Glucose homeostasis in Prader-Willi syndrome and potential implications of growth hormone therapy

Diabetes mellitus is becoming a more frequently recognized complication of Prader-Willi syndrome. It has been reported that as many as 7-20% of individuals with Prader-Willi syndrome may develop this complication. Diabetes mellitus adds to the complexity of an already complex treatment program, causes many serious complications that greatly affect the quality of life of these individuals, and can lead to serious morbidity and mortality. Recent studies suggest that growth hormone (GH) might offer significant advantages to individuals with Prader-Willi syndrome. However, as a known diabetogenic agent, GH might also increase the propensity to develop diabetes mellitus. For this reason, the characteristics of the diabetes mellitus that develops in individuals with Prader-Willi syndrome must be studied and fully understood. The initial assumption has been that the diabetes mellitus associated with this syndrome is identical to that seen in obese individuals without Prader-Willi syndrome, in whom genetic factors and obesity lead to insulin resistance. Severe insulin resistance in turn leads to pancreatic failure and hence the symptom complex of type 2 diabetes mellitus. To determine if this same pattern is present in patients with Prader-Willi syndrome, we evaluated both obese children and adults with the syndrome. These patients were compared with obese individuals without Prader-Willi syndrome matched for age, gender and weight and who had not yet developed diabetes but had equally longstanding obesity. We compared the glucose and insulin responses of these two groups, using both oral and intravenous glucose challenges. The results demonstrated that individuals with Prader-Willi syndrome do not show the predicted insulin resistance that is seen in obese children without the syndrome. In fact, the individuals with Prader-Willi syndrome showed normal or increased insulin sensitivity. These data do not support the hypothesis that the high incidence of diabetes mellitus in patients with Prader-Willi syndrome is simply the result of obesity and therefore suggest a different aetiology.