People who have had Covid-19 are at increased risk of developing type 2 diabetes. This is the result of a study by DDZ, DZD and IQVIA, which has now been published in Diabetologia.

Studies show that the human pancreas can also be a target of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2 virus). Following a Covid-19 infection, reduced numbers of insulin secretory granules in beta cells and impaired glucose-stimulated insulin secretion have been observed. In addition, after Covid-19 disease, some patients developed insulin resistance and had elevated blood glucose levels although they had no previous history of diabetes. SARS-CoV-2 infection may lead to a strong release of pro-inflammatory signaling substances (cytokines). Activation of the immune system may persist for months after a SARS-CoV-2 infection and impair insulin effectiveness (muscle, fat cells, liver).

To date, however, it is unclear whether these metabolic changes are transient or whether Covid-19 disease increases the risk of persisting diabetes. To investigate this question, researchers from the German Diabetes Center (DDZ), German Center for Diabetes Research (DZD) and IQVIA (Frankfurt) conducted a retrospective cohort study.

The cohort study included a representative panel of 1,171 physician practices across Germany (March 2020 to January 2021: 8.8 million patients). Follow-up continued until July 2021. “The aim of our study was to investigate the incidence of diabetes after infection with SARS-CoV-2,” said first author Wolfgang Rathmann, head of the Epidemiology Research Group at the DDZ. As a control group, the researchers selected people with acute upper respiratory tract infections (AURI), which are also frequently caused by viruses. The two cohorts were matched for sex, age, health insurance, month of Covid-19 or AURI diagnosis, and comorbidities (obesity, hypertension, high cholesterol, heart attack, stroke). Patients on corticosteroid therapy were excluded from the study.

During the study period, 35,865 people were diagnosed with Covid-19. “Our analyses showed that patients with Covid-19 developed type 2 diabetes more frequently than people with AURI. The incidence of diabetes with Covid-19 infection was 15.8 compared to 12.3 per 1000 people per year with AURI. Statistical analysis resulted in an incidence rate ratio (IRR) of 1.28. Put simply, this means that the relative risk of developing type 2 diabetes was 28% higher in the Covid-19 group than in the AURI group,” Rathmann said, summarizing the results.
 
Although type 2 diabetes is unlikely to be a problem for the vast majority of people with mild Covid-19 disease, the authors recommend that anyone who has recovered from Covid-19 be alert to the warning signs and symptoms, such as fatigue, frequent urination and increased thirst and seek immediate treatment.

New research published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]), suggests a possible association between mild COVID-19 cases and subsequently diagnosing type 2 diabetes.

The analysis of health records from 1,171 general and internal medicine practices across Germany conducted by Professor Wolfgang Rathmann and Professor Oliver Kussfrom the German Diabetes Center at Heinrich Heine University, Dusseldorf, Germany, and Professor Karel Kostev (IQVIA*, Frankfurt, Germany) found that adults who recover from mostly mild COVID-19 appear to have a significantly higher risk of developing type 2 diabetes than a matched control group who had other types of respiratory infections, which are also frequently caused by viruses.

If confirmed, these results indicate that diabetes screening in individuals after recovery from mild forms of COVID-19 should be recommended, researchers say. This potential link between COVID-19 and diabetes is also being investigated in various ongoing studies, including on the CoviDiab registry** and other studies connected to so-called ‘long COVID’.

Previous studies have noted that inflammation caused by SARS-CoV‑2 may damage insulin-producing beta cells, causing them to die or change how they work, resulting in acute hyperglycaemia (high blood glucose). Tissues becoming less reactive to insulin due to inflammation in the body is also thought to be a possible cause. Sedentary lifestyles brought on by lockdowns could also be playing a role. This may explain why new-onset hyperglycaemia and insulin resistance have been reported in COVID-19 patients with no prior history of diabetes.

However, it is unclear whether these metabolic changes are temporary or whether individuals with COVID-19 may be at increased risk of developing chronic diabetes. Furthermore, there is a lack of studies investigating the incidence of diabetes after recovery from COVID-19 in mild cases.

To provide more evidence, the researchers analysed electronic health records from the Disease Analyzer database, which included information on 8.8 million adults who visited 1,171 general and internal medicine practices across Germany between March 2020 and January 2021. This included 35,865 patients who were diagnosed with COVID-19. The incidence of diabetes after COVID-19 was compared with a cohort of individuals (average age 43 years; 46% women) who were diagnosed with an acute upper respiratory tract infection (AURI) (but not COVID-19) within the same timeframe, matched for sex, age, health insurance coverage, index month of COVID-19 or AURI diagnoses and comorbidities (obesity, high blood pressure, high cholesterol, heart attack, stroke). Regression models were used to calculate incidence rate ratios (IRRs) for type 2 diabetes and other forms of diabetes.

