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

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

doi:10.3945/ajcn.114.092601

Cited by 145 publications

(119 citation statements)

References 59 publications

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“…Overall, the estimated D6D and SCD1 activities were strongly associated and the estimated D5D activity was inversely associated with the development of type 2 diabetes, as previously reported [14,27]. We also showed that the most abundant SFAs were associated with an elevated risk of diabetes, in agreement with two recent studies showing associations with type 2 diabetes [17,28]. Total SFAs were associated with impaired insulin sensitivity and insulin secretion in our study, offering a mechanistic explanation for how SFAs may impair glucose tolerance and lead to type 2 diabetes.…”

Section: Discussionsupporting

confidence: 81%

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Plasma fatty acids as predictors of glycaemia and type 2 diabetes

et al. 2015

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Aims/hypothesis Our aim was to investigate the fasting proportions of fatty acids and estimated desaturase and elongase activities in three different lipid fractions in plasma, phospholipids (PLs), cholesteryl esters (CEs) and triacylglycerols (TGs), as predictors for the worsening of glycaemia (area under the glucose curve in an OGTT [glucose AUC]) and incident type 2 diabetes in a 5.9 year follow-up of the Metabolic Syndrome in Men population-based cohort. Methods Fatty acid proportions were measured in plasma PL, CE and TG fractions in 1,364 Finnish men aged 45-68 years at baseline. The prospective follow-up study included only men who were non-diabetic at baseline and had data available at follow-up (n=1,302). A total of 71 participants developed new type 2 diabetes during follow-up.Results After adjusting for confounding factors, total saturated fatty acids, palmitoleic acid (16:1n-7), dihomo-γ-linolenic acid (20:3n-6) and estimated stearoyl-CoA desaturase 1 and Δ 6 -desaturase (D6D) enzyme activities significantly predicted the worsening of glycaemia whereas total polyunsaturated fatty acid, linoleic acid (18:2n-6) and elongase activity predicted a decrease in the glucose AUC. Estimated D6D activity and dihomo-γ-linolenic acid (20:3n-6) were associated with an increased risk of incident type 2 diabetes. Results were consistent across the three different lipid fractions. However, fatty acid proportions in the PL and CE fractions were stronger predictors for glycaemia and incident type 2 diabetes compared with fatty acid proportions in the TG fraction. Conclusions/interpretation Selected fatty acid proportions of plasma lipid fractions and their ratios, which reflect desaturase and elongase enzyme activities, may be good biomarkers for the worsening of glycaemia and incident type 2 diabetes.

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Section: Discussionsupporting

confidence: 81%

“…First, the diagnosis of type 2 diabetes has often been selfreported or based only on fasting glucose measurement [7,16], or diagnostic criteria have not been reported [17]. Second, none of previously published studies evaluated incident diabetes based on an OGTT or on HbA 1c levels.…”

Section: Introductionmentioning

confidence: 99%

Plasma fatty acids as predictors of glycaemia and type 2 diabetes

et al. 2015

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“…This relationship between C16:0 and glucose intolerance has been previously reported in other studies 22,23 and enforces the validity of this study.…”

Section: -Hydroxyacyl-coa Lyase 1 (Hacl1) Study To Further Investigsupporting

confidence: 60%

Odd Chain Fatty Acids; New Insights of the Relationship Between the Gut Microbiota, Dietary Intake, Biosynthesis and Glucose Intolerance

Jenkins

Seyssel

Chiu

et al. 2017

Sci Rep

102

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Recent findings have shown an inverse association between circulating C15:0/C17:0 fatty acids with disease risk, therefore, their origin needs to be determined to understanding their role in these pathologies. Through combinations of both animal and human intervention studies, we comprehensively investigated all possible contributions of these fatty acids from the gut-microbiota, the diet, and novel endogenous biosynthesis. Investigations included an intestinal germ-free study and a C15:0/C17:0 diet dose response study. Endogenous production was assessed through: a stearic acid infusion, phytol supplementation, and a Hacl1 −/− mouse model. Two human dietary intervention studies were used to translate the results. Finally, a study comparing baseline C15:0/C17:0 with the prognosis of glucose intolerance. We found that circulating C15:0/C17:0 levels were not influenced by the gut-microbiota. The dose response study showed C15:0 had a linear response, however C17:0 was not directly correlated. The phytol supplementation only decreased C17:0. Stearic acid infusion only increased C17:0. Hacl1 −/− only decreased C17:0. The glucose intolerance study showed only C17:0

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“…The replacement of SFAs with MUFAs and PUFAs or replacement of trans-fat with MUFAs was inversely associated with CVD [11].…”

mentioning

confidence: 95%

“…Experimentally determined SFA 14:0 and 16:0 status correlates positively with increased total cholesterol (TC/HDL) ratio while FA intake does not [1,6]. The status and intake of C-18 SFA (stearic) is neutral on lipids, lauric C-12 increases LDL, HDL (18:1 n7) is inversely associated with T2 DM [11].…”

mentioning

confidence: 99%

Saturated Fats and Coronary Heart Disease

Houston¹

2017

Ann Nutr Disord & Ther

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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

Cited by 145 publications

References 59 publications

Plasma fatty acids as predictors of glycaemia and type 2 diabetes

Plasma fatty acids as predictors of glycaemia and type 2 diabetes

Odd Chain Fatty Acids; New Insights of the Relationship Between the Gut Microbiota, Dietary Intake, Biosynthesis and Glucose Intolerance

Saturated Fats and Coronary Heart Disease

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