1. The metabolic effects of intraperitoneal and subcutaneous insulin delivery were compared in a crossover manner in six C-peptide-negative diabetic patients with end-stage renal disease on continuous ambulatory peritoneal dialysis. Each treatment period lasted at least 3 months. Hyperinsulinaemic euglycaemic clamp was performed and glucose turnover assessed using [3-3H]glucose as a tracer.

2. During intraperitoneal delivery the daily insulin dose was 2.4 times higher than during subcutaneous administration and glycaemic control was significantly better (HbA1c 7.63% ± 0.46% and 9.52% ± 0.51% during intraperitoneal and subcutaneous insulin respectively, P < 0.01). The number of hypoglycaemic episodes was lower during intraperitoneal insulin than during subcutaneous therapy.

3. Intraperitoneal insulin resulted in an enhanced glucose disposal rate (P < 0.01) and reduced fasting hepatic glucose production (P < 0.01). High-density lipoprotein-cholesterol decreased and the ratio of low-density lipoprotein/high-density lipoprotein-cholesterol increased significantly (P < 0.05) during intraperitoneal insulin delivery.

4. The results suggest that intraperitoneal insulin, while resulting in better glycaemic control and improved insulin sensitivity than subcutaneous insulin, increases serum triacylglycerol and total cholesterol and reduces high-density lipoprotein-cholesterol, possibly via a direct effect on the liver.

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