Exercise as targeted therapy in type 2 diabetes: a phenotype-informed clinical prioritisation framework for adapted...

Type 2 diabetes (T2D) is a heterogeneous cardio-nephro-hepato-metabolic disease whose clinical expression is shaped by multimorbidity, obesity, sarcopenia, frailty, chronic complications, cardiovascular disease, chronic kidney disease, and functional decline - dimensions that frequently coexist rather than defining mutually exclusive categories. International guidelines appropriately recognise the multidimensional benefits of physical activity, including cardiorespiratory fitness, muscle strength, body composition, physical function, and quality of life; however, translating this increasing clinical complexity into personalised, prioritised exercise prescriptions remains an unresolved operational challenge.

To propose a phenotype-informed clinical prioritisation framework for Adapted Physical Activity (APA) in T2D that complements condition-specific exercise recommendations by supporting clinicians in identifying the dominant clinical complexity domain and corresponding therapeutic priority at a given point in the patient's trajectory.

Evidence from international guidelines, consensus statements, systematic reviews, and meta-analyses was synthesised within a conceptual model integrating functional status, frailty, sarcopenia, and cardiorenal risk as determinants of exercise prescription.

Four overlapping domains of clinical complexity are described: adiposopathic insulin-resistant; muscle failure (frailty-sarcopenia); cardiorenal-metabolic; and complication-driven. For each, the dominant therapeutic priority, exercise modality, intensity, and safety considerations are defined with explicit evidence linkage. A six-step clinical algorithm integrates multidimensional assessment, risk stratification, identification of the dominant clinical complexity domain, prioritised prescription, and dynamic reassessment.

Adapted Physical Activity should be prescribed using the same principles of multidimensional assessment, therapeutic prioritisation, monitoring, and dynamic adaptation that increasingly guide modern diabetes pharmacotherapy - supporting the diabetologist's evolving role as a clinician of complexity within a precision exercise medicine approach.