Role of Conventional Childhood Risk Factors Versus Genetic Risk in the Development of Type 2 Diabetes and Impaired Fasting Glucose in Adulthood: The Cardiovascular Risk in Young Finns Study.

Abstract

We examined whether the addition of novel genetic risk variant data to conventional childhood risk factors improves risk assessment of impaired fasting glucose (IFG) and type 2 diabetes in adulthood. An association of a weighted genetic risk score (wGRS) based on 73 risk variants with IFG and type 2 diabetes was analyzed in 2,298 participants of the Cardiovascular Risk in Young Finns Study who were followed for 24-31 years from childhood to adulthood. In addition, the value of the wGRS in pediatric prediction of type 2 diabetes was examined. Of the 2,298 participants, 484 (21.8%) and 79 (3.4%) had IFG or type 2 diabetes in adulthood, respectively. Adjusting for age, sex, baseline BMI, parental diabetes, mother's BMI, fasting insulin concentration, systolic blood pressure, and smoking status, wGRS was associated with an increased risk of IFG (odds ratio 1.64 [95% CI 1.33-2.01] per unit increase in the wGRS) and type 2 diabetes (2.22 [1.43-3.44]). Incorporating wGRS into pediatric risk models improved model discrimination and reclassification properties. Area under the receiver operating curve improved for IFG (from 0.678 to 0.691, P = 0.015), combined IFG and type 2 diabetes outcome (from 0.678 to 0.692, P = 0.007), and type 2 diabetes (from 0.728 to 0.749, P = 0.158). The net reclassification improvement and integrated discrimination improvement were significant for all outcomes. A multifactorial approach combining genetic and clinical risk factors may be useful in identifying children at high risk for adult IFG and type 2 diabetes.