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Type 2 Diabetes Polygenic Score Predicts the Risk of Glucocorticoid-Induced Hyperglycemia in Patients Without Diabetes

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posted on 2023-06-23, 00:10 authored by Aaron J. Deutsch, Philip H. Schroeder, Ravi Mandla, Sarah Kang, Feyza Erenler, Josep M. Mercader, Miriam S. Udler, Jose C. Florez, Laura N. Brenner

  

Objective: To assess whether increased genetic risk for type 2 diabetes (T2D) is associated with the development of hyperglycemia after glucocorticoid treatment. 

Research Design and Methods: We performed a retrospective analysis of individuals with no diagnosis of diabetes who received a glucocorticoid dose equivalent to 10 mg of prednisone or more. We analyzed the association between hyperglycemia and a T2D global extended polygenic score, which was constructed through a meta-analysis of two published genome-wide association studies. 

Results: Out of 546 individuals who received glucocorticoids, 210 developed hyperglycemia and 336 did not. The polygenic score was significantly associated with glucocorticoid-induced hyperglycemia (p = 0.038, OR = 1.4 per standard deviation of the polygenic score). 

 Conclusions: Individuals with increased genetic risk for T2D have a higher risk of glucocorticoid-induced hyperglycemia. This finding offers a mechanism for risk stratification as part of a precision approach to medical treatment.

Funding

A.J.D. was supported by NIH/NIDDK T32DK007028. L.N.B was supported by NIH/NIDDK 1F32DK115086 - 01A1. J.M.M. was supported by American Diabetes Association Innovative and Clinical Translational Award 1-19-ICTS-068, American Diabetes Association grant #11-22-ICTSPM-16 and by NHGRI U01HG011723.

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