Serum Mediators in Patients with Both Type 2 Diabetes Mellitus and Pruritus


  • Guan-Yi He Department of Dermatology, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei City, Taiwan; Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei City, Taiwan
  • Tai-Yi Hsu 4School of Medicine, College of Medicine, China Medical University, Taichung City, Taiwan; Department of Emergency Medicine, China Medical University Hospital, Taichung City, Taiwan; Department of Public Health, China Medical University, Taichung City, Taiwan
  • Ching-Wen Chen Subdivision of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
  • Feng-Jung Nien Department of General Medicine, National Taiwan University Cancer Center, Taipei City, Taiwan
  • Huan-Yuan Chen Institute of Biomedical Sciences, Academia Sinica, Taipei City, Taiwan
  • Chia-Yu Chu Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei City, Taiwan
  • Li-Fang Wang Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 8, Zhongshan S. Road, Zhongzheng District, Taipei City 100226, Taiwan



chemokine CXCL10, diabetes mellitus, granulocyte-macrophage colony-stimulating factor;, interferon-inducible protein 10, pruritus


Chronic pruritus is an unpleasant sensory perception that negatively affects quality of life and is common among patients with type 2 diabetes mellitus. Current antipruritic therapies are insufficiently effective. Thus, the mediation of diabetic pruritus by histamine-independent pathways is likely. The aim of this study was to identify possible mediators responsible for diabetic pruritus. A total of 87 patients with type 2 diabetes mellitus were analysed, of whom 59 had pruritus and 28 did not. The 2 groups were assessed for baseline demographics, serum biochemistry parameters, cytokines, and chemokines. This study also investigated the associations of these factors with the severity of itching. Neither haemoglobin A1c nor serum creatinine levels were correlated with severity of itching. Significantly higher levels of interleukin-4 (p = 0.004), interleukin-13 (p = 0.006), granulocyte-macrophage colony-stimulating factor (p < 0.001) and C-X-C motif chemokine ligand 10 (p = 0.028) were observed in the patients with pruritus than in those without pruritus. Moreover, the levels of these mediators were positively correlated with the severity of itching. Thus, novel antipruritic drugs can be developed to target these molecules. This is the first study to compare inflammatory mediators comprehensively in patients with diabetes mellitus with pruritus vs those without pruritus. 


Download data is not yet available.


Khan MAB, Hashim MJ, King JK, Govender RD, Mustafa H, Al Kaabi J. Epidemiology of type 2 diabetes - global burden of disease and forecasted trends. J Epidemiol Glob Health 2020; 10: 107-111. DOI:

Lima AL, Illing T, Schliemann S, Elsner P. Cutaneous manifestations of diabetes mellitus: a review. Am J Clin Dermatol 2017; 18: 541-553. DOI:

Stefaniak AA, Krajewski PK, Bednarska-Chabowska D, Bolanowski M, Mazur G, Szepietowski JC. Itch in adult population with type 2 diabetes mellitus: clinical profile, pathogenesis and disease-related burden in a cross-sectional study. Biology (Basel) 2021; 10: 1332. DOI:

Stefaniak A, Chlebicka I, Szepietowski J. Itch in diabetes: a common underestimated problem. Adv Dermatol Allergol/Postępy Dermatologii i Alergologii 2019; 38: 177-183. DOI:

Teoh Y, Yeo B, Koh M, Teo R. Pruritus in the elderly and its impact on quality of life. J Am Acad Dermatol 2012; 66: AB11. DOI:

Weisshaar E, Szepietowski JC, Dalgard FJ, Garcovich S, Gieler U, Giménez-Arnau AM, et al. European S2k guideline on chronic pruritus. Acta Derm Venereol 2019; 99: 469-506. DOI:

Ko MJ, Chiu HC, Jee SH, Hu FC, Tseng CH. Postprandial blood glucose is associated with generalized pruritus in patients with type 2 diabetes. Eur J Dermatol 2013; 23: 688-693. DOI:

Yang QP, Chen YY, Li Z, Xu M. Major risk factors analysis of pruritus complicated by type 2 diabetes mellitus and the effect of comprehensive nursing intervention. Front Surg 2022; 9: 842884. DOI:

Wang F, Kim BS. Itch: a paradigm of neuroimmune crosstalk. Immunity 2020; 52: 753-766. DOI:

