key: cord-0837156-n78d3730
authors: Ekiz, Timur; Kara, Murat; Özçakar, Levent
title: Letter to the editors in response to: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be harmful in patients with diabetes during COVID-19 pandemic (Cure et al.)
date: 2020-05-05
journal: Diabetes Metab Syndr
DOI: 10.1016/j.dsx.2020.04.054
sha: d1f0873a0b19ae4b3a7617ad8a5cf412cc6adfbb
doc_id: 837156
cord_uid: n78d3730

nan

We read with great interest the article by Cure et al. [1] in Diabetes and Metabolic Syndrome: Clinical Research and Reviews. The authors commented about the possible harmful effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with diabetes mellitus during the COVID-19 pandemic.

While we congratulate them for having tried to study this debated issue; we, herein, wish to advocate the possible ''beneficial'' roles of these drugs as well.

Since hypertension is one of the most significant risk factors for severe disease and mortality in COVID-19 and ACE2 is the entry receptor of 2 SARS-CoV-2 [1, 2] , the renin angiotensin system (RAS) has received much focus [1, 2] . First, based on a few animal studies showing increased ACE2 expression due to RAS inhibitors, it is yet quite skeptical to discontinue RAS inhibitors, particularly in high-risk patients [2] . Further, a recent study has shown the protective effects of ACEIs/ARBs against mortality in COVID-19 [3] . ACEIs/ARBs users (almost 20% had diabetes mellitus) had lower risk of all-cause mortality [3] .

Second, ACEI/ARB should actually be considered separately -as they inhibit different steps in the classical RAS pathway. ACEIs inhibit the step from angiotensin I to angiotensin II, whereas ARBs block angiotensin II type I (AT1) receptor. Indeed, both inhibit the deleterious effects of the classical pathway (i.e. angiotensin II/AT1 receptor interaction) such as peripheral vasoconstriction, skeletal muscle atrophy, fibrosis, and increased insulin resistance. However, ACEIs perform a multilevel block in both classical and non-classical pathways, which result in a strong augmentation of the non-classical pathway (i.e. angiotensin 1-7/Mas receptor axis). This activation also causes positive effects on the skeletal muscle anabolic processes. Lastly, ACEIs decrease the degradation of bradykinin, a potent vasodilator, and thus enhance the perfusion of different soft tissues including the muscle [4] .

In this sense, another noteworthy example for the protective effects of ACEIs/ARBs would be the improvement of sarcopenia (age-related loss of muscle mass/function).

Inhibition of the RAS activity exerts vasodilator, anti-hypertrophic, and anti-fibrotic effects on muscles [4] . It has been shown that ACEI users had higher lower extremity muscle mass than those using other antihypertensive drugs. For instance, in a three-year longitudinal study, ACEIs prevented the decline in knee extensor strength and gait speed [5] .

Accordingly, we simply highlight that increased RAS activity causes both hypertension and sarcopenia; and ACEI (and possibly ARB) use can actually be preventive for both conditions during the Covid-19 pandemic.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be harmful in patients with diabetes during COVID-19 pandemic

Aldosterone System Inhibitors in Patients with Covid-19

Association of inpatient use of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers with mortality among patients with hypertension hospitalized with COVID-19

Different cross-talk sites between the renin-angiotensin and the kallikreinkinin systems

Relation between use of angiotensin-converting enzyme inhibitors and muscle strength and physical function in older women: an observational study

Dr. Timur Ekiz reports no conflict of interest.

Dr. Levent Özçakar reports no conflict of interest.