Evidence for insulin degradation by muscle and fat tissue in an insulin resistant diabetic patient.

The period before, during and after resistance to subcutaneous insulin in a 20-year-old, non-obese insulin-dependent patient with 'brittle' diabetes is documented and clinical observations are correlated with experimental results of insulin degradation in vitro. Treatment with intravenous but not subcutaneous aprotinin markedly reduced subcutaneous insulin requirements. Insulin resistance recurred following cessation of aprotinin. Serum free insulin levels were low during the subcutaneous resistant phase compared with those during the more sensitive phase. Insulin degradation in vitro by adipose tissue and muscle taken from the patient during a resistant phase was increased compared with degradation by tissue taken during a sensitive phase and by tissue from normal subjects. Chromatography of incubation media revealed that during the resistant phase, tissue from the patient degraded insulin to small fragments. It is concluded that, in this patient, insulin resistance was caused by excessive degradation in both muscle and adipose tissue.