Insulin-Like Growth Factor Binding Protein-1 to Screen for Insulin Resistance in Children

Abstract

Diabetes and atherosclerosis are burgeoning health problems complicating obesity-associated insulin resistance (IR). Early detection of IR in children is a key to preventative strategies. Since peripheral insulin levels insensitively reflect hepatic insulin fluxes, we studied the insulin-regulated hepatic insulin-like growth factor binding proteins (IGFBPs)-1 and -3 as possible screening markers of childhood IR. The tolbutamide-modified frequently sampled intravenous glucose tolerance test (FSIVGTT) and the oral glucose tolerance test (OGTT) were performed in 118 subjects < 21 years old with obesity. The relationships between insulin sensitivity index by minimal modeling (SiIVGTT), other Sis derived from fasting and OGTT insulin and glucose values, and the candidate serum markers were sought. Significant correlation was found between IGFBP-1 and SiIVGTT, similar to the correlations of insulin sensitivity indices with SiIVGTT. In children < or = 10 years old, correlation of IGFBP-1 with SiIVGTT was the strongest. All (100%) subjects with IR defined by SiIVGTT < 4.5 +/- 0.5 x 10(-4) min(-1) /(microIU/mL) had inappropriately low IGFBP-1 levels. IGFBP-3 was not correlated with SiIVGTT. IGFBP-1 levels decrease with obesity and IR. We propose that in young subjects, especially children under the age of 10 years, IGFBP-1 is a convenient and sensitive marker of IR, whereas elevated fasting insulin is less sensitive but more specific.