In search of the subcutaneous-insulin-resistance syndrome

In numerous patients with diabetes mellitus, a defect in the absorption of subcutaneously injected insulin has been suspected as an explanation for diabetic instability. The common clinical characteristic of these patients is poor metabolic control when insulin is injected subcutaneously, but good metabolic control when the insulin is infused intravenously. We have used three approaches to attempt to identify patients with "subcutaneous-insulin resistance." First, we performed a series of studies of subcutaneous-insulin absorption in 16 patients referred to us with a presumptive diagnosis of resistance to subcutaneous insulin; in none of these patients did we detect an abnormal response of blood glucose levels to insulin administered subcutaneously. Plasma free-insulin levels rose normally after injection. Second, we assayed insulin-degrading activity in subcutaneous biopsy specimens obtained from 25 patients throughout North America and Europe who had been diagnosed as resistant to subcutaneous insulin. In none of these patients did the insulin-degrading activity of subcutaneous tissue exceed the mean value (+/- 2 SD) of eight subcutaneous biopsy specimens obtained from control patients with diabetes. Third, we performed studies of tritiated-insulin absorption in three additional diabetic patients and three control patients with nonbrittle diabetes. These studies also suggested normal absorption of insulin. In none of the patients we studied were we able to confirm the clinical diagnosis of subcutaneous-insulin resistance. We therefore conclude that this syndrome is extremely rare and that misdiagnosis is common.