Imagine you have corona and are in quarantine for two weeks. Before you became ill, you were active in sports and followed a healthy diet. Then your illness will have healed so far. But you realize that there is still something wrong with you. You are constantly thirsty, have to go to the bathroom more often than usual and sometimes feel worn out. Since the symptoms seem strange to you, go to your family doctor. This person tells you that the symptoms are very characteristic of a particular disease. Your blood sugar level is measured and suddenly there is a new diagnosis in the room - diabetes mellitus.

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Although the two diseases Covid-19 and diabetes seem to have little to do with each other, such cases occur occasionally as described above. People who were healthy before the COVID infection develop diabetes as a result of their illness. For some, their blood sugar returned to normal after recovery. Others had diabetes persisted. This prompted scientists to investigate a possible connection between the two diseases. Interestingly, there are still no definitive answers to the question of whether the incidence, i.e. the incidence of type 1 and/or 2 diabetes mellitus, increases following COVID-19 infection. So far, there have been no uniform observations on this in studies.
It has been known for some time that diabetes is a risk factor for a more severe course of Covid. But very few people are likely to know that there are also interactions in the other direction.

How the two diseases could be linked is discussed in this article.

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Basics of blood sugar regulation

The body has a complicated system for keeping sugar (glucose) in the body constant. This is necessary to provide cells with a sufficient supply of energy suppliers. However, the glucose level in the blood should also not be too high, as otherwise vascular damage and metabolic derailments can occur. The body regulates sugar levels primarily with the help of two hormones that are released in the pancreas.

insulin

Insulin is released from the pancreas after carbohydrate-rich meals and ensures the absorption of glucose into the cells. This makes it available to cells to generate energy. In addition, the hormone has an anabolic effect. This means that the body stores excess energy in the form of larger molecules such as proteins/fat/glycogen. This means that alternative energy sources are available when there is a lack of sugar. Insulin is produced in the beta cells of the pancreas and released from there into the blood.

glucagon

Glucagon is the antagonist of insulin and ensures the release of sugar from stores (especially from glycogen in the liver). This happens when you are hungry, for example. Glycogen can be thought of as a chain of sugar molecules strung together. When sugar is required for energy production, the sugar molecules can be split off and released into the blood. With blood, sugar goes where it is needed, e.g. to the brain or muscles.

In diabetes mellitus, either the production of insulin (type 1) or its effect on target cells (type 2) is defective. As a result, the glucose concentration in the blood cannot be properly regulated. Complications of impaired glucose concentration include nerve damage, kidney damage, retinal damage and arterial occlusive disease.

But what does all this have to do with COVID-19?

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Interrelationships between diabetes and long Covid

Existing diabetes can influence the course of a Covid-19 infection. At the same time, Covid-19 disease can influence and trigger diabetes:

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Covid-19 in diabetes: A risk factor for severe cases

In Germany, around 372,000 patients with type 2 diabetes, around 11,000,000 patients with type 1 diabetes. These patient groups are particularly at risk of Covid-19: Data sets from England, Scotland and Sweden showed that the risk of severe cases is increased. For example, the risk of intensive care treatment and the risk of death is approximately two to four times higher in type 1 diabetics and two to five times higher in type 2 diabetics than in comparable patients without diabetes. In type 2 diabetics, the risk increases, particularly among younger patients; in type 1 diabetics, the risk increases with increasing age and progression of the disease. This risk is particularly increased in patients with elevated HbA1c levels, overweight, history of blood sugar abnormalities, poorer kidney function, and micro and macrovascular damage [1]. According to Prof. Naveed Sattar from the University of Glasgow, diabetes is “a far greater risk factor than cardiovascular diseases.”

In addition to vaccination protection, it is important to follow optimal diabetes therapy. This also includes lifestyle measures such as sufficient exercise and a healthy and balanced diet. In acute cases of an infection, the rapid normalization of hyperglycaemia offers protection against severe progression.

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Diabetes due to Covid-19: An overview

Some research results suggest that Covid-19 disease can lead to diabetes. We present some of these Sutdias here.