Individuals with a history of COVID-19 or diabetes, and those using corticosteroids within 30 days after the index dates were excluded. During an average follow-up of 119 days for COVID-19 and 161 days for AURI, the numbers of hospitalisations were similar in both groups (COVID-19: 3.2% vs controls: 3.1%; median number of hospital stays: 1 in both cohorts).

The researchers found that new cases of type 2 diabetes were more common in patients who tested positive for COVID-19 than those with an AURI (15.8 vs 12.3 per 1000 people per year) giving an incidence rate ratio (IRR) of 1.28. In simple terms, this means that the relative risk of developing type 2 diabetes in the COVID group was 28% higher than in the AURI group. The IRR for the COVID group was not increased in other unspecified forms of diabetes.

“COVID-19 infection may lead to diabetes by upregulation of the immune system after remission, which may induce pancreatic beta cell dysfunction and insulin resistance, or patients may have been at risk for developing diabetes due to having obesity or prediabetes, and the stress COVID-19 put on their bodies speeded it up”, says lead author Professor Wolfgang Rathmann. “The risk of abnormally high blood sugar in individuals with COVID-19 is most likely a continuum, depending on risk factors such as injury to beta cells, an exaggerated inflammatory response, and changes in pandemic-related weight gain and decreased physical activity”, adds co-author Professor Oliver Kuss.

Prof Rathmann adds: “Since the COVID-19 patients were only followed for about three months, further follow-up is needed to understand whether type 2 diabetes after mild COVID-19 is just temporary and can be reversed after they have fully recovered, or whether it leads to a chronic condition.”

Although type 2 diabetes is not likely to be a problem for the vast majority of people who have mild COVID-19, the authors recommend that anyone who has recovered from COVID-19 be aware of the warning signs and symptoms such as fatigue, frequent urination, and increased thirst, and seek treatment right away.

The authors note some limitations to their study, including that limited information on hospitalisations and individuals diagnosed with COVID-19 outside of general practice (e.g. in hospitals or at COVID-19 test centres) may limit the accuracy of the results. Similarly, they were unable to control for body mass index because the data were not available and the incidence of type 1 diabetes was not investigated due to the small number of cases. Finally, they note that their findings might not be generalisable to other populations.

Many COVID-19 patients newly diagnosed with diabetes during hospital admission may in fact have a temporary form of the disease related to the acute stress of the viral infection and may return to normal blood sugar levels soon after discharge, a study by Massachusetts General Hospital (MGH) has found. These patients are more likely to be younger, non-white, and on Medicaid or uninsured compared to individuals with previously diagnosed diabetes, suggesting many of these “new-onset” cases may simply be pre-existing but undiagnosed diabetes in individuals with limited access to healthcare services, according to the study published in Journal of Diabetes and Its Complications.

High rates of newly diagnosed diabetes mellitus (NDDM) have been reported in COVID-19 hospital admissions around the world. It is still unclear, however, if this phenomenon represents truly new diabetes or previously undiagnosed cases, what the cause of these elevated blood sugars may be, and whether patients’ blood sugars improve after resolution of COVID-19 infection. Pre-existing diabetes in people with COVID-19 has been associated with higher rates of hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and death.

“We believe that the inflammatory stress caused by COVID-19 may be a leading contributor to ‘new-onset’ or newly diagnosed diabetes,” says lead author Sara Cromer, MD, an investigator with the Department of Medicine-Endocrinology, Diabetes and Metabolism at MGH. “Instead of directly causing diabetes, COVID-19 may push patients with pre-existing but undiagnosed diabetes to see a physician for the first time, where their blood sugar disorder can be clinically diagnosed. Our study showed these individuals had higher inflammatory markers and more frequently required admission to hospital ICUs than COVID-19 patients with pre-existing diabetes.”

For its study, the MGH team looked at 594 individuals who exhibited signs of diabetes mellitus when admitted to MGH at the height of the pandemic in the spring of 2020. Of that group, 78 had no known diagnosis of diabetes prior to admission. Researchers learned that many of these newly diagnosed patients — versus those with pre-existing diabetes — had less severe blood sugar levels but more severe COVID-19. Follow-up with this cohort after hospital discharge revealed that roughly half its members reverted to normal blood sugar levels and that only eight percent required insulin after one year.

“This suggests to us that newly diagnosed diabetes may be a transitory condition related to the acute stress of COVID-19 infection,” explains Cromer. Indeed, this key finding supports the clinical argument that newly diagnosed diabetes is likely caused by insulin resistance — the inability of cells to properly absorb blood sugar in response to insulin, resulting in higher-than- normal build-up of glucose in the blood – rather than by insulin deficiency, caused by direct and permanent injury to the beta cells which manufacture insulin.

“Our results suggest that acute insulin resistance is the major mechanism underlying newly diagnosed diabetes in most patients with COVID-19, and that insulin deficiency, if it occurs at all, is generally not permanent,” says Cromer.  “These patients may only need insulin or other medications for a short time, and it’s therefore critical that physicians closely follow them to see if and when their conditions improve.”