THE EFFECTS OF SUBCUTANEOUS INSULIN-LIKE GROWTH-FACTOR-I INFUSION IN INSULIN-DEPENDENT DIABETES-MELLITUS

Insulin-dependent diabetes can be associated with low insulin-like gro wth factor-I(IGF-I) levels despite normal or even high GH secretion. T he basis of the diabetic abnormalities in GH-IGF dynamics that contrib ute to insulin resistance and impaired fuel metabolism are not well un derstood. To further investigate these matters, this study evaluated b aseline IGF system parameters and responses to recombinant human IGF-I in four diabetic adolescents and six pubertal stage-matched controls. Spontaneous overnight and arginine-stimulated GH secretion, insulin, IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), and IGFBP-3 levels wer e measured before, during, and after daily 10-h sc infusions of saline or IGF-I (20 mu g/kg.h). Baseline overnight GH secretion and IGFBP-1 and -3 levels were not significantly different in the two groups, but IGF-I levels were significantly lower and IGF-II levels were higher in diabetic subjects. IGF-I infusion produced a 3-fold increase in serum IGF-I levels and a reciprocal profound reduction in IGF-II levels in both groups. IGFBP-1 levels increased dramatically in diabetics and mo destly in normal subjects in response to IGF-I infusion, but IGFBP-3 l evels were not significantly altered. Spontaneous overnight and argini ne-stimulated GH secretion were suppressed by about 50% in both groups after IGF-I infusion. Insulin requirements were substantially reduced in diabetics receiving IGF-I, and insulin secretion was suppressed in normal subjects, with no evidence of a change in insulin half-life. B lood glucose remained stable in both groups throughout saline and IGF- I infusions, and no hypoglycemia or other adverse effect occurred duri ng IGF-I infusions. Further studies are necessary to determine whether the addition of IGF-I to insulin replacement therapy may stably reduc e the insulin requirement, maintain normal GH levels, and perhaps achi eve better metabolic and anabolic balance in the treatment of insulin- dependent diabetes.