T1DM is characterized by autoimmune destruction of beta-cell of the pancreases causing absolute insulin deficiency. According to the American Diabetes Association (ADA), T1DM has three stages. In stage 1, there are only positive antibodies with normal glucose parameters. Impaired glucose parameters (i.e., prediabetes) develop in stage 2, and in stage 3, abnormal glucose testing meets the diagnostic criteria for DM.6
The COVID-19 pandemic has significantly impacted patients with DM in general. One systemic review conducted in the USA from fifteen studies including both adults and children concluded that the prevalence of T1DM in COVID-19 patients ranged from 0.15–28.98%, while the rate of COVID-19 in patients with T1DM ranged from 0–16.67%.7 There is an ongoing registry project called COVIDIAB (https://covidiab.e-dendrite.com/) conducted by the King's College London and Monash University to collect data of all COVID-19 patients with new-onset DM and to study the association between the two conditions.
The patient in our study had a mild COVID-19 infection that did not need hospitalization, and no laboratory tests were done during his illness to check his glycemic levels. Then after two months, he presented with full-blown symptomatic hyperglycemia that did not reach the level of DKA. Subsequent tests confirmed T1DM with low C-peptide and positive anti-GAD. Again, this case raised a question regarding the relationship between COVID-19 and T1DM.
While it is well established that genetics play a major role in T1DM, viral infections role – particularly enteroviruses such as coxsackievirus – as triggers for T1DM has been supported in human studies.8 In addition, researcher of the TEDDY study found a temporal link between respiratory infections and islet cell autoantibody seroconversion, where 454 children seroconverted after 87,327 recorded infectious respiratory episodes. 9
As regards COVID-19 relationship with T1DM, one theory suggests that SARS-CoV-2 can enter the islets cells of the pancreases through the ACE-2 receptors and lead to beta-cell damage.2 (3) Fignani et al. detected ACE2 in human pancreatic islets, and it was expressed in beta-cells more than alpha-cells. ACE2 was also highly detected in pancreas microvasculature pericytes. They also found that pro-inflammatory cytokines increased the expression of ACE2 in the beta-cells.10
Is it the local microvasculature inflammation that leads to beta-cell destruction? Or is it just a coincidence, i.e., the stress response induced by an acute infection unmasks an already ongoing undiagnosed T1DM? Or is it SARS-CoV-2 that causes an exacerbation of immunity? Hollstein et al. reported a case of 19 years old man diagnosed with autoantibody-negative T1DM, 5–7 weeks following a COVID-19 infection, and suggested a cytolytic effect of COVID-19 on beta-cells.11 Dehghani et al. also reported a 23 years old man who was found to have T1DM with an HbA1c of 12.2% at the time of having COVID-19 infection.12 However, in our patient, autoimmune T1DM was diagnosed two months after COVID-19 infection, which points more towards an exacerbation of immunity.
Another vital issue to mention, the patient had non-medically treated subclinical hypothyroidism in 2018 with a similar level of TSH in 2021 (6.51 mIU/L in 2018 and 6.37 mIU/L in 2021). Anti-thyroid peroxidase (Anti-TPO) was positive after COVID-19, but it was not measured before. So here, the relationship between COVID-19 and positive anti-TPO remains an open question that needs more research.