An Update on Prader-Willi Syndrome with Diabetes Mellitus

Abstract

Prader-Willi syndrome (PWS) often develops type 2 diabetes mellitus (T2DM) related to severe obesity. The prevalence of T2DM in adults with PWS (7-20%) exceeds greatly the prevalence in the general population (5-7%). It is uncommon for pre-pubertal children with PWS to develop overt diabetes or glucose intolerance. GH therapy and genotype did not influence the development of altered glucose metabolism. It has been assumed that T2DM in PWS develops as a consequence of morbid obesity and concomitant insulin resistance. However recent studies suggest the relationship between morbid obesity and T2DM development is more complex and appears to differ in PWS subjects compared to non-PWS subjects. PWS patients had relatively lower fasting insulin levels and increased adiponectin levels compared with BMI-matched obese control despite of similar levels of leptin. So PWS children may be protected to some extent form of obesity-associated insulin resistance. Although there's no data, it seems logical to approach diabetes management including weight loss and increased exercise, using similar pharmacological agents as with non-PWS obesity-related diabetes such as metformin or thiazolidinedione, with the introduction of insulin as required. On the other hand, several recent T2DM in PWS case reports suggest favorable outcomes using Glucagon-like peptide 1 (GLP-1) analog with regard to ghrelin reduction, control of glucose and appetite, weight loss and pre-prandial insulin secretion. The role of GLP-1 agonist therapy is promising, but has not yet been fully elucidated.

Hypothalamic neuropeptides and neurocircuitries in Prader Willi syndrome

“…187 By contrast, concomitant studies reported that approximately 25% of PWS individuals are diabetic in other European cohorts, 188,189 and even a higher percentage is suggested in an Asian population, with approximately 30% of T2DM incidence in PWS. 190 Despite the clear incidence of T2DM within PWS population, there are discrepant reports in the literature on the role of defective glucose-regulation in the pathophysiology of PWS. Furthermore, increased plasma concentrations of additional metabolism-controlling hormones (i.e.…”