German Study Warns That Even Mild SARS-CoV-2 Infections Are Triggering New Onset Type 2 Diabetes In Many!

A new study conducted by researchers from the German Diabetes Center at the Leibniz Center for Diabetes Research-Heinrich Heine University-Germany and the Medical Faculty and University Hospital Düsseldorf-Heinrich Heine University-Germany has alarmingly shown that even mild SARS-CoV-2 infections are triggering new onset type 2 diabetes in many.

Graphical Abstract
 
The study team aimed investigate diabetes incidence after infection with COVID-19. Individuals with acute upper respiratory tract infections (AURI), which are frequently caused by viruses, were selected as a non-exposed control group.
 
The study team performed a retrospective cohort analysis of the Disease Analyzer, which comprises a representative panel of 1171 physicians’ practices throughout Germany (March 2020 to January 2021: 8.8 million patients).
 
Newly diagnosed diabetes was defined based on ICD-10 codes (type 2 diabetes: E11; other forms of diabetes: E12–E14) during follow-up until July 2021 (median for Covid-19, 119 days; median for AURI 161 days). Propensity score matching (1:1) for sex, age, health insurance, index month for COVID-19/AURI and comorbidity (obesity, hypertension, hyperlipidaemia, myocardial infarction, stroke) was performed. Individuals using corticosteroids within 30 days after the index dates were excluded. Poisson regression models were fitted to obtain incidence rate ratios (IRRs) for diabetes.
 
In all, there were 35,865 individuals with documented COVID-19 in the study period. After propensity score matching, demographic and clinical characteristics were similar in 35,865 AURI controls (mean age 43 years; 46% female).
 
The study findings indicated that individuals with COVID-19 showed an increased type 2 diabetes incidence compared with AURI (15.8 vs 12.3 per 1000 person-years).
 
Utilizing marginal models to account for correlation of observations within matched pairs, an IRR for type 2 diabetes of 1.28 (95% CI 1.05, 1.57) was estimated. The IRR was not increased for other forms of diabetes.

The study findings show that COVID-19 confers an increased risk for type 2 diabetes.
 
Importantly the study findings support the active monitoring of glucose dysregulation after recovery from mild forms of SARS-CoV-2 infection.
 
The study findings were published in the peer reviewed journal: Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]).
https://link.springer.com/article/10.1007/s00125-022-05670-0
 
Thailand Medical News had already previously covered numerous studies that showed SARS-CoV-2 infections caused hyperglycemia and also new onset diabetes in many who were infected with the SARS-CoV-2 virus.
 
https://www.thailandmedical.news/news/new-york-study-shows-almost-50-percent-of-covid-19-patients-will-develop-hyperglycemia-as- a-result-of-sars-cov-2-triggering-adipose-tissue-dysfunction
 
https://www.thailandmedical.news/news/breaking-covid-19-latest-study-shows-patients-not-previously-diagnosed-with-diabetes-exhibiting-hyperglycemia-and-increased-mortality
 
https://www.thailandmedical.news/news/covid-19-news-doctors-worldwide-are-reporting-increases-of-new-onset-diabetes-cases-most-probably-triggered-by-covid-19
 
https://www.thailandmedical.news/news/breaking-sars-cov-2-infection-induces-increase-of-gp73-that-causes-dysglycaemia-increased-gp73-could-also-imply-future-liver-disease-and-liver-cancer
 
https://www.thailandmedical.news/news/study-reveals-sars-cov-2-binding-to-host-dpp4-receptors-causes-dysregulation-of-proteins-associated-with-diabetes,-leading-to-severe-covid
 
https://www.thailandmedical.news/news/study-warns-of-an-emerging-surge-in-diabetes-in-otherwise-healthy-individuals-as-a-result-of-covid-19
 
https://www.thailandmedical.news/news/covid-19-triggers-hyperglycemia-and-also-disrupts-fat-cells-and-causes-decreased-production-of-the-hormone-adiponectin-especially-in-severe-stages
 
https://www.thailandmedical.news/news/covid-19-research-study-calls-for-control-of-hyperglycemia-in-both-diabetics-and-non-diabetics-to-prevent-covid-19-severity
 
https://www.thailandmedical.news/news/covid-19-asean-news-indonesian-researchers-find-that-fasting-blood-glucose-levels-upon-hospitalization-linked-to-covid-19-severity
 
The new study findings are the first to show a correlation specifically to mild SARS-CoV-2 infections and new onset type 2 diabetes.
 
