title: Counterregulation during spontaneous nocturnal hypoglycemia in prepubertal children with type 1 diabetes.
abstract: OBJECTIVE
  To examine counterregulatory responses during spontaneous nocturnal hypoglycemia in prepubertal children with type 1 diabetes.
  
  
  METHODS
  A total of 29 prepubertal patients with type 1 diabetes underwent two overnight profiles. Data were analyzed from 16 children (median [range] 8.7 [5.9-12.9] years of age) with a night of hypoglycemia and a nonhypoglycemic night. Children hypoglycemic (< 3.5 mmol/l) on night 1 were given 25% extra carbohydrate as uncooked cornstarch with their usual evening snack on night 2 to avoid hypoglycemia. Glucose, growth hormone, and cortisol were measured every 15 min, catecholamines every 30 min, and glucagon, pancreatic polypeptide, insulin, and ketones every 60 min. A group of 15 healthy control subjects, aged 9.5 (5.6-12.1) years, underwent one overnight profile.
  
  
  RESULTS
  Median duration of hypoglycemia was 225 (30-630) min, and glucose nadir was 2.0 (1.2-3.3) mmol/l. Insulin levels were not different on the two nights (P = 0.9, analysis of variance), but children with diabetes had higher insulin levels than normal control subjects between 2300 and 0300, maximal at 0200 (mean +/- SEM 57.4 +/- 5.7 vs. 31.6 +/- 5.0 pmol/l, P = 0.002). Peak epinephrine was higher on the night of hypoglycemia (0.98 [0.52-2.09] nmol/l) versus nonhypoglycemia (0.32 [0.21-0.62] nmol/l), P = 0.001, but norepinephrine (1.29 [1.07-2.64] vs. 1.26 [1.04-1.88] nmol/l, P = 0.5), glucagon (93 [64.2-125.6] vs. 100.5 [54.6-158] ng/l, P = 0.6), pancreatic polypeptide (410.2 [191-643.2] vs. 270.8 [158.2-777.8] ng/l, P = 0.5), and cortisol (513 [300-679] vs. 475 [235-739] nmol/l, P = 0.6) were not different. Glucose threshold for epinephrine release was very low, 1.9 +/- 0.2 mmol/l. There was a short-lived rise in growth hormone from 75-105 min after onset of hypoglycemia, maximal at 90 min (7.8 +/- 1.2 vs. 3.5 +/- 0.9 ng/ml, P = 0.02).
  
  
  CONCLUSIONS
  The prolonged nature of nocturnal hypoglycemic episodes may be explained in part by defective counterregulation. The risk of nocturnal hypoglycemia needs to be reduced before intensification of insulin therapy can be contemplated in this age-group.
authors.affiliation: Department of Paediatrics, John Radcliffe Hospital, Oxford, U.K.
authors.forename: K A
authors.initials: KA
authors.lastname: Matyka
authors.forename: E C
authors.initials: EC
authors.lastname: Crowne
authors.forename: P J
authors.initials: PJ
authors.lastname: Havel
authors.forename: I A
authors.initials: IA
authors.lastname: Macdonald
authors.forename: D
authors.initials: D
authors.lastname: Matthews
authors.forename: D B
authors.initials: DB
authors.lastname: Dunger
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D002940:Circadian Rhythm; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D004837:Epinephrine / Q000097:blood; D005934:Glucagon / Q000097:blood; D006442:Glycated Hemoglobin / Q000032:analysis; D006728:Hormones / Q000097:blood*; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007003:Hypoglycemia / Q000097:blood / Q000503:physiopathology* / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D007657:Ketone Bodies / Q000097:blood; D009638:Norepinephrine / Q000097:blood; D010191:Pancreatic Polypeptide / Q000097:blood; D011627:Puberty; D012016:Reference Values
chemical_list: D001786:Blood Glucose; D004837:Epinephrine; D005934:Glucagon; D006442:Glycated Hemoglobin; D006728:Hormones; D019382:Human Growth Hormone; D006854:Hydrocortisone; D007004:Hypoglycemic Agents; D007328:Insulin; D007657:Ketone Bodies; D009638:Norepinephrine; D010191:Pancreatic Polypeptide