Heterogeneity In Phenotype And Early Metabolic Response To Lifestyle Interventions In Type 2 Diabetes In China Utilizing A Tree-like Representation

<p dir="ltr">Deciphering the heterogeneity of type 2 diabetes in prognosis and treatment effect is essential. We aimed to use a novel dimensionality reduction approach to describe type 2 diabetes phenotype continuum and to visualize the difference in lifestyle intervention efficacy in Chinese patients.<b> </b>Based on<b> </b>17816 newly-diagnosed type 2 diabetes participants (≥40 years) from a nationwide cohort, 12 key phenotypes were residualized for age and sex to construct a two-dimensional tree-structure. The tree demonstrated the continuous type 2 diabetes spectrum and region-specific characteristics, with a mixed-phenotypic trunk and three extreme-phenotypic branches. When mapping 325 external type 2 diabetes participants from a randomized controlled trial onto the original tree,<b> </b>lifestyle intervention induced a migration towards the left part of tree, indicating an overall metabolic improvement. In specific, diet intervention was more effective for glycemic control in upper tree featured by moderate diabesity and elevated insulin, while exercise intervention was more effective in left tree featured by less adiposity and better overall metabolic status. In summary,<b> </b>this<b> </b>analysis depicted the tree-structure representing the underlying pathophysiological features of newly-diagnosed type 2 diabetes patients and identified tree regions with different sensitivity to diet or exercise intervention, thereby had the potential for lifestyle intervention selection.</p>