SARS-CoV-2 in the human body
‍A group of researchers from Stanford University has taken and examined pancreatic samples from deceased COVID-19 patients. Coronaviruses could be detected in pancreatic beta cells. Coronaviruses normally enter cells via the so-called ACE-2 receptor. This receptor is primarily present in the lungs. In contrast, it is hardly found in pancreatic cells. However, pancreatic cells express neuropilin-1 on their surface. In the next step, the researchers tried to simulate the infection of the BETA cells in the laboratory. They found that cells produced significantly less insulin under the influence of corona viruses and died off in some cases. Observations that can also be made in the case of type 1 diabetes mellitus. If neuropilin-1 is blocked, the viruses are less able to penetrate the cells [2].

Researchers from Ulm University were also able to achieve similar results. They were able to detect corona viruses in pancreatic cells in four autopsied patients, even when virus particles were no longer detectable in the lungs. Viruses have also been detected in other areas of the pancreas that are relevant for digestion. The effects of this are still unclear. But the severe immune response that a corona infection can cause may also derail an already impaired metabolism.
In some patients, pancreatic cell damage can still be detected months after the infection. It is not yet clear to what extent this impairment will persist in the long term or whether patients can fully recover [3].

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Covid-19 and increased risk of type 2 diabetes
‍A study from St. Louis, USA examined the incidence of type 2 diabetes mellitus in 181,280 patients who had experienced a COVID-19 infection and were alive 30 days after the positive test result. A distinction was also made according to the severity of the course (non-hospitalized, hospitalized, treatment in intensive care). The COVID-19 group was compared with a control group of approximately 4 million patients. This has shown a 40% increase in the risk of type 2 diabetes mellitus among the COVID-19 group. If you break down the results by severity of the COVID-19 course, there is a connection between the risk of diabetes and the respective course. Non-hospitalized patients had an approximately 1.2 times risk, hospitalized patients an approximately 2.6 times risk and intensive care patients an approximately 3.6 times risk compared to the control group [4].

A meta-analysis of studies involving around 3700 patients, i.e. a comprehensive analysis of many individual studies, revealed that 14.4% of the patients examined and hospitalized with COVID-19 developed diabetes mellitus after the illness [5].

However, when collecting the data, there were disruptive factors that could falsify the results of the investigation: An inactive lifestyle with little exercise/sport is one of the most important risk factors for the development of type 2 diabetes mellitus. During the pandemic, many people were forced to live a more inactive lifestyle. Home office, closed sports facilities and hardly any opportunities for sporting activity could also explain an increase in diabetes cases following Covid disease.
The study from St. Louis looked at US veterans. These are mostly older, white men who often had high blood pressure or were overweight. These factors generally increase the risk of diabetes. The average age of the population is significantly lower.
In addition, it may also be that the people in the control group have also been infected with COVID-19 unnoticed and thus falsify the evaluation.
In addition, it should be noted that some COVID-19 patients were treated with glucocorticoids, which can also have a diabetic effect. This means that blood sugar levels rise when glucocorticoids (e.g. cortisone) are administered. The medication could therefore also be a reason for the increased risk of diabetes in COVID-19 patients.

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synopsis

Diabetes is a complex disease with far-reaching long-term consequences. There is evidence that corona disease can trigger diabetes. However, the causal relationship between a COVID-19 infection and the onset of diabetes mellitus has not yet been conclusively clarified. This requires further research. However, should this hypothesis continue to be confirmed, patients would have to be screened for diabetes following a corona infection in order to intercept possible long-term consequences. It is also possible that the pancreas will recover on its own after some time and that the metabolism will return to normal. As is often the case in science, it is important to verify the new findings through further research in order to be able to make a clear statement.

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[1] Schumacher, B. (2021): That makes Covid-19 so dangerous for diabetics. MMW Fortschr Med. 163 (13): 18-19

[2] Wu, CT. et al (2021): SARS-CoV-2 infections human pancreatic β cells and elicits β cell impairment. Cell Metab. 2021 Aug 3; 33 (8) :1565-1576.e5

[3] Müller, J. et al (2012): SARS-CoV-2 infections and replicates in cells of the human endocrine and exocrine pancreas. Nat Metab. 2021 Feb; 3 (2) :149-165

[4] Al-Aly, Z. (2023): Diabetes after SARS-CoV-2 infection. Lancet Diabetes Endocrinol. 2023 Jan; 11 (1) :11-13.

[5] Ssentongo, P. et al. (2022): Association of COVID-19 with Diabetes: a Systematic Review and Meta-Analysis. Sci Rep. 2022; 12:20191.