In the pandemic "Corona Virus Disease 2019" (COVID-19) people with diabetes have a high risk to require ICU admission. The management of diabetes in Intensive Care Unit is always challenging, however, when diabetes is present in COVID-19 the situation seems even more complicated. An optimal glycemic control, avoiding acute hyperglycemia, hypoglycemia and glycemic variability may significantly improve the outcome. In this case, intravenous insulin infusion with continuous glucose monitoring should be the choice. No evidence suggests stopping angiotensin-converting-enzyme inhibitors, angiotensin-renin-blockers or statins, even it has been suggested that they may increase the expression of Angiotensin-Converting-Enzyme-2 (ACE2) receptor, which is used by "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to penetrate into the cells. A real issue is the usefulness of several biomarkers, which have been suggested to be measured during the COVID-19. N-Terminal-pro-Brain Natriuretic-Peptide, D-dimer and hs-Troponin are often increased in diabetes. Their meaning in the case of diabetes and COVID-19 should be therefore very carefully evaluated. Even though we understand that in such a critical situation some of these requests are not so easy to implement, we believe that the best possible action to prevent a worse outcome is essential in any medical act.

Clalit Health Services and Technion Faculty of Medicine Haifa Israel

Clinic for Endocrinology Diabetes and Metabolic Diseases Faculty of Medicine University of Belgrade Belgrade Serbia

Clinical Center of Diabetes Nutrition and Metabolic Diseases Faculty of Medicine Ovidius University of Constanta Constanta Romania

Department of Internal Medicine 3 1st Faculty of Medicine Charles University Prague Czech Republic

Forschergruppe Diabetes e 5 at Munich Helmholtz Centre Munich Germany

IRCCS MultiMedica Via Gaudenzio Fantoli 16 15 20138 Milan Italy

Unit of Endocrinology Diabetology Nutrition Jean Verdier Hospital APHP Paris Nord University Sorbonne Paris Cité CINFO CRNH IdF Bondy France

University of Osijek School of Medicine Osijek Croatia

University of Zagreb School of Medicine Zagreb Croatia

Vuk Vrhovac University Clinic for Diabetes Endocrinology and Metabolic Diseases Merkur University Hospital Zagreb Croatia

See more in PubMed

Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, China Medical Treatment Expert Group for Covid-19) et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382:1708–1720. PubMed PMC

Gentile S, Strollo F, Ceriello A. COVID-19 infection in Italian people with diabetes: lessons learned from our future (an experience to be used) Diabetes Res Clin Pract. 2020;162:108137. PubMed PMC

Goyal P, Choi JJ, Pinheiro LC, Schenck EJ, Chen R, Jabri A, et al. Clinical characteristics of Covid-19 in New York City. N Engl J Med. 2020;382:2372–2374. PubMed PMC

Yan Y, Yang Y, Wang F, Ren H, Zhang S, Shi X, et al. Clinical characteristics and outcomes of patients with severe covid-19 with diabetes. BMJ Open Diabetes Res Care. 2020;8:e001343. PubMed PMC

Sardu C, Gargiulo G, Esposito G, Paolisso G, Marfella R. Impact of diabetes mellitus on clinical outcomes in patients affected by Covid-19. Cardiovasc Diabetol. 2020;19:76. PubMed PMC

Chase G, Desaive T, Bohe J, Cnop M, De Block C, Gunst J, et al. Improving glycemic control in critically ill patients: personalized care to mimic the endocrine pancreas. Crit Care. 2018;22:182. PubMed PMC

Stoudt K, Chawla S. Don’t sugar coat it: glycemic control in the intensive care unit. J Intensive Care Med. 2019;34(11–12):889–896. doi: 10.1177/0885066618801748. PubMed DOI PMC

Guo W, Li M, Dong Y, Zhou H, Zhang Z, Tian C, et al. Diabetes is a risk factor for the progression and prognosis of COVID-19. Diabetes Metab Res Rev. 2020 doi: 10.1002/dmrr.3319. PubMed DOI PMC

