Abstract
BackgroundObesity 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.MethodsIn 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.ResultsWe 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).ConclusionsThese 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 registrationDRKS00009277. Registered 31 August 2015 - Retrospectively registered.
Highlights
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)
Whereas the percentages of major mononuclear leukocyte subsets (CD4+ and CD8+ T cells, CD19+ B cells, CD56+NK cells, and CD14+monocytes) did not significantly correlate with body mass index (BMI), Homeostasis model of assessment for insulin resistance (HOMA-insulin resistant (IR)) or ISIOGTT, we found that the percentages of naïve
We found that frequencies of naïve CD4+ and CD8+ T cells correlated positively with ISIOGTT, but negatively with BMI and HOMA-IR, whereas frequencies of central memory CD4+ T cells correlated negatively with ISIOGTT, but positively with BMI and HOMA-IR
Summary
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). Obesity is associated with systemic and adipose tissue inflammation [12,13,14]. Excessive energy intake is thought to be a major contributor of obesity and leads to the accumulation of lipids in adipocytes and the expansion of adipose tissue. Blüher and colleagues have shown that macrophage infiltration into visceral adipose tissue, higher inflammatory parameters and circulating adipokines can predict insulin resistance in morbidly obese patients [17]. Only limited and partially discordant data are available on the association of systemic and adipose tissue inflammation with insulin resistance, especially in older patients
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