Management of diabetes in patients with COVID-19
Authors: Adrian Li, Sophie Harris, Dulmini Kariyawasam, Dipesh C Patel, Stephen M Thomas
Journal: The Lancet Diabetes & Endocrinology (2020)

The recent Personal View by Stefan Bornstein and colleagues1Bornstein SR Rubino F Khunti K et al.Practical recommendations for the management of diabetes in patients with COVID-19.Lancet Diabetes Endocrinol. 2020; 8: 546-550Summary Full Text Full Text PDF PubMed Scopus (624) Google Scholar highlights possible susceptibility factors in patients with diabetes and obesity that could predispose to severe COVID-19-related illness. The authors incorporated useful general management guidance, but we feel that the descriptions of acute presentations were not sufficiently detailed to aid clinical management. We wish to expand on the acute metabolic presentations related to hyperglycaemia, which have been challenging to manage in the acute setting. These considerations are based on observations from a large regional clinical network that informed a national diabetes COVID-19 response team to from the Association of British Clinical Diabetologists help produce new specific guidance to aid acute management. Our clinical network has reported severe acute glycaemic presentations associated with COVID-19 infections. An excess case incidence of diabetes-related ketoacidosis, often with concurrent significant hyperosmolality (>320 mOsm/L), was reported. In some cases, high levels of ketosis (>5 mmol/L) had rapid onset and appeared to be disproportionate to blood glucose levels.2Diabetes UK Guidance for inpatient diabetes care.https://www.diabetes.org.uk/resources-s3/public/2020-04/To%20the%20Diabetes%20Team_Final%20%28002%29.pdfDate: 2020Date accessed: June 27, 2020Google Scholar These acute presentations have been noted in patients both with and without pre-existing diabetes and in patients of different ethnicities. Early measurement of capillary blood ketone concentration is therefore advised in all patients with acute hyperglycaemia to allow prompt diagnosis. Of note, use of SGLT2 inhibitors for diabetes, which can promote ketosis in a minority of individuals, does not appear to be a feature in the majority of cases (unpublished data). The article by Bornstein and colleagues1Bornstein SR Rubino F Khunti K et al.Practical recommendations for the management of diabetes in patients with COVID-19.Lancet Diabetes Endocrinol. 2020; 8: 546-550Summary Full Text Full Text PDF PubMed Scopus (624) Google Scholar correctly hypothesises a possible direct COVID-19-related effect on pancreatic β cell function predisposing to ketosis, which has been reported with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), through increased expression of ACE2 receptor. Fluid replacement decisions in individuals presenting with diabetes-associated emergencies have been complex. There have been concerns about the rapidity of the onset of ketosis, concurrent potential lung injury, and pronounced kidney injury, with reports of rhabdomyolysis. Thus, prudent use of intravenous fluid replacement judged on an individual basis is advised in managing cases of diabetes-related ketoacidosis and hyperosmolality to avoid adverse lung and renal complications. Extreme insulin resistance was acknowledged by Bornstein and colleagues.1Bornstein SR Rubino F Khunti K et al.Practical recommendations for the management of diabetes in patients with COVID-19.Lancet Diabetes Endocrinol. 2020; 8: 546-550Summary Full Text Full Text PDF PubMed Scopus (624) Google Scholar Compatible with this, our network have described significant insulin resistance with unusually high insulin requirements in ventilated patients, which is acknowledged in national guidance from the Association of British Clinical Diabetologists. We postulate that very high insulin requirements might be driven by the COVID-19-related hyperinflammatory state, with contribution from feeding regimens and glucotoxicity. The observed uncontrolled hyperglycaemia in patients with diabetes and COVID-19 might be explained by higher levels of inflammation compared with patients without diabetes, as reported in a retrospective case series from China.3Guo W Li M Dong Y et al.Diabetes is a risk factor for the progression and prognosis of COVID-19.Diabetes Metab Res Rev. 2020; (published online March 31.)https://doi.org/10.1002/dmrr.3319Crossref Scopus (966) Google Scholar Indeed, our unpublished subset of patients presenting with hyperglycaemia consistently showed elevated concentrations of the acute phase protein ferritin, with a median concentration of 1049 μg/L and a range of 744–2594 μg/L (normal range 30–400 μg/L). Pro-inflammatory cytokines have been demonstrably elevated in people with type 2 diabetes.4Pradhan AD Manson JE Rifai N Buring JE Ridker PM C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus.JAMA. 2001; 286: 327-334Crossref PubMed Scopus (3571) Google Scholar In particular, IL-6, which coordinates the cytokine release syndrome, has been shown to increase blood glucose in a dose-dependent manner.5Tsigos C Papanicolaou DA Kyrou I Defensor R Mitsiadis CS Chrousos GP Dose-dependent effects of recombinant human interleukin-6 on glucose regulation.J Clin Endocrinol Metab. 