Abstract
Objective: We investigated the relationships of maternal circulating individual free fatty acids (FFA) with insulin resistance, insulin secretion and inflammatory biomarkers during mid-pregnancy. Research design and methods: The data were drawn from a prospective cohort of generally healthy pregnant women (n=1368, African-American 36%, Hispanic 48%, Caucasian 16%) in Camden, NJ. We quantitatively determined 11 FFAs, seven cytokine/adipokine, homeostatic model assessment of insulin resistance (HOMA-IR) and C-peptide levels from the fasting blood samples that were collected at 16 weeks of gestation. Multivariate analyses were performed along with separate analyses for each individual FFA.
Results: High HOMA-IR (p<0.001) and C-peptide (p<0.0001) levels were positively associated with a twofold to fourfold increased risk for developing gestational diabetes mellitus (GDM). Negative relationships were found with specific FFAs (molecular percentage, palmitoleic, oleic, linolenic, myristic acids) and HOMA-IR and C-peptide levels (p<0.01 to p<0.0001). In contrast, palmitic, stearic, arachidonic, dihomo-γ-linolenic (DGLA) and docosahexaenoic acids were positively associated with HOMA-IR and C-peptide (p<0.01 to p<0.0001). The individual FFAs also predicted cytokine/adipokine levels. For example, women who had elevated DGLA (highest quartile) were twice as (adjusted OR 2.06, 95% CI 1.42 to 2.98) likely to have higher interleukin (IL)-8 (p<0.0001) levels. Conversely, women with high palmitoleic, oleic, and linolenic acid levels had reduced odds (≥2-fold, p<0.01 to p<0.001) for having higher IL-8, IL-6 or tumor necrosis factor-alpha levels. Conclusion: Our results suggest that maternal individual FFAs uniquely affect insulin resistance and secretion. The effects are either direct or indirect via modulation of the inflammatory response. Modifying the composition of FFAs may help in reducing the risk of GDM.
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Key Points
Excessive insulin resistance (IR) and significant β-cell dysfunction are key components for the development of gestational diabetes mellitus (GDM). Previous studies demonstrated that experimentally created acute elevations in circulating total FFA concentration cause increases in IR in healthy non-pregnant subjects, and type 2 diabetes mellitus (T2DM) and in pregnant women with and without GDM. Elevated total FFA levels significantly increase insulin secretion in normal subjects, but not in T2DM and GDM; here insulin secretion is defective. Thus, the relationship of the individual FFAs, instead of total FFA, to IR and insulin secretion in human pregnancy needs further investigation.
In this prospective cohort of young pregnant women, different associations of circulating individual FFAs with measurements of IR and secretion were observed. Opposite relationships between specific FFAs and inflammatory biomarkers (cytokine/adipokine) were also observed. The results indicate that individual FFAs have unique metabolic impacts by mid-pregnancy. The strongest negative relationship was for the essential FA, α-linolenic acid, whereas DGLA, an endogenously produced n-6 FA, was one of the most positive correlates to HOMA-IR. Inflammation is a widely known contributor linked to increased IR.