Free Fatty Acids–Mediated Inflammation and Insulin Resistance/Insulin Production in Healthy and Gestational Diabetes Pregnant Women

Abstract

We investigated the relationship of individual free fatty acid (FFA, GCMS), inflammatory biomarkers (multiplex assay) with insulin resistance (HOMA-IR) and production (C-peptide) levels during pregnancy from the Camden Study - a prospective longitudinal cohort (n=1,784, African-American 36%, Hispanic 48%, Caucasian 16%, age 22 ± 5.2 year., BMI 25.6 ± 6.1 kg/m2). Multivariate analyses were performed along with separate analyses for each individual FFA. All of the analyses were adjusted for maternal age, pre-pregnancy BMI, parity, cigarette smoking and ethnicity. The results obtained at entry to care (16 weeks gestation) are summarized: (i) Elevated HOMA-IR and C-peptide levels were associated with a 50% to 2-fold (p<0.01 to p<0.0001) increased risk for developing gestational diabetes mellitus (GDM); (ii) Specific FFAs (%) (palmitoleic, oleic, linolenic acids) were significantly associated with decreased HOMA-IR and C-peptide levels (p<0.01 to p<0.0001); In contrast, palmitic, stearic, arachidonic acids and dihomo-γ-linolenic acid were associated with increased HOMA-IR and C-peptide (p<0.01 to p<0.0001); (iii) TNF-α, IL-8 and resistin levels were positively and adiponectin was negatively correlated with HOMA-IR and C-peptide (p<0.001 to p<0.0001); and (iv) FFAs predicted cytokine levels. For example, women with elevated palmitic acid were 50% (p<0.01) more likely to have higher IL-8 and TNF-α (highest quartile), whereas women with higher palmitoleic, oleic, linolenic acids levels had a reduced risk (∼2-fold, p<0.01 to p<0.001) of having higher IL-8, IL-6 and TNF-α levels. Our data suggest that different FFAs are involved in the regulation of insulin resistance and production during pregnancy. The effects are either direct or indirect via modulating inflammatory responses. Thus, recognition and modifying individual FFAs are important in lowering the risk for impaired glucose tolerance and the development of GDM. Disclosure X. Chen: None. T.P. Stein: None. T.O. Scholl: None. R.A. Steer: None.