Diabetes mellitus is becoming a more frequently recognized complication of
Prader-Willi syndrome. It has been reported that as many as 7-20% of indivi
duals with Prader-Willi syndrome may develop this complication. Diabetes me
llitus adds to the complexity of an already complex treatment program, caus
es many serious complications that greatly affect the quality of life of th
ese individuals, and can lead to serious morbidity and mortality. Recent st
udies suggest that growth hormone (GH) might offer significant advantages t
o 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 unders
tood. 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 a
nd hence the symptom complex of type 2 diabetes mellitus. To determine if t
his same pattern is present in patients with Prader-Willi syndrome, we eval
uated 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 equal
ly longstanding obesity. We compared the glucose and insulin responses of t
hese two groups, using both oral and intravenous glucose challenges. The re
sults 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 norma
l or increased insulin sensitivity. These data do not support the hypothesi
s that the high incidence of diabetes mellitus in patients with Prader-Will
i syndrome is simply the result of obesity and therefore suggest a differen
t aetiology.