Familial early-onset type 2 diabetes in Chinese patients: obesity and genetics have more significant roles than autoimmunity.

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 < or = 40 years) and a family history of diabetes were studied. They were screened for mutations in the genes encoding glucokinase, hepatocyte nuclear factor (HNF)-4alpha, and HNF-1alpha. 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-4alpha, 5% for HNF-1alpha, 3% for mt3243, 2% for amylin 520G, 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.