Risks and burdens of incident diabetes in long COVID: a cohort study

Abstract

Background: There is growing evidence suggesting that beyond the acute phase of SARS-CoV-2 infection, people with COVID-19 could experience a wide range of post-acute sequelae, including diabetes. However, the risks and burdens of diabetes in the post-acute phase of the disease have not yet been comprehensively characterised. To address this knowledge gap, we aimed to examine the post-acute risk and burden of incident diabetes in people who survived the first 30 days of SARS-CoV-2 infection.

Methods: In this cohort study, we used the national databases of the US Department of Veterans Affairs to build a cohort of 181 280 participants who had a positive COVID-19 test between March 1, 2020, and Sept 30, 2021, and survived the first 30 days of COVID-19; a contemporary control (n=4 118 441) that enrolled participants between March 1, 2020, and Sept 30, 2021; and a historical control (n=4 286 911) that enrolled participants between March 1, 2018, and Sept 30, 2019. Both control groups had no evidence of SARS-CoV-2 infection. Participants in all three comparison groups were free of diabetes before cohort entry and were followed up for a median of 352 days (IQR 245-406). We used inverse probability weighted survival analyses, including predefined and algorithmically selected high dimensional variables, to estimate post-acute COVID-19 risks of incident diabetes, antihyperglycaemic use, and a composite of the two outcomes. We reported two measures of risk: hazard ratio (HR) and burden per 1000 people at 12 months.

Findings: In the post-acute phase of the disease, compared with the contemporary control group, people with COVID-19 exhibited an increased risk (HR 1·40, 95% CI 1·36-1·44) and excess burden (13·46, 95% CI 12·11-14·84, per 1000 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. Additionally, 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 (95% CI 16·59-19·51) per 1000 people at 12 months. Risks and burdens of post-acute outcomes increased 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). All the results were consistent in analyses using the historical control as the reference category.

Interpretation: In the post-acute phase, we report increased risks and 12-month burdens of incident diabetes and antihyperglycaemic use in people with COVID-19 compared with a contemporary control group of people who were enrolled during the same period and had not contracted SARS-CoV-2, and a historical control group from a pre-pandemic era. Post-acute COVID-19 care should involve identification and management of diabetes.

Funding: US Department of Veterans Affairs and the American Society of Nephrology.

Figure 1

Risks and burdens of post-acute COVID-19 diabetes outcomes compared with the contemporary control group The outcomes were ascertained from day 30 after COVID-19 infection until the end of follow-up. Adjusted hazard ratios and 95% CIs are presented in a base 10 logarithmic scale. Adjusted event rates per 1000 people at 12 months for the COVID-19 group and the contemporary control group, and the excess burden per 1000 people at 12 months and related 95% CIs are also presented.

Figure 2

Risks and burdens of post-acute COVID-19 diabetes outcomes by severity of the acute infection compared with the contemporary control group Severity of the acute infection was defined as non-hospitalised (blue), hospitalised (purple), and admitted to intensive care (orange). The outcomes were ascertained from day 30 after COVID-19 infection until the end of follow-up. Adjusted hazard ratios and 95% CIs are presented in a base 10 logarithmic scale. Adjusted event rates per 1000 people at 12 months for each care setting during the acute infection, contemporary control group, and excess burden per 1000 people at 12 months and related 95% CIs are also presented.

Figure 3

Risks of post-acute diabetes outcomes among people with COVID-19 (A) Diabetes risk score quartile. (B) Individual risk factors including age, race, cardiovascular disease, hypertension, hyperlipidaemia, prediabetes, and BMI. The outcomes were ascertained from day 30 after COVID-19 infection until the end of follow-up. Adjusted hazard ratios and 95% CIs are presented in a base 10 logarithmic scale. Excess burden per 1000 people at 12 months and 95% CIs are also presented.