The research team, led by Armand Mbanya and Felipe Lobelo of The Southeast Permanente Medical Group and Emory University, analyzed the charts of 2,071 patients with laboratory-confirmed COVID-19 diagnosed between March 3, 2020, and September 11, 2020, during the first pandemic wave in metro Atlanta. Rather than lumping patients into the familiar binary of diabetes versus no diabetes, the investigators stratified them into five groups based on hemoglobin A1c (HbA1c), the glycated hemoglobin measure that reflects average blood glucose over roughly three months. Patients were classified as normoglycemic (HbA1c at or below 5.6 percent), prediabetic (5.7 to 6.4 percent), or diabetic with good control (below 7 percent), moderate control (7 to 9 percent), or poor control (above 9 percent), the last threshold aligned with the Healthcare Effectiveness Data and Information Set definition of poor diabetes management.

The distribution of the cohort itself tells a story. Nearly half of the infected patients, 986 individuals or 47.6 percent, had no diabetes. But 658 patients, 31.8 percent, had prediabetes, a condition affecting roughly one in three American adults that rarely triggers the clinical vigilance reserved for diagnosed diabetes. Another 183 patients (8.8 percent) had well-controlled diabetes, 162 (7.8 percent) had moderately controlled disease, and 82 (4 percent) had HbA1c above 9 percent. The prediabetes figure is striking on its own: nearly a third of all confirmed COVID-19 cases in this integrated health system occurred in patients whose glucose metabolism was already dysregulated, even if no physician had yet sounded the alarm.

The gradient in outcomes was unmistakable. Hospitalization rates rose in lockstep with worsening glycemic control, a pattern that held with high statistical significance (p < 0.0001). Patients with HbA1c above 9 percent fared worst: 38.3 percent required hospitalization and 14.8 percent were admitted to the intensive care unit, the highest proportions in the study. Normoglycemic patients without diabetes were hospitalized significantly less often than every other group. Prediabetic patients occupied an uncomfortable middle ground, hospitalized less often than those with moderately or poorly controlled diabetes, but their raw mortality proportion was the highest of any group in the sample, a finding the authors attribute in part to the structure of the health system itself. Diagnosed diabetic patients at Kaiser Permanente are followed closely, while many prediabetic patients may be undiagnosed or recently identified, leaving them with less proactive metabolic care heading into infection.

To move beyond raw associations, the team built multivariable logistic regression models adjusting for a remarkable breadth of confounders: age, sex, race and ethnicity, insurance type, household income, the neighborhood deprivation index, comorbidity burden measured by the Charlson Comorbidity Index, medications, quality-of-care metrics, and lifestyle behaviors including self-reported weekly exercise and smoking. In the fully adjusted model, prediabetes was independently associated with 1.43 times the odds of hospitalization (95 percent confidence interval 1.09 to 1.87), while insulin use carried 3.02 times the odds (95 percent confidence interval 1.95 to 4.68). Age, smoking (odds ratio 1.72), obesity (1.38), and physical inactivity (1.32) each independently raised hospitalization risk, while living in northeast Atlanta counties with higher median incomes and better housing quality was associated with lower risk (odds ratio 0.66).

When the investigators compared glycemic subgroups directly against one another, the dose-response relationship sharpened further. Relative to normoglycemic patients, those with prediabetes had 1.64 times the adjusted odds of hospitalization, patients with moderately controlled diabetes had 2.24 times the odds, and those with HbA1c above 9 percent had 3.3 times the odds. Most tellingly, prediabetic patients required hospitalization at rates not statistically distinguishable from patients with well-controlled diabetes, whose adjusted odds ratio of 1.04 relative to normoglycemia was essentially neutral. In other words, on the hospitalization endpoint, untreated glucose dysregulation in the prediabetic range behaved like established diabetes that happens to be well managed, a comparison the authors describe as prediabetes being a significant risk factor for severe COVID-19, comparable to poorly controlled diabetes in its clinical weight.

