ABNORMAL ALPHA-CELL HYPOGLYCEMIC RECOGNITION IN CHILDREN WITH INSULIN-DEPENDENT DIABETES-MELLITUS (IDDM)

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 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.