key: cord-0905909-7v4nau0p authors: Aravind, S.R.; Saboo, Banshi; Misra, Anoop title: Strict Glycemic Control is Needed in Times of COVID19 Epidemic in India: A Call for Action for all Physicians()()()()() date: 2020-08-10 journal: Diabetes Metab Syndr DOI: 10.1016/j.dsx.2020.08.003 sha: b41212eb45ee1f9947463ae48a923a5c29e94a23 doc_id: 905909 cord_uid: 7v4nau0p nan Diabetes India, National Diabetes Obesity and Cholesterol Foundation (NDOC), and Diabetes Expert Group* During the current COVID -19 pandemic, there is sufficient data to suggest that diabetes is an important comorbid disease which can increase severity and mortality related to .Key pathological factors that contribute to increased mortality in patients with diabetes are; defect in T-cell immunity, baseline high levels cytokines and presence of co-morbidities [1, 2] .Those with comorbidities ((obesity, coronary heart disease, hypertension, chronic kidney disease chronic obstructive pulmonary disease, immune suppressed conditions etc.) and elderly are particularly at high risk [1, 3] . It is possible that Indians with diabetes may have lower mortality than seen in western countries because of younger age of contracting COVID19 but this issues remains unproven [4, 5] . With this background, in the following sections we discuss the role of patients' glycemic status before they have COVID-19 infection, at the time of admission, and during the hospital stay, vis-à-vis morbidity and mortality, and briefly outline key management issues (Table 1) . Previous studies have shown that a high proportion of patients with diabetes in India have poor glycemic control [6] [7] [8] , and that many already have diabetes-related complications [8] [9] [10] . Uncontrolled hyperglycemia could be exacerbated by disordered lifestyle during lockdown and consequent weight gain. Such patients with uncontrolled hyperglycemia will obviously have high blood glucose levels during admission and also during hospitalization when they contract COVID19.This is the first scenario which is quite well known. The second scenario is when a patient not known to have diabetes is develops COVID-19 infection and high blood glucose and even ketoacidosis is detected at admission to the hospital [11] . High blood glucose levels at the time of hospitalization may be due to undetected diabetes or as a result of recent weight gain during complete and partial lockdown [12] . Weight gain during lockdown may be due to multiple factors; disordered diet, poor exercise, and widespread mental stress, as previously shown [12, 13] . In India, unwarranted use of dexamethasone in mild COVID19 infection and other seasonal flu, increases the risk of hyperglycemia. High fasting blood glucose (FBG) at the time of hospitalization in people not known to have diabetes puts them at higher risk (HR 2.30 [95% CI 1.49,3.55]) for mortality than those who have normoglycemia. The odds ratio for 28-day in-hospital complications in those with FBG≥7.0 mmol/l (126 mg/dL) and 6.1-6.9 mmol/l (110-125 mg/dL) vs <6.1 mmol/l was 3.99 (95% CI 2.71, 5.88) or 2.61 (95% CI 1.64, 4.41), respectively [14] . The third scenario is hyperglycemia in pregnancy. Pregnancy in diabetes and gestational diabetes, should be intensively controlled with the help of self-monitoring of blood glucose (SMBG) and continuous blood glucose monitoring system (CGMS). Screening of women with capillary glucose should be done to avoid visiting laboratory [15] . Consultations for antenatal checks, nutritionist, and diabetes educators must be done as appropriate with the use of teleconsultation. The fourth scenario is in-hospital hyperglycemia that needs to be controlled well. However there are a number of factors which pose challenges; triggers for hyperglycemia [surge of cytokines ("cytokine storm"), frequent use of corticosteroids, etc.], ketoacidosis and hyperosmolar states, inability to monitor blood glucose levels frequently because of reduced contact between healthcare worker and patients, and non-inclusion of diabetes expert in the critical care team in many hospitals. Data suggesting markedly lower risk of all-cause mortality in the hospitalised patients with well-controlled blood glucose (adjusted HR, 0.14; 95% CI,0.03-0.60; p = 0.008) compared to those from the poorly controlled blood glucose group [16] should encourage us to go all out for aggressive glycemic control. Fifth scenario is new onset of diabetes which is now being reported during COVID19 infection [17] . Besides unmasking of previous hyperglycemic state, beta cell injury is a likely possibility in such cases. In this context, it is important to know that angiotensin converting enzyme-2 (ACE2) receptors, through which SARS-CoV-2 attaches to the cells, are present on the cells of endocrine pancreas, at even greater density than in the Type 1 and Type 2 alveoli in lungs [18] . It is, therefore, possible (but not proven) that beta cell destruction may occur due to COVID19 attack on pancreatic beta cells, similar to alveolar injury in lungs. Indeed, 17% of patients with severe COVID19 have been shown to have pancreatic injury in one study [19] . It is possible that injury to beta cells, already under attack from cytokines (cytokine-induced apoptosis) [20] , could cause acute insulinopenia, and ketoacidosis [11] . Previously, acute-onset diabetes has been shown with SARS-CoV infection and beta cell injury has been implicated in its pathogenesis [18] .Viral 'sepsis' could induce resistance to action of insulin, posing additional challenges to management (e.g. high insulin requirement). There are a number of other factors which may affect glycemic control in patients with diabetes in India. Patients were not able to contact their physicians during lockdown, or do not visit them due to fear that hospitals are hotspots of COVID19. Telemedicine is not acceptable to many patients (especially the elderly) who are not technologically abled [21, 22] . Economic problems exacerbated by lockdown and COVID19 [23] may lead to noncompliance to medications and insulin. Non-availability of insulin and glucose strips during the period of lockdown was shown to worsen the glycemic control in patients with type 1 diabetes [24] . We can make efforts to efficiently manage each