We investigates the relationship between glycemic traits, specifically Type 2 diabetes mellitus (T2DM), fasting glucose, fasting insulin, glycated hemoglobin, and 2 hour post load glucose and thoracic aortic morphology and diseases. The results indicate an inverse association between elevated glycemic traits and aortic diameters, as well as a reduced risk of thoracic aortic aneurysm. Specifically, genetic predictors beta-cell proinsulin mechanism in T2DM, drive these associations. Key genes such as AGER, GLRX, TCF7L2, and GCK are implicated in this process, highlighting their potential for leveraging these genetic targets to explore therapeutic avenues for the prevention and treatment of TAAD Given their role in glycemic control medication.

We thank the Type 2 Diabetes Global Genomics Initiative (T2DGGI) for generation of association summary statistics without UKBB and MVP; H.T. is supported by the Gates-Cambridge Trust and NIH Oxford-Cambridge scholars program;MGL was supported by the Doris Duke Foundation (Award 2023-0224) and US Department of Veterans Affairs Biomedical Research and Development Award IK2-BX006551, and has received research funding to the institution trial from Myome unrelated to this work. The content of this manuscript does not represent the views of the Department of Veterans Affairs or the United States Government; D.K. Is an employee at and has equity in Bitterroot Bio unrelated to the current research;

CT received K01 award and AHA funding support

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