Zhu L, She ZG, Cheng X, Qin JJ, Zhang XJ, Cai J, et al. Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing Type 2 diabetes. Cell Metabol. 2020;31:1068–1077. PubMed PMC

Iacobellis G, Penaherrera CA, Bermudez LE, Mizrachi EB. Admission hyperglycemia and radiological findings of SARS-COv2 in patients with and without diabetes. Diabetes Res Clin Pract. 2020;164:108185. PubMed PMC

Shetty S, Inzucchi SE, Goldberg PA, Cooper D, Siegel MD, Honiden S. Adapting to the new consensus guidelines for managing hyperglycemia during critical illness: the Updated Yale Insulin Infusion Protocol. Endocr Pract. 2012;18:363–370. PubMed

Sharif K, Ghadir S, Jakubowicz D, Amital H, Bragazzi NL, et al. Improved outcome of patients with diabetes mellitus with good glycemic control in the Cardiac Intensive Care Unit: a retrospective study. Cardiovasc Diabetol. 2019;18:4. PubMed PMC

Sardu C, D’Onofrio N, Balestrieri ML, Barbieri M, Rizzo MR, Messina V, et al. Outcomes in patients with hyperglycemia affected by COVID-19: can we do more on glycemic control? Diabetes Care. 2020;43:1408–1415. PubMed PMC

Ceriello A, Zarich SW, Testa R. Lowering glucose to prevent adverse cardiovascular outcomes in a critical care setting. J Am Coll Cardiol. 2009;53(5 Suppl):S9–S13. PubMed

Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, HLH Across Speciality Collaboration, UK COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395:1033–1034. PubMed PMC

Bellaver P, Schaeffer AF, Dullius DP, Viana MV, Leitão CB, Rech TH. Association of multiple glycemic parameters at intensive care unit admission with mortality and clinical outcomes in critically ill patients. Sci Rep. 2019;9:18498. PubMed PMC

Borzì V, Frasson S, Gussoni G, Di Lillo M, Gerloni R, Augello G, Research Department of FADOI et al. Risk factors for hypoglycemia in patients with type 2 diabetes, hospitalized in internal medicine wards: findings from the FADOI-DIAMOND study. Diabetes Res Clin Pract. 2016;115:24–30. PubMed

Ceriello A, Novials A, Ortega E, La Sala L, Pujadas G, Testa R, et al. Evidence that hyperglycemia after recovery from hypoglycemia worsens endothelial function and increases oxidative stress and inflammation in healthy control subjects and subjects with type 1 diabetes. Diabetes. 2012;61:2993–2997. PubMed PMC

Chao WC, Tseng CH, Wu CL, Shih SJ, Yi CY, Chan MC. Higher glycemic variability within the first day of ICU admission is associated with increased 30-day mortality in ICU patients with sepsis. Ann Intensive Care. 2020;10:17. PubMed PMC

Kulkarni H, Bihari S, Prakash S, Huckson S, Chavan S, Mamtani M, et al. Independent association of glucose variability with hospital mortality in adult intensive care patients: results from the Australia and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation Binational Registry. Crit Care Explor. 2019;1:e0025. PubMed PMC

Takahashi H, Iwahashi N, Kirigaya N, Kataoka S, Minamimoto Y, Gohbara M, et al. Glycemic variability determined with a continuous glucose monitoring system can predict prognosis after acute coronary syndrome. Cardiovasc Diabetol. 2018;17:116. PubMed PMC

Todi S, Bhattacharya M. Glycemic variability and outcome in critically ill. Indian J Crit Care Med. 2014;18:285–290. PubMed PMC

Ceriello A, Monnier L, Owens D. Glycaemic variability in diabetes: clinical and therapeutic implications. Lancet Diabetes Endocrinol. 2019;7:221–230. PubMed

Wang A, Zhao W, Xu Z, Gu Timely blood glucose management for the outbreak of 2019 novel coronavirus disease (COVID-19) is urgently needed. Diabetes Res Clin Pract. 2019;2020(162):108118. PubMed PMC

