Maternal C-Peptide and Insulin Sensitivity, but Not BMI, Associate with Fatty Acids in the First Trimester of Pregnancy

Abstract

Maternal obesity in pregnancy is a pro-inflammatory condition exposing the fetus to an adverse environment. Here, we tested associations of maternal obesity (primary exposures: BMI, leptin) and metabolic parameters (secondary exposures: glucose, C-peptide, and insulin sensitivity) with total serum concentrations of fatty acids in the first trimester of human pregnancy. This cross-sectional study included 123 non-smoking women with singleton pregnancy. In maternal serum, cotinine, leptin, and C-peptide (ELISA), glucose (hexokinase-based test) and fatty acids (gas chromatography) were quantified, and the insulin sensitivity index (ISHOMA) was calculated. Concentrations of fatty acid classes and total fatty acids did not differ between BMI or leptin categories. However, n-3 polyunsaturated fatty acids (PUFA) were decreased in the category with the highest C-peptide concentration (n-3 PUFA: CI −35.82–−6.28, p < 0.006) and in the lowest ISHOMA category (n-3 PUFA: CI −36.48–−5.61, p < 0.008). In a subcohort, in which fetal sex was determined (RT-qPCR of placental tissue), C-peptide was significantly associated with docosahexaenoic acid (DHA) in mothers bearing a female (n = 46), but not male (n = 37) fetus. In conclusion, pregnant women with high fasting C-peptide and low ISHOMA had decreased n-3 PUFA, and DHA was lower with higher C-peptide only in mothers bearing a female fetus.

Distinct maternal metabolites are associated with obesity and glucose-insulin axis in the first trimester of pregnancy

“…The fact that palmitoleic acid is the precursor of palmitoleoyl ethanolamide may suggest an influence of diet. However, in a previous study we did not find a significant association between C-peptide and palmitoleic acid in the same cohort [19]. As an alternative explanation, N-acetylethanolamides are endogenously synthesised and their concentration is regulated by synthesizing and degrading enzymes such as N-acyl phosphatidyl ethanolamine-specific phospholipase D (NAPE-PLD) and fatty acid amide hydrolase (FAAH) [51].…”

“…Second, in addition to BMI, defining obesity, and circulating maternal leptin as proxy for adiposity, we included maternal glucose, C-peptide and IS HOMA as metabolic exposures since a proportion of individuals with obesity may be metabolically ‘healthy’ [ 20 ]. This approach proved better suited to understand fatty acid metabolism in the first trimester of pregnancy [ 19 ]. Third, we used untargeted metabolomics avoiding inherent selection bias of metabolites and offering the possibility to identify novel metabolites.…”

“…In particular, overweight and obesity were associated with increased C-peptide concentration and reduced insulin sensitivity, but unchanged glucose concentrations, compared to normal weight pregnant women [ 18 ]. Also, fatty acids were changed, not by BMI, but rather by C-peptide and insulin sensitivity (IS HOMA ), which were associated with decreased concentrations of omega-3 polyunsaturated fatty acids [ 19 ].…”

Insulin Resistance Is Associated with an Unfavorable Serum Lipoprotein Lipid Profile in Women with Newly Diagnosed Gestational Diabetes

“…SFAs and MUFAs were positively related and PUFAs, omega-3 FAs, and omega-6 FAs inversely related to insulin resistance. Similarly, in the first trimester, maternal insulin resistance is associated with lower omega-3 FAs [ 49 ]. Although all analyses in the present study were made assuming insulin resistance to be the predictor, the causality might be to some extent vice versa.…”

Ingestão De Ácidos Graxos Poli-Insaturados Ômega-3 Na Gestação E Suas Contribuições Para O Neurodesenvolvimento Fetal

“…Também pode melhorar o Homeostatic Model Assessment (HOMA-β) e a resistência à insulina. Finalmente, pode melhorar o metabolismo da glicose e lipídios das pacientes (BANDRES-MERIZ et al, 2021;HUANG et al, 2021).…”