High prevalence of diabetes and pre-diabetes in adults with Williams syndrome

• Published in: American journal of medical genetics. Part C, Seminars in medical genetics Vol. 154C; no. 2; pp. 291 - 298
• Main Authors: Pober, B.R., Wang, E., Caprio, S., Petersen, K.F., Brandt, C., Stanley, T., Osborne, L.R., Dzuria, J., Gulanski, B.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.05.2010; Wiley-Liss
• Subjects: Adult; Animal models; Biological and medical sciences; Blood Glucose - metabolism; Case-Control Studies; Chromosomes; Cohort Studies; Diabetes mellitus; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fasting; Female; Gene mapping; Glucose metabolism; Glucose tolerance; Hemizygosity; Humans; impaired glucose tolerance; Insulin; Insulin - blood; Male; Medical genetics; Medical sciences; oral glucose tolerance test; Prediabetic State - blood; Prediabetic State - complications; Prediabetic State - epidemiology; Prevalence; Sex Characteristics; syntaxin 1; syntaxin-1A (STX-1A); United States; Williams syndrome; Williams Syndrome - blood; Williams Syndrome - complications; Williams Syndrome - epidemiology; Williams syndrome chromosome region (WSCR); United States; Chromosomal aberration; Endocrinopathy; Human; Prevalence; oral glucose tolerance test; Diabetes mellitus; Oral administration; Chromosome; Glucose tolerance test; Williams syndrome; syntaxin-1A (STX-1A); Adult; Williams syndrome chromosome region (WSCR); Impaired glucose tolerance; Public health
• ISSN: 1552-4868; 1552-4876; 1552-4876
• DOI: 10.1002/ajmg.c.30261

A standard oral glucose tolerance test (OGTT) was administered to 28 adults with Williams syndrome (WS). Three quarters of the WS subjects showed abnormal glucose curves, meeting diagnostic criteria for either diabetes or the pre‐diabetic state of impaired glucose tolerance. Fasting mean glucose and median insulin levels did not differ significantly in the total WS cohort versus age–gender–BMI matched controls, though the glucose area under the curve was greater in the WS subjects. HbA1c levels were not as reliable as the OGTT in diagnosing the presence of diabetes. Given the high prevalence of impaired glucose regulation, adults with WS should be screened for diabetes, and when present should be treated in accordance with standard medical practice. Hemizygosity for a gene mapping to the Williams syndrome chromosome region (WSCR) is likely the major factor responsible for the high frequency of diabetes in WS. Syntaxin‐1A is a prime candidate gene based on its location in the WSCR, its role in insulin release, and the presence of abnormal glucose metabolism in mouse models with aberrantly expressed Stx‐1a. © 2010 Wiley‐Liss, Inc.