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Diabetes and Vascular Disease

SUN-596 - Post-COVID-19 New-Onset Diabetes: Hepatic Insulin Resistance Drives Glycemia and Informs Management

Sunday, June 14, 2026
9:00 AM - 4:00 PM CT
Location: ENDOExpo; Poster Floor


Background: The clinical course and underlying pathophysiology of new-onset type 2 diabetes following SARS-CoV-2 infection remain poorly defined.

Methods: We evaluated one-year glycemic outcomes and mechanistic trajectories of insulin resistance using complementary retrospective and prospective study designs. A retrospective cohort of 149 adults with newly diagnosed diabetes post COVID-19 were followed for 1 year. We defined diabetes remission as HbA1c < 6.5% without glucose-lowering medications. In parallel, a prospective subcohort underwent hyperinsulinemic–euglycemic clamp and fasting blood samplings at baseline and 12 months to characterize insulin sensitivity in skeletal muscles (peripheral resistance). We also calculated HOMA-IR to assess hepatic insulin resistance.

Results: In the retrospective cohort, 23 of 149 patients (15.4%) achieved diabetes remission. This outcome was strongly associated with milder glycemia at diagnosis, as reflected in lower presenting glucose and HbA1c levels. However, body mass index and inflammatory markers showed no significant association. Notably, remission rates declined progressively with increasing baseline HbA1c, illustrating an inverse relationship between initial glycemic burden and likelihood of recovery. In the prospective sub cohort, baseline clamp-derived M-values demonstrated substantial heterogeneity, ranging from severe peripheral insulin resistance to preserved insulin sensitivity, while fasting-derived HOMA-IR values spanned normal to severe hepatic insulin resistance. At one-year follow-up, the mean M-value remained stable at the group level, but individual metabolic trajectories varied markedly. Changes in HbA1c correlated strongly with changes in HOMA-IR, whereas associations with changes in M-value were weak, indicating that hepatic insulin resistance was more closely linked to glycemic progression than peripheral insulin sensitivity.

Conclusion: New-onset diabetes following COVID-19 is often persistent, with remission primarily seen in those with mild hyperglycemia at diagnosis. Metabolic profiling underscores significant pathophysiological heterogeneity, identifying hepatic insulin resistance as the key driver of glycemic progression. These findings provide clear support for implementing individualized, mechanism-based monitoring and management for post-COVID diabetes.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*