Maternal/Fetal Determinants of Insulin Resistance in Women During Pregnancy and in Offspring Over Life

Abstract

Insulin resistance is a component of the pathophysiology of both type 2 diabetes and gestational diabetes mellitus (GDM), but is also characteristic of normal glycemic physiology during pregnancy. In recent years, many studies have tried to understand determinants of insulin resistance in normal pregnancy and GDM, revealing that the placenta is capable of secreting many cytokines and hormones, classically considered as adipokines. More specifically, it appears that leptin and TNFα could be implicated in gestational insulin resistance and GDM pathophysiology. In addition, the maternal metabolic milieu was also identified as a key determinant of later insulin resistance in offspring, a phenomenon often described as 'fetal programming'. This article reviews the established risk factors and the more novel suspected biomarkers involved in maternal insulin resistance during pregnancy as well as the maternal and early life determinants of insulin resistance in offspring later in their life. We are also highlighting recent reports of the potential mechanisms involved in 'programming' of insulin resistance such as epigenetic modulation.

The Association Between Diabetes Mellitus Among American Indian/Alaska Native Populations with Preterm Birth in Eight US States from 2004–2011

“…This association has major implications for AI/ AN women and could contribute to a ''vicious cycle'' described by Lacroix et al [34]. Infants born preterm have an increased risk of developing DM later in life compared to term infants; subsequently, when these offspring begin having children they place their infants at an increased risk of preterm birth [34]. In a population that currently has the highest incidence of DM in the United States this cycle may be a contributing factor and, without intervention, could continue to increase the incidence of DM in the AI/ AN population [5,13].…”

“…As a result of disabilities stemming from preterm birth, the US healthcare system spent more than 26 billion dollars in 2005 [1]. This association has major implications for AI/ AN women and could contribute to a ''vicious cycle'' described by Lacroix et al [34]. Infants born preterm have an increased risk of developing DM later in life compared to term infants; subsequently, when these offspring begin having children they place their infants at an increased risk of preterm birth [34].…”

Bisphenol-A Treatment During Pregnancy in Mice: A New Window of Susceptibility for the Development of Diabetes in Mothers Later in Life

“…In accordance with this, the metabolic disturbances produced by BPA exposure during pregnancy may predispose mothers to type 2 diabetes later in life, as occurs in GDM (14,17,18). In the present study, we evaluated the long-term maternal outcomes of this phenomenon.…”

Susceptibility to type 2 diabetes mellitus—from genes to prevention

“…52 The epidemiological observations that T2DM is associated with both low and high birth weight have raised numerous hypotheses around what is now called the ‘fetal programming’ of metabolic diseases. 53 Both genetic and environmental factors are likely to be involved in these phenomena.…”