Aprotinin induced lipohypertrophy and glomerulonephritis in an insulin dependent diabetic

In an insulin dependent diabetic who was hyperglycaemic and ketotic despite 3,000u of insulin injected subcutaneously in 2 divided doses daily, 50u of intravenous insulin infused over 24 hr restored normal glucose homeostasis. A combination of insulin (800u) and aprotinin (10,000u) given twice daily also produced adequate glucose homeostasis for a period of 12 months. The patient then developed local hypertrophy of subcutaneous tissue at the injection site and her diabetic control deteriorated. Non-selective proteinura followed and she developed nephrotic syndrome. Renal biopsy revealed a membraneous glomerulonephritis with subepithelial immune complexes, appearances consistent with a drug-induced glomerulonephritis. Withdrawal of aprotinin led to a gradual remission of nephrotic syndrome and proteinuria over several months. During this period, her diabetes was well controlled with continuous subcutaneous infusion of insulin at a dose of 500u/24 hr. This case report demonstrates: (1) the effective use of aprotinin for prolonged periods in insulin dependent diabetics with abnormal absorption of subcutaneously injected insulin; (2) aprotinin induced lipohypertrophy which was not observed when insulin was injected alone; (3) aprotinin-associated glomerulonephritis and nephrotic syndrome; (4) the effective use of CSII - at higher insulin doses - in such patients with subcutaneous malabsorption of insulin.