Sequential studies of glucose tolerance and red blood cell insulin receptors in normal human pregnancy

Insulin binding to erythrocytes was sequentially studied in 12 healthy pregnant women during the anabolic (11-22 wk) and the catabolic (31-38 wk) gestational phases. For comparison, we studied 12 nonpregnant subjects at mid-luteal and mid-follicular menstrual phases. Oral glucose tolerance tests were also performed during these studies. There was a progressive worsening of the glucose tolerance from the anabolic to the catabolic phase associated with fasting hypoglycemia and hyperinsulinemia. The worsening of glucose tolerance was accompanied by a progressive increment of insulin secretion. Insulin binding to red blood cells increased progressively from the anabolic to the catabolic phase, due to an increased number of receptors per cell, associated with a reduction in the apparent affinity at the low occupancy levels. We concluded that the insulin resistance of pregnancy was not accompanied by an impaired binding of insulin to its receptors, at least in the RBC. The data suggest that the defect of insulin action lies at a site distal to the receptor.