Comparison of the Mechanisms Underlying Carbohydrate Intolerance in Subclinical Diabetic Women During Pregnancy and During Post-partum Oral Contraceptive Steroid Treatment1

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Abstract
Changes in glucose tolerance and insulin metabolism were measured in 12 subclinical diabetic and 14 nondiabetic women treated with oral contraceptive agents (OCA's) containing mestranol from the sixth week post partum. These women were designated as subclinical diabetics if glucose tolerance was abnormal during the antecedent pregnancy and returned to normal 5 weeks post partum (gestational diabetes). After 2 weeks of treatment with 0.08 mg mestranol daily, or 0.1 mg mestranol plus 1 mg ethynodiol diacetate daily, oral glucose tolerance was abnormal in 2 of 12 subclinical diabetic subjects and deteriorated in an additional 4; only 3 of 14 nondiabetic subjects had deteriorated glucose tolerance and none were abnormal. Although the mean total integrated plasma insulin responses for the 4-hr test period (ΣI240) increased 2-fold in the nondiabetic and subclinical diabetic subjects with normal glucose tolerance after OCA's, it did not change significantly in the 2 subjects who had abnormal glucose tolerance tests. There was no significant change in the initial rate of apparent insulin production, as measured by the index of insulinogenic reserve at 1 hr (ΣI/ΣG60), in either group while on OCA's. No further changes in glucose or insulin metabolism were observed after 6 months' treatment. These changes could not be correlated with alterations in circulating growth hormone, triglycerides or cholesterol. By contrast, both pregnancy and prednisolone provocation were universally diabetogenic in the subclinical diabetics and were associated with a diminished ΣI/ΣG60 despite the fact that their total apparent insulin production (ΣI240) was increased, though not significantly, by gestation and was significantly increased by glucocorticoid treatment. Rhesus monkeys treated with 2 mg mestranol daily for 2 weeks not only developed an increased plasma insulin response to iv glucose while maintaining normal carbohydrate tolerance but also showed decreased sensitivity to the hypoglycemic action of exogenous insulin. These results indicate that OCA's containing mestranol are less likely to impair carbohydrate tolerance in subclinical diabetic patients than pregnancy or glucocorticoids because mestranol does not retard the initial rate of peripheral plasma appearance of insulin. Only those subjects with limited ability to increase insulin production developed glucose intolerance after mestranol treatment, presumably because of failure to compensate for insulin resistance which appears to be induced by mestranol.

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