The detailed analysis of health records from 1,171 general and internal medicine practices across Germany conducted by Professor Dr Wolfgang Rathmann and Professor Dr Oliver Kuss from the German Diabetes Center at Heinrich Heine University, Dusseldorf, Germany, and Professor Dr 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.
 
The study team stresses that these study findings indicate that diabetes screening in individuals after recovery from mild forms of COVID-19 should be recommended.
 
It should be noted that this correlation 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'.
 
Past studies have noted that inflammation caused by the SARS-CoV 2 virus may damage insulin-producing beta cells, causing them to die or change how they work, resulting in acute hyperglycaemia (high blood glucose). https://pubmed.ncbi.nlm.nih.gov/33129968/
 
It was also thought that tissues becoming less reactive to insulin due to inflammation in the body is also 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. https://pubmed.ncbi.nlm.nih.gov/34035524/
 
It is however unclear whether these metabolic changes are temporary or whether individuals with COVID-19 may be at increased risk of developing chronic diabetes.
 
To date, there has been a lack of studies investigating the incidence of diabetes after recovery from COVID-19 in mild cases.
 
In order to provide more evidence, the study tean analyzed 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 occurrence 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.
 
For the study, all individuals with a history of COVID-19 or diabetes, and those using corticosteroids within 30 days after the index dates were excluded.
 
It was found that during an average follow-up of 119 days for COVID-19 and 161 days for AURI, the numbers of hospitalizations were similar in both groups (COVID-19: 3.2% vs controls: 3.1%; median number of hospital stays: 1 in both cohorts).
 
The study team alarmingly 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 other word, 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.
 
Lead author Professor Dr Wolfgang Rathmann told Thailand Medical News, "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.”
 
Co-author Professor Dr Oliver Kuss added, "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.”
 
Professor Rathmann further added, "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."
 
The study team strongly advocates that anyone who has recovered from COVID-19 be aware of the warning signs and symptoms of early onset type 2 diabetes such as fatigue, frequent urination, and increased thirst, and seek treatment right away.
 
The study team did highlight some limitations to their study, including that limited information on hospitalizations and individuals diagnosed with COVID-19 outside of general practice (e.g. in hospitals or at COVID-19 test centers) may limit the accuracy of the results.
 
Also, the team 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.
 
They also added that their study findings might not be generalizable to other populations.
 
The study team however also notes that there are still a number of unanswered questions for future research.
 
Firstly, it is unclear whether pre-existing diabetes becomes apparent during COVID-19 as a consequence of immunological activation or stress hyperglycemia.
 
Secondly, it should be investigated if post-COVID diabetes may be reversed after full recovery.
 
Thirdly, the management of new-onset diabetes after COVID-19 should be evaluated.
 
Diabetes ketoacidosis has been observed in some individuals without known diabetes even months after COVID-19. https://pubmed.ncbi.nlm.nih.gov/32706395/
 
Hence, serological testing for diabetes-associated autoantibodies and C-peptide may be indicated in individuals without known risk factors for diabetes after COVID-19.
 
Finally, the risk of hyperglycemia in individuals with COVID-19 is most likely a continuum, depending on risk factors such as injury of beta cells, an exaggerated proinflammatory response and changes in health behavior during the pandemic. In particular, by using fixed cut-off points for the definition of incident diabetes, this study may have missed changes in hyperglycemia risk below these cut-off points. Future studies should investigate the effects of SARS-CoV-2 infections on glucose and HbA1c measurements on a continuous scale.
 
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