{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T03:39:23Z","timestamp":1792467563070,"version":"4.5.0"},"reference-count":27,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82501013"],"award-info":[{"award-number":["82501013"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2026M792479"],"award-info":[{"award-number":["2026M792479"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To determine the prevalence of a low\u2010molecular\u2010weight protein (LMWP)\u2010defined tubular phenotype in adults with Type 2 diabetes, normoalbuminuria and preserved estimated glomerular filtration rate (eGFR), its relation to UACR, and its human kidney context.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      We studied 4046 adults with Type 2 diabetes, UACR &lt;\u200930\u2009mg\/g, eGFR \u2265\u200960\u2009mL\/min\/1.73\u2009m\n                      <jats:sup>2<\/jats:sup>\n                      , and paired morning urinary \u03b11\u2010microglobulin (\u03b11MG) and \u03b22\u2010microglobulin (\u03b22MG). The phenotype required \u03b11MG &gt;\u200912\u2009mg\/L and \u03b22MG &gt;\u20090.20\u2009mg\/L. We tested associations with UACR and performed medication, admission\u2010context, high\u2010eGFR and liver\u2010function sensitivity analyses. Independent microdissected tubular, single\u2010cell\/single\u2010nucleus and CosMx datasets were analysed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The phenotype was present in 797 patients (19.7%). UACR alone did not discriminate the phenotype (AUC 0.466, 95% CI: 0.443\u20130.489), and ln(UACR+1) was not associated with it after clinical adjustment (OR: 0.873, 95% CI: 0.710\u20131.075;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.201). Medication adjustment produced a similar estimate (OR: 0.871, 95% CI: 0.708\u20131.072;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.191), with consistent findings in the other sensitivity analyses. In microdissected tubules, a 10\u2010gene injury score was higher in DKD (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001); sample\u2010level injured proximal\u2010tubular fractions were highest in DKD in the single\u2010cell atlas (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.029), and spatial profiling resolved five injured proximal\u2010tubular subclusters.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>An LMWP\u2010defined tubular phenotype was present in nearly one in five adults with Type 2 diabetes despite normoalbuminuria and preserved eGFR, and was poorly captured by UACR. Independent human kidney datasets showed related proximal\u2010tubular injury\u2010associated programmes with marked cellular and spatial heterogeneity. These findings support tubular phenotyping as a complementary approach to kidney assessment in Type 2 diabetes and warrant prospective validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71447","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T03:00:02Z","timestamp":1792465202000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Clinically Occult Tubular Phenotype in Type 2 Diabetes Despite Normoalbuminuria and Preserved\n                    <scp>eGFR<\/scp>\n                    : Multiscale Human Kidney Evidence"],"prefix":"10.1111","author":[{"given":"Hui","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Human Resources The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changlong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8878-828X","authenticated-orcid":false,"given":"Bin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,19]]},"reference":[{"issue":"4","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"S117","DOI":"10.1016\/j.kint.2023.10.018","article-title":"KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease","volume":"105","author":"Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group","year":"2024","journal-title":"Kidney International"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc26-S011"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.16359"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.16269"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.0000000000000333"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc23-2196"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2025.04.057"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000528918"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.2.338"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2012.02.019"},{"issue":"3","key":"e_1_2_11_12_1","article-title":"KIM\u20101 as a Biomarker of Kidney Tubular Damage in Normoalbuminuric Patients With Type 2 Diabetes Mellitus and Insulin Resistance","volume":"47","author":"Oliveira L. 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