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

Abstract

Abstract. The metabolism of unlabelled human monocomponent insulin was studied in a group of six patients being treated with combined oestrogen‐progestogen oral contraceptives (OC) and compared with a group of ten normal subjects. The parameters of insulin metabolism were determined by a priming dose ‐ continuous infusion technique which enabled measurements of metabolic clearance rate (MCR) of insulin to be made at four 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/min. at 16 μU/ml to 11.4 ml/kg/min. at a mean concentration of 280 μU/ml. In the OC group, MCR averaged 20.5 ml/kg/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 hypoglycaemia) 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 hyperglycaemia was less marked than normal. The results indicate a significant alteration in insulin metabolism in these subjects, which may contribute to the impairment of carbohydrate tolerance seen in some women taking combined OC.