Abnormal regulation of insulin-like growth factor binding proteins in adolescents with insulin-dependent diabetes.
We have measured fasting 0800 h insulin-like growth factor binding proteins (IGFBP)-1 and IGFBP-3, in 52 diabetic adolescents and 74 puberty-matched control subjects with short stature and normal hormonal status. We have also measured overnight hourly profiles of IGFBP-1, glucose, free insulin, and GH in 12 of the diabetic adolescents. With advancing age and pubertal status, IGFBP-1 declined and IGFBP-3 increased significantly in the control, but not the diabetic group. Fasting IGFBP-1 levels were elevated 4-fold compared to controls. Median IGFBP-3 was significantly lower in the diabetic compared to the control group in pubertal stages III and V. Elevated IGFBP-1 was significantly correlated with metabolic control in poorly controlled subjects (mean 12-month glycosylated haemoglobin greater than 8.5%). In the overnight profiles, mean hourly IGFBP-1 was inversely related to insulin, but not glucose. As free insulin levels declined, IGFBP-1 rose, associated with rising predawn blood sugars. The integrated 3-h IGFBP-1 value (0500-0800 h) was significantly correlated with the corresponding glucose integrated value. IGFBP-1 area under the curve for the whole overnight profile was significantly correlated with glycosylated hemoglobin in 11 of the 12 subjects. IGFBP-1 from diabetic adolescents has been shown to inhibit IGF-I bioactivity. We postulate that IGFBP-1 may have a role in growth impairment of poorly controlled diabetes and may contribute to the dawn phenomenon.
Batch
J A
JA
Department of Endocrinology, Royal Children's Hospital, Melbourne, Australia.
Baxter
R C
RC
Werther
G
G
D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005215:Fasting; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D011627:Puberty; D012016:Reference Values
D001786:Blood Glucose; D002352:Carrier Proteins; D006442:Glycated Hemoglobin; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I