INSULIN-LIKE-GROWTH-FACTOR BINDING PROTEIN-1 LEVELS IN THE DIAGNOSIS OF HYPOGLYCEMIA CAUSED BY HYPERINSULINISM

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.