Novel Biomarkers of Inflammation for the Management of Diabetes: Immunoglobulin-Free Light Chains

Abstract

Virus infection, inflammation and genetic factors are important factors in the pathogenesis of diabetes mellitus. The nuclear factor-kappa B (NF-κB) is a family of transcription factors that bind the enhancer of the κ light chain gene of B cell immunoglobulin. NF-κB plays an essential role in the activation and development of B cells, and the activation of NF-κB is critical in the inflammation and development of diabetes mellitus. Recently, immunoglobulin-free light chain (FLC) λ was found to be increased in the sera of patients with diabetes mellitus, and the FLC λ and κ/λ ratios are more specific and sensitive markers for the diagnosis of diabetes relative to glycated hemoglobin A1c. Thus, FLCs may be promising biomarkers of inflammation that could relate to the activation of NF-κB. We suggest that NF-κB could be a target for an anti-inflammatory strategy in preventing and treating diabetes when FLCs are modified. FLCs could be a surrogate endpoint in the management of diabetes. In this review, the role of inflammation in the pathogenesis of diabetes, as well as the novel inflammatory biomarkers of FLCs for the management of diabetes, are discussed.

Keywords: B cells; anti-inflammation; biomarker; diabetes; hepatitis C virus; immunoglobulin; inflammation; light chain; nuclear factor-kappa B; virus.

Figure 1

Immunoglobulin-free light chains (FLCs) in patients with type 2 diabetes and healthy controls (Adapted from [13]).

Figure 2

The area under the receiver operating curve (ROC-AUC) of the FLC κ, λ and κ/λ ratio and glycated hemoglobin (HbA1c). ROC-AUC of the FLC κ/λ ratio showed the largest compared with other FLC variables (Adapted from [13]).

Figure 3

Comparisons of ROC-AUC between FLC variables and HbA1c. The ROC-AUC of the FLC κ/λ ratio was larger than that of HbA1c (Adapted from [13]).

Figure 4

FLCs as inflammatory biomarkers of diabetes. Risk factors of diabetes such as viral infection, hyperglycemia and obesity activate nuclear factor kappa B (NF-κB), which regulates transcription of immunoglobulin-free light chains in the immunoglobulin-producing B cells and plasma cells and production of many inflammatory molecules, leading to inflammation. Thus, FLCs were proposed to be biomarkers of NF-κB activation and inflammation. Metformin, DPP-4 inhibitors and GLP-1 receptor agonists inhibit NF-κB activation and inflammation, and SGLT2 inhibitors and anti-IL-1 therapy inhibit inflammation.