After initial reports of new-onset hyperglycaemia coinciding with infection in the early phases of the pandemic, several large cohort studies now suggest an overall increased risk of new-onset diabetes mellitus (DM) for both type 1 diabetes (T1D)1,2 and type 2 diabetes (T2D)3,4,5,6 following COVID-19 infection. For T1D, however, epidemiological data are controversial — German2 and Scottish1 registries noted an increase in T1D diagnosis in children and adolescent shortly after a peak in SARS-CoV-2 infection numbers, whereas a larger population-based, repeated, cross-sectional study from Canada7 did not. Delayed diagnoses of naturally occurring T1D as an indirect result of the pandemic are likely confounding these results, while the challenge to verify past COVID-19 infection in children with new-onset diabetes further complicates association studies.
At the same time, evidence for a connection of COVID-19 with new-onset T2D appears more robust. Surveys of electronic patient records suggest an overall increased risk of new-onset DM up to 12 weeks post infection3, an increased likelihood of being prescribed insulin within 91 days of COVID-19 diagnosis3 and an excess burden of incident diabetes and hyperglycaemia (where > 77% were stratified as T2D) at 12-month follow up4. If and when glycaemic control is re-established after recovery from COVID-19 in those patients remains unclear. In some cohorts, glucose control had improved in 63–79% of patients 6 months after recovery5,8 and improved in 41–79% of patients 10 months after recovery5,6. Up to 56% of patients remained hyperglycaemic6. A separate cohort of hospitalized COVID-19 patients with dysglycaemia during acute infection displayed reversion to physiological glycaemic control in the post-acute phase in a 7 month follow-up9.
Despite uncertainties regarding prevalence and persistence, dysglycaemia may thus represent a potential aspect of post-acute sequelae of SARS-CoV-2 (PASC), also commonly referred to as ‘long COVID’ (or ‘LC’). However, these findings also do not necessarily imply a direct diabetogenic effect of SARS-CoV-2 infection, as hyperglycaemia is also observed after non-COVID acute respiratory distress syndrome, possibly as a result of systemic inflammation10. Nonetheless, occurrence of new-onset T2D3,4,5,6 and insulin resistance8 post-COVID suggests that SARS-CoV-2 infection may promote β-cell exhaustion in at-risk cohorts.
Notably, breakthrough infection after vaccination was not associated with a significantly lower incidence of DM in the context of PASC, when compared to infections of unvaccinated individuals. However, a decreased risk of insulin use suggests ameloration of the severity of metabolic dysregulation by pre-exisiting immunity11. Furthermore, a recent preprint suggests an accumulating risk of new-onset DM with multiple re-infections12. Due to ethical reasons, correlative time-resolved data on insulin and glucose levels with degree of β-cell infection in humans will be invariably lacking, which will restrict our experimental knowledge to animal models, including non-human primates. Overall, the long-term risk for and burden of new-onset DM of any type following COVID-19, especially in light of newly emerging, immune-evasive variants and multiple subsequent infections, can only be clarified by population-level studies providing long term follow-up data and comprehensive data sets in the coming years.