Childhood predictors of young-onset type 2 diabetes

Abstract

Objective: Optimal prevention of young-onset type 2 diabetes requires identification of the early-life modifiable risk factors. We aimed to do this using longitudinal data in 1,604 5- to 19-year-old initially nondiabetic American Indians.

Research design and methods: For type 2 diabetes prediction, we derived an optimally weighted, continuously distributed, standardized multivariate score (zMS) comprising commonly measured metabolic, anthropometric, and vascular traits (i.e., fasting and 2-h glucose, A1C, BMI, waist circumference, fasting insulin, HDL cholesterol, triglycerides, and 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, 2-h glucose, HDL cholesterol, 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 predictive power similar to that of zMS (P = 0.33). Although intrauterine diabetes exposure or parental history of young-onset 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 cholesterol during childhood and adolescence may have the most success in preventing diabetes.

FIG. 1.

Interaction between parental history of young-onset (<30 years of age) type 2 diabetes and offspring metabolic, anthropometric, and vascular traits on risk of young-onset type 2 diabetes in the offspring. Data are for offspring aged 5.0–19.9 years (n = 267 ODP and n = 531 ONDP). HRR is per standardized unit with 95% CI. P interaction, P value for interaction term of variable by parental diabetes status. Data are adjusted for age, sex, and fraction of Indian heritage and divided into tertiles for each variable. Incidence of diabetes was then calculated for each tertile stratified by diabetes status of the parents.□, offspring of parents free from type 2 diabetes at 30 years of age (ONDP); ∎, offspring of at least one parent who developed type 2 diabetes by 30 years of age (ODP).