Familial Early-Onset Type 2 Diabetes in Chinese Patients

Familial Early-Onset Type 2 Diabetes in Chinese Patients Obesity and genetics have more significant roles than autoimmunity Maggie C.Y. Ng , PHD 1 , Shao-Chin Lee , PHD 1 , Gary T.C. Ko , FRCP 1 , June K.Y. Li , MRCP 1 , Wing-Yee So , MRCP 1 , Yasmeen Hashim , PHD 2 , Anthony H. Barnett , MD 3 , Ian R. Mackay , MD 4 , Julian A.J.H. Critchley , FRCP 1 , Clive S. Cockram , FRCP 1 and Juliana C.N. Chan , FRCP 1 1 Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR 2 Diabetes Research Laboratories, Radcliffe Infirmary, University of Oxford, Oxford 3 Department of Medicine, University of Birmingham, Birmingham, U.K. 4 Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia Abstract OBJECTIVE —We examined the prevalence of different forms of diabetes in Hong Kong Chinese patients with familial early-onset type 2 diabetes and compared their clinical features with patients with familial late-onset type 2 diabetes. RESEARCH DESIGN AND METHODS —A total of 145 young patients with early-onset diabetes (age and age at diagnosis ≤40 years) and a family history of diabetes were studied. They were screened for mutations in the genes encoding glucokinase, hepatocyte nuclear factor (HNF)-4α, and HNF-1α. The mitochondrial DNA A→G at nucleotide 3243 (mt3243) and amylin S20G mutations were studied, and antibodies to GAD (anti-GADs) were also examined. RESULTS —The prevalence of putative diabetogenic gene mutations and autoimmune markers were 4% for glucokinase, 0% for HNF-4α, 5% for HNF-1α, 3% for mt3243, 2% for amylin S20G, and 4% for anti-GAD. Compared with late-onset patients, the patients with early-onset diabetes had a higher prevalence of a parental history of diabetes and were generally more obese. When classified by obesity indexes (BMI and waist circumference), the obese patients, especially those with early-onset diabetes, had a clustering of cardiovascular risk factors and increased rates of retinopathy and albuminuria. CONCLUSIONS —Genetic factors (up to 14%) and obesity (55%) play more significant roles than autoimmunity (4%) in familial type 2 diabetes in young Chinese patients. The significance of obesity-related genes and other gene-gene and gene-environment interactions in these young patients remains to be determined. ACR, albumin-to-creatinine ratio anti-GAD, antibody to GAD BP, blood pressure HDL-C, HDL cholesterol LDL-C, LDL cholesterol HOMAIR, h