{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:56:02Z","timestamp":1790916962304,"version":"4.1.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"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>The triglyceride-glucose (TyG) index is a reliable surrogate marker of insulin resistance and has been closely linked to type 2 diabetes mellitus (T2DM) risk. However, it remains unclear whether the TyG index is nonlinearly associated with cross-sectional glycemic status categories, from normal glucose to T2DM, and whether inflammatory indicators may partly account for this association. We therefore aimed to examine this nonlinear association and to estimate potential indirect associations through inflammatory indicators.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective analysis of cross-sectional data was conducted, including 1,117 participants. Generalized additive models (GAM) combined with restricted cubic spline (RCS) regression were used to examine the nonlinear association between the TyG index and stages of glucose metabolism. Stage specificity analyses were performed across normal glucose, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), combined IFG and IGT, and T2DM. In exploratory cross-sectional indirect association analyses, inflammatory markers accounted for part of the cross-sectional association between the TyG index and glycemic outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A significant nonlinear relationship was identified between the TyG index and T2DM (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.05), with an inflection point at TyG = 9.14. The TyG index showed a progressively increasing trend across advancing disease stages. In exploratory cross-sectional analyses of potential indirect associations, only MLDLR and NLDLR exhibited significant statistical indirect associations linking the TyG index to 2-hour postprandial plasma glucose (2hPG). However, because all variables were measured concurrently, causal mediation cannot be inferred. These exploratory findings may warrant further investigation in longitudinal studies, particularly across early stages of dysglycemia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The TyG index was nonlinearly associated with cross-sectional glycemic categories. Exploratory cross-sectional mediation analyses further revealed statistically significant indirect associations through MLDLR and NLDLR in the TyG index\u20132hPG relationship. These observations suggest that inflammatory markers may be related to glycemic deterioration primarily via postprandial-related pathways in early dysglycemia, although causal inference cannot be drawn from cross-sectional data. These findings are hypothesis-generating and support the prospective evaluation of the TyG index for risk stratification in primary-care settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1931822","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:41:40Z","timestamp":1790916100000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association between triglyceride-glucose index and stages of T2DM: potential indirect effects of inflammatory indicators"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiayi","family":"Tian","sequence":"first","affiliation":[{"name":"School of Public Health, Ningxia Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Li","sequence":"additional","affiliation":[{"name":"Center of Laboratory Medicine, General Hospital of Ningxia Medical University","place":["Yinchuan, Ningxia, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyi","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health, Ningxia Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingning","family":"Chang","sequence":"additional","affiliation":[{"name":"Center of Laboratory Medicine, General Hospital of Ningxia Medical University","place":["Yinchuan, Ningxia, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianglong","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Public Health, Ningxia Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhao","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Public Health, Ningxia Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Public Health, Ningxia Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Li","sequence":"additional","affiliation":[{"name":"Center of Laboratory Medicine, General Hospital of Ningxia Medical University","place":["Yinchuan, Ningxia, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.2337\/dc23-S002","article-title":"Classification and diagnosis of diabetes: Standards of care in diabetes-2023","volume":"46","author":"Elsayed","year":"2023","journal-title":"Diabetes Care"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(25)01635-6","article-title":"Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021","volume":"402","year":"2023","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1186\/s12902-024-01682-6","article-title":"Lipid accumulation product and type 2 diabetes risk: a population-based study","volume":"24","author":"Sadafi","year":"2024","journal-title":"BMC Endocr Disord"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/s2213-8587(19)30093-2","article-title":"Morbidity and mortality after lifestyle intervention for people with impaired