{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T14:57:09Z","timestamp":1784818629002,"version":"3.55.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Type 2 diabetes mellitus (T2DM) is a major global health challenge, with diabetic kidney disease (DKD) representing one of its most serious complications. Although zinc deficiency is common in diabetes, large-scale clinical evidence on its role as a predictor of new-onset DKD is limited.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a retrospective cohort study using the TriNetX Analytics Network Platform to analyze patients aged \u226518\u202fyears who underwent zinc testing (2010\u20132023). Patients were classified into zinc deficiency (serum zinc &amp;lt;70\u202f\u03bcg\/dL) and control groups (70\u2013120\u202f\u03bcg\/dL). After 1:1 propensity score matching, we analyzed the risk of new-onset DKD at two-year follow-up. The secondary outcomes included the risks of all-cause mortality, acute kidney injury (AKI), chronic kidney disease (CKD), poor glycemic control (HbA1c\u202f\u2265\u202f7%), and ophthalmic complications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The final matched cohort included 20,470 patients (10,235 per group) with a mean age of 54\u202fyears. Zinc deficiency was associated with a 42% increased risk of new-onset DKD (hazard ratio [HR] 1.42, 95% confidence interval [CI]: 1.20\u20131.68, <jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001). Additional significant associations included all-cause mortality (HR: 1.65, 95% CI: 1.40\u20131.95, <jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001), AKI (HR: 1.47, 95% CI: 1.27\u20131.69, <jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001), and CKD development (HR: 1.18, 95% CI: 1.02\u20131.37, <jats:italic>p<\/jats:italic>\u202f=\u202f0.028). No significant associations were observed with poor glycemic control or ophthalmic complications. Subgroup analyses showed stronger associations in patients with diabetes duration &amp;lt;5\u202fyears (HR 1.65, 95% CI: 1.35\u20132.02, <jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Zinc deficiency is an independent predictor of new-onset DKD and adverse outcomes in T2DM, particularly in early disease. These findings support zinc deficiency as a potential biomarker for risk stratification and highlight the need for prospective studies to evaluate whether zinc supplementation can reduce risk.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2025.1653151","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T08:10:34Z","timestamp":1758701434000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Zinc deficiency predicts new-onset diabetic kidney disease in type 2 diabetes: a retrospective cohort study"],"prefix":"10.3389","volume":"12","author":[{"given":"Kuo-Chuan","family":"Hung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Sian","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Wei","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Chen","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping-Heng","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-Tsung","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Kai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Ming","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Wen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"S27","DOI":"10.2337\/dc25-S002","article-title":"2. Diagnosis and classification of diabetes: standards of care in diabetes-2025","volume":"48","year":"2025","journal-title":"Diabetes Care"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e2004","DOI":"10.1002\/hsr2.2004","article-title":"Diabetes mellitus, the fastest growing global public health concern: early detection should be focused","volume":"7","author":"Hossain","year":"2024","journal-title":"Health Sci Rep"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2884","DOI":"10.1007\/s11695-023-06762-5","article-title":"Marginal ulcers following one-anastomosis gastric bypass: a systematic review and Meta-analysis","volume":"33","author":"Lee","year":"2023","journal-title":"Obes Surg"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"110","DOI":"10.2174\/1570161117666190405165151","article-title":"Macrovascular complications of type 2 diabetes mellitus","volume":"18","author":"Viigimaa","year":"2020","journal-title":"Curr Vasc Pharmacol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1007\/s00592-023-02037-8","article-title":"Long-term HbA1c variability and macro\u2212\/micro-vascular complications in type 2 diabetes mellitus: a meta-analysis update","volume":"60","author":"Sartore","year":"2023","journal-title":"Acta Diabetol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"107","DOI":"10.2991\/jegh.k.191028.001","article-title":"Epidemiology of type 2 diabetes - global burden of disease and forecasted trends","volume":"10","author":"Khan","year":"2020","journal-title":"J Epidemiol Glob