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Diabetes. 2013 Oct;62(10):3610-7. doi: 10.2337/db13-0362. Epub 2013 Jul 8.

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.

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1
Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics.

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.

PMID:
23835328
PMCID:
PMC3781471
DOI:
10.2337/db13-0362
[Indexed for MEDLINE]
Free PMC Article
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