Circulating Interleukin-22 Is a Biomarker for Newly Diagnosed Type 2 Diabetes Mellitus and Associated with Hypoglycemic Effect of Sitagliptin

Peiye Sun,* Yuxi Xiao,* Yuan Dong, Yixiang Feng, Hongting Zheng, Xiaoyu Liao Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, the second Affiliated Hospital of Army Medical University, Chongqing, People’s Repub...

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Main Authors: Sun P, Xiao Y, Dong Y, Feng Y, Zheng H, Liao X
Format: Article
Language:English
Published: Dove Medical Press 2025-03-01
Series:Diabetes, Metabolic Syndrome and Obesity
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Online Access:https://www.dovepress.com/circulating-interleukin-22-is-a-biomarker-for-newly-diagnosed-type-2-d-peer-reviewed-fulltext-article-DMSO
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author Sun P
Xiao Y
Dong Y
Feng Y
Zheng H
Liao X
author_facet Sun P
Xiao Y
Dong Y
Feng Y
Zheng H
Liao X
author_sort Sun P
collection DOAJ
description Peiye Sun,&ast; Yuxi Xiao,&ast; Yuan Dong, Yixiang Feng, Hongting Zheng, Xiaoyu Liao Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, the second Affiliated Hospital of Army Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyu Liao; Hongting Zheng, Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, the second Affiliated Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China, Tel +8602368774669 ; +8602368755709, Fax +8602368755707, Email liaoxiaoyu@tmmu.edu.cn; fnf7703@tmmu.edu.cnPurpose: 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.Keywords: IL-22, type 2 diabetes, sitagliptin, intestinal inflammation
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spelling doaj-art-8698c854d363434299b53ee6e75d44c82025-08-20T02:03:05ZengDove Medical PressDiabetes, Metabolic Syndrome and Obesity1178-70072025-03-01Volume 18703713100750Circulating Interleukin-22 Is a Biomarker for Newly Diagnosed Type 2 Diabetes Mellitus and Associated with Hypoglycemic Effect of SitagliptinSun PXiao YDong YFeng YZheng HLiao XPeiye Sun,&ast; Yuxi Xiao,&ast; Yuan Dong, Yixiang Feng, Hongting Zheng, Xiaoyu Liao Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, the second Affiliated Hospital of Army Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyu Liao; Hongting Zheng, Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, the second Affiliated Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China, Tel +8602368774669 ; +8602368755709, Fax +8602368755707, Email liaoxiaoyu@tmmu.edu.cn; fnf7703@tmmu.edu.cnPurpose: 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.Keywords: IL-22, type 2 diabetes, sitagliptin, intestinal inflammationhttps://www.dovepress.com/circulating-interleukin-22-is-a-biomarker-for-newly-diagnosed-type-2-d-peer-reviewed-fulltext-article-DMSOil-22type 2 diabetessitagliptinintestinal inflammation
spellingShingle Sun P
Xiao Y
Dong Y
Feng Y
Zheng H
Liao X
Circulating Interleukin-22 Is a Biomarker for Newly Diagnosed Type 2 Diabetes Mellitus and Associated with Hypoglycemic Effect of Sitagliptin
Diabetes, Metabolic Syndrome and Obesity
il-22
type 2 diabetes
sitagliptin
intestinal inflammation
title Circulating Interleukin-22 Is a Biomarker for Newly Diagnosed Type 2 Diabetes Mellitus and Associated with Hypoglycemic Effect of Sitagliptin
title_full Circulating Interleukin-22 Is a Biomarker for Newly Diagnosed Type 2 Diabetes Mellitus and Associated with Hypoglycemic Effect of Sitagliptin
title_fullStr Circulating Interleukin-22 Is a Biomarker for Newly Diagnosed Type 2 Diabetes Mellitus and Associated with Hypoglycemic Effect of Sitagliptin
title_full_unstemmed Circulating Interleukin-22 Is a Biomarker for Newly Diagnosed Type 2 Diabetes Mellitus and Associated with Hypoglycemic Effect of Sitagliptin
title_short Circulating Interleukin-22 Is a Biomarker for Newly Diagnosed Type 2 Diabetes Mellitus and Associated with Hypoglycemic Effect of Sitagliptin
title_sort circulating interleukin 22 is a biomarker for newly diagnosed type 2 diabetes mellitus and associated with hypoglycemic effect of sitagliptin
topic il-22
type 2 diabetes
sitagliptin
intestinal inflammation
url https://www.dovepress.com/circulating-interleukin-22-is-a-biomarker-for-newly-diagnosed-type-2-d-peer-reviewed-fulltext-article-DMSO
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