Julia Sbierski-Kind1,2, David Goldeck3, Nikolaus Buchmann4, Joachim Spranger5,6,7, Hans-Dieter Volk8,9,10, Elisabeth Steinhagen-Thiessen5, Graham Pawelec11,12, Ilja Demuth5,8,9,10, Dominik Spira5. 1. Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Department of Endocrinology and Metabolism, Berlin Institute of Health, Chariteplatz 1, 10117, Berlin, Germany. Julia.Sbierski-Kind@ucsf.edu. 2. Present Address: Dept. of Laboratory Medicine, University of California, San Francisco, HSW1201U, Box 0451, 513 Parnassus Ave, San Francisco, CA, 94143-0451, USA. Julia.Sbierski-Kind@ucsf.edu. 3. Fairfax Centre, Kidlington, UK. 4. Clinic for Cardiology, Charité Universitätsmedizin Berlin, Berlin, Germany. 5. Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Department of Endocrinology and Metabolism, Berlin Institute of Health, Chariteplatz 1, 10117, Berlin, Germany. 6. Center for Cardiovascular Research (CCR), Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Berlin, Germany. 7. German Center for Cardiovascular Research (DZHK), partner site Berlin, Berlin, Germany. 8. Berlin Institute of Health (BIH) Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, Berlin, Germany. 9. Berlin Center for Advanced Therapies (BeCAT), Charité - Universitätsmedizin Berlin, Berlin, Germany. 10. Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany. 11. Department of Immunology, University of Tübingen, Tübingen, Germany. 12. Health Sciences North Research Institute, Sudbury, ON, Canada.
Abstract
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.
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 IRobese 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.
Entities:
Keywords:
Aging; Insulin resistance; Obesity; Systemic inflammation; T cell senescence
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