Zhou J, Tan J. Diabetes patients with COVID-19 need better blood glucose management in Wuhan, China. Metabolism. 2020;107:154216. PubMed PMC

Klonoff DC. Intensive insulin therapy in critically ill hospitalized patients: making it safe and effective. J Diabetes Sci Technol. 2011;5:755–767. PubMed PMC

Knopp JL, Chase JG. Clinical recommendations for managing the impact of insulin adsorptive loss in hospital and diabetes care. J Diabetes Sci Technol. 2020 doi: 10.1177/1932296820915875. PubMed DOI PMC

Salinas PD, Mendez CE. Glucose management technologies for the critically ill. J Diabetes Sci Technol. 2019;13:682–690. PubMed PMC

Fernández Cruz A, Ruiz-Antorán B, Muñoz Gómez A, Sancho López A, Mills Sánchez P, Centeno Soto GA, Puerta de Hierro COVID-19 Study Group, et al.. Impact of glucocorticoid treatment in SARS-COV-2 infection mortality: a retrospective controlled cohort study. Antimicrob Agents Chemother. 2020:AAC.01168-20. PubMed PMC

Berton AM, Prencipe N, Giordano R, Ghigo E, Grottoli S. Systemic steroids in patients with COVID-19: pros and contras, an endocrinological point of view. J Endocrinol Invest. 2020 doi: 10.1007/s40618-020-01325-2. PubMed DOI PMC

Prattichizzo F, La Sala L, Rydén L, Marx N, Ferrini M, Valensi P, et al. Glucose-lowering therapies in patients with type 2 diabetes and cardiovascular diseases. Eur J Prev Cardiol. 2019;26(2 suppl):73–80. PubMed

Ceriello A, Stoian AP, Rizzo M. COVID-19 and diabetes management: what should be considered? Diabetes Res Clin Pract. 2020;163:108151. PubMed PMC

Mehra MR, Ruschitzka F, Patel AN. Retraction-Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet. 2020;395:1820. PubMed PMC

Colson P, Rolain JM, Lagier JC, Brouqui P, Raoult D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents. 2020;55:105932. PubMed PMC

Quatraro A, Consoli G, Magno M, Caretta F, Nardozza A, Ceriello A, et al. Hydroxychloroquine in decompensated, treatment-refractory noninsulin-dependent diabetes mellitus. A new job for an old drug? Ann Intern Med. 1990;112:678–681. PubMed

Marfella R, Paolisso P, Sardu C, Bergamaschi L, D’Angelo EC, Barbieri M, et al. Negative impact of hyperglycaemia on tocilizumab therapy in Covid-19 patients. Diabetes Metab. 2020 doi: 10.1016/j.diabet.2020.05.005. PubMed DOI PMC

Alhazzani W, Møller MH, Arabi YM, Loeb M, Ng Gong M, Fan E, et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19) Intensive Care Med. 2020;46:854–887. PubMed PMC

Uijtendaal EV, Zwart-van Rijkom JEF, de Lange DV, Arief Lalmohamed AF, van Solinge WW, Egberts TCG. Influence of a strict glucose protocol on serum potassium and glucose concentrations and their association with mortality in intensive care patients. Crit Care. 2015;19:270. PubMed PMC

Nilsson PM, Cederholm J, Zethelius BR, Eliasson BR, Eeg-Olofsson K, Gudbj Rnsdottir S. Trends in blood pressure control in patients with type 2 diabetes: data from the Swedish National Diabetes Register (NDR) Blood Press. 2011;20:348–354. PubMed

Pal R, Bhansali A. COVID-19, diabetes mellitus and ACE2: the conundrum. Diabetes Res Clin Pract. 2020;162:108132. doi: 10.1016/j.diabres.2020.108132. PubMed DOI PMC

Reynolds HR, Adhikari S, Pulgarin C, Troxel AB, Iturrate E, Johnson SB. Renin–angiotensin–aldosterone system inhibitors and risk of Covid-19. N Engl J Med. 2020;382:2441–2448. PubMed PMC

