{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T04:31:05Z","timestamp":1786336265407,"version":"build-2736575974"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"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 and purpose<\/jats:title>\n                    <jats:p>Diabetic kidney disease (DKD) is a major microvascular complication of type 2 diabetes mellitus (T2DM). High-density lipoprotein cholesterol (HDL-C) has traditionally been considered renoprotective, yet growing evidence suggests that HDL subclasses may differ in biological function. This study aimed to investigate the association between HDL subclasses, particularly HDL2b, and chronic kidney disease (CKD) in Chinese adults with T2DM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this cross-sectional study, patients with T2DM were enrolled. CKD was defined as urinary albumin-to-creatinine ratio (UACR) \u22653.0 mg\/mmol and\/or estimated glomerular filtration rate (eGFR) \u226460 mL\/min\/1.73 m\u00b2. HDL subclasses were measured using capillary electrophoresis-based microfluidics. Participants were categorized into quartiles of HDL-C, HDL2b, and HDL3. Multivariable logistic regression models were constructed with progressive adjustment for anthropometric indices, hypertension, insulin resistance (HOMA-IR), and inflammatory markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 481 patients with T2DM, 136 (28.3%) had CKD. Patients with CKD exhibited significantly lower HDL2b levels (P\u00a0=\u00a00.001), together with greater insulin resistance and systemic inflammation (all P&amp;lt;0.05). HDL2b showed stronger inverse correlations than total HDL-C with adiposity, glycemic indices, insulin resistance, and inflammatory markers (all P&amp;lt;0.05). In multivariable logistic regression, higher HDL2b was independently associated with a lower risk of CKD. Compared with the lowest quartile, the third and fourth quartiles were associated with reduced odds of CKD (Q3: OR\u00a0=\u00a00.425, 95% CI 0.220\u20130.821, P\u00a0=\u00a00.012; Q4: OR\u00a0=\u00a00.367, 95% CI 0.188\u20130.717, P\u00a0=\u00a00.001). The inverse association between HDL2b and CKD was stronger in participants with higher insulin resistance (P for interaction=0.044).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Higher HDL2b, but not total HDL-C or HDL3, is independently associated with lower risk of CKD in T2DM. HDL2b may serve as a sensitive biomarker for early renal risk stratification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1868445","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T04:23:07Z","timestamp":1786335787000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of HDL2b with chronic kidney disease in type 2 diabetes mellitus populations"],"prefix":"10.3389","volume":"17","author":[{"given":"Hongjuan","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Nephrology, Maoming People\u2019s Hospital","place":["Maoming, China"]},{"name":"Depertment of Nephrology, The Third Affiliated Hospital of South Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilei","family":"Ye","sequence":"additional","affiliation":[{"name":"People\u2019s Hospital of Dianbai District","place":["Maoming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guobao","family":"Hong","sequence":"additional","affiliation":[{"name":"Depertment of Nephrology, The Third Affiliated Hospital of South Medical University","place":["Guangzhou, China"]},{"name":"Department of Nephrology, The Affiliated Shunde Hospital of Jinan University","place":["Foshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Maoming People\u2019s Hospital","place":["Maoming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Maoming People\u2019s Hospital","place":["Maoming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hequn","family":"Zou","sequence":"additional","affiliation":[{"name":"Depertment of Nephrology, The Third Affiliated Hospital of South Medical University","place":["Guangzhou, China"]},{"name":"Department of Nephrology, The Chinese University of HongKong","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Deng","sequence":"additional","affiliation":[{"name":"Guangdong Ardent Biomed Co. Ltd","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2019.107843","article-title":"Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9(th) edition","volume":"157","author":"Saeedi","year":"2019","journal-title":"Diabetes Res Clin Pract"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2337\/db16-0766","article-title":"Type 2 diabetes: Demystifying the global epidemic","volume":"66","author":"Unnikrishnan","year":"2017","journal-title":"Diabetes"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2337\/dci22-0046","article-title":"Youth-onset type 2 diabetes: The epidemiology of an awakening epidemic","volume":"46","author":"Perng","year":"2023","journal-title":"Diabetes Care"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2019.4498","article-title":"Prevalence of prediabetes among adolescents and young adults in the United States, 2005-2016","volume":"174","author":"Andes","year":"2020","journal-title":"JAMA Pediatr"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.2337\/dc25-s002","article-title":"2. Classification and diagnosis of diabetes: Standards of care in diabetes-2023","volume":"46","author":"ElSayed","year":"2023","journal-title":"Diabetes Care"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.2337\/dc22-0860","article-title":"Risk factors for the development of retinopathy in prediabetes and type 2 diabetes: The Diabetes Prevention Program experience","volume":"45","author":"White","year":"2022","journal-title":"Diabetes Care"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1172\/jci170341","article-title":"Endogenous adenine mediates kidney injury in diabetic models and predicts diabetic kidney disease in