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Genetic risk scores in the prediction of plasma glucose, impaired insulin secretion, insulin resistance and incident type 2 diabetes in the METSIM study

Diabetologia - Clinical and Experimental Diabetes and Metabolism Sep 18, 2017

Stancákova A, et al. - The aim of this study was to explore the correlation of six genetic risk scores (GRSs) with changes in plasma glucose, insulin sensitivity, insulin secretion and incident type 2 diabetes in the prospective METabolic Syndrome In Men (METSIM) study. The outcomes highlighted that GRS for type 2 diabetes (GRST2D), GRSs for fasting plasma glucose ([FPG] (GRSFPG) and GRSIS were correlated with the worsening of FPG and an increase in incident type 2 diabetes. GRST2D was additionally correlated with a decrease in insulin secretion, and GRS2hPG with an increase in 2 h plasma glucose (2hPG).

Methods
  • In this study, researchers generated weighted GRSs for fasting plasma glucose ([FPG] GRSFPG, 35 SNPs), 2 h plasma glucose ([2hPG] GRS2hPG, 9 SNPs), insulin secretion (GRSIS, 17 SNPs), insulin resistance (GRSIR, 9 SNPs) and BMI (GRSBMI, 95 SNPs) and a non-weighted GRS for type 2 diabetes (GRST2D, 76 SNPs) in up to 8749 non-diabetic Finnish men.
  • They applied linear regression to test correlations of the GRSs with changes in glycaemic traits over time.

Results
  • It was noted that GRST2D, GRSFPG and GRSIS were correlated with an increase in FPG, GRST2D with an increase in glucose AUC and a decrease in insulin secretion, and GRS2hPG with an increase in 2hPG during the follow-up (p < 0.0017 for all models).
  • Evidence showed that GRST2D, GRSFPG and GRSIS were correlated with incident type 2 diabetes (p < 0.008 for all models).
  • The data indicated that GRSBMI and GRSIR were not significantly correlated with any changes in glycaemic traits.
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