Insulin Metabolism, Insulin Sensitivity and Hormonal Responses to Insulin Infusion in Patients Taking Oral Contraceptive Steroids

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Abstract
The metabolism of unlabeled human monocomponent insulin was studied in a group of 6 patients being treated with combined estrogen-progestogen oral contraceptives (OC) and compared with a group of 10 normal subjects. The parameters of insulin metabolism were determined by a priming dose-continous infusion technique which enabled measurements of metabolic clearance rate (MCR) of insulin to be made at 4 separate steady state hormone concentrations spanning the physiological range. In normal subjects MCR was greatest at low insulin concentrations, falling from 24.7 ml/kg per min at 16 .mu.U [microunits]/ml to 11.4 ml/kg per min at a mean concentration of 280 .mu.U/ml. In the OC group, MCR averaged 20.5 ml/kg per min and did not change with increasing plasma insulin concentration. The plasma half-disappearance time (T 1/2) was longer than normal in the OC group (5.6 vs 4.4 min., P < 0.05) despite a higher MCR. The prolonged T 1/2 indicated that the apparent distribution space was increased in those on OC (166.6 vs. 82.7 ml/kg, P < 0.0025). The results are interpreted as indicating increased capillary permeability to insulin and increased peripheral degradation. The fact that MCR did not fall in the OC group with increasing plasma insulin concentrations whereas it did in normal subjects suggested that OC leads to the loss of saturable component of insulin degradation that is present in normal subjects. Insulin sensitivity (as judged by induced hypoglyemia) was reduced in the OC group while growth hormone responses were within the normal range. Plasma cortisol was increased in those taking OC but the response to insulin induced hyperglycemia was less marked than normal. A significant alteration in insulin metabolism in these subjects is indicated, which may contribute to the impairment of carbohydrate tolerance seen in some women taking combined OC.