The diagnosis of
hypoglycemia caused by
hyperinsulinism may be difficult because
insulin levels are not uniformly elevated at the time of
hypoglycemia.
Insulin-like growth factor binding protein-1 (IGFBP-1) is a 28 kd
protein whose secretion is acutely inhibited by
insulin. We hypothesized that serum levels of
IGFBP-1 would be a useful marker of
hyperinsulinism. We measured
IGFBP-1 levels during the course of standardized fasting studies in hospitalized children; 36 patients became
hypoglycemic during the fasting studies, and samples obtained at the point of
hypoglycemia were analyzed. On the basis of the currently used diagnostic criteria, 13 children had
hyperinsulinism, 16 had ketotic
hypoglycemia or no disorder, 3 had
hypopituitarism or
isolated growth hormone deficiency, 2 had
glycogen storage disease type 1 and 2 had
fatty 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
hypoglycemia. Mean
IGFBP-1 levels at
hypoglycemia for the entire group with
hyperinsulinism were 52.4 +/- 11.5 ng/ml, significantly different from levels seen in control subjects (p < 0.0001). In children with moderately controlled
hyperinsulinism (fasting tolerance > 4 hours), mean
IGFBP-1 levels at the time of
hypoglycemia were 71.5 +/- 16.9 ng/ml.
IGFBP-1 levels in the children with poorly controlled
hyperinsulinism (fasting 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 inversely 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 additional marker of
insulin action that might help to differentiate
hyperinsulinism from other
hypoglycemic disorders.