Zhang P, Zhu L, Cai J, Lei F, Qin JJ, Xie J, et al. Association of inpatient use of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers with mortality among patients with hypertension hospitalized with COVID-19. Circ Res. 2020;126:1671–1681. PubMed PMC

Cariou B, Hadjadj S, Wargny M, Pichelin M, Al-Salameh A, Allix I, Amadou C, et al. Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study. Diabetologia. 2020 doi: 10.1007/s00125-020-05180-x. PubMed DOI PMC

Guo T, Fan Y, Chen M, Wu X, Zhang L, He T, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19) JAMA Cardiol. 2019;5:811–818. PubMed PMC

Valensi P, Pariès J, Brulport-Cerisier V, Torremocha F, Sachs RN, Vanzetto G, et al. Predictive value of silent myocardial ischemia for cardiac events in diabetic patients: influence of age in a French multicenter study. Diabetes Care. 2005;28:2722–2727. PubMed

Valensi P, Meune C. Congestive heart failure caused by silent ischemia and silent myocardial infarction: diagnostic challenge in type 2 diabetes. Herz. 2019;44:210–217. PubMed

Valensi PE, Johnson NB, Maison-Blanche P, Extramania F, Motte G, Coumel P. Influence of cardiac autonomic neuropathy on heart rate dependence of ventricular repolarization in diabetic patients. Diabetes Care. 2002;25:918–923. PubMed

Ziegler D, Zentai CP, Perz S, Rathmann W, Haastert B, Döring A, KORA Study Group et al. Prediction of mortality using measures of cardiac autonomic dysfunction in the diabetic and nondiabetic population: the MONICA/KORA Augsburg Cohort Study. Diabetes Care. 2008;31:556–561. PubMed

Liu PP, Blet A, Smyth D, Li H. The science underlying COVID-19: implications for the cardiovascular system. Circulation. 2020 doi: 10.1161/circulationaha.120.047549. PubMed DOI

https://www.escardio.org/Education/COVID-19-and-Cardiology/ESC-COVID-19-Guidance. Accessed 24 May 2020.

Cosson E, Nguyen MT, Pham I, Pontet M, Nitenberg A, Valensi P. N-terminal pro-B-type natriuretic peptide: an independent marker for coronary artery disease in asymptomatic diabetic patients. Diabet Med. 2009;26:872–879. PubMed

Giorda CB, Cioffi G, de Simone G, Di Lenarda A, Faggiano P, Latini R, DYDA Investigators et al. Predictors of early-stage left ventricular dysfunction in type 2 diabetes: results of DYDA study. Eur J Cardiovasc Prev Rehabil. 2011;18:415–423. PubMed

Tang O, Daya N, Matsushita K, Coresh J, Sharrett AR, Hoogeveen R, et al. Performance of high-sensitivity cardiac troponin assays to reflect comorbidity burden and improve mortality risk stratification in older adults with diabetes. Diabetes Care. 2020;43:1200–1208. PubMed PMC

Preiss D, Sattar N. Research digest: cardiac biomarkers for risk prediction. Lancet Diabetes Endocrinol. 2016;4:890. PubMed

Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood. 2020;135:2033–2040. PubMed PMC

Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfus I, Driggin E, et al. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up. J Am Coll Cardiol. 2020;75:2950–2973. PubMed PMC

Ceriello A, Taboga C, Giacomello R, Falleti E, De Stasio G, Motz E, Lizzio S, Gonano F, Bartoli E. Fibrinogen plasma levels as a marker of thrombin activation in diabetes. Diabetes. 1994;43:430–432. PubMed

Zakai NA, McClure LA, Judd SE, Kissela B, Howard G, Safford M, et al. D-dimer and the risk of stroke and coronary heart disease. The REasons for Geographic and Racial Differences in Stroke (REGARDS) Study. Thromb Haemost. 2017;117:618–624. PubMed PMC

Ceriello A. Coagulation activation in diabetes mellitus: the role of hyperglycaemia and therapeutic prospects. Diabetologia. 1993;36:1119–1125. PubMed