Health"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e70098","DOI":"10.1111\/1753-0407.70098","article-title":"Global, regional, and National Prevalence of chronic type 2 diabetic kidney disease from 1990 to 2021: a trend and health inequality analyses based on the global burden of disease study 2021","volume":"17","author":"He","year":"2025","journal-title":"J Diabetes"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1902","DOI":"10.1111\/dom.16183","article-title":"Trends and analysis of risk factor differences in the global burden of chronic kidney disease due to type 2 diabetes from 1990 to 2021: a population-based study","volume":"27","author":"Wang","year":"2025","journal-title":"Diabetes Obes Metab"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.kisu.2017.10.003","article-title":"Diagnosis of diabetic kidney disease: state of the art and future perspective","volume":"8","author":"Persson","year":"2018","journal-title":"Kidney Int Suppl (2011)"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1495306","DOI":"10.3389\/fendo.2025.1495306","article-title":"Machine learning-based risk predictive models for diabetic kidney disease in type 2 diabetes mellitus patients: a systematic review and meta-analysis","volume":"16","author":"Li","year":"2025","journal-title":"Front Endocrinol (Lausanne)"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"2486558","DOI":"10.1080\/0886022X.2025.2486558","article-title":"Machine learning algorithms for diabetic kidney disease risk predictive model of Chinese patients with type 2 diabetes mellitus","volume":"47","author":"Zou","year":"2025","journal-title":"Ren Fail"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1159\/000541510","article-title":"A risk prediction model for new-onset chronic kidney disease in the elderly","volume":"56","author":"Luo","year":"2025","journal-title":"Am J Nephrol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1080\/27697061.2025.2461215","article-title":"Clinical outcomes in diabetic patients with zinc deficiency: a multi-institutional population-based study","volume":"44","author":"Wu","year":"2025","journal-title":"J Am Nutr Assoc"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"Cc04-8","DOI":"10.7860\/JCDR\/2014\/10090.5082","article-title":"Zinc status in type 2 diabetic patients: relation to the progression of diabetic nephropathy","volume":"8","author":"Al-Timimi","year":"2014","journal-title":"J Clin Diagn Res"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/S0065-2776(08)00003-5","article-title":"Roles of zinc and zinc signaling in immunity: zinc as an intracellular signaling molecule","volume":"97","author":"Hirano","year":"2008","journal-title":"Adv Immunol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.3390\/cells13161359","article-title":"Zinc and diabetes: a connection between micronutrient and metabolism","volume":"13","author":"Ahmad","year":"2024","journal-title":"Cells"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"e61776","DOI":"10.1371\/journal.pone.0061776","article-title":"Is serum zinc level associated with prediabetes and diabetes?: a cross-sectional study from Bangladesh","volume":"8","author":"Islam","year":"2013","journal-title":"PLoS One"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.3390\/nu14071353","article-title":"Role of zinc in diabetic kidney disease","volume":"14","author":"Gembillo","year":"2022","journal-title":"Nutrients"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jtemb.2017.03.006","article-title":"The beneficial effects of zinc on diabetes-induced kidney damage in murine rodent model of type 1 diabetes mellitus","volume":"42","author":"Yang","year":"2017","journal-title":"J Trace Elem Med Biol"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-025-04663-5","article-title":"Zinc deficiency aggravates high-fat diet-induced renal injury by regulating oxidative stress and inflammation via the Nrf2\/HO-1 pathway","author":"Guan","year":"2025","journal-title":"Biol Trace Elem Res"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"2084","DOI":"10.1007\/s12011-024-04306-1","article-title":"Zinc deficiency causes glomerulosclerosis and renal interstitial fibrosis through oxidative stress and increased lactate metabolism in rats","volume":"203","author":"Huang","year":"2025","journal-title":"Biol Trace Elem Res"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1186\/s12882-022-03040-x","article-title":"Association of Serum Zinc Level with severity of chronic kidney disease in diabetic patients: a cross-sectional study","volume":"23","author":"Kubota","year":"2022","journal-title":"BMC Nephrol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1748","DOI":"10.1038\/s41430-022-01181-8","article-title":"Relationship of serum copper and zinc with kidney function and urinary albumin to creatinine ratio: cross-sectional data from the NHANES 2011-2016","volume":"76","author":"Jiang","year":"2022","journal-title":"Eur J Clin Nutr"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1053\/j.jrn.2022.04.004","article-title":"Serum