Introduction: Williams syndrome (WS) is a rare, multisystemic genomic disorder. While the natural history of the disease in childhood is quite well-known, few descriptions of the adult WS medical complications have been published.
Method: Twenty-two young adult patients with WS (13 females, 9 males, age: 29.2±5.4 years) were studied. A 75 g oral glucose tolerance test (OGTT) was performed in all but one with known diabetes mellitus (DM). β-Cell function was estimated with HOMA-B% and with insulinogenic index at 30 min (ΔI/ΔG30). The insulin sensitivity was assessed with HOMA-IR, QUICKI and composite insulin sensitivity Matsuda index (ISI).
Results: Impaired glucose tolerance (IGT) was diagnosed in 12 subjects and DM in one, thus showing that 59% of this population had impaired glucose metabolism. ICA and GAD antibodies were absent. Logistic regression showed that the presence of impaired glucose metabolism was not associated with BMI (P=0.267, B=0.118), age (P=0.977, B=0.004), family history of diabetes (P=0.653, B=0.747), which are known risk factors for DM. WS subjects with IGT were more insulin-resistant than WS with normal glucose metabolism (HOMA-IR 2.3±0.9 vs 1.0±0.6, P=0.008; QUICKI 0.34±0.02 vs 0.39±0.04, P=0.002, ISI 3.2±1.4 vs 7.4±2.8, P=0.006). WS subjects with normal glucose tolerance compared to healthy adults matched for gender, age and BMI did not show any difference in β-cell function, insulin sensitivity, insulin levels during OGTT, but showed higher glucose levels at 120′ after glucose load.
Conclusion: Given the high prevalence of impaired glucose regulation, adults with WS should be screened for diabetes or IGT. The reasons of this high prevalence of impaired glucose metabolism are not known. We excluded autoimmunity and usual risk factors for DM. Hemizygosity for a gene mapping to the WS chromosome region is likely the factor responsible for the high frequency of diabetes and IGT in WS.
30 Apr - 04 May 2011
European Society of Endocrinology