Type 2 diabetes has traditionally been framed as a disorder of hyperglycemia caused by insulin resistance (IR) and progressive beta-cell failure. That model remains biologically useful, but it is clinically incomplete. Contemporary outcome trials show that therapies with modest glycemic effects, particularly glucagonlike peptide-1 (GLP-1) receptor agonists, dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and metabolic surgery-substantially reduce cardiovascular events, heart failure (HF), chronic kidney disease (CKD) progression, and weight-related morbidity. This mismatch suggests that type 2 diabetes is better understood as a cardiometabolic systems disease in which hyperglycemia is an important downstream manifestation, but not the sole driver of clinical risk. In this narrative review and perspective, cardiometabolic load is defined as the cumulative burden of visceral adiposity, ectopic liver and pancreatic fat, adipocyte dysfunction, endothelial injury, cardiorenal stress, inflammation, and reduced muscle reserve. A pragmatic five-phenotype model for clinical use is proposed: visceral adiposity dominant, sarcopenic IR, cardiorenal dominant, metabolic dysfunction-associated steatotic liver disease (MASLD)/lipotoxicity dominant, and beta-cell fragile. The framework is placed alongside existing data-driven diabetes clustering systems, and approaches for validation are outlined through prospective testing of risk prediction and treatment response. The model is also linked to prior work on fetal programming and Marshallese cardiometabolic risk, where early-life adversity, nutritional transition, and social determinants can create severe metabolic disease at modest body mass index (BMI). A phenotypebased approach may better align therapy with dominant biology while preserving the established importance of glycemic control.
doi: 10.17756/jocd.2026-058
Citation: Goulden PA. 2026. Reframing Type 2 Diabetes as Cardiometabolic Disease: A Five-phenotype Model Beyond Glycated Hemoglobin. J Obes Chronic Dis 10(1): 4-11.
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