of these scenarios of uncontrolled glycaemia. All of us must strongly advice and advocate for good glycaemic control in all patients specifically those with COVID19 aiming for low morbidity and mortality [25] . Glycemia must be controlled at all times; when not hospitalized, during pregnancy, during quarantine, at the time of admission, and during hospital stay. Practice of SMBG should be emphasized. Patients with risk for foot lesions/infections should be counselled for proper foot care and self-examination of feet, and treated as much as possible using tele consults [26] . All patients diagnosed with COVID19, even if not known to have diabetes, must get screening blood glucose measurement done [27] . Blood glucose monitoring in hospital should be done frequently, by patient or healthcare provider, keeping safety in mind. When available, CGMS with real time sensor and virtual reader is a good option. Metformin should be continued until it cannot be tolerated, or patient is unable to take it since it may decrease mortality in COVID19 [28] . Insulin must be used to control surge of blood glucose which may also occur due to steroid therapy and/or sepsis. Hypoglycemia, which may occur due to nausea, vomiting, aversion to food, mismatched IV fluids or use of hydroxychloroquine, should be looked for and corrected. Aggressive fluid and electrolyte therapy for marked hyperglycemia and ketoacidosis must be balanced against possible cardiac and renal compromise. Ideally, diabetes expert must be part of the caregiver team in hospital. However, J o u r n a l P r e -p r o o f often a diabetologist/endocrinologist is not there to provide care in hospitalised patients, hence, development of an easy-to-use guidance algorithm for drug and insulin would be useful [29] . A critical and often neglected point is the advice given to the patient at discharge from hospital. The 'return to normalcy' in severe COVID19 can take a long time and the residual effects of the infection are only now being understood. The job of a physician does not end with the discharge of the patient. Proper education and guidance of these patients-for good monitoring and glycemic control at home is imperative. To enable good metabolic and blood pressure control, we must proactively connect with the patients (phone calls, messages) and emphasize (through tele consults, messages, face-to-face consults) that importance of glucose control is more relevant now than ever before [30] . Messages regarding correct diet, exercise (any exercise, indoor exercises), adequate sleep, and adherence to therapy must be re-iterated. Patients must be advised unequivocally that weight gain must be avoided, and blood pressure should be maintained as close to normal as possible. Elderly must be carefully counselled so that hypoglycemia does not occur. Individuals without diabetes should be advised to lose weight if obese, follow correct lifestyle and get blood glucose tested. Uninterrupted insulin supply must be ensured for patients with type 1 diabetes. We believe that the available information on COVID19 and diabetes necessitates a call for action for all medical community in general and experts in diabetes in particular, to ensure implementation of previously recommended and evidence-based interventions for the patients, even more aggressively than hitherto been the case. Rajput Rajesh (Rohtak) Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations Diabetes and COVID-19: evidence, current status and unanswered research questions COVID-19 in people living with diabetes: An international consensus Characteristics and Outcomes of Hospitalized Young Adults with Mild COVID-19 COVID19 in South Asians/Asian Indians: Heterogeneity of data and implications for pathophysiology and research Glycemic control among individuals with self-reported diabetes in India--the ICMR-INDIAB Study Current status of management, control, complications and psychosocial aspects of patients with diabetes in India: Results from the DiabCare India Real-world evidence of glycemic control among patients with type 2 diabetes mellitus in India: the TIGHT study Diabetes mellitus and its complications in India Clinical management of type 2 diabetes in south Asia Diabetic ketoacidosis precipitated by COVID-19: A report of two cases and review of literatureDiabetes Metab Syndr 2020 Effects of nationwide lockdown during COVID-19 epidemic on lifestyle and other medical issues of patients with type 2 diabetes in north India Increase in risk for type 2 diabetes due to lockdown for COVID19 pandemic in apparently non-diabetic individuals in India: A cohort analysisDiabetes and Met Syndr Fasting blood glucose at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes: a multi-centre retrospective study The Diagnosis and Management of Gestational Diabetes Mellitus in the Context of the COVID-19 Pandemic Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes New-Onset Diabetes in Covid-19 Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes ACE2 Expression in Pancreas May Cause Pancreatic Damage After SARS-CoV-2 Infection beta-cell apoptosis and defense mechanisms: lessons from type 1 diabetes Roadblock in application of telemedicine for diabetes management in India during COVID19 pandemic Acceptability and Utilization of Newer Technologies and Effects on Glycemic Control in Type 2 Diabetes: Lessons Learnt from Lockdown COVID-19 pandemic and challenges for socio-economic issues, healthcare and National Health Programs in India Impact of lockdown in COVID 19 on glycemic control in patients with type 1 Diabetes Mellitus Clinical considerations for patients with diabetes in times of COVID-19 epidemic Redefining diabetic foot disease management service during COVID-19 pandemic Proposed guidelines for screening of hyperglycemia in patients hospitalized with COVID-19 in low resource settings Metformin Treatment Was Associated with Decreased Mortality in COVID-19 Patients with Diabetes in a Retrospective Analysis Basal-Bolus Insulin Regimen for Hospitalised Patients with COVID-19 and Diabetes Mellitus: A Practical Approach Diabetes during the COVID-19 pandemic: A global call to reconnect with patients and emphasize lifestyle changes and optimize glycemic and blood pressure control