Abnormal alpha cell hypoglycemic recognition in children with insulin dependent diabetes mellitus (IDDM)

J Pediatr Endocrinol. Jul-Sep 1994;7(3):225-34. doi: 10.1515/jpem.1994.7.3.225.


Children with IDDM have diminished glucagon responses to hypoglycemia. We evaluated possible mechanisms in 60 children and adolescents with IDDM (age 15.4 +/- 2.6 years, duration 7.8 +/- 3.5 years [mean +/- SD]) and without diabetic complications. These were: 1) suppression by hyperinsulinism, 2) autonomic neuropathy, 3) a pan-islet cell defect, and 4) a glucotoxic effect. Glucagon and pancreatic polypeptide responses to hypoglycemia (insulin bolus 0.15-0.75 U/kg) were studied after insulin withdrawal and 3 days of intensive insulin therapy. Responses to arginine and mixed meal were also studied. The control group consisted of children with non-growth hormone deficient short stature. IDDM children had lower glucagon responses to hypoglycemia than controls (p < 0.001), the response to arginine did not differ from controls, and was greater than the response to hypoglycemia (p < 0.001). Responses to hypoglycemia after insulin withdrawal and intensive therapy did not differ. Basal pancreatic polypeptide levels were lower in IDDM than in controls (p < 0.05) but responses to hypoglycemia did not differ between groups. Thus the diminished glucagon response to hypoglycemia reflects a defect in hypoglycemic recognition or response by the alpha cells.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Arginine
  • Child
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Diabetic Neuropathies / physiopathology
  • Female
  • Food
  • Glucagon / blood
  • Homeostasis*
  • Humans
  • Hypoglycemia / physiopathology*
  • Insulin / administration & dosage
  • Insulin / therapeutic use
  • Islets of Langerhans / physiopathology*
  • Male
  • Pancreatic Polypeptide / blood


  • Insulin
  • Pancreatic Polypeptide
  • Glucagon
  • Arginine