GROWTH-HORMONE AND DIABETES-MELLITUS - A REVIEW OF 63 YEARS OF MEDICAL-RESEARCH AND A GLIMPSE INTO THE FUTURE

The diabetogenic action of pituitary extracts containing growth hormon e has been recognised for more than 60 years and the importance of gro wth hormone in the development and progression of diabetic retinopathy for more than 30 years. Hypophysectomy was the first effective treatm ent for retinopathy but was discontinued because of the risk of severe hypoglycaemia that it produced and the development of an alternative, less dangerous therapy - photocoagulation. The precise role and signi ficance of growth hormone in diabetes care, however, remains to this d ay a mystery. The fact that modem, highly purified biosynthetic prepar ations of growth hormone still retain full diabetogenic potency and th e fact that diabetes develops in up to 25% of patients with acromegaly indicate growth hormone's potential for involvement in the aetiology of diabetes mellitus, although most will agree that this is not likely to be an important factor in the large majority of 'idiopathic' cases . There is strong evidence to indicate a substantial hypersecretion of growth hormone in 'idiopathic' diabetes mellitus (particularly insuli n-dependent cases and those with retinopathy), which appears to be mor e related to residual pancreatic insulin secretion than to metabolic c ontrol. Since the advent of biosynthetic growth hormone in sufficient quantity to perform trials in adults, we are more aware of growth horm one's considerable potency in the regulation of body composition, grow th factor production and intermediary metabolism. In this article, we review the literature and, from this and our own work, propose a new h ypothesis which links the hypersecretion of growth hormone to reduced hepatic secretion of insulin-like growth-factor I (IGF-1) as a direct result of reduced portal insulin levels in diabetes mellitus. The hype rsecretion of growth hormone exposes peripheral organs such as the ret ina and kidney to conditions favouring the expression of growth-hormon e-dependent growth factors such as IGF-I which may contribute to the d evelopment of diabetic microvascular disease by autocrine and/or parac rine effects. If this hypothesis proves to be true, it offers new oppo rtunities for the prevention of diabetic microvascular complications t hrough suppression of growth hormone secretion which in turn will incr ease insulin sensitivity and facilitate good glycaemic control.