Counterregulation during spontaneous nocturnal hypoglycemia in prepubertal children with type 1 diabetes

• Published in: Diabetes care Vol. 22; no. 7; pp. 1144 - 1150
• Main Authors: MATYKA, K. A, CROWNE, E. C, HAVEL, P. J, MACDONALD, I. A, MATTHEWS, D, DUNGER, D. B
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01-07-1999
• Subjects: Biological and medical sciences; Blood Glucose - metabolism; Catecholamines; Child; Child, Preschool; Chromatography; Circadian Rhythm; Diabetes; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Epinephrine - blood; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Glucagon; Glucagon - blood; Glucose; Glycated Hemoglobin A - analysis; Growth hormones; Hormones - blood; Human Growth Hormone - blood; Humans; Hydrocortisone - blood; Hypoglycemia; Hypoglycemia - blood; Hypoglycemia - physiopathology; Hypoglycemia - prevention & control; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Insulin; Insulin - adverse effects; Insulin - blood; Insulin - therapeutic use; Ketone Bodies - blood; Medical sciences; Metabolism; Norepinephrine - blood; Pancreatic Polypeptide - blood; Polypeptides; Puberty; Reference Values; Research design; Teenagers; Variance analysis; United States; North America; America; United Kingdom > UK; Endocrinopathy; Human; Immunopathology; Pancreatic hormone; Glucagon; Night; Steroid hormone; Pathogenesis; Somatotropin hormone; Autoimmune disease; Catecholamine; Hydrocortisone; Hypoglycemia; Glucocorticoid; Insulin; Blood plasma; Adenohypophyseal hormone; Adrenal hormone; Hormonal regulation; Insulin dependent diabetes; Complication; Hormonal investigation; Child
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/diacare.22.7.1144

Counterregulation during spontaneous nocturnal hypoglycemia in prepubertal children with type 1 diabetes.
K A Matyka ,
E C Crowne ,
P J Havel ,
I A Macdonald ,
D Matthews and
D B Dunger
Department of Paediatrics, John Radcliffe Hospital, Oxford, U.K.
Abstract
OBJECTIVE: To examine counterregulatory responses during spontaneous nocturnal hypoglycemia in prepubertal children with type
1 diabetes. RESEARCH DESIGN AND 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.