Diminished insulin clearance during late pregnancy in patients with type I diabetes mellitus.
1. Intensive insulin treatment of patients with Type I diabetes mellitus during pregnancy is associated with a high frequency of serious hypoglycaemic events. A potential change in insulin metabolism during pregnancy may affect both the frequency and the severity of insulin-induced hypoglycaemia.2. In 10 patients with Type I diabetes, during the third trimester of pregnancy and 5 to 13 months after delivery, hypoglycaemia was induced by the hyperinsulinaemic hypoglycaemic clamp technique. A constant high-dose intravenous insulin infusion was administered for 150 min and arterial blood glucose was clamped at 2.2 mmol/l by counterregulation with intravenous glucose. During the experiment venous samples were collected for later analysis of free plasma insulin, whereby the metabolic clearance rate of insulin could be calculated.3. The desired blood glucose level was approached after approximately 60 min of insulin infusion. After just 30 min the insulin levels were significantly higher during pregnancy compared with after delivery. In addition, the steady-state insulin level from 90 to 150 min was significantly higher during pregnancy.4. From the steady-state insulin levels at 90 to 150 min, the metabolic clearance rate of insulin was calculated, being 24% higher after delivery.5. We conclude that there is a decreased metabolic clearance rate of insulin during pregnancy. This might be due to altered blood-flow distribution, decreased hepatic insulin extraction and relative increase in body fat during pregnancy. A decreased clearance of insulin will contribute to the risk for serious hypoglycaemic events in patients with Type I diabetes during pregnancy.