{"title":"循环白细胞介素-22是新诊断的2型糖尿病的生物标志物,与西格列汀的降糖作用有关。","authors":"Peiye Sun, Yuxi Xiao, Yuan Dong, Yixiang Feng, Hongting Zheng, Xiaoyu Liao","doi":"10.2147/DMSO.S509866","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Interleukin-22 (IL-22) has been demonstrated to be involved in the regulation of glucose metabolism, insulin resistance and inflammation response, which indicates that IL-22 might be associated with the occurrence and progression of diabetes. This study aimed to assess serum IL-22 levels in participants with type 2 diabetes mellitus (T2DM) and analyze the association between IL-22 levels and T2DM risk.</p><p><strong>Methods: </strong>Serum IL-22 concentrations of recruited healthy participants (n=48), newly diagnosed T2DM participants (n=46), and T2DM participants receiving placebo (n=7) or dipeptidyl peptidase-4 inhibitors (DPP-4i) sitagliptin monotherapy (n=7) were measured using a commercial enzyme-linked immunosorbent assay (ELISA) kit. Mice fed a high-fat diet (HFD) were administered sitagliptin and evaluated for IL-22 and intestinal inflammation-related indicators.</p><p><strong>Results: </strong>Serum IL-22 levels were higher in the T2DM group (127.16 ± 75.35) than in healthy controls (69.18 ± 32.83, <i>p</i> < 0.001), significantly negatively correlated with high-density lipoprotein cholesterol (HDL-C), and positively correlated with body mass index (BMI), glycosylated hemoglobin (HbA1c) and fasting plasma glucose (FPG), regardless of adjustment for sex and age. Multivariate logistic regression analysis showed that serum IL-22 levels were associated with the risk of T2DM (OR = 2.37, 95% CI = 1.27-4.42, <i>p</i> = 0.007). Additionally, sitagliptin treatment decreased the levels of IL-22 in the serum and colon tissues of T2DM participants and HFD mice. Moreover, intestinal inflammation was improved, and retinoid acid-related orphan receptor γt (RORγt, a marker of Th17 cells)- positive cells in the colon of HFD mice were decreased after sitagliptin treatment, which might be related to the reduction of IL-22.</p><p><strong>Conclusion: </strong>Serum IL-22 is a significant independent risk factor for T2DM, implying that circulating IL-22 may be a predictive biomarker and therapeutic target for T2DM.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"18 ","pages":"703-713"},"PeriodicalIF":2.8000,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887505/pdf/","citationCount":"0","resultStr":"{\"title\":\"Circulating Interleukin-22 Is a Biomarker for Newly Diagnosed Type 2 Diabetes Mellitus and Associated with Hypoglycemic Effect of Sitagliptin.\",\"authors\":\"Peiye Sun, Yuxi Xiao, Yuan Dong, Yixiang Feng, Hongting Zheng, Xiaoyu Liao\",\"doi\":\"10.2147/DMSO.S509866\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Interleukin-22 (IL-22) has been demonstrated to be involved in the regulation of glucose metabolism, insulin resistance and inflammation response, which indicates that IL-22 might be associated with the occurrence and progression of diabetes. This study aimed to assess serum IL-22 levels in participants with type 2 diabetes mellitus (T2DM) and analyze the association between IL-22 levels and T2DM risk.</p><p><strong>Methods: </strong>Serum IL-22 concentrations of recruited healthy participants (n=48), newly diagnosed T2DM participants (n=46), and T2DM participants receiving placebo (n=7) or dipeptidyl peptidase-4 inhibitors (DPP-4i) sitagliptin monotherapy (n=7) were measured using a commercial enzyme-linked immunosorbent assay (ELISA) kit. Mice fed a high-fat diet (HFD) were administered sitagliptin and evaluated for IL-22 and intestinal inflammation-related indicators.</p><p><strong>Results: </strong>Serum IL-22 levels were higher in the T2DM group (127.16 ± 75.35) than in healthy controls (69.18 ± 32.83, <i>p</i> < 0.001), significantly negatively correlated with high-density lipoprotein cholesterol (HDL-C), and positively correlated with body mass index (BMI), glycosylated hemoglobin (HbA1c) and fasting plasma glucose (FPG), regardless of adjustment for sex and age. Multivariate logistic regression analysis showed that serum IL-22 levels were associated with the risk of T2DM (OR = 2.37, 95% CI = 1.27-4.42, <i>p</i> = 0.007). Additionally, sitagliptin treatment decreased the levels of IL-22 in the serum and colon tissues of T2DM participants and HFD mice. Moreover, intestinal inflammation was improved, and retinoid acid-related orphan receptor γt (RORγt, a marker of Th17 cells)- positive cells in the colon of HFD mice were decreased after sitagliptin treatment, which might be related to the reduction of IL-22.