Massive insulin resistance apparently due to rapid clearance of circulating insulin

A 23-year-old insulin-dependent diabetic woman demonstrated increasing resistance to insulin administered by all routes, eventually requiring up to 20,000 units per day intravenously. Therapeutic trials of human and chemically modified insulin and of aprotinin were unsuccessful. Inappropriately low plasma free insulin levels (less than 60 mU/liter) during administration of extremely high insulin dosages (300 to 10,000 units per day) suggested that resistance was caused by rapid clearance of circulating insulin. There were several short periods of normal insulin sensitivity with hyperinsulinemia (more than 300 mU/liter) persisting long after intravenous insulin withdrawal, suggesting reentry to the circulation of intact, previously sequestered insulin. For four years, she has been treated with ambulatory continuous intravenous insulin infusion, which has been complicated by septicemia and central venous thrombosis. Her condition remains poorly controlled with documented intravenous insulin requirements of 2 to 20 units/hour.