Rp. Hoffman et al., ABNORMAL ALPHA-CELL HYPOGLYCEMIC RECOGNITION IN CHILDREN WITH INSULIN-DEPENDENT DIABETES-MELLITUS (IDDM), Journal of pediatric endocrinology, 7(3), 1994, pp. 225-234
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 hyperins
ulinism, 2) autonomic neuropathy, 3) a pan-islet cell defect, and 4) a
glucotoxic effect. Glucagon and pancreatic polypeptide responses to h
ypoglycemia (insulin bolus 0.15-0.75 U/kg) were studied after insulin
withdrawal and 3 days of intensive insulin therapy. Responses to argin
ine and mixed meal were also studied. The control group consisted of c
hildren 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 re
sponse to hypoglycemia (p<0.001). Responses to hypoglycemia after insu
lin withdrawal and intensive therapy did not differ. Basal pancreatic
polypeptide levels were lower in IDDM than in controls (p<0.05) but re
sponses to hypoglycemia did not differ between groups. Thus the dimini
shed glucagon response to hypoglycemia reflects a defect in hypoglycem
ic recognition or response by the alpha cells.