Aims/hypothesis: Hypoxia and oxidative stress have been implicated in both metabolic syndrome and COVID-19-associated dysglycaemia, yet it remains unclear whether shared or distinct mechanisms underlie β-cell dysfunction across these conditions. We investigated hypoxia- and oxidative stress-related pathways in relation to β-cell function during acute COVID-19, post-COVID metabolic states, and COVID-negative metabolic syndrome. Methods: In this prospective observational study, 100 adults were stratified into three groups: active COVID-19 (n = 32), post-COVID with newly diagnosed carbohydrate metabolism disorders (n = 35), and COVID-negative individuals with metabolic syndrome (n = 33). Circulating markers of hypoxia (HIF-1α), oxidative stress (8-epi-prostaglandin F2α), and antioxidant response (NFE2L2) were measured alongside α- and β-cell functional markers, including C-peptide, proinsulin, glucagon, and derived indices of β-cell processing and secretory efficiency. Non-parametric statistical analyses were applied. Results: Circulating HIF-1α levels differed significantly across study groups (p < 0.001), with the highest concentrations observed during active COVID-19, intermediate levels in COVID-negative individuals with metabolic syndrome, and the lowest levels in the post-COVID group. In contrast, oxidative stress, assessed by 8-epi-prostaglandin F2α, differed significantly across groups (p < 0.001), increasing from acute COVID-19 to post-COVID and reaching the highest levels in metabolic syndrome; however, the difference between the post-COVID and metabolic syndrome groups did not remain significant after correction for multiple testing. NFE2L2 concentrations did not differ significantly between groups. Marked β-cell dysfunction was observed predominantly in COVID-negative individuals with metabolic syndrome, characterized by reduced C-peptide levels, elevated glucagon concentrations, increased proinsulin/C-peptide ratios, and reduced C-peptide/glucose ratios (all overall group comparisons p < 0.001). In contrast, β-cell secretory indices were relatively preserved during acute and post-COVID states despite pronounced alterations in hypoxia and oxidative stress markers. Conclusions/interpretation: Hypoxia- and oxidative stress-related pathways exhibit distinct, context-dependent patterns across acute COVID-19, post-COVID dysglycaemia, and metabolic syndrome. Acute COVID-19 is characterized by pronounced hypoxia signalling with relative preservation of β-cell function, whereas chronic metabolic syndrome is associated with sustained oxidative stress and impaired β-cell processing and secretory efficiency. These findings suggest that diabetes-related β-cell dysfunction is more closely associated with chronic oxidative and metabolic stress than with transient infection-related hypoxia during SARS-CoV-2 infection.
Tsvetkova et al. (Thu,) studied this question.