Ceriello A, Giacomello R, Stel G, Motz E, Taboga C, Tonutti L, et al. Hyperglycemia-induced thrombin formation in diabetes The possible role of oxidative stress. Diabetes. 1995;44:924–928. PubMed

Ceriello A, Marchi E, Palazzni E, Quatraro A, Giugliano D. Low molecular weight heparin restores antithrombin III activity from hyperglycemia induced alterations. Diabetes Metab. 1990;16:86–92. PubMed

Nusca A, Tuccinardi D, Proscia C, Melfi R, Manfrini S, Nicolucci A, et al. Incremental role of glycaemic variability over HbA1c in identifying type 2 diabetic patients with high platelet reactivity undergoing percutaneous coronary intervention. Cardiovasc Diabetol. 2019;18:147. PubMed PMC

Prattichizzo F, De Nigris V, Spiga R, Mancuso E, La Sala L, Antonicelli R, et al. Inflammageing and metaflammation: the yin and yang of type 2 diabetes. Ageing Res Rev. 2018;41:1–17. PubMed

Ceriello A. Acute hyperglycaemia: a ‘new’ risk factor during myocardial infarction. Eur Heart J. 2005;26:328–331. PubMed

Ceriello A, Esposito K, Piconi L, Ihnat MA, Thorpe JE, Testa R, et al. Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes. 2008;57:1349–1354. PubMed

Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, et al. ESC Scientific Document Group: 2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020;41:255–323. PubMed

Dashti-Khavidaki S, Khalili H. Considerations for statin therapy in patients with COVID-19. Pharmacotherapy. 2020;40:484–486. PubMed PMC

Tikoo K, Patel G, Kumar S, Karpe PA, Sanghavi M, Malek V, et al. Tissue specific up regulation of ACE2 in rabbit model of atherosclerosis by atorvastatin: role of epigenetic histone modifications. Biochem Pharmacol. 2015;93:343–351. PubMed

Makris D, Manoulakas E, Komnos A, Papakrivou E, Tzovaras N, Hovas A, Zintzaras E, Zakynthinos E. Effect of pravastatin on the frequency of ventilator-associated pneumonia and on intensive care unit mortality: open-label, randomized study. Crit Care Med. 2011;39:2440–2446. PubMed

Rogers AJ, Guan J, Trtchounian A, et al. Association of elevated plasma interleukin-18 level with increased mortality in a clinical trial of statin treatment for acute respiratory distress syndrome. Crit Care Med. 2019;47:1089–1096. PubMed PMC

Schnell O, Cappuccio F, Genovese S, Standl E, Valensi P, Ceriello A. Type 1 diabetes and cardiovascular disease. Cardiovasc Diabetol. 2013;12:156. PubMed PMC

Sechterberger MK, van Steen SC, Boerboom EM, van der Voort PH, Bosman RJ, Hoekstra JB, et al. Higher glucose variability in type 1 than in type 2 diabetes patients admitted to the intensive care unit: a retrospective cohort study. J Crit Care. 2017;38:300–303. PubMed

Tatti P, Tonolo G, Zanfardino A, Iafusco D. CoVid-19 and Type 1 Diabetes: every cloud has a silver lining. Searching the reason of a lower aggressiveness of the CoronaVirus disease in Type 1 Diabetes. Diabetes Res Clin Pract. 2020 doi: 10.1016/j.diabres.2020.108270. PubMed DOI PMC

Guzik TJ, Mohiddin SA, Dimarco A, Patel V, Savvatis K, Marelli-Berg FM, et al. COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options. Cardiovasc Res. 2020 doi: 10.1093/cvr/cvaa106. PubMed DOI PMC

Ceriello A, Standl E, Catrinoiu D, Itzhak B, Lalic NM, Rahelic D, Diabetes and Cardiovascular Disease (D&CVD) EASD Study Group et al. Issues of cardiovascular risk management in people with diabetes in the COVID-19 era. Diabetes Care. 2020;43:1427–1432. doi: 10.2337/dc20-0941. PubMed DOI