EFFECT OF INTRAPERITONEAL INSULIN DELIVERY ON GROWTH-HORMONE BINDING-PROTEIN, INSULIN-LIKE GROWTH-FACTOR (IGF)-I, AND IGF-BINDING PROTEIN-3IN IDDM

Low plasma insulin-like growth factor (IGF)-I despite high circulating growth hormone (GH) in insulin-dependent diabetes mellitus (IDDM) ind icate a hepatic GH resistance. This state may be reflected by the redu ction of the circulating GH binding protein (GHBP), corresponding to t he extracellular domain of the GH receptor, and the reduction of insul in-like growth factor binding protein (IGFBP)-3, major IGF-I binding p rotein, upregulated by GH. We carried out two studies. In the first, p lasma GHBP activity was compared in patients with IDDM on continuous s ubcutaneous insulin infusion (CSII) or on conventional therapy and in healthy subjects. In the second study, the 18 patients on CSII at base line were then treated by continuous intraperitoneal insulin infusion with an implantable pump (CPII) and prospectively studied for GH-IGF-I axis. Although HbA(1c) was lower in patients on CSII than in those on conventional therapy, GHBP was similarly reduced in both when compare d to control subjects (10.2 +/- 0.8 and 11.6 +/- 0.9% vs 21.0 +/- 1.3, p < 0.01). CPII for 12 months resulted in: a slight and transient imp rovement in HbA(1c) (Time (T)0: 7.6 +/- 0.2%, T3:7.1 +/- 0.2%, T12: 7. 5 +/- 0.2%, p < 0.02), improvement in GHBP (T0: 10.2 +/- 0.8%, T12: 15 .5 +/- 1.5, p < 0.0001), near-normalization of IGF-I (T0: 89.4 +/- 8.8 ng/ml, T12: 146.9 +/- 15.6, p < 0.002) and normalization of IGFBP-3 ( T0: 1974 +/- 121 ng/ml, T12: 3534 +/- 305, p < 0.0001). The hepatic GH resistance profile in IDDM does not seem to be related to glycaemic c ontrol, but partly to insufficient portal insulinization. Intraperiton eal insulin deliver, allowing primary portal venous absorption, may in fluence GH sensitivity, and improve hepatic IGF-I and IGFBP-3 generati on.