 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. Design: 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. This trial was registered at clinicaltrials.gov as NCT00005133.

KW - Biomarker

KW - Diabetes mellitus

KW - Diet

KW - Fatty acids

KW - Metabolism

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