1997; 82: 4167-4170Crossref PubMed Scopus (284) Google Scholar We postulate that acute presentations of marked ketosis, mixed diabetes-related ketoacidosis with hyperosmolality, and severe insulin resistance might be reiterated in similar populations of diverse ethnicity within and beyond the UK. Although prevention of SARS-CoV-2 infection is a key strategy, early recognition and specific clinical management to mitigate acute manifestations of diabetes could lead to improved patient outcomes. SH reports non-financial support from Sanofi and personal fees from Eli Lilly and Oviva. DCP reports personal fees from AstraZeneca, Eli Lilly, Merck Sharp & Dohme, and Takeda; personal fees and funding for a round-table discussion from Boehinger Ingelheim; and personal fees and non-financial support from Napp Pharmaceuticals, Novo Nordisk, and Sanofi. DCP is also an executive committee member of the Association of British Clinical Diabetologists. SMT reports speaker fees from Novo Nordisk and Sanofi, outside of the submitted work. AL and DK declare no competing interests. Management of diabetes in patients with COVID-19 – Authors' replyWe are pleased to learn about the interest in our paper on the practical recommendations for the management of diabetes in patients with COVID-19.1 These Correspondences address important aspects regarding the use of medications and the risk of hypoglycaemia or obesity, and we are thankful for these comments. Full-Text PDF Management of diabetes in patients with COVID-19We read with great interest the Personal View by Stefan Bornstein and colleagues1 on the management of diabetes in patients with COVID-19. During these unprecedented times, more guidance is required to care for this high-risk population. The authors recommend intensification of glucose control to prevent COVID-19, suggesting an HbA1c of less than 53 mmol/mol (<7%) and plasma glucose concentration of 4–8 mmol/L (72–144 mg/dL) for most patients, and 5–8 mmol/L (90–144 mg/dL) for frail patients. These glycaemic goals for the older population are much tighter than suggested in most guidelines. Full-Text PDF Practical recommendations for the management of diabetes in patients with COVID-19Diabetes is one of the most important comorbidities linked to the severity of all three known human pathogenic coronavirus infections, including severe acute respiratory syndrome coronavirus 2. Patients with diabetes have an increased risk of severe complications including Adult Respiratory Distress Syndrome and multi-organ failure. Depending on the global region, 20–50% of patients in the coronavirus disease 2019 (COVID-19) pandemic had diabetes. Given the importance of the link between COVID-19 and diabetes, we have formed an international panel of experts in the field of diabetes and endocrinology to provide some guidance and practical recommendations for the management of diabetes during the pandemic. Full-Text PDF Management of diabetes in patients with COVID-19We read with interest the practical recommendations for management of diabetes in patients with COVID-19 by Stefan Bornstein and colleagues1 in The Lancet Diabetes & Endocrinology. However, in the panel describing special considerations for anti-diabetic drugs, we note that two commonly used groups, sulfonylureas and pioglitazone, are missing. Of these, pioglitazone, a PPAR-γ agonist, merits further discussion because it interacts with both the mechanisms that might play a role in patients with diabetes with COVID-19, as described by Bornstein and colleagues. Full-Text PDF Management of diabetes in patients with COVID-19Stefan Bornstein and colleagues1 seem to be the first to react to an unprecedented challenge regarding management of diabetes in patients with COVID-19 by offering practical recommendations. The authors state that patients with diabetes have an increased risk of severe COVID-19 complications, including acute respiratory distress syndrome. Full-Text PDF Management of diabetes in patients with COVID-19We read with interest the recommendations on the management of diabetes in patients with COVID-19 by Stefan Bornstein and colleagues.1 However, their suggestion of discontinuing metformin in patients with severe symptoms of COVID-19 (to reduce the risk of lactic acidosis) raises a number of issues. We believe that it is important to maintain a thoughtful approach to metformin therapy in patients with diabetes and COVID-19. Full-Text PDF