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

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.

Maternal High-Fat-High-Carbohydrate Diet-Induced Obesity Is Associated with Increased Appetite in Peripubertal Male but Not Female C57Bl/6J Mice.

Diet-induced maternal obesity might play a critical role in altering hypothalamic development, predisposing the offspring to obesity and metabolic disease later in life. The objective of this study was to describe both phenotypic and molecular sex differences in peripubertal offspring energy homeostasis, using a mouse model of maternal obesity induced by a high-fat-high-carbohydrate (HFHC) diet. We report that males, not females, exposed to a maternal HFHC diet had increased energy intake. Males exposed to a maternal HFHC diet had a 15% increased meal size and a 46% increased frequency, compared to the control (CON) males, without a change in energy expenditure. CON and HFHC offspring did not differ in body weight, composition, or plasma metabolic profile. HFHC diet caused decreased hypothalamic glucocorticoid expression, which was further decreased in males compared to females. Maternal weight, maternal caloric intake, and male offspring meal frequency were inversely correlated with offspring hypothalamic insulin receptor (IR) expression. There was a significant interaction between maternal-diet exposure and sex in hypothalamic IR. Based on our preclinical data, we suggest that interventions focusing on normalizing maternal nutrition might be considered to attenuate nutritional influences on obesity programming and curb the continuing rise in obesity rates.

Erythropoiesis and Red Cell Indices Undergo Adjustments during Pregnancy in Response to Maternal Body Size but not Inflammation.

During human pregnancy, iron requirements gradually increase, leading to higher amounts of erythropoietin (EPO) and reticulocytes, and changes in erythrocyte size and density. Women with pregestational obesity experience "obesity hypoferremia" during pregnancy, which alters iron homeostasis. In this study we aimed to describe the relationship between EPO and iron nutrition status during nonanemic pregnancy, and to explore whether obesity and inflammation influence erythropoiesis and red cell indices. We conducted a secondary analysis of a cohort followed throughout pregnancy. Participants were nonanemic women assigned to two study groups based on pregestational body mass index (pgBMI): adequate weight (AW, n = 53) or obesity (Ob, n = 40). All received a multivitamin supplement. At gestational ages (GA) 13, 21, 28 and 34, we measured hemoglobin and red cell indices with an ACT-5DIFF hematology counter, and reticulocyte percentage by manual cell counting. EPO, interleukin (IL-6) and markers of iron status, i.e., hepcidin, serum transferrin receptor (sTfr) and ferritin, were measured by ELISA. Bivariate correlations showed that EPO was positively associated with pgBMI, GA, sTfr and IL-6, but negatively associated with hepcidin, ferritin and hemoglobin, and unrelated to iron intake. Generalized linear models adjusted for confounding factors showed that EPO and erythrocyte concentrations were significantly higher in women in the Ob group, while mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and red cell distribution width (RDW) were lower; reticulocytes and mean corpuscular hemoglobin concentration (MCHC) were not different. Differences were not altered when controlling for inflammation (IL-6). These changes suggest that, in addition to altering iron metabolism, a larger maternal body size during pregnancy results in higher erythropoiesis without increasing hemoglobin, which is exhibited in the latter being distributed among more and smaller erythrocytes.

Factors associated with the need for insulin as a complementary treatment to metformin in gestational diabetes mellitus / Fatores associados à necessidade de insulina como tratamento complementar à metformina na diabetes mellitus gestacional

Abstract Objective To evaluate the factors associated with the need for insulin as a complementary treatment to metformin in pregnant women with gestational diabetes mellitus (GDM). Methods A case-control study was performed from April 2011 to February 2016 with pregnant women with GDM who needed complementary treatments besides diet and physical exercise. Those treated with metformin were compared with those who, in addition to metformin, also needed the combination with insulin. Maternal characteristics and glycemic control were evaluated. Multinomial logistic regression models were developed to evaluate the influence of different therapies on neonatal outcomes. Results A total of 475 pregnant women who needed pharmacological therapy were evaluated. Of these, 366 (77.05%) were submitted to single therapy with metformin, and 109 (22.94%) needed insulin as a complementary treatment. In the analysis of the odds ratio (OR), fasting glucose (FG)<90 mg/dL reduced the odds of needing the combination (OR: 0.438 [0.235-0.815]; p=0.009], as well as primiparity (OR: 0.280 [0.111-0.704]; p=0.007]. In obese pregnant women, an increased chance of needing the combination was observed (OR: 2,072 [1,063-4,039]; p=0,032). Conclusion Obesity resulted in an increased chance of the mother needing insulin as a complementary treatment to metformin, while FG<90 mg/dL and primiparity were protective factors.

Resumo Objetivo Avaliar os fatores associados à necessidade de insulina como tratamento complementar à metformina em gestantes com diabetes mellitus gestacional (DMG). Métodos Um estudo caso-controle foi realizado de abril de 2011 a fevereiro de 2016 comgestantes portadoras de DMG que necessitaram de tratamentos complementares além de dieta e exercícios físicos. Aquelas tratadas commetformina foram comparadas com aquelas que, além da metformina, também precisaram de combinação com insulina. Foram avaliadas as características maternas e de controle glicêmico. Modelos de regressão logística multinomial foram construídos para avaliar a influência das diferentes terapias nos desfechos neonatais. Resultados Foram avaliadas 475 gestantes que necessitaram de terapia farmacológica. Destas, 366 (77,05%) utilizaram terapia única com metformina, e 109 (22,95%) necessitaram de insulina como tratamento complementar. Na análise da razão de possibilidades (RP), a glicemia de jejum (GJ)<90mg/dL reduziu as chances de necessidade da combinação (RP: 0,438 [0,235-0,815]; p=0,009), bem como a primiparidade (RP: 0,280 [0,111-0,704]; p=0,007). Em gestantes obesas, foi observada uma chance maior de necessidade da combinação (RP: 2.072 [1.063-4.039]; p=0,032). Conclusão A obesidade resultou em um aumento na chance de a mãe precisar de insulina como tratamento complementar à metformina, enquanto a GJ<90 mg/dL e a primiparidade foram fatores de proteção.