MON-631 Double Diabetes Case Series: A Hybrid Pathology Requiring Hybrid Therapy

Abstract Disclosure: J.S. Martins Torrontegui: None. L.L. Ponce Rosas: None. A. Al-Thunaibat: None. P.S. Sidhu: None. A. Abualnil: None. C. Penaherrera: None. From the time when the Ebers Papyrus first described symptoms resembling diabetes to the recent classification of its various forms, one central concept has remained: the link between hyperglycemia and its characteristic symptoms. While the core pathology (hyperglycemia) has always unified these disorders, the depth of our understanding has allowed for increasingly precise descriptions and classifications of what we now recognize as a diverse group of metabolic diseases. As our knowledge has advanced, it may now be time to formally recognize a new category within this group: Type 1.5 diabetes, or double diabetes. This hybrid condition is more common than previously thought, with approximately 1 in 4 individuals with Type 1 diabetes mellitus (T1DM) presenting features of Type 2 diabetes mellitus (T2DM), such as metabolic syndrome, adding insulin resistance to the autoimmune basis of T1DM. This reflects a complex overlap of genetic, metabolic, and environmental factors, and may warrant distinct recognition in both diagnosis and management. We present a case series of four patients with double diabetes. The first case is a 24-year-old woman with T1DM who developed polycystic ovary syndrome (PCOS), progressively increasing insulin requirements, and significant weight gain despite no changes in dietary habits. The second case is a 68-year-old woman diagnosed with T1DM at age 19 and treated with an insulin pump for 10 years, who presented with acanthosis nigricans, and rising insulin needs following chemotherapy and corticosteroid treatment for uterine cancer. The third case involves a 38-year-old woman with childhood-onset T1DM who reported difficulty losing weight and developed morbid obesity, hyperlipidemia, acanthosis nigricans, and elevated insulin requirements. The final case is a 26-year-old woman with a medical history including necrobiosis lipoidica diabeticorum, PCOS, obesity, hypothyroidism, and T1DM, who required over 120 units of insulin daily to achieve glycemic control, features consistent with T2DM pathophysiology. Notably, all patients in this series demonstrated significant improvement in glycemic control after the initiation of GLP-1 receptor agonist therapy. These cases raise an important question: Since patients with double diabetes exhibit both insulin resistance and autoimmune-driven β-cell destruction, shouldn’t we also address the insulin resistance directly with the therapy? Given that intensive insulin therapy is often associated with weight gain and subsequent insulin resistance, glucose-lowering drugs seem to be a reasonable option to be added to patients already treated with insulin. Additionally, could GLP-1a help manage this dual pathology by addressing insulin resistance, weight gain and glucose control? Further investigation is needed to identify and develop appropriate recommendations for the effective management of double diabetes. Presentation: Monday, July 14, 2025