Familial Early-Onset Type 2 Diabetes in Chinese Patients
Obesity and genetics have more significant roles than autoimmunity
- Maggie C.Y. Ng, PHD1,
- Shao-Chin Lee, PHD1,
- Gary T.C. Ko, FRCP1,
- June K.Y. Li, MRCP1,
- Wing-Yee So, MRCP1,
- Yasmeen Hashim, PHD2,
- Anthony H. Barnett, MD3,
- Ian R. Mackay, MD4,
- Julian A.J.H. Critchley, FRCP1,
- Clive S. Cockram, FRCP1 and
- Juliana C.N. Chan, FRCP1
- 1Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR
- 2Diabetes Research Laboratories, Radcliffe Infirmary, University of Oxford, Oxford
- 3Department of Medicine, University of Birmingham, Birmingham, U.K.
- 4Department 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, homeostasis model assessment for insulin resistance
- HNF, hepatocyte nuclear factor
- MODY, maturity-onset diabetes of the young
- PCR, polymerase chain reaction
- PWH, Prince of Wales Hospital
- RFLP, restriction fragment–length polymorphism
- TC, total cholesterol
- TG, triglyceride
Footnotes
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Address correspondence and reprint requests to Dr. Maggie C. Y. Ng, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR. E-mail: maggieng{at}cuhk.edu.hk.
Received for publication 30 August 2000 and accepted in revised form 3 January 2001.
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