{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:58:03Z","timestamp":1787504283571,"version":"build-2736575974"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"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. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diabetic complications represent a major source of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). However, the role of age in the development and progression of complications across different stages remains incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This cross-sectional study included 489 patients with T2DM. Diabetic complications were classified as macrovascular disease (MaVD), microvascular disease (MVD), and peripheral neuropathy (PN). The number of complications (0, 1, 2, \u22653) was used to assess complication burden. Logistic regression, partial proportional odds models, interaction analysis, and restricted cubic spline (RCS) models were applied to evaluate the association between age and diabetic complications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The overall prevalence of complications was 75.66% and increased progressively with age. Age was independently associated with the presence of diabetic complications after adjustment for confounders (OR\u00a0=\u00a01.06, 95% CI: 1.03\u20131.08). The effect of age was more pronounced during the transition from no complications to multiple complications, but attenuated at higher stages. Subtype analysis showed that age was most consistently associated with microvascular disease, while the association with peripheral neuropathy was borderline and not significant for macrovascular disease after full adjustment. A significant interaction between age and diabetes duration was observed, indicating that the effect of age was stronger in early-stage disease but diminished with longer duration. RCS analysis demonstrated a positive and approximately linear association between age and complication risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Age is independently associated with diabetic complications in T2DM, particularly in the early and intermediate stages of complication development. The effect of age varies by complication subtype and is modified by diabetes duration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1782406","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T04:47:09Z","timestamp":1778215629000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Age and diabetic complications in type 2 diabetes: the role of disease duration and stage-dependent effects"],"prefix":"10.3389","volume":"17","author":[{"given":"Xu","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, the 1st Medical Center, Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbin","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, the 3rd Medical Center, Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzhong","family":"Ji","sequence":"additional","affiliation":[{"name":"Chinese PLA Medical School","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Luan","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Qingdao Third People\u2019s Hospital","place":["Shandong, Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingzhu","family":"Nan","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Beijing Anzhen hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, the 1st Medical Center, Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/5527460","article-title":"A prediction model based on noninvasive indicators to predict the 8-year incidence of type 2 diabetes in patients with nonalcoholic fatty liver disease: a population-based retrospective cohort study","volume":"2021","author":"Cai","year":"2021","journal-title":"BioMed Res Int"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2020.107613","article-title":"Molecular complexities underlying the vascular complications of diabetes mellitus - a comprehensive review","volume":"34","author":"Paul","year":"2020","journal-title":"J Diabetes Complications"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc-2019-000835","article-title":"Physical activity, sedentary leisure-time and risk of incident type 2 diabetes: a prospective study of 512\u2013000 Chinese adults","volume":"7","author":"Bennett","year":"2019","journal-title":"BMJ Open Diabetes Res Care"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0304173","article-title":"Are soluble E-selectin, ICAM-1, and VCAM-1 potential predictors for the development of diabetic retinopathy in young adults, 15\u201334 years of age? A Swedish prospective cohort study","volume":"19","author":"Ekelund","year":"2024","journal-title":"PloS One"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000039759","article-title":"Prevalence of nephropathy among diabetic patients in North American region: a systematic review and meta-analysis","volume":"103","author":"Zahra","year":"2024","journal-title":"Med (Baltimore)"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2021.108877","article-title":"Peripheral versus central insulin and leptin resistance: role in metabolic disorders, cognition, and neuropsychiatric diseases","volume":"203","author":"Erichsen","year":"2022","journal-title":"Neuropharmacology"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.5114\/aoms\/159048","article-title":"The effects of oral trehalose on glycaemia, inflammation, and quality of life in patients with type 2 diabetes: a pilot randomized controlled trial","volume":"19","author":"Hashemian","year":"2023","journal-title":"Arch Med Sci"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/dom.70288","article-title":"Continuous glucose monitoring and microvascular complications in diabetes: bridging glycemic metrics with clinical outcomes","volume":"28","author":"Anagnostopoulou","year":"2026","journal-title":"Diabetes Obes Metab"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/life15010081","article-title":"The prevalence of metabolic syndrome and hypertriglyceridemic waist based on sociodemographic variables and healthy habits in healthcare workers: a retrospective study","volume":"15","author":"T\u00e1rraga Marcos","year":"2025","journal-title":"Life (Basel)"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/metabo15060380","article-title":"New players in metabolic syndrome","volume":"15","author":"Nedeva","year":"2025","journal-title":"Metabolites"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2147\/dmso.s447784","article-title":"Fecal