Even a year after infection, there’s greater risk for adults and kids.
Covid is leaving a trail of diabetes in its wake, two studies show, with a 15% increased incidence in England and kids progressing to type 1 diabetes at twice the rate of their uninfected peers in Germany.
The numbers – and there are many of them – suggest at least considering diabetes in any post-covid infection follow-up, according to the authors of both papers.
Drawing on records for over 16 million people in England since the start of the covid pandemic, researchers from the US and the UK have found severe covid significantly increased the risk of diabetes – both type 1 and type 2 – but vaccination greatly reduced that risk.
Incidence of type 2 diabetes remained elevated by 30% more than a year after covid diagnosis in unvaccinated people. Type 1 diabetes incidence was elevated during the year post-infection, but not beyond. The associations were higher for people who’d been hospitalised with covid.
“Encouraging vaccination – which, in addition to reducing the immediate severity of covid-19, reduces the immediate and longer-term risk of incident type 2 diabetes after covid-19 – is essential,” the authors write.
“Routine testing for diabetes after severe covid-19, particularly in people at previous elevated risk of diabetes, and ensuring treatment and continued monitoring to identify those whose diabetes persists or resolves, should be considered.”
The researchers compared diabetes incidence for up to 102 weeks after covid infection with diabetes incidence before or without covid infection. They looked at what happened to people before and after vaccines become available, before and after the omicron and delta variants became dominant, and compared those who were vaccinated with those who weren’t.
Across the entire study, unvaccinated people who had covid had almost nine times the risk of developing diabetes in the first four weeks compared with uninfected people. Risk remained elevated by 64% in the second year after infection, the study found.
Before vaccines were available, incidence of type 2 diabetes after covid was over four times higher than for infected people in weeks one to four of infection, subsiding to 24% higher after that period. Patients who were vaccinated before infection had only a 66% higher risk in the first four weeks after covid infection compared to the uninfected.
People hospitalised with covid before vaccines were available had 28 times the risk of developing type 2 diabetes compared with people with covid who were not hospitalised, declining to twice the risk a month after infection. Those infected but not hospitalised had nearly twice the risk of the uninfected in the first month, and an 11% higher risk subsequently.
Six months after covid infection, standardised analysis showed 135 per 100,000 people in the pre-vaccination era developed type 2 diabetes, compared with 58 per 100,000 in the vaccinated group and 225 per 100,000 in those not vaccinated when vaccines were available.
“Little difference was observed in excess risk by sex, ethnicity, and presence or absence of prediabetes and obesity,” the authors write.
Type 2 diabetes was persistent (still needing treatment at four months) in around 60% of those diagnosed post-covid infection.
“Patterns were similar for type 1 diabetes, although excess incidence did not persist beyond 1 year after a covid-19 diagnosis,” the authors write.
Overall, being unvaccinated gave people infected with covid four times the risk of developing type 1 diabetes compared to those uninfected, in the first month. Before the availability of vaccines, people infected with covid had around two and a half times the risk of being diagnosed with type 1 diabetes in the first month, compared to the uninfected. In the vaccination era, the risk for infected patients was 60% higher for vaccinated patients and more than four times higher for the unvaccinated, compared with the uninfected.
Patients hospitalised with covid in pre-vaccination times had more than 50 times the risk of developing type 1 diabetes in the first four weeks after infection compared to those not infected. Those not hospitalised had around 65% higher chance than those who hadn’t had covid.
“No consistent evidence of excess incidence of gestational diabetes after covid-19 was observed in any group,” the authors note.
Children, covid and type 1 diabetes
German results published in a JAMA research letter revealed that children who contracted covid-19 progressed from presymptomatic to clinical type 1 diabetes at twice the rate of those who didn’t catch covid.
“[T]he covid-19 pandemic was associated with an accelerated progression to clinical disease and … this acceleration was confined to those with covid-19,” the authors write.
“The findings are consistent with previously reported acceleration of progression in children with presymptomatic type 1 diabetes by viral infection.”
The researchers from the Institute of Diabetes Research at Helmholtz Munich and the Centre for Regenerative Therapies at the Technical University of Dresden (TUD) looked at over 750 children aged 3-5.3 years who they knew had early-stage type 1 diabetes.
They drew on a cohort of children in Bavaria tested for presymptomatic type 1 diabetes. Since 2015, parents have been invited to screen their children between the ages of two and 10 for islet autoantibodies as part of the Fr1da study. Having two islet antibodies is defined as presymptomatic type 1 diabetes. Around three in 1000 children are found to have presymptomatic T1DM according to the ongoing study.
They followed up 358 children between 2015 and 1 March 2020 and 396 after the pandemic began, for a median of 2.6 years in both groups. All were monitored for progression at three-month to six-month intervals. In the pre-pandemic follow-up group, 57 participants developed clinical type 1 diabetes – an incidence rate of 6.4 per 100 person-years – and 113 did so in the pandemic group – an incidence rate of 12.1, or nearly double.
In the pandemic follow-up group, 236 of the 396 had a reported covid infection or evidence of antibodies. The type 1 diabetes incidence rate in this group was 8.6 without covid infection and 14 with covid infection.
The results are consistent with previous analysis comparing the incidence rate for type 1 diabetes in children in Bavaria in the period 2018-19 to the period 2020-21. Using medical claims data for just over a million children, the researchers found that children had a 57% higher risk of type 1 diabetes during the covid period, regardless of known infection status, and 69% higher where covid infection was confirmed.
Type 1 and 2?
It is not yet known how covid could increase the incidence of both type 1 diabetes, a chronic autoimmune disorder, and type 2 diabetes, a chronic metabolic disorder. Research is moving fast in this area.
“The pathophysiology of types 1 and 2 diabetes are distinct, as are the theoretical pathways by which covid-19 might cause them,” the authors of a systematic review published last year in JAMA said.
A review published in April this year concluded that “SARS-CoV-2 infection presents itself as a risk factor for developing diabetes mellitus [type 1 and 2], possibly through (1) the destruction of insulin-producing cells, (2) increased hepatic gluconeogenesis, and (3) insulin resistance through an elevated inflammatory state and lactate production.”
Commentary on the English study, also published in The Lancet, said “[t]he mechanisms of persistent risks are not clear, but evidence suggests sustained immune dysfunction and T-cell activation for years after the initial infection and viral persistence in several organ systems—including those responsible for glucose homoeostasis”.
The authors of the English study excluded diabetes diagnoses made on the same day as covid infection confirmation to minimise the chance that previously undiscovered diabetes cases unearthed as part of routine testing on infection were elevating the figures.
They put forward the idea that diagnosis down the track could be a result of damage to pancreatic β cells or systemic inflammatory responses in patients who were not pre-diabetic.
Research referred to in the German paediatric type 1 diabetes study suggests “progression from islet autoimmunity to type 1 diabetes may increase after an enterovirus infection characterised by the presence of viral RNA in blood”.
