T cell phenotypes associated with insulin resistance: results from the Berlin Aging Study II

Background: Obesity is associated with chronic low-grade inflammation leading to metabolic and cardiovascular diseases, but a subset of obese individuals is considered insulin sensitive (IS). The underlying pathophysiologic mechanisms remain elusive and clinical studies on the relationship between inflammatory markers and metabolically healthy obesity (MHO) are scarce.

Methods: In this cross-sectional analysis, we included a sample of 437 older participants (60-84 years) from the Berlin Aging Study II (BASE-II). Peripheral blood mononuclear cells were isolated, immune cell subsets were analyzed with multiparameter flow cytometry and systemic cytokine levels were measured. Immune cell parameters were correlated with metabolic measures and multiple linear regression analysis was conducted and adjusted for various demographic and clinical factors.

Results: We found that frequencies of naïve and memory CD4⁺ and CD8⁺ T cells inversely correlated with measures for insulin sensitivity in the older population. Moreover, the percentages of naïve CD4⁺ and CD8⁺ T cells were significantly higher, whereas activated T cells and IL-6 levels were lower in IS compared to insulin resistant (IR) obese individuals. The percentages of naïve CD4⁺ and CD8⁺ T cells were predictive for impaired insulin sensitivity (ß = 0.16, p = 0.01 and ß = 0.11, p = 0.04), and the association of naïve CD4⁺ T cells with insulin sensitivity persisted after multivariate adjustment (ß = 0.14, p = 0.02).

Conclusions: These findings support the hypothesis that parameters of systemic inflammation can differentiate IS from IR obese individuals that are at higher risk for cardiometabolic diseases and may have clinical implications with regard to obesity treatment stratification.

Trial registration: DRKS00009277 . Registered 31 August 2015 - Retrospectively registered.