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

Abstract

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.

Fatty acid profile and estimated desaturase activities in whole blood are associated with metabolic health

“…MUFAs (C16:1 and 18:1) are major components of triglycerides, cholesterol esters and phospholipids, produced by de novo lipogenesis and carried in VLDL in the circulation [15]. This incorporation of MUFAs in VLDL, could partly explain the observed association between high levels of MUFAs and the MU phenotype, characterized by high levels of triglycerides, total cholesterol and LDL-C. Our findings are also supported by results from a NHANES survey where higher plasma concentration of SFAs and MUFAs were associated with increased levels of fasting plasma glucose and HbA1c [32]. The same pattern was found in the FINRISK study.…”

A comprehensive metabolic profiling of the metabolically healthy obesity phenotype

“…They concluded that low PUFA and high MUFA levels are biomarkers for future cardiovascular risk [18]. In the NHANES-study, they found that high plasma concentrations of SFA and MUFA were associated with elevated HbA1c and fasting plasma glucose levels [43]. In our study there was a positive correlation between HbA1c and 22:5n3.…”

Albumin-mediated alteration of plasma zinc speciation by fatty acids modulates blood clotting in type-2 diabetes

“…Firstly, the three saturated and two mono-unsaturated NEFAs are all considered to be primary products of de novo lipogenesis. 58 There are indications that plasma NEFAs resulting from this process are most strongly associated with diabetes incidence. 29 Secondly, all five have either been shown to, or can be predicted to, bind to the NEFA binding site FA2 with high affinity.…”