Maternal overweight is not an independent risk factor for increased birth weight, leptin and insulin in newborns of gestational diabetic women: observations from the prospective ‘EaCH’ cohort study

Abstract

BackgroundBoth gestational diabetes mellitus (GDM) as well as overweight/obesity during pregnancy are risk factors for detrimental anthropometric and hormonal neonatal outcomes, identified to ‘program’ adverse health predispositions later on. While overweight/obesity are major determinants of GDM, independent effects on critical birth outcomes remain unclear. Thus, the aim of the present study was to evaluate, in women with GDM, the relative/independent impact of overweight/obesity vs. altered glucose metabolism on newborn parameters.MethodsThe prospective observational ‘Early CHARITÉ (EaCH)’ cohort study primarily focuses on early developmental origins of unfavorable health outcomes through pre- and/or early postnatal exposure to a ‘diabetogenic/adipogenic’ environment. It includes 205 mother-child dyads, recruited between 2007 and 2010, from women with treated GDM and delivery at the Clinic of Obstetrics, Charité – Universitätsmedizin Berlin, Germany. Recruitment, therapy, metabolite/hormone analyses, and data evaluation were performed according to standardized guidelines and protocols. This report specifically aimed to identify maternal anthropometric and metabolic determinants of anthropometric and critical hormonal birth outcomes in ‘EaCH’.ResultsGroup comparisons, Spearman’s correlations and unadjusted linear regression analyses initially confirmed that increased maternal prepregnancy body-mass-index (BMI) is a significant factor for elevated birth weight, cord-blood insulin and leptin (all P < 0.05). However, consideration of and adjustment for maternal glucose during late pregnancy showed that no maternal anthropometric parameter (weight, BMI, gestational weight gain) remained significant (all n.s.). In contrast, even after adjustment for maternal anthropometrics, third trimester glucose values (fasting and postprandial glucose at 32nd and 36th weeks’ gestation, HbA1c in 3rd trimester and at delivery), were clearly positively associated with critical birth outcomes (all P < 0.05).ConclusionsNeither overweight/obesity nor gestational weight gain appear to be independent determinants of increased birth weight, insulin and leptin. Rather, 3rd trimester glycemia seems to be crucial for respective neonatal outcomes. Thus, gestational care and future research studies should greatly consider late pregnancy glucose in overweight/obese women with or without GDM, for evaluation of critical causes and interventional strategies against ‘perinatal programming of diabesity’ in the offspring.

Visceral Adipose Tissue Inflammatory Factors (TNF-Alpha, SOCS3) in Gestational Diabetes (GDM): Epigenetics as a Clue in GDM Pathophysiology

“…The research presented here is part of the prospective observational 'Early CHARITÉ (EaCH)' cohort study [16,17,19,44]. Genes involved in the inflammatory process were further investigated on the cases in which the optimal material and factors (such as transcription, metabolic and hormonal) could be measured in a complete set so as to avoid a missing data bias.…”

“…Standardized procedures/methods, recruitment, exclusion criteria, analytical approaches etc. are described elsewhere in detail [44]. The study groups were matched for maternal age, socio-economic status (SES), ethnic origin, parity and specifically, prepregnancy BMI.…”

“…No oral antidiabetic drugs were administered in the GDM group, eight were treated by diet and eleven were treated with diet and additional insulin therapy to achieve glycemic control. Further clinical parameters such as plasma insulin, C-peptide, glucose and HOMA-IR were determined for these cases as described elsewhere [16,17,44,47]. The research design and methodology were conducted in accordance with the Declaration of Helsinki, revised in 2004, and approved by the local Ethics Committee (Ethikausschuss 2 am Campus Virchow-Klinikum, Charité Universitätsklinikum Berlin, EA2/026/04).…”

Visceral adipose tissue alteration of PI3KR1 expression is associated with gestational diabetes but not promoter DNA methylation

“…This research is part of the prospective observational 'Early CHARITÉ (EaCH)' cohort study [11,12,16]. Here, we investigated additional genes involved in the insulin pathway on just those cases in which the optimal material and factors (such as transcription, metabolic and hormonal) could be measured in a complete set in order to avoid missing data bias.…”

In Utero One‐Carbon Metabolism Interplay and Metabolic Syndrome in Cardiovascular Disease Risk Reduction

“…Interestingly, research indicates that an intrauterine obesogenic environment elicit a systemic pro‐inflammatory response, which begins in the hypothalamic circuitries that function to maintain energy homeostasis and could trigger a cascade of events leading to obesity long after the inductive events have occurred . Further, during the second trimester of pregnancy, the metabolic needs of the fetus dramatically increases in order to support the developing tissues . It is understood that the compensatory adjustments at this stage of pregnancy exacerbate an obesogenic metabolic memory (including reduced leptin levels) in the offspring, and could influence their susceptibility to developing MeS and related complications such as CVD regardless of the postnatal environment .…”