A recent article posted to the journal Diabetes/Metabolism Research and Reviews explored the risk of a type 1 diabetes wave after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic.
Editorial: Should we expect a wave of type 1 diabetes following SARS-CoV-2 pandemic?. Image Credit: Image Point Fr / Shutterstock
Introduction
Mounting reports indicated that SARS-CoV-2 exhibited tropism for different organs and tissue, and coronavirus disease 2019 (COVID-19)-related long-term sequelae exist. Further, recent studies discovered that glucose homeostasis could be disrupted during and long after an acute SARS-CoV-2 infection, with enhanced insulin resistance and beta-cell destruction lasting six months. Since hyperglycemia worsens COVID-19 outcomes, these glycometabolic anomalies are particularly relevant.
The clinical characterization of these metabolic anomalies, on the other hand, appeared to be comparable to that of post-stress diabetes or type 2 diabetes. Surprisingly, the influence of the COVID-19 pandemic on a possible increase in the occurrence of type 1 diabetes mellitus in the future is unknown. However, since SARS-CoV-2 infection's impacts on the immune system have been recorded, the association between COVID-19 and type 1 diabetes should be investigated further.
In the present study, the authors assessed the influence of SARS-CoV-2 on immunity, beta-cell functioning, and the chances of a wave of type 1 diabetes mellitus after the COVID-19 pandemic.
Impact of SARS-CoV-2 on immune system
COVID-19 might result in a hyperinflammatory condition increasing the susceptibility to autoimmune events. A moderated rise in the concentrations of some peripheral cytokines leading to cytokine storm was documented among SARS-CoV-2 patients requiring intensive care unit (ICU) treatment. Furthermore, COVID-19 has different effects on numerous lymphocyte subsets identical to other hyperinflammatory conditions like graft-versus-host disease-induced cytokine release syndrome.
According to a new study, a shift in cytokine profile persists even after the acute phase of SARS-CoV-2 infection has passed, reflecting immunological weakening. The inhibition of programmed cell death protein 1 (PD-1), currently investigated for the treatment of autoimmune diabetes, can reverse these changes. The autoimmune reactions triggered by immunological imbalance and cytokine storm in multisystem inflammatory syndrome in children (MIS-C) during COVID-19 were similar to Kawasaki disease. Other COVID-19-linked possible autoimmune diseases include Guillain-Barre syndrome and autoimmune hemolytic anemia. Antinuclear antibodies and lupus anticoagulants, among other autoantibodies, have been found in COVID-19 patients.
Respiratory viral infections, such as those by CoVs, increase the likelihood of autoimmune diabetes. Presently, there has been no evidence linking type 1 diabetes and SARS-CoV-2. Furthermore, particular autoantibodies have only been discovered in individual case studies, not in a cohort of COVID-19 patients. Regardless, given the lag in the peak of SARS-CoV-2 infection and the presence of linked autoimmune disorders such as Kawasaki disease or MIS-C, a future uptick in the frequency of incidences of type 1 diabetes cannot be ruled out.
Influence of COVID-19 on beta-cell activity
SARS-CoV-2 could infect the pancreas by binding to the angiotensin-converting enzyme 2 (ACE2) receptor, found in pancreatic beta-cells and, to a small degree, islet microvasculature and pancreatic alpha-cell. In addition, SARS-CoV-2 causes a cytokine storm, creating a systemic pro-inflammatory environment that may aid glucose metabolism modifications.
An existing study reported a significant frequency of new-onset hyperglycemia in a group of 551 hospitalized COVID-19 patients. Additionally, persistent glucose surveillance and intravenous arginine stimulation revealed concealed metabolic/hormonal abnormalities that lasted up to six months after hospital release, accompanied by increasing insulin resistance and beta-cell hyperstimulation, eventually leading to beta-cell exhaustion.
Existing evidence implied that disruption to the endocrine pancreas occurs during COVID-19. However, estimating the damage to beta-cell mass, the risk variables that predispose to similar impact following viral infection, and whether this may progress to insulin-dependent diabetes via classic pathogenetic processes or novel routes were challenging.
New onset of type 1 diabetes mellitus in SARS-CoV-2 pandemic
The first example of new-onset type 1 diabetes in a young lady barely one month following SARS-CoV-2 infection backed up the theory that COVID-19 may favor the development of type 1 diabetes. In any case, the preliminary epidemiological findings were inconclusive.
The Italian Society for Pediatric Endocrinology and Diabetes conducted a study to compare the frequency of diabetic ketoacidosis in those with new-onset or existing type 1 diabetes in the pandemic months of February to April 2020 to the same months of the preceding year. Although the number of new cases of type 1 diabetes decreased by 23% in 2020, a more severe type of diabetic ketoacidosis was observed. Besides, the inference could be contributed by delayed diagnosis, limited access to pediatric clinics, and less exposure to seasonal viruses promoting type 1 diabetes because of COVID-19-related social distancing.
In northwest London, the United Kingdom (UK), some investigators reported a hike of 12-15 novel cases of type 1 diabetes within the first three months of the pandemic, indicating nearly an 80% surge over prior years in the same area. Further, population-based research in Germany found that the proportion of type 1 diabetes cases reported remained stable, but severe ketoacidosis in children and teenagers experiencing new-onset type 1 diabetes heightened significantly.
Latest data from the United States (US) revealed a substantial increase in diabetes diagnoses among pediatric patients one-month post-COVID-19 relative to non-SARS-CoV-2 patients aged <18 years and those with an acute respiratory illness other than COVID-19 in the pre-pandemic timeframe. However, type 1 and 2 diabetes patients cannot be distinguished from this data. Yet, nearly 48.5% of these patients exhibited diabetic ketoacidosis during diagnosis, compared to just 13.6% in non-SARS-CoV-2 patients. Another analysis from the US validated these findings, revealing a 57% rise in type 1 diabetes patients hospitalized during the pandemic year compared to the previous five pre-pandemic years, as well as a 49.7% increase in diabetic ketoacidosis patients over the same timeframe.
The authors mentioned that a link probably exists between COVID-19 and the onset of type 1 diabetes. However, the small number of cases observed and the short registration time might have affected the results of the available investigations. Further, the epidemiology records may have been altered by social distancing. Moreover, children were less susceptible to SARS-CoV-2 infection, experienced a milder illness course, and their immune responses differed significantly from adults. Hence, larger observation groups and extended observation times in the pandemic phase would be required to appropriately investigate this relationship.
Conclusions
To summarize, the present study indicated that COVID-19 might favor the complicated etiology of type 1 diabetes, although many concerns remain unanswered. This included the duration of SARS-CoV-2-induced beta-cell destruction and the probable mechanism causing it. For uncovering these topics, initiatives like the SARS-CoV-2-linked diabetes registry that was part of the global registry of new-onset COVID-19 related diabetes (COVIDIAB) project should be supported.
Moreover, given the large number of worldwide populations vulnerable to SARS-CoV-2, an increase in type 1 diabetes cannot be ruled out in the future. This was a fascinating yet understudied issue, and as the pandemic progresses, worldwide efforts are necessary to gain a better understanding of the disease's physiopathological underpinnings. Meanwhile, to prevent dangerous presentations that might coincide with a surge of new-onset type 1 diabetes, the researchers recommended an amping up of COVID-19 surveillance techniques.
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