The Roles of Adipose Tissue and Inflammation in Gestational Diabetes Mellitus

Abstract

Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance with first onset or first identification in pregnancy. It is one of the most common complications of pregnancy with a prevalence ranging from 3% to upwards of 16% depending on the screened population and whether a 1 or 2-step screening algorithm is utilized. Its occurrence has historically been predominantly attributed to pro-diabetogenic placental hormone secretion. However, there is emerging evidence to indicate that its mechanistic underpinnings are more complex; similar to type 2 Diabetes Mellitus (T2DM), adipose tissue dysfunction and associated inflammation may be key etiologic factors for the development of GDM. In support of this view, women with a history of GDM are at high risk of subsequent T2DM development and their offspring at increased risk of obesity and metabolic syndrome across their life span. With immediate and long term consequences of GDM on mother and offspring, etiologic understanding that can inform therapeutic and preventative targets is essential. This review article explores the existing literature as it relates to associations of GDM with expansion of adipose tissue depots, secretion of adipose derived biologically active factors, and inflammation and inflammatory related substances.

Adipose Tissue Insulin Resistance in Gestational Diabetes

“…10 For example, AT expandability during pregnancy has been proposed to play a role in the etiology of GDM as supported by gene expression and histological properties of GDM subcutaneous AT. 23,24 According to this view, similarly to what is found in men with metabolic syndrome, 12 decreased ability to store energy in adipocytes plays a role in accentuating IR during pregnancy.…”

“…8,9 Recent research has highlighted the important role of adipose tissue (AT) dysfunction in GDM. 10 AT dysfunction is characterized by excessive lipolysis (adipocyte IR) and inflammation, leading to an increase in adipocyte-derived circulating lipids and cytokines that mechanistically play a role in defective total body insulin-mediated glucose utilization mainly in skeletal muscle. In general IR, including adipocyte IR, is acquired with obesity but not all obese individuals develop adipocyte and systemic IR.…”

Contribution of high fat diet to the development of gestational diabetes mellitus in rats

“…Several studies have reported that, insulin resistance and subsequent development of GDM are influenced by adipose tissue (AT) expansion among other factors (Simas and Corvera, 2014;Aziz et al, 2016;Li et al, 2016;Ngala et al, 2017). During pregnancy, AT expands in response to increased fetal growth (Simas and Corvera, 2014) and can expand further due to consumption of a high fat diet (HFD) (Musial et al, 2017). Fetal growth and HFD mediated AT expansion induce insulin resistance during pregnancy and are pivotal to the development of GDM (Aziz et al, 2016).…”

“…Normally fat storage occurs within SAT, when its storage capacity is exhausted, the fats are stored in ectopic depots around the visceral organs (Smith and Kahn, 2017). The ability of SAT and VAT to accommodate fat storage with hyperplasia rather than hypertrophic expansion may determine the risk for GDM (Simas and Corvera, 2014).…”

“…Therefore, the current study investigated the contribution of differential AT deposition and expansion due to HFD in GDM development using Wistar rats. Knowledge on the mechanisms of the AT expansion and its contribution to the development of GDM is crucial in the search for management strategies (Simas and Corvera, 2014).…”