PT  - JOURNAL ARTICLE
AU  - Andersson, Ehm A.
AU  - Allin, Kristine H.
AU  - Sandholt, Camilla H.
AU  - Borglykke, Anders
AU  - Lau, Cathrine J.
AU  - Ribel-Madsen, Rasmus
AU  - Sparsø, Thomas
AU  - Justesen, Johanne M.
AU  - Harder, Marie N.
AU  - Jørgensen, Marit E.
AU  - Jørgensen, Torben
AU  - Hansen, Torben
AU  - Pedersen, Oluf
TI  - 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
AID  - 10.2337/db13-0362
DP  - 2013 Oct 01
TA  - Diabetes
PG  - 3610--3617
VI  - 62
IP  - 10
4099  - http://diabetes.diabetesjournals.org/content/62/10/3610.short
4100  - http://diabetes.diabetesjournals.org/content/62/10/3610.full
SO  - Diabetes2013 Oct 01; 62
AB  - 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.