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

Abstract

Purpose

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

Acknowledgments

For their technical help, we thank the Gansu Provincial Key Laboratory of Endocrine and Metabolic Diseases and their whole personnel.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This research was supported by a grant from the National Natural Science Foundation of China (grant number: 81860091).