Effect of near physiologic insulin therapy on hypoglycemia counterregulation in type-1 diabetes

Objectives: The aim of this study was to examine hormonal counterregulation during insulin-induced hypoglycemia in type-1 diabetic patients during long-term near normoglycemic insulin therapy and intensive clinical care. Methods: Type-1 diabetic patients (age 35.3 +/- 2 years, body mass index 22.8 +/- 1 kg.m(-2), mean diabetes duration 13.6 (11-17 years), mean HbA1c during the last year 6.6 +/- 0.1%) and nondiabetic subjects were studied during (0-120 min) and after (120-240 min) hypoglycemic (3.05 mmol/l) hyperinsulinernic (-330 pmol/l) clamp tests. Results: During hypoglycemia peak plasma concentrations of glucagon (199 +/- 16 vs. 155 +/- 11 ng/l, p < 0.05), epinephrine (4,514 ± 644 vs. 1,676 ± 513 pmol/l, p < 0.001), norepinephrine (2.21 +/- 0.14 vs. 1.35 +/- 0.19 nmol/l, p < 0.01) and cortisol (532 ± 44 vs. 334 ± 61 nmol/1) were reduced in the diabetic patients. Plasma lactate did not change from baseline values (0.51 ± 0.06 mmol/l) in diabetic but doubled in healthy subjects (1.13 ± 0.111 mmol/l, p < 0.001 vs. control). During the posthypoglycemic recovery period plasma concentrations of free fatty acids were higher in diabetic patients at 240 min (1.34 +/- 0.12 vs. 2.01 +/- 0.23 mmol/l, p < 0.05). Conclusion: Despite long-term near physiologic insulin substitution and the low incidence of hypoglycemia, hormonal hypoglycemia counterregulation was impaired in type-1 diabetic patients after a diabetes duration of more than 10 years. Copyright (C) 2002 S. Karger AG, Basel.