Genetic risk score of 46 type 2 diabetes risk variants associates with changes in plasma glucose and estimates of pancreatic beta-cell function over 5 years of follow-up

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Ehm Astrid Andersson Galijatovic, Kristine H Allin, Camilla H Sandholt, Anders Borglykke, Cathrine J Lau, Rasmus Ribel-Madsen, Thomas Sparsø, Johanne M Justesen, Marie N Harder, Marit E Jørgensen, Torben Jørgensen, Torben Hansen, Oluf Pedersen

More than 40 genetic risk variants for type 2 diabetes have been validated. We aimed to test if a genetic risk score associates with the incidence of type 2 diabetes and with 5-year changes in glycemic traits and if 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 improved their 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 beta-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 beta-cell function. Individuals who gain weight may be more susceptible to the cumulative impact of type 2 diabetes risk variants on fasting plasma glucose.
Original languageEnglish
Issue number10
Pages (from-to)3610
Number of pages3,617
Publication statusPublished - 8 Jul 2013

ID: 47256038