Role of renin-angiotensin system/angiotensin converting enzyme-2 mechanism and enhanced COVID-19 susceptibility in type 2 diabetes mellitus.

Coronavirus disease 2019 (COVID-19) is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus. It has affected over 768 million people worldwide, resulting in approximately 6900000 deaths. High-risk groups, identified by the Centers for Disease Control and Prevention, include individuals with conditions like type 2 diabetes mellitus (T2DM), obesity, chronic lung disease, serious heart conditions, and chronic kidney disease. Research indicates that those with T2DM face a heightened susceptibility to COVID-19 and increased mortality compared to non-diabetic individuals. Examining the renin-angiotensin system (RAS), a vital regulator of blood pressure and pulmonary stability, reveals the significance of the angiotensin-converting enzyme (ACE) and ACE2 enzymes. ACE converts angiotensin-I to the vasoconstrictor angiotensin-II, while ACE2 counters this by converting angiotensin-II to angiotensin 1-7, a vasodilator. Reduced ACE2 expression, common in diabetes, intensifies RAS activity, contributing to conditions like inflammation and fibrosis. Although ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels, concerns arise regarding the potential elevation of ACE2 receptors on cell membranes, potentially facilitating COVID-19 entry. This review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome coronavirus 2 infection and associated complications in T2DM. Potential treatment strategies, including recombinant human ACE2 therapy, broad-spectrum antiviral drugs, and epigenetic signature detection, are discussed as promising avenues in the battle against this pandemic.

Pharmacogenetic impact of SLC22A1 gene variant rs628031 (G/A) in newly diagnosed Indian type 2 diabetes patients undergoing metformin monotherapy.

OBJECTIVES: Type 2 diabetes (T2D) imposes an enormous burden all over the world in both developed and developing countries. Inter-individual differences are attributed to polymorphisms in candidate genes resulting in altered absorption, transportation, distribution, and metabolism of oral antidiabetic drugs (OADs). Hence, the present study was undertaken to evaluate the pharmacogenetic impact of SLC22A1 gene variant rs628031 (G/A) on metformin monotherapy in newly diagnosed untreated T2D patients. METHODS: Newly diagnosed T2D patients ( n = 500) were enrolled according to inclusion/exclusion criteria. Initially, enrolled subjects were prescribed metformin monotherapy and followed up for at least 12 weeks. Response to metformin was evaluated in 478 patients who revisited for follow-up by measuring HbA1c. RESULT: Out of 478 patients, 373 were responders to metformin monotherapy while 105 were non-responders. The pharmacogenetic impact was evaluated by genotype, haplotype, and pharmacogenetic analyses. 'GG' genotype and 'G' allele of SLC22A1 rs628031 G/A were observed in 48.8% and 67.7% of Met responders, respectively, while 20.9% and 49.1 % were in non-responders. Therefore, there was a 2.18-fold increase in the success rate of Met therapeutics. CONCLUSION: Individuals carrying the 'GG' genotype or 'G' allele for SLC22A1 gene variant rs628031 G/A are better responders for Metformin monotherapy.

Angiotensin-Converting-Enzyme 2 and Renin-Angiotensin System Inhibitors in COVID-19: An Update.

Ever since its outbreak, Corona Virus Disease 2019(COVID-19) caused by SARS-CoV-2 has affected more than 26 million individuals in more than 200 countries. Although the mortality rate of COVID-19 is low, but several clinical studies showed, patients with diabetes mellitus (DM) or other major complication at high risk of COVID-19 and reported more severe disease and increased fatality. The angiotensin-converting-enzyme 2 (ACE2), a component of renin-angiotensin-system (RAS); acts on ACE/Ang-II/AT1recptor axis, and regulates pathological processes like hypertension, cardiac dysfunction, Acute Respiratory Distress Syndrome (ARDS) etc. The progression of T2DM and hypertension show decreased expression and activity of ACE2. There are several treatment strategies for controlling diabetes, hypertension, etc; like ACE2 gene therapies, endogenous ACE2 activators, human recombinant ACE2 (hrACE2), Angiotensin-II receptor blockers (ARBs) and ACE inhibitors (ACEi) medications. ACE2, the receptors for SARS-CoV2, facilitates virus entry inside host cell. Clinicians are using two classes of medications for the treatment of COVID-19; one targets the SARS-CoV-2-ACE2 interaction, while other targets human immune system. The aim of this review is to discuss the role of ACE2 in diabetes and in COVID-19 and to provide an analysis of data proposing harm and benefit of RAS inhibitor treatment in COVID-19 infection as well as showing no association whatsoever. This review also highlights some candidate vaccines which are undergoing clinical trials.