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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
- Source :
- Diabetes. October 1, 2013, Vol. 62 Issue 10, p3610, 8 p.
- Publication Year :
- 2013
-
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.<br />Type 2 diabetes is a complex metabolic disorder where both environment and genetic disposition act in concert to cause the disease. Over the last few years, genome-wide association studies and [...]
Details
- Language :
- English
- ISSN :
- 00121797
- Volume :
- 62
- Issue :
- 10
- Database :
- Gale General OneFile
- Journal :
- Diabetes
- Publication Type :
- Periodical
- Accession number :
- edsgcl.344826580
- Full Text :
- https://doi.org/10.2337/db13-0362