THE EFFECTS OF rhIGF-1 ON GH,IEF-BP3 BND IGF-BP1 CONCENTRHTIONS BND INSULIN SENSITIVITY IN ADOLESCENTS UITH INSULIN DEPENDENT DIABETES MELLITUS (IDDW)

Abstract

Insulin resistance and poor growth during adolescene in IDDM have been linked with reduced IGF bioactivity and elevated GH levels. In a double blind placebo controlled study we have examined the effects of a single sc injection of rhIGF-1 (40ug/kg) on total IGF-I, IGF-BP1, IGF-BP3 and GH concentrations in 9 adolescents with IDDM (aged 14-18y, Tanner Stage 4 or 5, HbA1 range 7.1-17X). RhIGF-I or placebo were given at 18.00h, blood glucose was clasped around 5mmol/L between 02.00-008.00h to assess insulin sensitivity, and sampling was continued for a total of 22 h. Peak IGF-I levels were achieved at 5.5h and declined with a T/2 of 17.3h. Mean levels were 350±26 ng/ml after rhIGF-I vs 204±21 ng/nl on control night (p<.001). Both IGF-BP1 and IGF-BP3 tended to be higher after rhIGF-I.IGF bioactivity was increased by 56X. Overall mean GH concentrations were reduced after rhIGF-I (16.9±3.2 vs 27.7±4.6 mU/l, p<0.001) and there was no evidence of rebound GH secretion over 22h. During the stable clamp period, insulin requirements following rhIGF-I were reduced (0.25±0.12 vs 0.31±0,07 mU/kg/min, p<0.03) as were levels of free insulin (31.9 ± 2.7 vs 67.9 ± .16 mU/L, p<0.001). BOHbutyrate and acetoacetate tended to be lower during rhIGF-I administration whereas lactate levels were unchanged. RhIGF-I adninistration in adolescents with IDDM results in a significant result of increased free IGF-I or reduced GH concentrations.