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We investigated whether long-term metabolic trajectories beginning in prediabetes delineate subgroups with differential complication risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                    <jats:p>Clinical data from 1,732 Diabetes Prevention Program\/Outcomes Study participants (follow-up 19 years) were analyzed across 12 phenotypes. Tensor decomposition was used to capture longitudinal patterns, and Gaussian mixture modeling was used to define longitudinal clusters. Cluster-specific complications were quantified with Cox and logistic regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Four clusters emerged. Clusters 1 and 2 (73% of participants) maintained stable glycemia, blood pressure, and lipids. Although 49% and 71%, respectively, developed T2D, cumulative micro- and macrovascular events remained low. Cluster 3 (12%) showed the steepest rise in insulin resistance and hyperglycemia, with 92% of the subgroup progressing to T2D and a markedly higher rate of retinopathy (odds ratio [OR] 8.8, 95% CI 3.9\u201320.1) and neuropathy (OR 3.4, 95% CI 2.1\u20135.5). Cluster 4 (15%) presented with baseline microalbuminuria often prior to the development of T2D (73%). It was distinguished by progressive estimated glomerular filtration rate decline and a doubling of cardiovascular events (hazard ratio 2.0, 95% CI 1.4\u20133.0), despite serum lipids comparable with other groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>Two-thirds of individuals with prediabetes follow metabolically resilient trajectories, whereas distinct insulin-resistant or renal-dysfunction trajectories precede micro- or macrovascular complications, respectively. The optimal window for macrovascular complication prevention in individuals with prediabetes microalbuminuria may precede progression to T2D.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/dc25-0866","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T16:07:41Z","timestamp":1756224461000},"page":"1704-1712","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":10,"title":["Longitudinal Metabolic Trajectories in Diabetes Prevention Program Participants Reveal Subgroups With Varying Micro- and Macrovascular Complication Risks"],"prefix":"10.2337","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9041-5167","authenticated-orcid":false,"given":"Emily","family":"Kobayashi","sequence":"first","affiliation":[{"name":"Bioinformatics and Systems Biology Graduate Program, University of California 1 , San Diego, La Jolla, CA"},{"name":"Division of Endocrinology and Metabolism, 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