Gestational Diabetes Mellitus: an Opportunity to Prevent Type 2 Diabetes and Cardiovascular Disease in Young Women

Graziano Di Cianni; Alessandra Ghio; Veronica Resi; Laura Volpe

Disclosures

Women's Health. 2010;6(1):97-105. 

In This Article

Glucose Homeostasis in Pregnancy

In order to better evaluate the potential long-term implications of GDM, we first considered the physiology of glucose homeostasis in pregnancy, underlining those modifications that are more likely to lead to the development of GDM.

Pregnancy is characterized by a complex endocrine–metabolic adaptation process including impaired insulin sensitivity, increased β-cell response, moderately increased blood glucose levels (particularly following the ingestion of a meal), and changes in the levels of circulating free fatty acids, triglycerides, cholesterol and phospholipids.[7] These changes do not reflect a pathological condition; rather, they represent a necessary and indispensable adaptation to meet the energy demands of the fetus and to prepare the maternal organism for delivery and lactation. In fact, the insulin resistance developing in pregnancy is likely to be a physiological event favoring glucose supply to the fetus. The reduced insulin-mediated utilization of glucose switches the maternal energy metabolism from metabolizing carbohydrates to lipid substrates (i.e., free fatty acids), redirecting carbohydrates toward the fetal tissues.[8]

The insulin resistance that develops during pregnancy is similar to that observed in T2DM, with impaired insulin action mainly as a result of postreceptor alterations involving glucose transport and intracellular metabolism in insulin-sensitive tissues.[9] The degree of insulin resistance seems to be influenced by obesity and inheritance. In fact, in obese women (BMI > 30; or weight > 150% of ideal body weight) the incidence of GDM is 1.4- to 20-fold higher than that in normal weight subjects.[10]

Despite insulin resistance, glucose homeostasis is maintained in normal pregnancies by a concomitant compensatory increase in insulin secretion. The intolerance to carbohydrates develops as soon as β-cell secretion is no longer sufficient to compensate for insulin resistance (Figure 1).[11]

Figure 1.

Endocrine–metabolic adaptation to meet the energy demand of the fetus.
AA: Amino acid; FFA: Free fatty acid.

Although the specific mechanism(s) of the alteration of insulin secretion and action remain uncertain, a substantial contribution is made by endocrine modifications that accompany pregnancy. Changes in β-cell function occur in parallel with the development of the feto–placental unit and the local production of hormones, such as estrogens, progesterone, cortisol, human chorionic somatotropin, placental lactogen, prolactin and growth hormone (Table 1). These hormones have been shown to induce insulin resistance both in vitro and in vivo.[12] Moreover, the increase of TNF-α, an inflammatory marker, is the strongest predictor of impaired insulin action during pregnancy, far stronger than gestational hormones such as human placental lactogen and steroids.[13]

In women with GDM, the impaired insulin-mediated glucose utilization and the inadequate increase in first-phase insulin secretion are the initial alterations of glucose homeostasis that cause the plasma glucose excursion after meal ingestion and post-oral glucose tolerance test (OGTT) hyperglicemia. The loss of early insulin release in these women is likely to contribute to the glucose intolerance and postprandial hyperglycemia, and is considered to be a marker of glucose homeostasis impairment. Xiang et al. estimated that women with GDM have a 67% reduction in pancreatic β-cell effect as compared with normal pregnant women.[14]

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