Diabetes, Metabolic Syndrome and Obesity (Oct 2022)
Association of Lipopolysaccharide-Toll-Like Receptor 4 Signaling and Microalbuminuria in Patients with Type 2 Diabetes Mellitus
Abstract
Lijuan Zhang,1,* Yuanjun Zhang,2,3,* Juxiang Liu,2,3,* Yonghong Li,4 Jinxing Quan2,3 1Department of Blood Transfusion, Gansu Provincial Hospital, Lanzhou, People’s Republic of China; 2Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, People’s Republic of China; 3Key Laboratory of Endocrine and Metabolic Diseases of Gansu Province, Lanzhou, People’s Republic of China; 4Institute of Clinical and Translational Medicine, Gansu Provincial Hospital, Lanzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinxing Quan, Tel +18109440427, Email [email protected]: Intestinal flora 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