microbiota transplantation: a prospective treatment for type 2 diabetes mellitus","volume":"17","author":"Zhou","year":"2024","journal-title":"Diabetes Metab Syndr Obes"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/mus.70015","article-title":"Diabetic neuropathies","volume":"72","author":"Anandan","year":"2025","journal-title":"Muscle Nerve"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.5551\/jat.65551","article-title":"A comprehensive analysis of diabetic complications and advances in management strategies","volume":"32","author":"Iwasaki","year":"2025","journal-title":"J Atheroscler Thromb"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.114907","article-title":"Mesangial cells in diabetic kidney disease: from mechanisms to therapeutic implications","volume":"21","author":"Feng","year":"2025","journal-title":"Int J Biol Sci"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.2196\/84261","article-title":"Bridging population patterns and individual prediction: framework for prospective multimorbidity study","volume":"14","author":"Zhang","year":"2026","journal-title":"JMIR Med Inform"},{"key":"B16","doi-asserted-by":"publisher","first-page":"9363","DOI":"10.1038\/s41598-022-13164-7","article-title":"Relationship between renal and liver function with diabetic retinopathy in patients with type 2 diabetes mellitus: a study based on cross-sectional data","volume":"12","author":"Yao","year":"2022","journal-title":"Sci Rep"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/1011415","article-title":"Clinical effects of primary nursing on diabetic nephropathy patients undergoing hemodialysis and its impact on the inflammatory responses","volume":"2022","author":"Guo","year":"2022","journal-title":"Evid Based Complement Alternat Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.101955","article-title":"Relationship between elevated plasma homocysteine levels and severity of peripheral neuropathy in patients with type 2 diabetes mellitus: a cross-sectional analysis","volume":"18","author":"Toqeer","year":"2026","journal-title":"Cureus"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/5295328","article-title":"Supplementation with Korean red ginseng improves current perception threshold in Korean type 2 diabetes patients: a randomized, double-blind, placebo-controlled trial","volume":"2020","author":"Park","year":"2020","journal-title":"J Diabetes Res"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.2139\/ssrn.5381800","article-title":"Global, regional, and national burden of chronic kidney disease in adults, 1990-2023, and its attributable risk factors: a systematic analysis for the Global Burden of Disease Study 2023","volume":"406","year":"2025","journal-title":"Lancet"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1383035","article-title":"Causal relationships between blood metabolites and diabetic retinopathy: a two-sample Mendelian randomization study","volume":"15","author":"Yang","year":"2024","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S274759","article-title":"ANGPTL8 gene polymorphism rs2278426 is related to carotid intima-media thickness in T2DM","volume":"13","author":"Guo","year":"2020","journal-title":"Diabetes Metab Syndr Obes"},{"key":"B23","doi-asserted-by":"publisher","first-page":"472","DOI":"10.12688\/f1000research.110927.1","article-title":"Plasma glucose, HbA1c, insulin and lipid profile in Sudanese type 2 diabetic patients with cardiovascular disease: a case control study","volume":"11","author":"Abdallah","year":"2022","journal-title":"F1000Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0342745","article-title":"Prognostic value of blood glucose trajectories in critically ill patients with intracerebral hemorrhage: a retrospective cohort study","volume":"21","author":"Zuo","year":"2026","journal-title":"PloS One"},{"key":"B25","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1186\/s12877-021-02676-y","article-title":"Assessment of frailty in elderly patients attending a multidisciplinary wound care centre: a cohort study","volume":"21","author":"Espaulella-Ferrer","year":"2021","journal-title":"BMC Geriatr"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.20944\/preprints202409.0511.v1","article-title":"Evaluation of the impact of advanced glycation end-products on peripheral neuropathy outcomes in type 2 diabetes","volume":"12","author":"Singh","year":"2024","journal-title":"Biomedicines"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-025-08281-3","article-title":"Synergistic use of 1,5-AG and HbA1c for early prediction of gestational diabetes: capturing BMI-dependent glycemic phenotypes","volume":"313","author":"Tano","year":"2026","journal-title":"Arch Gynecol Obstet"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.125.044112","article-title":"Differential effects of admission hemoglobin A(1c) by estimated glomerular filtration rate stages on mortality in acute ischemic stroke and diabetes","volume":"14","author":"Kim","year":"2025","journal-title":"J Am Heart Assoc"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/dme.14065","article-title":"Associations between HbA(1c) and continuous glucose monitoring-derived glycaemic variables","volume":"36","author":"Hirsch","year":"2019","journal-title":"Diabetes Med"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41440-025-02347-0","article-title":"Efficacy and safety of esaxerenone with and without sodium-glucose cotransporter-2 inhibitor use in hypertensive patients with type 2 diabetes mellitus: a pooled analysis of five clinical studies","volume":"48","author":"Motoki","year":"2025","journal-title":"Hypertens Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6518221","article-title":"The effects of glucagon-like peptide-1 receptor agonists and dipeptydilpeptidase-4 inhibitors on blood pressure and cardiovascular complications in diabetes","volume":"2021","author":"Yaribeygi","year":"2021","journal-title":"J Diabetes Res"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1782406\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T04:47:17Z","timestamp":1778215637000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1782406\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,8]]},"references-count":31,"alternative-id":["10.3389\/fendo.2026.1782406"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1782406","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,8]]},"article-number":"1782406"}}