zinc levels in chronic kidney disease patients, hemodialysis patients, and healthy controls: systematic review and Meta-analysis","volume":"33","author":"Elgenidy","year":"2023","journal-title":"J Ren Nutr"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1093\/ndt\/gfz065","article-title":"Renal handling of zinc in chronic kidney disease patients and the role of circulating zinc levels in renal function decline","volume":"35","author":"Damianaki","year":"2020","journal-title":"Nephrol Dial Transplant"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1007\/s11695-019-04260-1","article-title":"Association of Serum Zinc Concentration with preservation of renal function after bariatric surgery: a retrospective pilot study","volume":"30","author":"Hung","year":"2020","journal-title":"Obes Surg"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1900\/RDS.2008.5.102","article-title":"Effect of zinc supplementation on microalbuminuria in patients with type 2 diabetes: a double blind, randomized, placebo-controlled, cross-over trial","volume":"5","author":"Parham","year":"2008","journal-title":"Rev Diabet Stud"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"2458","DOI":"10.2337\/diacare.28.10.2458","article-title":"Comparison of the effects of vitamins and\/or mineral supplementation on glomerular and tubular dysfunction in type 2 diabetes","volume":"28","author":"Farvid","year":"2005","journal-title":"Diabetes Care"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1614287","DOI":"10.3389\/fnut.2025.1614287","article-title":"Vitamin D deficiency and diabetic retinopathy risk in patients with newly diagnosed type 2 diabetes mellitus: a retrospective analysis","volume":"12","author":"Hung","year":"2025","journal-title":"Front Nutr"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"10924","DOI":"10.1038\/s41598-025-96032-4","article-title":"Association between COVID-19 and the development of chronic kidney disease in patients without initial acute kidney injury","volume":"15","author":"Chen","year":"2025","journal-title":"Sci Rep"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1053\/j.jvca.2025.02.015","article-title":"Comparison of Sugammadex versus neostigmine for postoperative outcomes in coronavirus disease 2019 patients undergoing thoracic surgery: a cohort study","volume":"39","author":"Chiu","year":"2025","journal-title":"J Cardiothorac Vasc Anesth"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.ijid.2020.09.008","article-title":"Analysis of the predictive factors for a critical illness of COVID-19 during treatment - relationship between serum zinc level and critical illness of COVID-19","volume":"100","author":"Yasui","year":"2020","journal-title":"Int J Infect Dis"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.pcad.2018.07.003","article-title":"An overview and update on obesity and the obesity paradox in cardiovascular diseases","volume":"61","author":"Elagizi","year":"2018","journal-title":"Prog Cardiovasc Dis"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"3075","DOI":"10.2337\/dci22-0027","article-title":"Diabetes Management in Chronic Kidney Disease: a consensus report by the American Diabetes Association (ADA) and kidney disease: improving global outcomes (KDIGO)","volume":"45","author":"de Boer","year":"2022","journal-title":"Diabetes Care"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12011-019-01892-3","article-title":"Role of zinc supplementation on ischemia\/reperfusion injury in various organs","volume":"196","author":"Akbari","year":"2020","journal-title":"Biol Trace Elem Res"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.3945\/jn.109.106369","article-title":"Zinc deficiency affects DNA damage, oxidative stress, antioxidant defenses, and DNA repair in rats","volume":"139","author":"Song","year":"2009","journal-title":"J Nutr"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"953","DOI":"10.3390\/antiox11050953","article-title":"Type 2 diabetes and oxidative stress and inflammation: pathophysiological mechanisms and possible therapeutic options","volume":"11","author":"Vassalle","year":"2022","journal-title":"Antioxidants (Basel)"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3390\/jcm11102787","article-title":"Association between body mass index and renal outcomes modified by chronic kidney disease and Anemia: the obesity paradox for renal outcomes","volume":"11","author":"Hung","year":"2022","journal-title":"J Clin Med"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2025.1653151\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T08:10:36Z","timestamp":1758701436000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2025.1653151\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,24]]},"references-count":38,"alternative-id":["10.3389\/fnut.2025.1653151"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2025.1653151","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,24]]},"article-number":"1653151"}}