Lel. Katz et al., INSULIN-LIKE-GROWTH-FACTOR BINDING PROTEIN-1 LEVELS IN THE DIAGNOSIS OF HYPOGLYCEMIA CAUSED BY HYPERINSULINISM, The Journal of pediatrics, 131(2), 1997, pp. 193-199
The diagnosis of hypoglycemia caused by hyperinsulinism may be difficu
lt because insulin levels are not uniformly elevated at the time of hy
poglycemia. Insulin-like growth factor binding protein-1 (IGFBP-1) is
a 28 kd protein whose secretion is acutely inhibited by insulin. We hy
pothesized that serum levels of IGFBP-1 would be a useful marker of hy
perinsulinism. We measured IGFBP-1 levels during the course of standar
dized fasting studies in hospitalized children; 36 patients became hyp
oglycemic during the fasting studies, and samples obtained at the poin
t of hypoglycemia were analyzed. On the basis of the currently used di
agnostic criteria, 13 children had hyperinsulinism, 16 had ketotic hyp
oglycemia or no disorder, 3 had hypopituitarism or isolated growth hor
mone deficiency, 2 had glycogen storage disease type I, and 2 had fatt
y acid oxidation disorders. In control subjects (children with ketotic
hypoglycemia or no disorder), IGFBP-1 levels rose during fasting to a
mean of 343.8 +/- 71.3 ng/ml in the sample drawn at the time of hypog
lycemia. Mean IGFBP-1 levels at hypoglycemia for the entire group with
hyperinsulinism were 52.4 +/- 11.5 ng/ml, significantly different fro
m levels seen in control subjects (p < 0.0001). In children with moder
ately controlled hyperinsulinism (fasting tolerance > 4 hours), mean I
GFBP-1 levels at the time of hypoglycemia were 71.5 +/- 16.9 ng/ml. IG
FBP-1 levels in the children with poorly controlled hyperinsulinism (f
asting tolerance < 4 hours) failed to rise during fasting, with a mean
of 30.1 +/- 10.4 ng/ml in the final sample. IGFBP-1 levels were inver
sely correlated with serum insulin and C-peptide levels (r = -0.71 and
-0.72, respectively; p < 0.0001). Patients with other endocrinologic
or metabolic diseases that result in fasting hypoglycemia demonstrated
a rise in IGFBP-1 levels similar to that seen in ketotic hypoglycemia
. Low serum levels of IGFBP-1 at the time of hypoglycemia provide an a
dditional marker of insulin action that might help to differentiate hy
perinsulinism From other hypoglycemic disorders.