Abstract
The pathogenesis of growth failure in pediatric CRF may involve abnormalities of the IGF system. We have previously shown that serum IGF levels are normal in CRF, while levels of intact IGFBP-1, an IGF-inhibitory binding protein, are elevated. In normals, IGFBP-1 production is suppressed by insulin; fasting IGFBP-1 and insulin levels show a curvilinear inverse relationship. We studied this relationship in 20 patients [age=7.1 ± 3.5SD yr, 3F/17M, GFR (iothalamatc) = 28± 7SD mL/min/1.73m2] involved in a study of GH treatment of CRF. Fasting serum was collected at 0, 3 and 12 months (n = 60). Insulin and IGFBP-1 levels were measured using immunoassay kits (Diagnostic Systems Labs) with mean levels of insulin = 52±7(SE) pmol/L (nl 15-100) and IGFBP-1 =719± 72(SE) ng/niL (nl<150). The relationship between IGFBP-1 and insulin is described by an inverse curvilinear plot with a > 20-fold increase in IGFBP-1 levels at the inflection point as compared to normal and obese subjects. The “critical” suppressive insulin level may be slightly less than the level we have previously described for non-CRF patients (70-90 pmol/L). Since GFR was low and homogenous in this group, an independent relationship with IGFBP-1 could not be defined. Compared to baseline, IGFBP-1 levels were reduced 29% and 57% after 3 and 12 months of GH therapy (n=14 pts), while levels were 92% and 94% of baseline for untreated patients (n = 6). GH treatment had no effect on the inverse relationship of IGFBP-1 and insulin. Our results provide evidence that IGFBP-1 production is insulin-dependent in CRF as it is in normals, and that increased levels of this IGF-regulatory protein are probably determined primarily by impaired clearance. Furthermore, while exogenous GH lowers IGFBP-1 levels in CRF, this effect may be mediated by changes in insulin concentrations.
Supported by Genentech, Inc. and Diafpiostic Systems Laboratories, Inc.
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Lee, P., Powell, D. & Brewer, E. INTERRELATIONSHIP OFIGFBP-1 AND INSULIN IN PEDIATRIC CHRONIC RENAL FAILURE (CRF). Pediatr Res 33 (Suppl 5), S40 (1993). https://doi.org/10.1203/00006450-199305001-00224
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DOI: https://doi.org/10.1203/00006450-199305001-00224