Childhood predictors of young onset type 2 diabetes mellitus

Objective: Optimal prevention of young-onset type 2 diabetes requires identification of the earlylife modifiable risk factors. We aimed to do this using longitudinal data in 1,604 5-19yr old initially non-diabetic American Indians. Research Design and Methods: For type 2 diabetes prediction, we derived an optimallyweighted, continuously distributed, standardized multivariate score (zMS) comprised of commonly measured metabolic, anthropometric and vascular traits (i.e., fasting and 2hr glucose, HbA1c, BMI, waist circumference, fasting insulin, HDL-C, triglycerides, blood pressures), and compared the predictive power for each feature against zMS. Results: In separate Cox proportional hazard models, adjusted for age, sex, and ethnicity, zMS and each of its component risk factors were associated with incident type 2 diabetes. Stepwise proportional hazards models selected fasting glucose, 2hr glucose, HDL-C, and BMI as independent diabetes predictors; individually these were weaker predictors than zMS (p<0.01). However, a parsimonious summary score combining only these variables had similar predictive power as zMS (p=0.33). Although intrauterine diabetes exposure or parental history of youngonset diabetes increased a child’s absolute risk of developing diabetes, the magnitude of the diabetes-risk relationships for zMS and the parsimonious score were similar irrespective of familial risk factors. Conclusions: We have determined the relative value of the features of the metabolic syndrome in childhood for the prediction of subsequent type 2 diabetes. Our findings suggest that strategies targeting obesity, dysregulated glucose homeostasis and low HDL-C during childhood and adolescence may have most success in preventing diabetes.