patients","volume":"133","author":"Sharma","year":"2023","journal-title":"J Clin Invest"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/jch.14263","article-title":"Urine albumin-to-creatinine ratio within the normal range and risk of hypertension in the general population: A meta-analysis","volume":"23","author":"Ren","year":"2021","journal-title":"J Clin Hypertension (Greenwich Conn)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1186\/s13098-024-01256-5","article-title":"An elevated urinary albumin-to-creatinine ratio increases the risk of incident cardia-cerebrovascular disease in individuals with type 2 diabetes","volume":"16","author":"Tao","year":"2024","journal-title":"Diabetol Metab Syndrome"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1177\/21501327211003683","article-title":"Optimal early diagnosis and monitoring of diabetic kidney disease in type 2 diabetes mellitus: Addressing the barriers to albuminuria testing","volume":"12","author":"Christofides","year":"2021","journal-title":"J Primary Care Community Health"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v14.i7.1103","article-title":"Correlation between glycated hemoglobin A1c, urinary microalbumin, urinary creatinine, \u03b22 microglobulin, retinol binding protein and diabetic retinopathy","volume":"14","author":"Song","year":"2023","journal-title":"World J Diabetes"},{"key":"B12","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.bbacli.2017.07.002","article-title":"Antioxidative activity of high-density lipoprotein (HDL): Mechanistic insights into potential clinical benefit","volume":"8","author":"Brites","year":"2017","journal-title":"BBA Clin"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2024.06.002","article-title":"Association between very high HDL-C levels and mortality: A systematic review and meta-analysis","volume":"18","author":"Mamede","year":"2024","journal-title":"J Clin Lipidology"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2022.0912","article-title":"Association between high-density lipoprotein cholesterol levels and adverse cardiovascular outcomes in high-risk populations","volume":"7","author":"Liu","year":"2022","journal-title":"JAMA Cardiol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.11491116","article-title":"Diabetic kidney disease: Challenges, progress, and possibilities","volume":"12","author":"Alicic","year":"2017","journal-title":"Clin J Am Soc Nephrol CJASN"},{"key":"B16","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1186\/s12882-024-03808-3","article-title":"Understanding the heterogeneity and dysfunction of HDL in chronic kidney disease: Insights from recent reviews","volume":"25","author":"Xu","year":"2024","journal-title":"BMC Nephrol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlr.2024.100678","article-title":"Untargeted lipidomics reveals novel HDL metabotypes and lipid-clinical correlates","volume":"65","author":"Karmaus","year":"2024","journal-title":"J Lipid Res"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.2147\/dmso.s446859","article-title":"The association of HDL2b with metabolic syndrome among normal HDL-C populations in Southern China","volume":"17","author":"Chen","year":"2024","journal-title":"Diabetes Metab Syndrome Obes"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2024.06.003","article-title":"Association between the proportion of HDL-cholesterol subclasses and the severity of coronary artery stenosis in patients with acute myocardial infarction","volume":"18","author":"Geng","year":"2024","journal-title":"J Clin Lipidology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1871","DOI":"10.1038\/s41598-021-81636-3","article-title":"Association of proportion of the HDL-cholesterol subclasses HDL-2b and HDL-3 and macrovascular events among patients undergoing hemodialysis","volume":"11","author":"Lee","year":"2021","journal-title":"Sci Rep"},{"key":"B21","doi-asserted-by":"publisher","first-page":"7856","DOI":"10.3390\/ijms25147856","article-title":"High-density lipoprotein subclasses and their role in the prevention and treatment of cardiovascular disease: A narrative review","volume":"25","author":"Chen","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2024.1462406","article-title":"Impact of metabolic-associated fatty liver disease on the cholesterol efflux capacity of high-density lipoproteins in adolescents with type 2 diabetes","volume":"12","author":"Orozco Morales","year":"2024","journal-title":"Front Pediatr"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.2337\/dc25-s002","article-title":"2. Diagnosis and classification of diabetes: Standards of care in diabetes-2024","volume":"47","year":"2024","journal-title":"Diabetes Care"},{"key":"B24","doi-asserted-by":"publisher","first-page":"12699","DOI":"10.1038\/s41598-020-69498-7","article-title":"The performance of anthropometric tools to determine obesity: A systematic review and meta-analysis","volume":"10","author":"Sommer","year":"2020","journal-title":"Sci Rep"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.27.6.1487","article-title":"Use and abuse of HOMA modeling","volume":"27","author":"Wallace","year":"2004","journal-title":"Diabetes Care"},{"key":"B26","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/s41581-019-0191-y","article-title":"Measured and estimated glomerular filtration rate: Current status and future directions","volume":"16","author":"Levey","year":"2020","journal-title":"Nat Rev Nephrol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.2337\/dc26-s011","article-title":"11. Chronic kidney disease and risk management: Standards of care in diabetes-2026","volume":"49","year":"2026","journal-title":"Diabetes Care"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1080\/21691401.2021.1961798","article-title":"Potential role of anti-inflammatory HDL subclasses in metabolic unhealth\/obesity","volume":"49","author":"Tang","year":"2021","journal-title":"Artif