Validation of Hemoglobin A1c as a Biomarker of Long-Term Glycemic Control in Mouse Models of Obesity and Diabetes

Introduction and Objective: Fasting blood glucose is routinely measured in humans to assess daily glycemic control and diagnose diabetes, correlating with hemoglobin A1c (HbA1c). In mice, overnight fasting is common for blood glucose testing, but concerns about stress from prolonged fasting have led to recommendations for shorter fasting (6 hours). The reliability of single-point fasting glucose to reflect full-day glycemic control in mice remains unvalidated, complicating assessment due to their sensitivity to handling and stress. While HbA1c is a critical biomarker for long-term glycemic status in humans, its use and relationship with glucose control in mice are poorly studied. This study aimed to validate the use of HbA1c measurement (A1CNow, PTS Diagnostics) as an integrative measure of long-term glycemic control in mice compared to fasted, single point blood glucose measurements. Methods: C57BL/6NTac (n= 9-10 males/group) mice fed either a high-fat diet (D12492, 60 kcal% fat) to induce diet-induced obesity (DIO) or standard NIH-31 chow, were assessed for blood glucose, HbA1c, and body weight at 6, 14, 22, and 30 weeks of age. Sixteen-week-old non-obese diabetic (NOD) mice were included in a separate assay as a positive control. Results: The DIO group exhibited significantly elevated blood glucose, HbA1c, and body weight starting at 14 weeks. HbA1c showed a strong correlation with body weight (r 2 = 0.672; p < 0.0001). However, correlations between single point fasted blood glucose and both HbA1c (r 2 = 0.3) and body weight (r 2 = 0.02) were not significant. All NOD animals with glucose levels greater than 600 mg/dL had elevated HbA1c, with an average HbA1c of 9.22% glycated hemoglobin +/- 0.76 (SEM). Conclusion: We demonstrate that HbA1c provides an accurate and cost-effective integrative measure of glycemic control in a commonly used model of DIO and hyperglycemia. These findings suggest that HbA1c is a reliable measurement of chronic hyperglycemia in mice, and could enhance studies of glycemic control through diet and therapeutic interventions in mice. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.