Familial Early-Onset Type 2 Diabetes in Chinese Patients

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.