Cells Nanomed Biotechnol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-0625","article-title":"Differential association between HDL subclasses and the development of type 2 diabetes in a prospective study of Japanese Americans","volume":"38","author":"Hwang","year":"2015","journal-title":"Diabetes Care"},{"key":"B30","doi-asserted-by":"publisher","first-page":"13563","DOI":"10.3390\/ijms241713563","article-title":"Association of HDL subfraction profile with the progression of insulin resistance","volume":"24","author":"Piko","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/hsr2.1779","article-title":"A decreased level of high-density lipoprotein is a possible risk factor for type 2 diabetes mellitus: A review","volume":"6","author":"Bodaghi","year":"2023","journal-title":"Health Sci Rep"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-019-0970-2","article-title":"Are blood lipids associated with microvascular complications among type 2 diabetes mellitus patients? A cross-sectional study in Shanghai, China","volume":"18","author":"Yang","year":"2019","journal-title":"Lipids Health Dis"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1177\/1179551418792257","article-title":"The impact of insulin resistance and chronic kidney disease on inflammation and cardiovascular disease","volume":"11","author":"Kosmas","year":"2018","journal-title":"Clin Med Insights Endocrinol Diabetes"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2005.12.008","article-title":"C-reactive protein activates the nuclear factor-kappaB pathway and induces vascular cell adhesion molecule-1 expression through CD32 in human umbilical vein endothelial cells and aortic endothelial cells","volume":"40","author":"Liang","year":"2006","journal-title":"J Mol Cell Cardiol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.885516","article-title":"Association between high-sensitivity C-reactive protein and diabetic kidney disease in patients with type 2 diabetes mellitus","volume":"13","author":"Tang","year":"2022","journal-title":"Front Endocrinol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1111\/obr.13649","article-title":"Association of metabolic syndrome and chronic kidney disease","volume":"25","author":"Scurt","year":"2024","journal-title":"Obes Rev"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2025.120574","article-title":"High-density lipoprotein in cardiovascular diseases: From high quantity to high quality","volume":"578","author":"Zhang","year":"2026","journal-title":"Clinica Chimica Acta"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.3390\/biom10091348","article-title":"Current understanding of the relationship of HDL composition, structure and function to their cardioprotective properties in chronic kidney disease","volume":"10","author":"Marsche","year":"2020","journal-title":"Biomolecules"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0320803","article-title":"High density lipoprotein particle size and function associate with new cardiovascular events in patients with chronic kidney disease","volume":"20","author":"Mathew","year":"2025","journal-title":"PLoS One"},{"key":"B40","doi-asserted-by":"publisher","first-page":"601","DOI":"10.3390\/ijms21020601","article-title":"The role and function of HDL in patients with chronic kidney disease and the risk of cardiovascular disease","volume":"21","author":"Rysz","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.3390\/cells13131113","article-title":"High-density lipoprotein modifications: Causes and functional consequences in type 2 diabetes mellitus","volume":"13","author":"Zhang","year":"2024","journal-title":"Cells"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.28944","article-title":"Insulin resistance and type 2 diabetes mellitus: An ultimatum to renal physiology","volume":"14","author":"Sinha","year":"2022","journal-title":"Cureus"},{"key":"B43","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1186\/s12944-017-0594-3","article-title":"The role and function of HDL in patients with diabetes mellitus and the related cardiovascular risk","volume":"16","author":"Femlak","year":"2017","journal-title":"Lipids Health Dis"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.48","article-title":"Mineralocorticoid receptor activation and blockade: An emerging paradigm in chronic kidney disease","volume":"79","author":"Bertocchio","year":"2011","journal-title":"Kidney Int"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.505","article-title":"Aldosterone blockade and the mineralocorticoid receptor in the management of chronic kidney disease: Current concepts and emerging treatment paradigms","volume":"81","author":"Shavit","year":"2012","journal-title":"Kidney Int"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1042\/cs20256132","article-title":"Deficiency of mineralocorticoid receptor signalling in myeloid cells protects cardiac and kidney function in hypertensive diabetic mice","volume":"139","author":"Tesch","year":"2025","journal-title":"Clin Sci (London Engl 1979)"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00289.2025","article-title":"Spleen tyrosine kinase signaling in myeloid cells promotes macrophage infiltration, glomerulosclerosis, and interstitial fibrosis in diabetic kidney disease","volume":"329","author":"Chia","year":"2025","journal-title":"Am J Physiol Renal Physiol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1868445\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T04:23:08Z","timestamp":1786335788000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1868445\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,10]]},"references-count":47,"alternative-id":["10.3389\/fendo.2026.1868445"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1868445","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,10]]},"article-number":"1868445"}}