REN and obesity due to melanocortin 4 receptor deficiency: Various mechanisms have been proposed to explain this paradox, including possible greater metabolic reserve, a more attenuated response to the renin-angiotensin-aldosterone system, and more tolerable cardioprotective medications.[9,10] Our results are in line with emerging evidence that showed this reverse association may not exist in patients with HFrEF with coexisting DM.[1,3,4,11,12] If we examine it closely, what has changed is the obesity part in the DM group seems to lose their survival protective effect.