Mahlangu T, Dludla PV, Nyambuya TM, Mxinwa V, Mazibuko-Mbeje SE, Cirilli I, et al. A systematic review on the functional role of Th1/Th2 cytokines in type 2 diabetes and related metabolic complications. Cytokine 2020; 126: 154892. DOI:

Reich A, Chatzigeorkidis E, Zeidler C, Osada N, Furue M, Takamori K, et al. Tailoring the cut-off values of the visual analogue scale and numeric rating scale in itch assessment. Acta Derm Venereol 2017; 97: 759-760. DOI:

Reich A, Bożek A, Janiszewska K, Szepietowski JC. 12-item pruritus severity scale: development and validation of new itch severity questionnaire. Biomed Res Int 2017; 2017: 3896423. DOI:

Chen YY, Yang QP, Peng SP, Li ZZ, Yang HY, Fan XG, et al. Risk factors and psychological condition of pruritus in type 2 diabetes mellitus: a retrospective, propensity score-matched study. Eur Rev Med Pharmacol Sci 2022; 26: 5353-5361.

Turner MD, Nedjai B, Hurst T, Pennington DJ. Cytokines and chemokines: at the crossroads of cell signalling and inflammatory disease. Biochim Biophys Acta 2014; 1843: 2563-2582. DOI:

Storan ER, O'Gorman SM, McDonald ID, Steinhoff M. Role of cytokines and chemokines in itch. Handb Exp Pharmacol 2015; 226: 163-176. DOI:

Shibuya R, Takimoto-Ito R, Kambe N, Kabashima K. A new era with the development of cytokine-based therapy for pruritus. J Invest Dermatol 2022; 142: 47-52. DOI:

Al-Shukaili A, Al-Ghafri S, Al-Marhoobi S, Al-Abri S, Al-Lawati J, Al-Maskari M. Analysis of inflammatory mediators in type 2 diabetes patients. Int J Endocrinol 2013; 2013: 976810. DOI:

Furue M, Yamamura K, Kido-Nakahara M, Nakahara T, Fukui Y. Emerging role of interleukin-31 and interleukin-31 receptor in pruritus in atopic dermatitis. Allergy 2018; 73: 29-36. DOI:

Ko MJ, Peng YS, Chen HY, Hsu SP, Pai MF, Yang JY, et al. Interleukin-31 is associated with uremic pruritus in patients receiving hemodialysis. J Am Acad Dermatol 2014; 71: 1151-1159.e1151. DOI:

Hashimoto T, Nattkemper LA, Kim HS, Kursewicz CD, Fowler E, Shah SM, et al. Itch intensity in prurigo nodularis is closely related to dermal interleukin-31, oncostatin M, IL-31 receptor alpha and oncostatin M receptor beta. Exp Dermatol 2021; 30: 804-810. DOI:

Oweis AO, Al-Qarqaz F, Bodoor K, Heis L, Alfaqih MA, Almomani R, et al. Elevated interleukin 31 serum levels in hemodialysis patients are associated with uremic pruritus. Cytokine 2021; 138: 155369. DOI:

Gooderham MJ, Hong HC, Eshtiaghi P, Papp KA. Dupilumab: a review of its use in the treatment of atopic dermatitis. J Am Acad Dermatol 2018; 78: S28-s36. DOI:

Husein-ElAhmed H, Steinhoff M. Dupilumab in prurigo nodularis: a systematic review of current evidence and analysis of predictive factors to response. J Dermatolog Treat 2022; 33: 1547-1553. DOI:

Le Floc'h A, Allinne J, Nagashima K, Scott G, Birchard D, Asrat S, et al. Dual blockade of IL-4 and IL-13 with dupilumab, an IL-4Rα antibody, is required to broadly inhibit type 2 inflammation. Allergy 2020; 75: 1188-1204. DOI:

Fallahzadeh MK, Roozbeh J, Geramizadeh B, Namazi MR. Interleukin-2 serum levels are elevated in patients with uremic pruritus: a novel finding with practical implications. Nephrol Dial Transplant 2011; 26: 3338-3344. DOI:

Hon KL, Tsang KY, Kung JS, Leung TF, Lam CW, Wong CK. Clinical signs, staphylococcus and atopic eczema-related seromarkers. Molecules 2017; 22: 291. DOI:

