1. Genetic Risk Score of 46 Type 2 Diabetes Risk Variants Associates With Changes in Plasma Glucose and Estimates of Pancreatic β-Cell Function Over 5 Years of Follow-Up.
- Author
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Andersson, Ehm A., Allin, Kristine H., Sandholt, Camilla H., Borglykke, Anders, Lau, Cathrine J., Ribel-Madsen, Rasmus, Sparsø, Thomas, Justesen, Johanne M., Harder, Marie N., Jørgensen, Marit E., Jørgensen, Torben, Hansen, Torben, and Pedersen, Oluf
- Subjects
TYPE 2 diabetes ,GLYCEMIC index ,GLUCOSE ,DIABETES ,BODY mass index - Abstract
More than 40 genetic risk variants for type 2 diabetes have been validated. We aimed to test whether a genetic risk score associates with the incidence of type 2 diabetes and with 5-year changes in glycemic traits and whether the effects were modulated by changes in BMI and lifestyle. The Inter99 study population was genotyped for 46 variants, and a genetic risk score was constructed. During a median follow-up of 11 years, 327 of 5,850 individuals developed diabetes. Physical examinations and oral glucose tolerance tests were performed at baseline and after 5 years (n = 3,727). The risk of incident type 2 diabetes was increased with a hazard ratio of 1.06 (95% CI 1.03-1.08) per risk allele. While the population in general had improved glucose regulation during the 5-year follow-up period, each additional allele in the genetic risk score was associated with a relative increase in fasting, 30-min, and 120-min plasma glucose values and a relative decrease in measures of β-cell function over the 5-year period, whereas indices of insulin sensitivity were unaffected. The effect of the genetic risk score on 5-year changes in fasting plasma glucose was stronger in individuals who increased their BMI. In conclusion, a genetic risk score based on 46 variants associated strongly with incident type 2 diabetes and 5-year changes in plasma glucose and β-cell function. Individuals who gain weight may be more susceptible to the cumulative impact of type 2 diabetes risk variants on fasting plasma glucose. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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