Thyroid Hormone Signalling Alteration in Diabetic Nephropathy and Cardiomyopathy: a “Switch” to the Foetal Gene Programme

Purpose of the Review: In this study, we will analyse how diabetes induces the reactivation of organs’ developmental programmes and growth, discuss how thyroid hormone (TH) signalling orchestrates these processes, and suggest novel strategies for exploiting TH-mediated reparative and regenerative properties. Recent Findings: Diabetes is a global pandemic that poses an enormous threat to human health. The kidney and the heart are among the organs that are the most severely damaged by diabetes over time. They undergo profound metabolic, structural, and functional changes that may be due (at least partially) to a recapitulation of their early developmental programmes. There is growing evidence to suggest that this foetal reprogramming is controlled by the TH/TH receptor alpha 1 (TRα1) axis. Summary: We introduce the hypothesis that in diabetes—and probably in other diseases—TH signalling acts in an antagonistic manner: it recapitulates a foetal profile that is necessary to coordinate metabolic and structural adaptations to sustain energy preservation and growth, but in the long term the persistent changes in these pathways are detrimental.