Abstract Although hemoglobin A1c (HbA1c) is widely used to assess long-term glycemia, its reliability declines in conditions that alter red blood cell turnover or hemoglobin glycation. Pancreatic structural diseases, including pancreatic neuroendocrine tumors (pNETs) and intraductal papillary mucinous neoplasms (IPMNs), may further affect glucose regulation through impaired endocrine function. Systemic inflammation and specific hematologic conditions can also create discordant glycemic markers, complicating diagnosis, and management. We report a 59-year-old woman with autoimmune disease who presented with fatigue and fluctuating glucose levels. Her HbA1c remained within normal limits; however, continuous glucose monitoring (CGM) and an oral glucose tolerance test (OGTT) demonstrated marked hyperglycemia. Imaging revealed pancreatic lesions concerning for a pNET in the setting of known IPMNs. Laboratory evaluation was notable for elevated ferritin and clonal hematopoiesis of indeterminate potential (CHIP). Additional studies, including hemoglobin, albumin, renal and hepatic function, and hemoglobin electrophoresis, were normal, ruling out anemia and hemoglobinopathies. Her glycemic discordance likely reflects impaired insulin secretion due to pancreatic pathology combined with inflammation driven alterations in erythrocyte lifespan associated with CHIP. This case underscores the limitations of HbA1c in complex metabolic or inflammatory states and highlights the value of CGM and OGTT when A1c does not align with clinical findings.
Cardona et al. (Sat,) studied this question.