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Association of Systemic Chemokine Concentrations With Impaired Glucose Tolerance and Type 2 Diabetes

Results from the Cooperative Health Research in the Region of Augsburg Survey S4 (KORA S4)

¹ German Diabetes Clinic, German Diabetes Center, Leibniz Institute at Heinrich-Heine University, Düsseldorf, Germany
² Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Institute at Heinrich-Heine University, Düsseldorf, Germany
³ Department of Internal Medicine II–Cardiology, Medical Center, University of Ulm, Ulm, Germany
⁴ Institute of Epidemiology, GSF–National Research Center for Environment and Health, Neuherberg, Germany
⁵ Institute of Health Economics and Health Care Management, GSF–National Research Center for Environment and Health, Neuherberg, Germany

Chemokines are crucial immune mediators in many physiological and pathophysiological conditions. Chemokines have been hypothesized to be involved in macrophage infiltration into adipose tissue in obesity and might therefore play an important role in the development of obesity-related disorders like type 2 diabetes. Out of 1,653 individuals aged 55–74 years participating in a population-based survey in southern Germany (the Kooperative Gesundheitsforschung in der Region Augsburg [KORA] [Cooperative Health Research in the Region of Augsburg] Survey S4, 1999–2001), 236 individuals with type 2 diabetes, 242 subjects with impaired glucose tolerance (IGT), and 244 normoglycemic control subjects were studied for circulating concentrations of interleukin (IL)-8; RANTES (regulated on activation, normal T-cell expressed, and secreted); interferon-–inducible protein-10 (IP-10), and eotaxin. Systemic concentrations of RANTES were higher in individuals with IGT or type 2 diabetes than in control subjects, whereas IL-8 levels were elevated in type 2 diabetic patients only (P < 0.001 for all comparisons). IP-10 and eotaxin were not significantly associated with IGT or type 2 diabetes. Adjustment for age, sex, BMI, hypertension, LDL cholesterol, HDL cholesterol, uric acid, C-reactive protein, and IL-6 did not alter these findings. Our findings indicate that RANTES and IL-8 may be involved in the development of type 2 diabetes independent of metabolic syndrome–related risk factors and of each other. There is no general upregulation of chemokine production in type 2 diabetes, but rather an association of the disease with specific members of the chemokine family.

Abbreviations: CRP, C-reactive protein; IGT, impaired glucose tolerance; IL, interleukin; IP-10, interferon-–inducible protein-10; KORA, Kooperative Gesundheitsforschung in der Region Augsburg [Cooperative Health Research in the Region of Augsburg]; RANTES, regulated on activation, normal T-cell expressed, and secreted; Th, T-helper

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