glucose tolerance: 30-year results of the Da Qing Diabetes Prevention Outcome Study","volume":"7","author":"Gong","year":"2019","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1056\/NEJMoa012512","article-title":"Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin","volume":"346","author":"Knowler","year":"2002","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1007\/s11033-026-11509-3","article-title":"Insulin resistance induced by obesity: Mechanisms, metabolic implications and therapeutic approaches","volume":"53","author":"Choo","year":"2026","journal-title":"Mol Biol Rep"},{"key":"B7","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1089\/met.2008.0034","article-title":"The product of fasting glucose and triglycerides as surrogate for identifying insulin resistance in apparently healthy subjects","volume":"6","author":"Simental-Mend\u00eda","year":"2008","journal-title":"Metab Syndr Relat Disord"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2018.06.006","article-title":"The role of triglyceride glucose index in development of Type 2 diabetes mellitus","volume":"143","author":"Low","year":"2018","journal-title":"Diabetes Res Clin Pract"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25189802","article-title":"Hypoxia in human obesity: New insights from inflammation towards insulin resistance-a narrative review","volume":"25","author":"Mirabelli","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nature05482","article-title":"Mechanisms linking obesity to insulin resistance and type 2 diabetes","volume":"444","author":"Kahn","year":"2006","journal-title":"Nature"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2013.11.002","article-title":"Global estimates of diabetes prevalence for 2013 and projections for 2035","volume":"103","author":"Guariguata","year":"2014","journal-title":"Diabetes Res Clin Pract"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13133941","article-title":"An increasing triglyceride-glucose index is associated with a pro-inflammatory and pro-oxidant phenotype","volume":"13","author":"Adams-Huet","year":"2024","journal-title":"J Clin Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1186\/s12902-025-02042-8","article-title":"Relationship between TYG mediated pregnancy diabetes history and SII in American women: a retrospective cohort study of NHANES 2011-2018","volume":"25","author":"Duan","year":"2025","journal-title":"BMC Endocr Disord"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/2874122","article-title":"Lipid accumulation product as a predictor of prediabetes and diabetes: Insights from NHANES data (1999-2018)","volume":"2024","author":"Wang","year":"2024","journal-title":"J Diabetes Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2023.1163900","article-title":"The aggregate index of systemic inflammation (AISI): a novel predictor for hypertension","volume":"10","author":"Xiu","year":"2023","journal-title":"Front Cardiovasc Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-14-0442","article-title":"Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma","volume":"20","author":"Hu","year":"2014","journal-title":"Clin Cancer Res"},{"key":"B17","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1186\/s40001-025-02671-8","article-title":"Elevated neutrophil-monocyte-to-lymphocyte ratio increases risk of adverse outcomes in patients with chronic kidney disease and type 2 diabetes","volume":"30","author":"Li","year":"2025","journal-title":"Eur J Med Res"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/s11255-025-04564-5","article-title":"Exploring the influencing factors of abdominal aortic calcification events in chronic kidney disease (CKD) and non-CKD patients based on interpretable machine learning methods","volume":"57","author":"Lin","year":"2025","journal-title":"Int Urol Nephrol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.2147\/jir.s523194","article-title":"The prognostic value of neutrophil-to-lymphocyte ratio and lymphocyte-to-monocyte ratio in patients with hepatocellular carcinoma receiving HAIC-based conversion hepatectomy: a dual-center retrospective cohort study","volume":"18","author":"Li","year":"2025","journal-title":"J Inflammation Res"},{"key":"B20","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s12888-024-06463-y","article-title":"Association of systemic immune-inflammation index with all-cause and cardiovascular mortality among adults with depression: evidence from NHANES 2005-2018","volume":"25","author":"Yu","year":"2025","journal-title":"BMC Psychiatry"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn121430-20211008-01441","article-title":"Correlation between neutrophil\/lymphocyte ratio combined with low-density lipoprotein cholesterol\/high-density lipoprotein cholesterol ratio and severity of coronary artery disease in patients with acute coronary syndrome","volume":"34","author":"Yuan","year":"2022","journal-title":"Zhonghua Wei Zhong Bing Ji Jiu Yi Xue"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjms.2020.01.018","article-title":"Prognostic utility of monocyte to high-density lipoprotein ratio in patients with acute coronary syndrome: a meta-analysis","volume":"359","author":"Sun","year":"2020","journal-title":"Am J Med