Effect of severe obesity in childhood and adolescence on risk of type 2 diabetes in youth and early adulthood in an American Indian population.

Objectives: The risk of early-onset type 2 diabetes associated with the severity of obesity in youth is not well understood. This study aims to determine metabolic alterations and type 2 diabetes risk among American Indian children who are obese or severely obese. Methods: Incidence rates of diabetes before 20years (youth-onset) and 45 years were computed in 2728 children who were from 5 to <10years and 4317 adolescents who were from 10 to <18 years without diabetes examined between 1965 and 2007. Obesity was defined as age-sex-adjusted body mass index (BMI) >= 95th percentile, and its severity was quantified as the percentage of the 95th percentile (%BMIp95). Results: In the younger cohort, 0.9% of those non-obese and 2.9% of those with 100% to <120%BMIp95 had impaired glucose tolerance (IGT) compared to 8.6% of those with >= 140%BMIp95. In the older cohort, 2.9% of those non-obese and 9.8% of those with 100% to <120%BMIp95 had IGT compared to 13.3% of those with >= 160%BMIp95. The incidence of youth-onset diabetes was 3.8 and 4.9/1000 person-years in the child and adolescent cohorts, respectively, and before the age of 45 was 12.3 and 16.8/1000 person-years, respectively. Incidence rates of youth-onset diabetes in those with the most severe obesity (>= 140%BMIp95) were 2.3 to 5.1 times as high as in those with the least severe obesity (100 to <120%BMIp95), and for onset of diabetes before the age of 45 were 1.6 to 2.2 times as high. Conclusions: Severe obesity in an American Indian population is a major driver of type 2 diabetes developing in adolescents and young adults.