In Type 1 diabetes, high circulating growth hormone (GH) in conjunction with low plasma insulin-like growth factor-I (IGF-I) is indicative of a hepatic GH-resistance profile since the liver is the main source of circulating IGF-I. The reduction in specific growth hormone binding protein (GHBP), corresponding to the extracellular domain of the GH receptor, provides an indirect indication of the hepatic density of GH receptors, as does the reduction in IGFBP-3, the major IGF binding protein, which is GH-dependent. Type 1 diabetes is also associated with high levels of IGFBP-1, a binding protein down-regulated by insulin. Although most of these abnormalities have been described in situations of poor glycaemic control, hyperglycaemia does not seem to be the predominant factor in their pathogenesis. Even intensified subcutaneous insulin therapy does not normalize GH, IGF-I, GHBP and IGFBP-3 plasma levels. Some indirect evidence suggests that portal insulinopenia plays a role in the hepatic GH-resistance profile of Type 1 diabetes, i.e. discrepancies between the abnormalities reported in Type 1 and Type 2 diabetes, and the inverse relationship between residual insulin secretion in Type 1 diabetes and some of these abnormalities. Intraperitoneal insulin therapy administered to Type 1 diabetic patients by implantable pumps (without modification of glycaemic control) can improve GHBP activity, practically normalize plasma IGF-I and normalize IGFBP-3. The improvement in GH-IGF-I axis disorders obtained with intraperitoneal insulin therapy (which allows primary portal insulin absorption) provides direct evidence of the central role of portal insulin in the regulation of this system.