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In the action in diabetes and vascular disease (ADVANCE) trial, a study involving 11,140 subjects with T2DM who were followed for a median duration of 4.4 years, a higher HR was associated with a significantly increased risk of all-cause mortality, cardiovascular death, and major cardiovascular events (death, nonfatal acute myocardial infarction [AMI] or nonfatal stroke) [39]
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In animal and preclinical studies, it is associated with tissue-protective effects, modulation of inflammatory signaling, and support of angiogenesis and tendon-to-bone healing pathways
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