Childhood Predictors of Young-Onset Type 2 Diabetes

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.

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.

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.

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.

Excess global mortality attributable to type 2 diabetes in the year 2000 is estimated at one million deaths in developing nations and 1.9 million deaths in developed nations, or 2–8% of all deaths globally. Although conventionally type 2 diabetes has been considered a disease of adulthood, its occurrence during youth is increasingly common. Children exposed to diabetes in utero are at much greater risk of becoming obese and developing type 2 diabetes. Furthermore, individuals who develop type 2 diabetes in childhood and adolescence develop retinopathy and nephropathy at rates comparable with those of later-onset diabetes and by consequence have a substantial risk for microvascular complications at young ages. Thus, the prevention of young-onset type 2 diabetes presents a particularly important yet difficult challenge.

The optimal strategy for preventing any disease requires knowledge of its modifiable risk factors. In adult-onset diabetes, the risk factors include metabolic and anthropometric parameters such as hyperinsulinemia, impaired glucose regulation, obesity, and dyslipidemia, which when clustered together are often referred to as the metabolic syndrome. The strongest risk factors identified in adult Pima Indians are parental diabetes, BMI, insulin resistance, and impaired insulin secretion. Among Pima Indian children and adolescents free from diabetes, future type 2 diabetes is predicted by weight relative to height and concentrations of serum insulin and plasma glucose.