The biology underlying these statistics is increasingly well mapped. SARS-CoV-2 enters human cells through the angiotensin-converting enzyme 2 (ACE2) receptor, with the transmembrane serine protease TMPRSS2 priming the viral spike protein for entry and replication. Both pathways are dysregulated in cardiometabolic disease, and glycated ACE2 in diabetic tissue may act as an open door for viral entry into cardiomyocytes. High glucose levels directly increase viral replication in human monocytes, and glycolysis sustains that replication once it begins. Hyperglycemia also blunts the effectiveness of COVID-19 immunotherapy such as tocilizumab, drives endothelial dysfunction and hypercoagulability, and amplifies the cytokine storm that defines severe disease. Insulin itself may contribute to this inflammatory cascade by stimulating cytokine release, one proposed mechanism behind the threefold hospitalization odds observed among insulin users, who by definition carry the most advanced metabolic disease.

The study’s socioeconomic findings add a viral-news dimension that extends beyond the laboratory. Patients with the worst glycemic control lived in neighborhoods with the most unfavorable deprivation index (0.42 versus 0.04 for normoglycemic patients), had the lowest household incomes, and reported the least weekly exercise, averaging 52.5 minutes compared with 98.2 minutes for normoglycemic patients. Among prediabetic patients, higher neighborhood deprivation independently increased hospitalization odds (1.35), while commercial insurance, a proxy for healthcare access, halved them (0.49). Among patients with well-controlled diabetes, Black race was associated with 3.08 times the hospitalization odds, echoing umbrella reviews showing that Black and Hispanic individuals faced higher COVID-19 infection and hospitalization risks in the pre-vaccination era, at least partly attributable to higher comorbidity rates. The message is that glucose dysregulation and social disadvantage compound each other, concentrating severe COVID-19 risk in communities already burdened by obesity, inactivity, and limited access to care.

The authors are candid about limitations. The retrospective design, drawn from charts within a single integrated health system during the first pandemic wave before vaccines and antivirals were available, limits causal inference and generalizability. HbA1c values were the most recent measurements within 12 months of diagnosis, so glycemic control may have shifted between testing and infection, risking misclassification. Some social determinants data were measured at the area rather than individual level, and the small number of deaths (27 total, 1.3 percent) constrained statistical power for mortality endpoints. Notably, the prediabetes mortality finding, while statistically significant in unadjusted comparisons, did not survive as an independent predictor in the regression models, and the authors themselves flag the limited power around deaths as a key gap.

Still, the implications are hard to ignore. Previous landmark studies, including the CORONADO cohort and a single-center US analysis of hospitalized diabetic patients, found no association between HbA1c measured at admission and COVID-19 outcomes, leading some investigators to recommend against using HbA1c for in-hospital risk stratification. A meta-analysis by Prattichizzo and colleagues resolved part of the contradiction: pre-infection HbA1c was associated with COVID-19 mortality, but the association vanished when analysis was restricted to studies measuring HbA1c at admission. The Kaiser Permanente study, by anchoring glycemic status before infection, lands squarely on the side of the evidence suggesting that chronic glucose regulation, not acute admission hyperglycemia alone, determines who progresses to severe disease. With one in three American adults prediabetic and COVID-19 still circulating, the authors argue for proactive management, early detection of glucose dysfunction, vaccination outreach prioritized for metabolically at-risk populations, and prospective studies with more frequent glycemic monitoring. The quiet warning of this study is that the pandemic’s most vulnerable patients were never only those with diabetes. They were the millions walking around with glucose levels already drifting toward danger, unrecognized and untreated, long before the virus arrived.

Subject of Research: Glycemic control and COVID-19 outcomes across the continuum of glucose regulation: a retrospective cohort study

Article Title: Glycemic control and COVID-19 outcomes across the continuum of glucose regulation: a retrospective cohort study

Article References: Mbanya, A., Leung, S., Bienvenida, A., Leslie, E., Shin, S. R., Koplan, K. E., & Lobelo, F. (2026). Glycemic control and COVID-19 outcomes across the continuum of glucose regulation: a retrospective cohort study. Frontiers in Clinical Diabetes and Healthcare, 7, Article 1862850. https://doi.org/10.3389/fcdhc.2026.1862850

Image Credits: AI Generated

DOI: 10.3389/fcdhc.2026.1862850

Keywords: Glycemic, control, COVID-19, outcomes, across, continuum, glucose, regulation, retrospective, cohort, scientific research