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 less than or equal to 40 years) and a family history of diabetes were studied. They were screened for mutations in the genes encoding glucokinase, hepatocyte nuclear factor (HNF)-4 alpha, and HNF-1 alpha. 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-4 alpha. 5% For HNF-1 alpha, 3% for mt3243, 2% For amylin S20G, and 4% Eor 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 (SB) 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.