Impact of IL-6 receptor inhibitors on cerebrospinal fluid metabolites in type 2 diabetes patients.

Authors

Naidan Zhang, Chaixia Ji, Qi Xin, Baibing Xie, Chengliang Yuan

Published in

Medicine. Volume 105. Issue 32. Pages e50063. Aug 07, 2026.

Abstract

This study aimed to investigate whether interleukin-6 (IL-6) receptor inhibitors affect cerebrospinal fluid (CSF) metabolites in type 2 diabetes (T2D) patients. The initial phase employed drug-targeted Mendelian randomization to investigate the association between IL-6 receptor inhibitors and T2D across diverse populations. Subsequently, variables related to T2D were utilized as mediators in the relationship between IL-6 receptor inhibitors and CSF metabolites. Finally, the mediating effect of T2D was evaluated using mediation analysis. In the European cohort, the use of IL-6 receptor inhibitors was associated with a 25.3% reduction in the risk of T2D, as indicated by an odds ratio of 0.747 with a 95% confidence interval ranging from 0.556 to 0.938 (P = .003). In the East Asian cohort, IL-6 receptor inhibitors were associated with a 1.188-fold increase in the risk of elevated fasting insulin levels, with an odds ratio of 1.188 and a 95% confidence interval of 1.034 to 1.343 (P = .029). Mediation analysis revealed that IL-6 receptor inhibitors significantly elevated the levels of galacto-glycero-lipid (GG) in CSF, with 3.06% of the effect attributable to the reduced risk of T2D, and 96.94% directly resulting from the action of the IL-6 receptor inhibitors. The findings preliminarily indicated that race constituted a variable potentially influencing the differential effects of IL-6 receptor inhibitors among patients with type 2 diabetes (T2D) across various regions. While the administration of IL-6 receptor inhibitors might impact glucose concentrations in CSF, the role of T2D as a mediator in CSF metabolites was weak. The predominant determinant appeared to be the administration of IL-6 receptor inhibitors.

PMID:
42566624
Bibliographic data and abstract were imported from PubMed on 08 Aug 2026.

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