Association of Lipopolysaccharide-Toll-Like Receptor 4 Signaling and Microalbuminuria in Patients with Type 2 Diabetes Mellitus

• Published in: Diabetes, metabolic syndrome and obesity Vol. 15; pp. 3143 - 3152
• Main Authors: Zhang, Lijuan, Zhang, Yuanjun, Liu, Juxiang, Li, Yonghong, Quan, Jinxing
• Format: Journal Article
• Language: English
• Published: Macclesfield Dove Medical Press Limited 31.10.2022; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: Albumin; Analysis; Bacteria; Blood; Blood sugar; C-reactive protein; Cholesterol; Creatinine; Data analysis; Diabetes; Enzymes; Ethylenediaminetetraacetic acid; Glycosylated hemoglobin; High density lipoprotein; Hospitals; Insulin resistance; Interleukins; intestinal mucosal barrier; lipopolysaccharide; Medical research; microalbuminuria; Monoclonal antibodies; Normal distribution; Original Research; Oxidases; Pathophysiology; Patients; Proteins; Risk factors; toll-like receptor 4; Type 2 diabetes; type 2 diabetes mellitus; Urine; Variance analysis; China; United States > US; Germany; Chicago Illinois
• ISSN: 1178-7007; 1178-7007
• DOI: 10.2147/DMSO.S377776

Purpose: Intestinal fora imbalance has been implicated in the activation of innate immunity in the kidneys. However, little is known about the potential links between lipopolysaccharide (LPS)-toll-like. receptor 4 (TLR4) signaling activated by intestinal barrier dysfunction and microalbuminuria in type 2 diabetes mellitus (T2DM). Patients and Methods: 61 patients with T2DM were stratified based on the absence (n=32) or presence (n=29) of microalbuminuria. There were also 28 control subjects. Urinary albumin excretion rate (UAER), serum levels of LPS, D-lactic acid (DLA), diamine oxidase (DAO), fasting blood glucose (FBG), interleukin-6 (IL-6), glycosylated hemoglobin A1 (HbA1c), and high-sensitivity C-reactive protein (hs-CRP), and TLR4 expression in peripheral blood mononuclear cells (PBMCs) were measured. Results: hs-CRP, IL-6, LPS, DLA, DAO, and TLR4 were markedly increased in subjects with T2DM compared to the controls (P < 0.05 for all). Moreover, LPS was positively correlated with FBG, HbA1c, hs-CRP, IL-6, UAER, DLA, DAO, and TLR4 (P < 0.05 for all). In addition, TLR4 was positively correlated with UAER, hs-CRP, FBG, DLA, HbA1c, and LPS (P < 0.05 for all). In regression analyses, TLR4, LPS, HbA1c, and hs-CRP were independently associated with UAER (P < 0.05 for all), while FBG, LPS, TLR4, and hs-CRP (P < 0.05 for all) were found to be risk factors for microalbuminuria in T2DM. Conclusion: Intestinal integrity is compromised in subjects with T2DM, and the activation of LPS-TLR4 signaling might play an important role in the development of microalbuminuria in T2DM. Keywords: intestinal mucosal barrier, microalbuminuria, type 2 diabetes mellitus, lipopolysaccharide, toll-like receptor 4