Natural course of growth hormone hypersecretion in insulin-dependent diabetes mellitus

High growth hormone levels in patients with insulin-dependent diabetes were recognised 25 years ago. For many years this has been explained as an epiphenomenon of poor metabolic control. The natural course of the disease is characterised by gradual loss of residual beta-cell function and parallel elevations of plasma growth hormone and can be divided into three consecutive phases. It appears that the hormonal changes observed are determined by the IGF-1 generating capacity of the liver which, in turn, is dependent on the synergistic stimulating action of growth hormone and portal insulin. The first (initial) phase of insulin-dependent diabetes mellitus is characterised by the absence of insulin, high growth hormone levels and low plasma IGF-1. The pituitary growth hormone response to exercise and other stimuli is pathological. The second phase of disease ('C-peptide positive phase') is characterised by the return of some residual beta-cell insulin secretion, increased levels of growth hormone compared to non-diabetic subjects, physiological IGF-1 levels and near normal pituitary growth hormone responses to different agents. The third phase of the disease is characterised by complete loss of endogenous insulin secretion, very high plasma growth hormone levels, low normal plasma IGF-1 but impaired hepatic IGF-1 generating capacity. The control mechanisms of pituitary growth hormone secretion (long loop negative feedback and auto-feedback), are disturbed.