The clinical relevance of the aforementioned mechanisms is currently uncertain, but health-care practitioners should be aware of their implications for patients with diabetes. We have compiled a simple flowchart for the metabolic screening and management of patients with COVID-19 and diabetes or at risk for metabolic disease. This includes recommendations regarding both the need for primary prevention of diabetes as well as the avoidance of severe sequelae of diabetes triggered by unidentified or poorly managed diabetes ( figure ). Furthermore, special considerations on anti-diabetes drugs commonly used in patients with type 2 diabetes in view of COVID-19 are presented in the panel

Connected Health models and Telemedicine should be used to continue regular reviews and self-management education programmes virtually and ensure patients are adherent to therapy.

Dehydration and lactic acidosis will probably occur if patients are dehydrated, so patients should stop taking the drug and follow sick day rules

Older patients refers to those aged 70 and above. ARDS=Acute Respiratory Distress Syndrom. CGM=Continous Glucose Measurement. FGM=Flash Glucose Measurement. HbA 1c =haemoglobin A 1c . TIR=time in range. *Target concentrations for lower plasma glucose can be adjusted to 5 mmol/l (90 mg/dl) in frail patients. †HbA 1c testing might not be possible at the time, but previous measurements if available allow for differentiation of chronic and acute decompensation.

All patients without diabetes and particularly when at high risk for metabolic disease who have contracted the viral infection need to be monitored for new onset diabetes that might be triggered by the virus. All patients with COVID-19 disease and diabetes require continuous and reliable glycaemic control as suggested in the flowchart.

People with diabetes who have not yet been infected with the SARS-CoV-2 virus should intensify their metabolic control as needed as means of primary prevention of COVID-19 disease. This includes continuation and strict abidance with adequate control of blood pressure and lipids. Wherever possible, remote consultations using Connected Health models should be utilised to reduce exposure. They should also be encouraged to follow general advice from WHO, the CDC, and state and local governments about hand washing and physical distancing.

Management of hyperglycaemia and associated metabolic conditions

Most patients with type 2 diabetes have other components of the metabolic syndrome including hypertension and dyslipidaemia. Therefore, continuation with an appropriate antihypertensive and lipid-lowering regimen in all these patients is of crucial importance.

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Karakiulakis G

Roth M Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?. 14 de Simone G Position statement of the ESC Council on Hypertension on ACE-inhibitors and angiotensin receptor blockers. Treatment with ACE inhibitors and angiotensin 2 receptor blockers could increase the expression of ACE2, which could accelerate the entry of the virus into the cells.However, as SARS-CoV-2 might impair the protective ACE2/Mas receptor pathway and increase deleterious angiotensin-2 activity, the use of ACE inhibitors and angiotensin 2 receptor blockers could protect against severe lung injury following infection. On the basis of currently available evidence, we recommend that patients should continue with their antihypertensive regimens including ACE inhibitors and angiotensin 2 receptors. This view is endorsed by a recent position statement from the European Society of Cardiology and the Heart Failure Society of America, American College of Cardiology, American Heart Association, who strongly recommended continuation of treatment with ACE inhibitors and angiotensin 2 receptor blockers.

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Min JJ

Lee JH The effect of fluvastatin on cardiac fibrosis and angiotensin-converting enzyme-2 expression in glucose-controlled diabetic rat hearts. Statins have been shown to restore the reduction of ACE2 induced by high lipids such as low density lipoprotein or lipoprotein(a).The pleiotropic anti-inflammatory effects of statins have been attributed to the upregulation of ACE2. However, although we believe that modulation of ACE2 expression is associated with both infection and mortality rates in COVID-19, statins should not be discontinued because of the long-term benefits and the potential for tipping the balance towards a cytokine storm by rebound rises in interleukin(IL)-6 and IL-1ß if they were to be discontinued. Given the close links between diabetes and cardiovascular disease, we recommend control of lipid concentrations in all patients with COVID-19.

There are certain subgroups of people with diabetes who might require specific consideration. Elevated hemoglobin A 1c in people with type 1 diabetes compromises immune function rendering them more susceptible to any infectious disease. These individuals will need more intense monitoring and supportive therapy to reduce the risk of metabolic decompensation including DKA, in particular for those taking sodium glucose co-transporter 2 inhibitors (SGLT2). According to the expertise from the co-authors, an increase in the prevalence of severe DKA in COVID-19 positive patients with established type 1 diabetes has been observed, but this might in part be because of delayed hospital admission. Thus, making patients with type 1 diabetes aware of this complication and re-educating them about typical symptoms, home-measurement of urine or blood ketones, acute behaviour guidelines, and liberal and early inquiry of professional medical advice and sick day rules is crucial. Patients who have undergone transplantation of islets, pancreas or kidney, or those on immunosuppressive therapy will be at particularly increased risk; additionally, the potential effect of coronavirus infection on pancreatic function in this group is unknown and monitoring for a recurrence of insulin requirement in those who are insulin independent after their transplant is important.

The increasing number of patients with type 2 diabetes and concomitant fatty liver disease will probably have an increased risk for a more pronounced inflammatory response including the so-called cytokine storm, and these patients should be considered at increased risk of severe COVID-19 disease. Therefore, screening for hyperinflammation using laboratory trends (eg, increasing ferritin, decreasing platelet counts, high-sensitivity C-reactive protein, or erythrocyte sedimentation rate) are of crucial importance and might also help to identify subgroups of patients for whom immunosuppression (steroids, immunoglobulins, selective cytokine blockade) could improve the outcome.

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Murphy KE

Fernandez ML Impact of obesity and metabolic syndrome on immunity. 17 Luzi L

Radaelli MG Influenza and obesity: its odd relationship and the lessons for COVID-19 pandemic. The majority of patients with type 2 diabetes are living with conditions of overweight or obesity. Body mass index is an important determinant of lung volume, respiratory mechanics, and oxygenation during mechanical ventilation, especially in the supine position. Therefore, patients with obesity and diabetes could be at specific risk of ventilatory failure and complications during mechanical ventilation. Clinical experience with young patients with obesity and COVID-19 supports this notion. Furthermore, individuals with obesity or with diabetes have an altered innate and adaptive immune response, characterised by a state of chronic and low-grade inflammation with higher concentrations of the pro-inflammatory leptin and lower anti-inflammatory adiponectin.Additionally, obesity is often associated with physical inactivity leading to aggravated insulin resistance. This condition per se impairs immune response against microbial agents including macrophage activation and inhibition of pro-inflammatory cytokines and leads to a dysregulation of the immune response contributing to complications associated with obesity.

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et al. Altered lipid metabolism in recovered SARS patients twelve years after infection. Furthermore, SARS-CoV-2 can induce long-term metabolic alterations in patients who have been infected with the virus, as has been reported previously with the SARS virus.Therefore, a careful cardiometabolic monitoring of patients who have survived severe COVID-19 disease might be necessary.

Importantly, we should also bring attention to the subgroup of people with diabetes who work as health-care professionals. Given that COVID-19 might be more prevalent among the sick than is currently being diagnosed, health-care professionals with diabetes should be deployed away from front line clinical duties where possible. For cases in which this is not possible or desirable, high-grade protection or increased protection should be used.