Defective glucose counterregulation limits intensive therapy of diabetes mellitus.

Defective recovery from insulin-induced hypoglycemia, due to combined deficiencies of glucagon and epinephrine secretory responses to plasma glucose decrements, occurs in some patients with insulin-dependent diabetes mellitus (IDDM). Patients with IDDM determined to have inadequate glucose counterregulation during an insulin infusion test (40 mU X kg-1 X h-1) with bedside plasma glucose monitoring and clinical observation have been found to have a 25-fold greater risk of severe hypoglycemia during subsequent intensive therapy than patients with adequate glucose counterregulation. Thus, the efficacy of the glucose counterregulatory systems determines the limits of intensive therapy of IDDM.