</p><p><strong>Conclusion: </strong>Serum IL-22 is a significant independent risk factor for T2DM, implying that circulating IL-22 may be a predictive biomarker and therapeutic target for T2DM.</p>\",\"PeriodicalId\":11116,\"journal\":{\"name\":\"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy\",\"volume\":\"18 \",\"pages\":\"703-713\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-03-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887505/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/DMSO.S509866\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/DMSO.S509866","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
摘要
目的:白细胞介素22 (Interleukin-22, IL-22)已被证实参与糖代谢、胰岛素抵抗和炎症反应的调节,提示IL-22可能与糖尿病的发生发展有关。本研究旨在评估2型糖尿病(T2DM)患者血清IL-22水平,并分析IL-22水平与T2DM风险的关系。方法:采用商业酶联免疫吸附测定(ELISA)试剂盒,检测健康受试者(n=48)、新诊断T2DM受试者(n=46)和接受安慰剂(n=7)或二肽基肽酶-4抑制剂(DPP-4i)西格列汀单药治疗的T2DM受试者(n=7)的血清IL-22浓度。饲喂高脂饮食(HFD)的小鼠给予西格列汀,并评估IL-22和肠道炎症相关指标。结果:T2DM组血清IL-22水平(127.16±75.35)高于健康对照组(69.18±32.83,p < 0.001),且与高密度脂蛋白胆固醇(HDL-C)呈显著负相关,与体重指数(BMI)、糖化血红蛋白(HbA1c)、空腹血糖(FPG)呈正相关,不考虑性别和年龄调整。多因素logistic回归分析显示,血清IL-22水平与T2DM发病风险相关(OR = 2.37, 95% CI = 1.27 ~ 4.42, p = 0.007)。此外,西格列汀治疗降低了T2DM参与者和HFD小鼠血清和结肠组织中的IL-22水平。西格列汀治疗后,HFD小鼠肠道炎症得到改善,结肠中类维生素a酸相关孤儿受体γt (RORγt, Th17细胞的标志物)阳性细胞减少,这可能与IL-22的降低有关。结论:血清IL-22是T2DM的重要独立危险因素,提示循环IL-22可能是T2DM的预测性生物标志物和治疗靶点。
Circulating Interleukin-22 Is a Biomarker for Newly Diagnosed Type 2 Diabetes Mellitus and Associated with Hypoglycemic Effect of Sitagliptin.
Purpose: Interleukin-22 (IL-22) has been demonstrated to be involved in the regulation of glucose metabolism, insulin resistance and inflammation response, which indicates that IL-22 might be associated with the occurrence and progression of diabetes. This study aimed to assess serum IL-22 levels in participants with type 2 diabetes mellitus (T2DM) and analyze the association between IL-22 levels and T2DM risk.
Methods: Serum IL-22 concentrations of recruited healthy participants (n=48), newly diagnosed T2DM participants (n=46), and T2DM participants receiving placebo (n=7) or dipeptidyl peptidase-4 inhibitors (DPP-4i) sitagliptin monotherapy (n=7) were measured using a commercial enzyme-linked immunosorbent assay (ELISA) kit. Mice fed a high-fat diet (HFD) were administered sitagliptin and evaluated for IL-22 and intestinal inflammation-related indicators.
Results: Serum IL-22 levels were higher in the T2DM group (127.16 ± 75.35) than in healthy controls (69.18 ± 32.83, p < 0.001), significantly negatively correlated with high-density lipoprotein cholesterol (HDL-C), and positively correlated with body mass index (BMI), glycosylated hemoglobin (HbA1c) and fasting plasma glucose (FPG), regardless of adjustment for sex and age. Multivariate logistic regression analysis showed that serum IL-22 levels were associated with the risk of T2DM (OR = 2.37, 95% CI = 1.27-4.42, p = 0.007). Additionally, sitagliptin treatment decreased the levels of IL-22 in the serum and colon tissues of T2DM participants and HFD mice. Moreover, intestinal inflammation was improved, and retinoid acid-related orphan receptor γt (RORγt, a marker of Th17 cells)- positive cells in the colon of HFD mice were decreased after sitagliptin treatment, which might be related to the reduction of IL-22.
Conclusion: Serum IL-22 is a significant independent risk factor for T2DM, implying that circulating IL-22 may be a predictive biomarker and therapeutic target for T2DM.
期刊介绍:
An international, peer-reviewed, open access, online journal. The journal is committed to the rapid publication of the latest laboratory and clinical findings in the fields of diabetes, metabolic syndrome and obesity research. Original research, review, case reports, hypothesis formation, expert opinion and commentaries are all considered for publication.