Immunoglobulin Free Light Chains: A Biomarker of Diabetes

Abstract

Background: Inflammation is increasingly understood as playing an important role in type 2 diabetes mellitus (T2D) development. A critical mechanism of the inflammatory cascade in developing T2D is nuclear factor-kappa B (NF-kB) activation. As immunoglobulin free light chains (FLC) could be a biomarker of activation of NF-kB, we measured FLC in patients with T2D. Methods: The age range of the 77 patients with T2D and the 75 healthy control participants were 45 to 87 years (median 60) and 25 to 72 years (median 51), respectively.Serum FLC kappa and lambda were assayed by a competitive-inhibition multiplex Luminex assay. Findings: The concentration of circulating FLC kappa and the kappa/lambda ratio was lower, while in contrast, FLC lambda was higher, in patients with T2D than in healthy volunteers (p<0.0001).The area under the receiver operating curve (ROC-AUC) of the FLC kappa/lambda ratio showed the largest ROC-AUC compared with other FLC variables and hemoglobin A1c (HbA1c). With an optimal cutoff value of 1.3 for the FLC kappa/lambda ratio, the diagnostic performance for distinguishing between T2D and healthy control was a sensitivity of 0.96, a specificity of 1, a positive predictive value of 1, and a negative predictive value of 0.96. The odds ratio was 0.000018. Interpretation: These results suggest that FLC kappa/lambda may be more specific and sensitive for the diagnosis of T2D than HbA1c, and thus represents a potentially promising biomarker of inflammation which may reflect activation of NF-kB. Funding Statement: There was no specific funding for the study. Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: The Institutional Review Boards reviewed, and all study participants granted their consent to, the investigative use of blood specimens.