Residual insulin secretion is not coupled to a maintained glucagon response to hypoglycaemia in long-term type 1 diabetes

J Intern Med. 2002 Oct;252(4):342-51. doi: 10.1046/j.1365-2796.2002.01043.x.


Objectives: To evaluate the influence of residual beta-cell function on glucagon secretion and glucose counter-regulation following hypoglycaemia in type 1 diabetes.

Design and subjects: The hormonal counter-regulatory responses to standardized insulin-induced hypoglycaemia were investigated, 18 patients with type 1 diabetes of long duration and 12 healthy subjects were investigated. Nine of the diabetic patients (diabetes duration 17 +/- 1 years) had residual insulin secretion, as reflected by persistent urinary C-peptide excretion. The other nine diabetic patients (diabetes duration 21 +/- 1 years) were C-peptide negative.

Results: Similar hypoglycaemic nadirs were found in all groups (2.1-2.3 mmol L-1), whereas the recovery of plasma glucose levels was delayed similarly in the diabetic groups. In the control subjects, plasma glucagon increased ( approximately 50%). No significant glucagon response was registered in either of the two diabetic groups. The maximum plasma adrenaline and pancreatic polypeptides (PP) responses to hypoglycaemia were comparable in the two diabetic patient groups; the peak values being lower (P < 0.05) than in the controls. Plasma noradrenaline, growth hormone and cortisol responses to hypoglycaemia were similar in all three groups.

Conclusion: Residual beta-cell function in patients with long-term type 1 diabetes is not accompanied by preservation of the glucagon response to hypoglycaemia. As the two markers of autonomic function (adrenaline and PP) were similarly reduced in the two diabetic groups, the findings instead favour the concept that the defective glucagon secretory response to hypoglycaemia is because of autonomic nervous dysfunction.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Autonomic Nervous System / physiopathology
  • Blood Glucose / metabolism*
  • C-Peptide / urine*
  • Data Interpretation, Statistical
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Diabetes Mellitus, Type 1 / urine
  • Epinephrine / blood*
  • Female
  • Glucagon / blood
  • Glucagon / metabolism*
  • Growth Hormone / blood
  • Humans
  • Hydrocortisone / blood
  • Hypoglycemia / physiopathology*
  • Infusions, Intravenous
  • Injections, Subcutaneous
  • Insulin / administration & dosage
  • Insulin / metabolism*
  • Insulin / therapeutic use
  • Insulin Secretion
  • Islets of Langerhans / physiology
  • Islets of Langerhans / physiopathology*
  • Male
  • Middle Aged
  • Pancreatic Polypeptide / blood*
  • Radioimmunoassay
  • Time Factors


  • Blood Glucose
  • C-Peptide
  • Insulin
  • Pancreatic Polypeptide
  • Growth Hormone
  • Glucagon
  • Hydrocortisone
  • Epinephrine