key: cord-0831056-1q2tjy7d authors: Sosale, Aravind; Sosale, Bhavana; Kesavadev, Jothydev; Chawla, Manoj; Reddy, Sanjay; Saboo, Banshi; Misra, Anoop title: Steroid use during COVID-19 infection and hyperglycemia – What a physician should know date: 2021-06-10 journal: Diabetes Metab Syndr DOI: 10.1016/j.dsx.2021.06.004 sha: 8b453805446e952d230550cd37680d03492a51e2 doc_id: 831056 cord_uid: 1q2tjy7d BACKGROUND AND AIMS: The COVID-19 pandemic continues to challenge us. Despite several strides in management, steroids remain the mainstay for treatingmoderate to severe disease and with it arises challenges such as hyperglycemia. The review aims to enhance awareness amongst physicians on steroid use and hyperglycemia. METHODS: An advisory document describing various strategies for hyperglycemia management was prepared in the public interest by DiabetesIndia. RESULTS: The review provides awareness on steroids and hyperglycemia, adverse outcomes of elevated blood glucose levels and, advice at the time of discharge. CONCLUSIONS: The article emphasizes enhancing awareness on effective management of hyperglycemia during COVID-19. The COVID-19 pandemic continues to challenge us. Despite several strides in management, steroids remain the cornerstone for treatment of severe disease and with it come challenges like immunosuppression and hyperglycemia. Management of acute hyperglycemia in critically ill and non-critically ill individuals to improve recovery rates from acute infection and reduce mortality is of paramount importance. Managing hyperglycemia in this setting requires different skills, with a greater theoretical and practical knowledge of insulin therapy. This article aims to increase awareness amongst physicians for effective management of hyperglycemia. Steroids are medications used for treatment of several diseases, including COVID-19 (1, 2) . While it is lifesaving in several individuals with COVID-19 infection (from moderate to severe), its pharmacological action increases blood glucose and poses additional challenges in the management. There is also an ongoing concern on inappropriate timing, dosing and duration of steroid use in COVID-19 among certain sections of the medical fraternity (3) (4) (5) . Hence it is important to understand the risk benefit ratio and learn how to manage rising blood glucose when steroids are used. As per International Diabetes Federation, India has the challenge of: 1. 77 million people with diabetes 2. 25.2 million people with pre-diabetes (with Impaired Fasting Glucose or Impaired Glucose Tolerance) 3 . 43.9 million people who are undiagnosed, as diabetes is often asymptomatic. This document aims to increase awareness on the impact of steroids on blood sugar levels among all the 3 groups mentioned above and will provide an overview and guidance on monitoring and control of blood sugar levels. Steroids increase the blood sugar levels by various mechanisms. 1. Increase the hepatic gluconeogenesis or production of glucose from the liver by enhancing the effect of counter regulatory hormones (6). 3. Reduce uptake of glucose by the muscles and adipose tissue (7, 8) . 4 . May even reduce the action of Beta cells directly (9). 5. Elevations in the levels of inflammatory cytokines as seen in COVID-19 further worsen insulin resistance (10 In those on morning steroids, blood glucose risepost lunch and begin to fall post dinner. In those with long acting steroids or multiple doses of short acting steroids, hyperglycemia may be encountered throughout the day. 9. Continue daily SMBG monitoring and up titration of medications as glucose rise and down titration later during recovery or as steroids as tapered. 10 . As premeal and correction bolus, rapid acting analogue insulins are preferred due to its rapid action, short duration and with minimal risk of hypoglycemia (aspart, lispro, glulisine) compared to older regular human insulin. Initiate insulin when indicated and overcome physician inertia. Do not use sliding scale insulin as the practice is outdated and unscientific. 7. In most cases, blood glucose will return to normal in 4-6 weeks and no medication will be needed. Patients may be encouraged to continue lifestyle changes. 8. In some cases, blood glucose may not return to normal values and this could be termed as 'New onset Diabetes' and treatment would need to be continued. Glargine works for 24 hours and can be dosed either in the morning or at night but needs to be taken at the same time daily. NPH works for about 12 hours and may need to be dosed twice-a-day (BID) if 24-hour coverage is required. 2. If the patient has a morning steroid dose, with rising glucose post lunch, NPH can be administered in the morning. This enables the peak of NPH to coincide with the rise in blood glucose levels. 