The impact of COVID-19 illness on metabolic phenotypes underlying type 2 diabetes mellitus: a systematic review

We aimed to systematically review literature investigating the impact of COVID-19 on insulin resistance and beta-cell dysfunction in humans. Ovid MEDLINE and Embase were searched for studies published between December 2019 and May 2024. Observational studies examining adults with no history of type 2 diabetes comparing the development of insulin resistance and beta-cell dysfunction between COVID-19 exposed groups vs. controls were included. Risk of bias was assessed using adapted Newcastle-Ottawa and Joanna Briggs Institute scales. Among 6901 studies screened, 10 met the inclusion criteria. Across these studies, 37 individual measures of insulin resistance and beta-cell dysfunction were reported. Insulin resistance worsened significantly in 16 of 25 (64.0%) comparisons, whereas beta-cell dysfunction worsened significantly in 7 of 12 (58.3%) measures among COVID-19 patients when compared to controls. Five studies were considered low risk of bias. COVID-19 was associated with worsened insulin resistance and beta-cell dysfunction, suggesting infection may be a metabolic stressor that overwhelms gluco-regulatory mechanisms. Results, especially those for beta-cell function, should be interpreted cautiously given methodological limitations in the utilized measures. These findings highlight the pathophysiological aspects of type-2 diabetes impacted by COVID-19 infection and support the development of targeted monitoring and therapeutic strategies.