Genetic Studies of the Etiology of Type 2 Diabetes in Pima Indians

Obesity has become a major public health concern in the U.S., reaching epidemic proportions among adults and children. Recent national surveys show that American adults have experienced a 50% increase in the prevalence of overweight and obesity, while children and adolescents have experienced a 100% increase since the 1970s (rev. in 1). Coincident with this increase in obesity, the prevalence of type 2 diabetes has also reached epidemic proportions. The prevalence of diagnosed diabetes among adults in the U.S. has increased by 40% from 1990 to 1999, and is projected to increase by 165% between the years 2020 and 2050 (2,3). Recent studies have estimated the lifetime risk of diagnosed diabetes to be approximately one in three for males and two in five for females born in the U.S. in the year 2000 (4). Moreover, an alarming increase in the incidence of type 2 diabetes has now been reported in very young children (5). The escalating rates of both type 2 diabetes and obesity are likely due to changes in the environment, coupled with changes in human behavior and lifestyle. However, in most developed countries, food is now plentiful and lifestyle is generally sedentary, but not all people become obese, and furthermore, most obese people do not develop type 2 diabetes. It is likely that genetic factors underlie a significant portion of the susceptibility to both obesity and type 2 diabetes, and that expression of this susceptibility is dependent on environmental variables. The large variation in prevalence rates of type 2 diabetes among ethnic groups living in similar environments, the increased risk to siblings of affected individuals, and the high concordance rate for the disease in monozygotic twins compared with dizygotic twins indicate that this disease has a significant genetic component (rev. in 6). Studies in twins, …