Plasma fatty acids in de novo lipogenesis pathway are associated with diabetogenic indicators among adults: NHANES 2003-2004.

Background: Insulin regulates fatty acids (FAs) in the blood; conversely, FAs may mediate insulin sensitivity and are potentially modifiable risk factors of the diabetogenic state. Objective: The objective of our study was to examine the associations between plasma concentrations of FAs, fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) among individuals (n = 1433) in the NHANES (2003-2004). Design: Plasma concentrations of 24 individual FAs were considered individually and in subgroups, per chemical structure. Study participants were categorized in diabetogenic groups: Group 1 (HbA1c ≥6.5% or FPG ≥126 mg/dL), Group 2 (HbA1c 5.7% to <6.5% or FPG 100 to <126 mg/dL), and Group 3 (HbA1c <5.7% and FPG <100 mg/dL). We assessed associations between diabetogenic groups and plasma FAs in multivariate multinomial regressions (with Group 3 as the reference). Results: Overall, 7.0% of study participants were in Group 1; 33.3% were in Group 2. Plasma concentrations of several individual FAs, including even-chain saturated FAs (SFAs; myristic, palmitic, stearic acids) and monounsaturated FAs (MUFAs; cis-vaccenic, oleic acids), were respectively associated with greater odds of Groups 1 and 2 status, adjusting for covariates. Higher concentrations of SFA and MUFA subgroups (highest compared with lowest quartile) were associated with increased odds of Group 2 status [SFAs adjusted OR (aOR): 1.51 (95% CI: 1.05, 2.18); MUFAs aOR: 1.78 (95% CI: 1.11, 2.85)]. Higher eicosapentaenoic acid plasma concentration was associated with decreased odds of Group 1 status [quartile 4 aOR: 0.41 (95% CI: 0.17, 0.95)]. Conclusions: Higher plasma concentrations of SFAs and MUFAs, primary de novo lipogenesis products, were associated with elevated FPG and HbA1c in a nationally representative study population in the United States. Additional studies are necessary to elucidate potential causal relationships between FAs (from endogenous production and dietary consumption) and diabetogenic indicators, as well as clinical implications for managing diabetes and prediabetes.