ENDOCRINOLOGY OF PREGNANCY: Gestational diabetes mellitus: definition, aetiological and clinical aspects

Abstract

Gestational diabetes (GDM) is defined as a glucose intolerance resulting in hyperglycaemia of variable severity with onset during pregnancy. This review aims to revisit the pathogenesis and aetiology of GDM in order to better understand its clinical presentation and outcomes. During normal pregnancy, insulin sensitivity declines with advancing gestation. These modifications are due to placental factors, progesterone and estrogen. In a physiological situation, a compensatory increase in insulin secretion maintains a normal glucose homeostasis. GDM occurs if pancreatic b-cells are unable to face the increased insulin demand during pregnancy. GDM is most commonly a forerunner of type 2 diabetes (T2D) -the most prevalent form of diabetes. These women share similar characteristics with predisposed subjects to T2D: insulin resistance before and after pregnancy, and carry more T2D risk alleles. Auto-immune and monogenic diabetes are more rare aetiologies of GDM. Adverse pregnancy outcomes of GDM are mainly related to macrosomia caused by fetal hyperinsulinism in response to high glucose levels coming from maternal hyperglycaemia. Screening recommendations and diagnosis criteria of GDM have been recently updated. High risk patients should be screened as early as possible using fasting plasma glucose, and if normal, at 24-28 weeks of gestation using 75 g oral glucose tolerance test. The treatment of GDM is based on education with trained nurses and dieticians, and if necessary insulin therapy.

Increased cardiovascular disease risk in women with a history of recurrent miscarriage

“…Information about medical history, use of medication, intoxications, and pregnancy outcome was cross‐checked in obstetrical records to overcome recall bias. Gestational diabetes was defined as a glucose intolerance resulting in hyperglycemia with onset during pregnancy 18. Preeclampsia was defined as systolic blood pressure above 140 mm Hg and/or diastolic pressure above 90 mm Hg combined with proteinuria;19 pregnancy‐induced hypertension as systolic blood pressure above 140 mm Hg and/or diastolic pressure above 90 mm Hg or higher measured on 2 occasions (after 20 weeks of gestation);20 and preterm birth as a delivery before 37 weeks of gestation, intrauterine growth restriction as birthweight below the 10th percentile for gestational age and sex according to the Netherlands Perinatal Registry birthweight percentiles 21.…”

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

“…The risk of developing T2DM later in life is 7 to 8-fold higher in women with GDM and their offspring, and is associated with several epigenetic modifications. 66,67 Despite several studies provided compelling evidence that parental exposure to environmental triggers may have consequences on the following generations, the hypothesis that epigenetic mechanisms are responsible for the transgenerational inheritance of diabetes risk is still far from being demonstrated. Nevertheless, in the near future, it might be possible to hinder the unrestrained global spreading of diabetes, by preventing or reverting the occurrence of epigenetic diabetogenic changes in parental or even grandparental generations.…”

Type 2 diabetes-associated genetic variants of FTO, LEPR, PPARg, and TCF7L2 in gestational diabetes in a Brazilian population

“…In GDM, pancreatic beta cells are unable to produce enough insulin to compensate for the insulin resistance that commonly occurs during pregnancy (3,4). GDM and T2DM have similar pathophysiologic features, suggesting that GDM is also a polygenic disease (5).…”