A1 Refereed original research article in a scientific journal
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
Authors: Pitkanen N, Juonala M, Ronnemaa T, Sabin MA, Hutri-Kahonen N, Kahonen M, Lehtimaki T, Viikari JSA, Raitakari OT
Publisher: AMER DIABETES ASSOC
Publication year: 2016
Journal: Diabetes Care
Journal name in source: DIABETES CARE
Journal acronym: DIABETES CARE
Volume: 39
Issue: 8
First page : 1393
Last page: 1399
Number of pages: 7
ISSN: 0149-5992
eISSN: 1935-5548
DOI: https://doi.org/10.2337/dc16-0167
Abstract
OBJECTIVEWe 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.RESEARCH DESIGN AND METHODSAn 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.RESULTSOf 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.CONCLUSIONSA multifactorial approach combining genetic and clinical risk factors may be useful in identifying children at high risk for adult IFG and type 2 diabetes.
OBJECTIVEWe 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.RESEARCH DESIGN AND METHODSAn 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.RESULTSOf 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.CONCLUSIONSA multifactorial approach combining genetic and clinical risk factors may be useful in identifying children at high risk for adult IFG and type 2 diabetes.
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