Authors: Sten Madsbad, Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark
The COVID-19 infection is a double challenge for people with diabetes. Diabetes has been reported to be a risk factor for the severity of the disease and at the same time patients have to control glucose in a situation with a decreased and more variable food intake.
Background
COVID-19 (Coronavirus Disease-2019) is caused by the coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2), which has spread quickly to more than 160 countries across the world.1 The spreading mechanism of the virus is primarily by transmission of respiratory droplets between people.1 The incubation time is on average 6–8 days, followed by 1–2 weeks of symptomatic disease. It is characterised by a wide spectrum of symptoms including coughing, fever, myalgia and respiratory problems such as viral pneumonia, and respiratory failure. In worst cases, these can lead to death.2–11 Time from first onset to hospital admission has been on the average 6–7 days.2–11 A proportion of the infected are without symptoms (yet remain infectious) or have only mild symptoms.2–11
Diabetes as a risk factor
Diabetes is a risk factor for hospitalisation and mortality of the COVID-19 infection. Diabetes was a comorbidity in 22% of 32 non-survivors in a study of 52 intensive care patients.2 In another study of 173 patients with severe disease, 16.2% had diabetes, and in further study of 140 hospitalised patients, 12% had diabetes.3,4 When comparing intensive care and non-intensive care patients with COVID-19, there appears to be a twofold increase in the incidence of patients in intensive care having diabetes.11 Mortality seems to be about threefold higher in people with diabetes compared with the general mortality of COVID-19 in China.2–11
The number of comorbidities is a predictor of mortality in COVID-19. In addition to diabetes, the other common comorbidities were hypertension, in about 20% of cases, cardiovascular disease (16%), and lung disease (6%).2–11 Indeed, people with diabetes are a high-risk group for severe disease. Notably, diabetes was also a risk factor for severe disease and mortality in the previous SARS, MERS (Middle East respiratory syndrome) coronavirus infections and the severe influenza A H1N1 pandemic in 2009.12–4
What explain the increase risk of diabetes?
It is a fact that people with diabetes are at increased risk of infections including influenza and for related complications such as secondary bacterial pneumonia. Diabetes patients have impaired immune-response to infection both in relation to cytokine profile and to changes in immune-responses including T-cell and macrophage activation.15 Poor glycaemic control impairs several aspects of the immune response to viral infection and also to the potential bacterial secondary infection in the lungs.16 It is likely that many of the patients with diabetes in China have been in poor metabolic control when infected by COVID-19.
Many patients with type 2 diabetes are obese and obesity is also a risk factor for severe infection.17–9 It was illustrated during the influenza A H1N1 epidemic in 2009 that the disease was more severe and had a longer duration in about twofold more patients with obesity who were then treated in intensive care units compared with background population.14,17,18 Specically, metabolic active abdominal obesity is associated with higher risk.17-9 The abnormal secretion of adipokines and cytokines like TNF-alfa and interferon characterise a chronic low-grade in abdominal obesity and may induce an impaired immune-response.. 17–9 People with severe abdominal obesity also have mechanical respiratory problems, with reduced ventilation of the basal lung sections increasing the risk of pneumonia as well as reduced oxygen saturation of blood.20 Obese subjects also have an increased asthma risk, and those patients with obesity and asthma have more symptoms, more frequent and severe exacerbations and reduced response to several asthma medications. 20
Lastly, late diabetic complications such as diabetic kidney disease and ischaemic heart disease may complicate the situation for people with diabetes, making them frailer and further increasing the severity of COVID-19 disease and the need for care such as acute dialysis. Some findings indicate that COVID-19 could cause acute cardiac injury with heart failure, leading to deterioration of circulation.11
The most frequent comorbidities to COVID 19 are hypertension and diabetes. Both diseases are often treated with angiotensin-converting enzymes (ACE) inhibitors. Coronavirus binds to target cells through angiotensin-converting enzyme 2 (ACE2), which expressed in the epithelial cells in the lungs, blood vessels and in the intestine.21,22 In patients treated with ACE and angiotensin II receptor blockers, expression of ACE2 is increased.23 Therefore, it has been suggested that ACE2 expression may be increased in these two groups of patients with hypertension and diabetes, which could facilitate infection with COVID-19 and increase the risk of severe disease and fatality.
