New concepts in insulin resistance of pregnancy and gestational diabetes: long-term implications for mother and offspring.

Gestational diabetes (GDM) complicates 3 – 12% of all pregnancies and the prevalence in the United States has doubled as a result of the growing obesity epidemic and changes in diagnostic criteria (Kaufmann et al., 1995). The immediate sequellae for the fetus are fetal hyperinsulinaemia, macrosomia, delayed lung maturation, an increased risk of shoulder dystocia and newborn metabolic abnormalities, including neonatal hypoglycaemia. The mother experiences an increased risk of caesarean section, infectious complications and pre-eclampsia (Barbour and Reusch, 2001). However, the long-term implications may be more grave and include a 50% risk of the development of Type 2 diabetes (DM) in the mother. In a sense, pregnancy is a ‘stress test’ for the development of Type 2 DM. New data suggest that the offspring may also be vulnerable to the inutero exposure of excess nutrients and have an increased risk of obesity, impaired glucose intolerance and Type 2 diabetes as young adults (Silverman and Metzger, 1995; Dabelea et al., 2000). We have been only modestly effective in reducing the incidence of macrosomia in these infants, in spite of attempts at strict metabolic control in the mother. Thus, there remains a complete lack of consensus internationally regarding the resources that should be committed to the diagnosis and treatment of this condition in pregnancy. However, some might argue that our inability to impact macrosomia may be due to a misdirected focus on maternal glycaemia alone rather than fetal indicators of nutrient excess. Although the normal insulin resistance of pregnancy appears to benefit the fetus by assuring its adequate nutrition, these adaptations result in a pathological state in the woman who develops gestational diabetes. Placental hormones reprogramme maternal physiology in order to meet the significant challenge of accommodating the growth needs of the fetus within the physiological capabilities of the mother. However, in the mother who develops gestational diabetes, these changes become maladaptive.