Associations of Innate and Adaptive Immune Cell Subsets With Incident Type 2 Diabetes Risk: The MESA Study

Objective: Cell-mediated immunity is implicated in glucose homeostasis and insulin resistance. Whether the levels of innate and adaptive immune cells in peripheral blood are risk factors for incident type 2 diabetes (T2D) remains unknown. We hypothesized that the proportions of naive, memory, CD28^-, Th17, and T regulatory CD4⁺ cells would be associated with incident T2D. In secondary analyses, we evaluated the relationships of 28 additional immune cell phenotypes with T2D. Design: Immune cell phenotypes (n = 33) were measured by flow cytometry using cryopreserved cells collected from 1113 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) at the baseline examination (2000-2002). Cox proportional hazards models were used to evaluate associations of immune cell phenotypes with incident T2D over a median follow-up of 9.1 years, adjusted for age, sex, race/ethnicity, educational status, and body mass index. Results: Incident T2D was observed for 120 participants. None of the cell phenotypes included in the primary hypotheses were significantly associated with T2D (all P > 0.05). Among the secondary immune cells studied, a higher proportion of CD19⁺CD27⁺ B cells was associated with a reduced risk of T2D (hazard ratio: 0.72 (95% confidence interval: 0.56, 0.93), per 1-standard deviation (16%) increase). This association was no longer significant after correction for the multiple cell phenotypes tested (P > 0.0015). Conclusions: Our results suggest that the frequencies of several subsets of monocytes, innate lymphocytes, and CD4⁺ and CD8⁺ T cells in circulating blood are not related to the future onset of T2D. Higher levels of CD19⁺CD27⁺ B cells may be associated with decreased T2D risk.