In the post-acute phase, individuals with coronavirus disease 2019 (COVID-19) exhibited increased risks and 12-month burdens of incident diabetes and antihyperglycaemic use compared with a contemporary control group of people who were enrolled during the same period and had not contracted the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and a historical control group from a pre-pandemic era, according to a study published in The Lancet Diabetes and Endocrinology.
“Although the risks and burdens increased according to the severity of the acute infection (as proxied by the care setting), they were evident and not trivial among people who were not hospitalised for COVID-19 — this group represents most people with COVID-19. For example, the excess burden of diabetes among non-hospitalised individuals was 8.28 per 1,000 people at 12 months,” wrote Yan Xie, VA Saint Louis Health Care System, Saint Louis, Missouri, and colleagues.
Using the national databases of the US Department of Veterans Affairs, researchers built a cohort of 181,280 participants who had a positive COVID-19 test between March 1, 2020, and September 30, 2021, and survived the first 30 days of COVID-19, and two control groups with no evidence of SARS-CoV-2 infection comprising 4,118,441 contemporary controls enrolled between March 1, 2020, and September 30, 2021 and 4,286,911 historical controls enrolled between March 1, 2018, and September 30, 2019.
Participants in all three comparison groups were free of diabetes before cohort entry and were followed up for a median of 352 days (interquartile range 245–406). Inverse probability weighted survival analyses, including predefined and algorithmically selected high dimensional variables, were used to estimate post-acute COVID-19 risks of incident diabetes, antihyperglycaemic use, and a composite of the two outcomes.
Compared to the contemporary control group, 30-day survivors of COVID-19 exhibited an increased risk (hazard ratio [HR] 1.40, 95% confidence interval [CI] 1.36–1.44) and excess burden (13.46, 95% CI 12.11–14.84, per 1,000 people at 12 months) of incident diabetes, and an increased risk (1.85, 1.78–1.92) and excess burden (12.35, 11.36–13.38) of incident antihyperglycaemic use. Meanwhile, analyses to estimate the risk of a composite endpoint of incident diabetes or antihyperglycaemic use yielded a HR of 1.46 (95% CI 1.43–1.50) and an excess burden of 18.03 (16.59–19.51) per 1,000 people at 12 months.
Additionally, risks and burdens of post-acute outcomes were found to increase in a graded fashion according to the severity of the acute phase of COVID-19 (whether patients were non-hospitalised, hospitalised, or admitted to intensive care).
Further, subgroup analyses suggested that COVID-19 was associated with an increased risk of diabetes outcomes across age (≤65 years and >65 years), race (White and Black), sex, body-mass index categories (>18.5 to ≤25 kg/m², >25 to ≤30 kg/m², and >30 kg/m²), and area deprivation index quartiles. Similarly, COVID-19 was associated with an increased risk of diabetes across all risk score quartiles, including the lowest risk score quartile.
Analyses using the historical control as the reference category yielded consistent findings with those evaluating the COVID-19 versus contemporary control groups, whereby COVID-19 was associated with an increased risk of diabetes outcomes in comparisons of COVID-19 versus the overall historical control group, and across all the subgroups examined.
“Altogether, our results indicate that beyond the acute phase of COVID-19, survivors are at an increased risk of developing incident diabetes and antihyperglycaemic use,” the authors remarked. “Our subgroup analyses suggest that even people with a low risk of diabetes before exposure to COVID-19 exhibited increased risk compared to both contemporary and historical controls.”
In addition, the authors noted that “analyses of who is at risk of diabetes among people with COVID-19 suggest that the relationship between COVID-19 and diabetes exhibited a graded association according to baseline risk of diabetes suggesting that diabetes could manifest in people at low risk (compared with controls), and COVID-19 could likely amplify baseline risks and further accelerate manifestation of disease among individuals already at high risk.”
“Taken together, current evidence suggests that diabetes is a facet of the multifaceted long COVID syndrome and that post-acute care strategies of people with COVID-19 should include identification and management of diabetes,” the authors concluded.