Sci"},{"key":"B23","doi-asserted-by":"publisher","first-page":"99","DOI":"10.5090\/jcs.22.082","article-title":"The neutrophil-to-lymphocyte ratio as a predictor of postoperative outcomes in patients undergoing coronary artery bypass grafting","volume":"56","author":"Lim","year":"2023","journal-title":"J Chest Surg"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/hcs2.69","article-title":"Development trends of etiological research contents and methods of noncommunicable diseases","volume":"2","author":"Chen","year":"2023","journal-title":"Health Care Sci"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.47391\/JPMA.22-63","article-title":"Triglyceride glucose (TyG) index: a surrogate biomarker of insulin resistance","volume":"72","author":"Ramdas Nayak","year":"2022","journal-title":"J Pak Med Assoc"},{"key":"B26","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1007\/s00431-025-06632-5","article-title":"The triglyceride glucose index as a biomarker for different glucose disorders in overweight and obese children and adolescents","volume":"184","author":"Taha","year":"2025","journal-title":"Eur J Pediatr"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-020-03570-2","article-title":"The triglyceride and glucose index is a useful biomarker to recognize glucose disorders in apparently healthy children and adolescents","volume":"179","author":"Simental-Mend\u00eda","year":"2020","journal-title":"Eur J Pediatr"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.973655","article-title":"Elevated triglyceride-glucose (TyG) index predicts impaired islet \u03b2-cell function: a hospital-based cross-sectional study","volume":"13","author":"Chen","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.suppl_2.s114","article-title":"Interleukin-6 and diabetes: the good, the bad, or the indifferent","volume":"54","author":"Kristiansen","year":"2005","journal-title":"Diabetes"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2014.04.006","article-title":"Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes","volume":"105","author":"Esser","year":"2014","journal-title":"Diabetes Res Clin Pract"},{"key":"B31","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1126\/science.7678183","article-title":"Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance","volume":"259","author":"Hotamisligil","year":"1993","journal-title":"Science"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0153171","article-title":"Insulin resistance in relation to lipids and inflammation in type-2 diabetic patients and non-diabetic people","volume":"11","author":"Feng","year":"2016","journal-title":"PloS One"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-005-1684-8","article-title":"Human triglyceride-rich lipoproteins impair glucose metabolism and insulin signalling in L6 skeletal muscle cells independently of non-esterified fatty acid levels","volume":"48","author":"Pedrini","year":"2005","journal-title":"Diabetologia"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.2337\/db09-0349","article-title":"Genetic disruption of myostatin reduces the development of proatherogenic dyslipidemia and atherogenic lesions in Ldlr null mice","volume":"58","author":"Tu","year":"2009","journal-title":"Diabetes"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-016-0409-7","article-title":"Efficacy and safety of metformin and sitagliptin based triple antihyperglycemic therapy (STRATEGY): a multicenter, randomized, controlled, non-inferiority clinical trial","volume":"60","author":"Xu","year":"2017","journal-title":"Sci China Life Sci"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1186\/2042-6410-3-13","article-title":"Sex differences in human adipose tissues - the biology of pear shape","volume":"3","author":"Karastergiou","year":"2012","journal-title":"Biol Sex Differ"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-019-05040-3","article-title":"Sex differences in metabolic regulation and diabetes susceptibility","volume":"63","author":"Tramunt","year":"2020","journal-title":"Diabetologia"},{"key":"B38","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.ejim.2024.08.026","article-title":"Triglyceride glucose (TyG) index: a promising biomarker for diagnosis and treatment of different diseases","volume":"131","author":"Sun","year":"2025","journal-title":"Eur J Intern Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2025.106744","article-title":"From lipids to glucose: Investigating the role of dyslipidemia in the risk of insulin resistance","volume":"250","author":"Jahdkaran","year":"2025","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/bs.ircmb.2021.02.013","article-title":"Molecular mechanisms of lipotoxicity-induced pancreatic \u03b2-cell dysfunction","volume":"359","author":"Benito-Vicente","year":"2021","journal-title":"Int Rev Cell Mol Biol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1931822\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:41:46Z","timestamp":1790916106000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1931822\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,2]]},"references-count":40,"alternative-id":["10.3389\/fendo.2026.1931822"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1931822","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,2]]},"article-number":"1931822"}}