PLACENTAL INSULIN BINDING IN WOMEN AT HIGH-RISK OF DEVELOPING GESTATIONAL DIABETES-MELLITUS - EFFECT OF FAMILIAL DIABETES-MELLITUS AS A RISK FACTOR

Insulin binding to placental plasma membrane receptors was investigated in 11 women at risk of developing gestational diabetes mellitus (with a family history of diabetes mellitus, FDM) and 14 women with impaired glucose tolerance during the pregnancy (that is, gestational diabetes mellitus GDM) and 11 matched normal pregnant women (N). GDM patients had higher mean fasting and 2-hr plasma glucose values compared to the other two groups of pregnant women (p<0.001). Glycaemic control, as monitored by HbA(lc) and fructosamine values, was achieved throughout the pregnancy and showed improvement towards the late third trimester compared with their values in the first trimester for all the three groups. None of the subjects were obese as indicated by their Body Mass Index (BMI). Insulin levels were higher among FDM subjects (p<0.001). Percent insulin specific binding was decreased by <5% in placenta of GDM patients while in placenta from women with FDM insulin binding was reduced by 48% in comparison with the normal pregnant women. Furthermore this reduction was at a lower insulin concentration (10(-9) M). A detailed investigation of insulin in binding characteristics to placental membranes revealed that the binding displacement curves had similar trends but in FDM the insulin concentration needed to achieve a 50% inhibition was lower, suggesting a decreased receptor capacity in FDM compared with GDM and N. The present finding that there were no significant changes in the insulin binding characteristics in GDM and N suggests that in GDM dietary treatment could prevent the reduction in the placental insulin receptors. Furthermore, these data suggest that during pregnancy women with a family history of diabetes who showed a decreased insulin binding may give indications that they could develop an impairment of insulin tissue sensitivity in the late stage of pregnancy.