INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-2 AND INSULIN - STUDIES INCHILDREN WITH TYPE-1 DIABETES-MELLITUS AND MATURITY-ONSET DIABETES OFTHE YOUNG

The regulation of circulating insulin-like growth factor-binding prote in-2 (IGFBP-2) in humans is not well understood. In vitro and animal d ata have identified the role of insulin in the regulation of IGFBP-8, but such a relationship has not been established clearly in humans. In the present study, serum IGFBP-8 concentrations were assessed by West ern ligand blot and immunoblot analysis in children with newly diagnos ed and untreated insulin-dependent diabetes mellitus (IDDM) and maturi ty-onset diabetes of the young before and at various times after insul in therapy. For comparison, IGFBP-8 levels were also determined in lea n and obese age-matched controls. Children with IDDM were grouped acco rding to their serum bicarbonate levels at the time of presentation (g roup A, >20; group B, 13-20; group C, <13 milliequivalents/L). Densito metric analysis demonstrated that before insulin therapy, group A pati ents had serum IGFBP-8 levels comparable to those in lean controls, an d no significant change in IGFBP-2 was observed during insulin therapy . However, group B patients had a 2-fold elevation in IGFBP-2 levels b efore insulin therapy compared to lean controls. In these patients, IG FBP-2 tended to decrease at 1 week, but was not significantly reduced until 1 month after the initiation of insulin therapy. Group C patient s had a 2.5-fold elevation of IGFBP-2 before treatment, which normaliz ed by 1 month after treatment. Children with maturity-onset diabetes o f the young, who had insulin levels and body mass indexes greater than IDDM patients and lean controls, had significantly lower IGFBP-2 leve ls than both lean and obese controls. IGFBP-2 levels tended to decreas e further during insulin therapy. These results indicate that long sta nding alterations in serum insulin concentrations beyond the physiolog ical range have significant influence on serum IGFBP-2 levels in child ren and confirm earlier findings that serum IGFBP-2 levels are not acu tely regulated by insulin.