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DOES A DEFECT IN INSULIN LIKE GROWTH FACTOR-I (IGF-I) GENERATION EXIST IN INSULIN DEPENDENT DIABETES (IDDM)?

Elevated, normal and low IGF-I values have been reported in IDDM. To clarify the influence of blood glucose (BG) control on IGF-I in the young diabetic, we studied 19 IDDM (16±lyrs) before and after one week of intensified Rx. During conventional Rx, IGF-I levels were markedly reduced in comparison to age-matched healthy controls (198±20 vs. 448±34 ng/ml, p<0.001) and were negatively correlated with glycosylated Hb values (r=-0.55, p<0.02). Insulin infusion pump Rx, which lowered mean 24hr BG from 233±16 to 110±5 mg/dl, induced a rise in IGF-I (198±20 to 252±34 ng/ml, p<0.005) despite a 30% fall in mean 24hr growth hormone (GH) levels, (p<0.05). To evaluate this apparent defect in IGF-I generation, we administered exogenous GH (0.1U/kg IM × 4 days) to 8 prepubertal IDDM (11.4±0.3yrs) maintained on their usual Rx, and to 7 age-matched healthy controls. Despite a significant rise in BG from 176±21 to 276±22 mg/dl(p<0.001), exogenous GH resulted in a marked increase in IGF-I (from 63±11 to 146±27 ng/mg, p<0.02) indistinguishable from that observed in non-diabetic children (58±7 to 112±24 ng/ml).Conclusions: (1) Poorly controlled IDDM is associated with reduced IGF-I levels which can be restored by improved metabolic control. (2) This defect can be overcome by exogenous GH even in the face of poor metabolic control. (3) Low IGF-I values in IDDM in the presence of high GH levels may be due to reduced biological activity of endogenous GH.