Surendar J, Mohan V, Pavankumar N, Babu S, Aravindhan V. Increased levels of serum granulocyte-macrophage colony-stimulating factor is associated with activated peripheral dendritic cells in type 2 diabetes subjects (CURES-99). Diabetes Technol Ther 2012; 14: 344-349. DOI:

Pastore S, Fanales-Belasio E, Albanesi C, Chinni LM, Giannetti A, Girolomoni G. Granulocyte macrophage colony-stimulating factor is overproduced by keratinocytes in atopic dermatitis. Implications for sustained dendritic cell activation in the skin. J Clin Invest 1997; 99: 3009-3017. DOI:

Chen Q, Zhong H, Chen WC, Zhai Z, Zhou Z, Song Z, et al. Different expression patterns of plasma Th1-, Th2-, Th17- and Th22-related cytokines correlate with serum autoreactivity and allergen sensitivity in chronic spontaneous urticaria. J Eur Acad Dermatol Venereol 2018; 32: 441-448. DOI:

Luster AD. Chemokines - chemotactic cytokines that mediate inflammation. N Engl J Med 1998; 338: 436-445. DOI:

Ahmadi Z, Arababadi MK, Hassanshahi G. CXCL10 activities, biological structure, and source along with its significant role played in pathophysiology of type I diabetes mellitus. Inflammation 2013; 36: 364-371. DOI:

Tokuriki A, Seo N, Ito T, Kumakiri M, Takigawa M, Tokura Y. Dominant expression of CXCR3 is associated with induced expression of IP-10 at hapten-challenged sites of murine contact hypersensitivity: a possible role for interferon-gamma-producing CD8(+) T cells in IP-10 expression. J Dermatol Sci 2002; 28: 234-241. DOI:

Jinquan T, Jing C, Jacobi HH, Reimert CM, Millner A, Quan S, et al. CXCR3 expression and activation of eosinophils: role of IFN-gamma-inducible protein-10 and monokine induced by IFN-gamma. J Immunol 2000; 165: 1548-1556. DOI:

Nelson TE, Gruol DL. The chemokine CXCL10 modulates excitatory activity and intracellular calcium signaling in cultured hippocampal neurons. J Neuroimmunol 2004; 156: 74-87. DOI:

Qu L, Fu K, Yang J, Shimada SG, LaMotte RH. CXCR3 chemokine receptor signaling mediates itch in experimental allergic contact dermatitis. Pain 2015; 156: 1737-1746. DOI:

Walsh CM, Hill RZ, Schwendinger-Schreck J, Deguine J, Brock EC, Kucirek N, et al. Neutrophils promote CXCR3-dependent itch in the development of atopic dermatitis. Elife 2019; 8: e48448. DOI:

Klunker S, Trautmann A, Akdis M, Verhagen J, Schmid-Grendelmeier P, Blaser K, et al. A second step of chemotaxis after transendothelial migration: keratinocytes undergoing apoptosis release IFN-gamma-inducible protein 10, monokine induced by IFN-gamma, and IFN-gamma-inducible alpha-chemoattractant for T cell chemotaxis toward epidermis in atopic dermatitis. J Immunol 2003; 171: 1078-1084. DOI:

Xu H, Nakayama K, Ogawa S, Sugiura A, Kato T, Sato T, et al. [Elevated plasma concentration of IP-10 in patients with type 2 diabetes mellitus]. Nihon Jinzo Gakkai Shi 2005; 47: 524-530 (in Japanese).

Schulthess FT, Paroni F, Sauter NS, Shu L, Ribaux P, Haataja L, et al. CXCL10 impairs beta cell function and viability in diabetes through TLR4 signaling. Cell Metab 2009; 9: 125-139. DOI:

Chang CC, Wu CL, Su WW, Shih KL, Tarng DC, Chou CT, et al. Interferon gamma-induced protein 10 is associated with insulin resistance and incident diabetes in patients with nonalcoholic fatty liver disease. Sci Rep 2015; 5: 10096. DOI:

Additional Files



How to Cite

He, G.-Y., Hsu, T.-Y., Chen, C.-W. ., Nien, F.-J., Chen, H.-Y. ., Chu, C.-Y. ., & Wang, L.-F. . (2023). Serum Mediators in Patients with Both Type 2 Diabetes Mellitus and Pruritus. Acta Dermato-Venereologica, 103, adv00875.