3. If the patient shows hyperglycemia both during fasting and after all the 3 meals Note the following about Regular Insulins: 1. A short acting human insulin (regular insulin) needs to be given 30 mins before the meal. A rapid acting analog (aspart, lispro, glulisine) can be given 15 mins before the meal. Change and adjust insulin dose if there is hypoglycemia. If there is hypoglycemia, reduce the following day the insulin dose given before hypo by 5. In most cases, blood glucose will settle down as soon as the steroids are tapered and stopped, and doses may need to be reduced. Thus, continuing SMBG is critical to preventing hypoglycemia during recovery of 2-6 weeks post discharge. Perform daily SMBG to adjust insulin doses when steroids are initiated and tapered. 6. Those with Type 1 Diabetes: 1. It is essential to ensure that insulin is not stopped. SMBG frequency at 4-6 times per day must be continued and blood monitored for blood ketone levels. A basal insulin must always be given as it helps to prevent ketogenesis with 3 mealtime shots given before the meals. Principles to adjust insulin therapy remain the same as in those with type 2 diabetes. 3. Hydration must be maintained orally or with intravenous fluids. The TTD is calculated based on body weight. It is 0.5 U/kg for those with type 2 diabetes and 1 U/kg for those with type 1 diabetes. 2. Half (50% of this is given as the basal insulin and the other 50% is divided as 20% with breakfast, 20% with lunch and 10% with dinner as the mealtime bolus. 3. Please note that the starting dose is calculated as given above for ease and will differ from patient to patient. Monitoring helps in titration of dose. 4. Actual requirements may vary and may be much higher. Since insulin therapy is safe, it is important to titrate the insulin doses daily and achieve the SMBG targets. 5. Advice at the time of discharge 1. Comprehensive diabetes management including diet and lifestyle advise. 2. Risks associated with hyperglycemia and hypoglycemia. 3. Blood glucose monitoring at home and dosage adjustment as per patient requirement. 4. Self-Injection technique and site rotation. 5. Foot care and sick day rules. 6. Advice on reducing insulin as Steroid dosage gets tapered. 7. Those with 'Stress induced Diabetes' to continue monitoring and to seek the help of the physician for future prevention of diabetes. The COVID-19 pandemic has opened our eyes on the importance of controlling hyperglycemia. The focus of diabetes management over the years has moved towards an individualized approach towards reduction of cardiovascular disease, kidney disease and microvascular complications. Uncontrolled diabetes a silent killer, needs timely appropriate management for better health care outcomes -both short and long term. In this situation, it is essential that we don't lose the war against diabetes, while we focus on winning the battle against COVID-19. It is one of those situations where we need a win-win! J o u r n a l P r e -p r o o f This section asks about your financial relationships with entities in the bio-medical arena that could be perceived to influence,or that give the appearance of potentially influencing, what you wrote in the submitted work. You should disclose interactions with ANY entity that could be considered broadly relevant to the work. For example, if your article is about testing an epidermal growth factor receptor (EGFR) antagonist in lung cancer, you should report all associations with entities pursuing diagnostic or therapeutic strategies in cancer in general, not just in the area of EGFR or lung cancer. 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For example, if a government agency sponsored a study in which you have been involved and drugs were provided by a pharmaceutical company, you need only list the pharmaceutical company. Use of Corticosteroids in Coronavirus Disease 2019 Pneumonia: A Systematic Review of the Literature. Frontiers in Medicine Therapeutic role of corticosteroids in COVID-19: a systematic review of registered clinical trials Corticosteroids on the Management of Coronavirus Disease 2019 (COVID-19): A Systemic Review and Meta-Analysis Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet Clinical characteristics of coronavirus disease 2019 in China Dexamethasone in the era of COVID-19: friend or foe? An essay on the effects of dexamethasone and the potential risks of its inadvertent use in patients with diabetes Dexamethasone-induced impairment in skeletal muscle glucose transport is not reversed by inhibition of free fatty acid oxidation Glucocorticoid-induced insulin resistance in skeletal muscles: defects in insulin signalling and the effects of a selective glycogen synthase kinase-3 inhibitor Steroid-induced diabetes: a clinical and molecular approach to understanding and treatment Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans Use this section to report other relationships or activities that readers could perceive to have influenced, or that give the appearance of potentially influencing, what you wrote in the submitted work. 3. The purpose of this form is to provide readers of your manuscript with information about your other interests that could influence how they receive and understand your work. 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