Comment on Samovski et al. Effect of Marked Weight Loss on Adipose Tissue Biology in People With Obesity and Type 2 Diabetes. Diabetes Care 2025;48:1342–1351

We congratulate Samovski et al. (1) for their meticulous translational study in Diabetes Care demonstrating that marked weight loss remodels adipose tissue extracellular matrix (ECM) gene expression and attenuates circulating small extracellular vesicle (sEV) microRNAs, effects that are tightly linked to improved whole-body insulin sensitivity in adults with obesity and type 2 diabetes. The integration of deep molecular phenotyping with rigorous metabolic clamp methodology is an important advance. Nevertheless, several points merit consideration to refine causal inference and guide clinical translation.