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

Horm Res. 2001;56(5-6):151-8. doi: 10.1159/000048111.

Abstract

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 x 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) hyperinsulinemic (approximately 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/l) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxybutyric Acid / blood
  • Adult
  • Blood Glucose / analysis
  • C-Peptide / blood
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Fatty Acids, Nonesterified / blood
  • Glucose / administration & dosage
  • Glucose / pharmacology
  • Hormones / blood*
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemia / physiopathology*
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / adverse effects
  • Insulin / blood
  • Insulin / therapeutic use*
  • Lactic Acid / blood
  • Male
  • Middle Aged
  • Reference Values

Substances

  • Blood Glucose
  • C-Peptide
  • Fatty Acids, Nonesterified
  • Hormones
  • Hypoglycemic Agents
  • Insulin
  • Lactic Acid
  • Glucose
  • 3-Hydroxybutyric Acid