key: cord-0915436-lrxa88mt
authors: Sathish, Thirunavukkarasu; Anton, Mary Chandrika; Sivakumar, Tharsan
title: New‐onset diabetes in “long COVID”
date: 2021-05-06
journal: J Diabetes
DOI: 10.1111/1753-0407.13187
sha: d6969c4e29176a3137cfb876572a01b5052c515b
doc_id: 915436
cord_uid: lrxa88mt

nan

Dear Editor, Studies published in the Journal of Diabetes and elsewhere demonstrate the increased likelihood of new-onset diabetes (NOD) during the acute phase [1] [2] [3] [4] [5] [6] [7] or shortly after recovering from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 8-10 the virus causing coronavirus disease 2019 . Findings from these studies are supported by a recent Mendelian randomization analysis establishing a causal link between SARS-CoV-2 infection and NOD. 11 Emerging evidence shows that NOD is also observed in the post-acute COVID-19 phase, the so-called long COVID. 12, 13 In a retrospective cohort study of 47 780 discharged COVID-19 patients (mean age 65 years) in England, the rate of NOD was 29 (95% CI, 26-32) per 1000 person-years over a mean follow-up of 4.6 months. 14 In another retrospective cohort study of three data sources from a large United States health plan, among 193 113 COVID-19 patients aged ≤65 years, NOD was the sixth most common post-acute clinical sequelae over a median follow-up of 2.9 months. 15 Possible mechanisms explaining the occurrence of NOD with SARS-CoV-2 infection during the acute phase are cytolytic effects of the virus on pancreatic β-cells, 16 activation of the hypothalamic-pituitary-adrenal and sympathoadrenal axes causing an increase in counterregulatory hormones, activation of the renin-angiotensin system resulting in unopposed deleterious actions of angiotensin II, and enhanced autoimmunity. 17, 18 However, it is yet to be determined whether these mechanisms persist in the post-acute phase for the development of NOD in long COVID.

It is essential to screen COVID-19 patients for NOD during acute illness and after recovery for several reasons. Globally, 50% of adults remain undiagnosed, and this figure reaches up to 60% in some low-and middleincome countries. 19 Therefore, some of the NOD in hospitalized COVID-19 patients could reflect previously undiagnosed diabetes discovered incidentally by increased testing. 5 Secondly, acute infections can cause stress hyperglycemia, which may resolve once the infection and the coexistent inflammation subside. 20 Further, COVID-19 patients are increasingly being treated with glucocorticoids that are known to induce hyperglycemia. 21 As with stress hyperglycemia, blood glucose levels may return to the pre-illness stage after stopping steroids. Finally, autoantibodies against pancreatic β-cells triggered by respiratory viral infections usually develop over several months or years to cause type 1 diabetes. 22 The COVID-19 pandemic has now persisted for over a year, and researchers across the globe are studying its long-term effects. 2, [12] [13] [14] [15] 23, 24 It is now high time to consider NOD as a metabolic clinical sequela of SARS-CoV-2 infection to understand the role of COVID-19 in driving the diabetes pandemic.

KEYWORDS COVID-19, diabetes, long COVID, SARS-CoV-2, new-onset diabetes

Practical recommendations for the management of diabetes in patients with COVID-19

New-onset diabetes in Covid-19

Is newly diagnosed diabetes as frequent as preexisting diabetes in COVID-19 patients?

Newly diagnosed diabetes in COVID-19 patients

Newly diagnosed diabetes in patients with mild to moderate COVID-19

Proportion of newly diagnosed diabetes in COVID-19 patients: a systematic review and meta-analysis

What is the role of admission HbA1c in managing COVID-19 patients?

Autoantibody-negative insulin-dependent diabetes mellitus after SARS-CoV-2 infection: a case report

Type 1 diabetes onset triggered by COVID-19

SARS-CoV-2 infection-related diabetes mellitus

Exploring causal relationships between COVID-19 and cardiometabolic disorders: a bi-directional Mendelian randomization study. med-Rxiv

Post-acute COVID-19 syndrome

Facing up to long COVID

Post-covid syndrome in individuals admitted to hospital with covid-19: retrospective cohort study

SARS-CoV-2 infection and risk of clinical sequelae during the post-acute phase: a retrospective cohort study. medRxiv

A human pluripotent stem cell-based platform to study SARS-CoV-2 tropism and model virus infection in human cells and organoids

Potential metabolic and inflammatory pathways between COVID-19 and new-onset diabetes

COVID-19 and diabetes mellitus: from pathophysiology to clinical management

Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the international diabetes federation diabetes atlas

Stress hyperglycemia: an essential survival response!

Glucocorticoid-induced diabetes mellitus: an important but overlooked problem

Respiratory infections are temporally associated with initiation of type 1 diabetes autoimmunity: the TEDDY study

Covid-19: what do we know about "long covid"?

COVID-19 CVD Registry

No funding received.

The authors declare no potential conflict of interest.Thirunavukkarasu Sathish 1 Mary Chandrika Anton 2 Tharsan Sivakumar 3