Longitudinal studies of plasma glucose, non-esterified fatty acids (Nefa), and insulin and blood pyruvate levels during oral and intravenous glucose tolerance tests are described in three groups of women treated with combined oral contraceptive preparations: (A) 91 women tested before and during therapy; (B) 39 women tested during therapy and again after this had been discontinued; and (C) 22 women tested twice during therapy. The mean fasting plasma glucose level was unchanged during therapy. In terms of the total area between the plasma-glucose curve and the abscissa, oral and intravenous glucose tolerance deteriorated during therapy in 78% and 70% of group A women, respectively. Thirteen per cent of group A women developed chemical diabetes mellitus during therapy. In group B, oral glucose tolerance improved in 90% and intravenous glucose tolerance improved in 85% after therapy was discontinued. Group C, with an initial mean oral glucose tolerance similar to that of group B during therapy, showed no significant mean change of oral glucose tolerance on retesting. Mean plasma Nefa levels, both before and after oral or intravenous glucose, were unchanged during therapy in groups A and B. During therapy the mean fasting blood pyruvate level was raised in group A and mean blood pyruvate levels were also higher in both groups during oral and intravenous glucose tolerance tests. The mean fasting plasma insulin levels were unchanged during therapy in both groups, but plasma insulin levels were significantly raised in group A after oral and intravenous glucose. Mean plasma insulin levels during oral and intravenous glucose tolerance tests in group B, however, were not significantly different on and off therapy. It is suggested that the impaired glucose tolerance is `steroid diabetes' caused by raised plasma cortisol (hydrocortisone) levels secondary to the oestrogen component of the oral contraceptive. The clinical consequences of these abnormalities remain to be determined. Some individual case studies are presented which exemplify the metabolic abnormalities described above.
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