This study examined whether genetic variants alone or in combination with clinical risk factors could predict the progression to type 2 diabetes in two prospective cohorts. A total of 16 single-nucleotide polymorphisms (SNPs) were genotyped in 16,061 Swedish (Malmö Preventive Project) and 2,770 Finnish (Botnia study) subjects. Type 2 diabetes developed in 11.7% (n=2,201) of individuals during the median follow-up of 23.5 years. In both studies, a family history of diabetes, an elevated body mass index, an increased blood pressure, as well as high triglycerides, a low apolipoprotein AI concentration, and increased liver enzyme levels were predictors of the development of type 2 diabetes. Impaired insulin secretion and action were also strong predictors of type 2 diabetes. In the Malmö Preventive Project, current smoking was also a predictor of future type 2 diabetes while an increased waist circumference predicted type 2 diabetes in the Botnia study (this measurement was not available in the Malmö Preventive Project). Variants in 11 genes were significantly associated with the development of type 2 diabetes independent of clinical risk factors, and 8 of these genes were related to impaired beta-cell function. The inclusion of common genetic variants associated with type 2 diabetes, although significant, only slightly improved the prediction of type 2 diabetes compared to the information provided by clinical risk factors alone. Therefore, based on these results, the relevance of measuring genetic markers of type 2 diabetes risk remains uncertain.
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