Krasimira Aleksandrova1, Dagmar Drogan2, Cornelia Weikert3, Matthias B Schulze4,5,6, Andreas Fritsche5,7, Heiner Boeing8, Tobias Pischon6,9,10,11,12. 1. Senior Scientist Group Nutrition, Immunity and Metabolism, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. 2. Quality and Health Services Research Unit, AOK Research Institute, Berlin, Germany. 3. German Federal Institute for Risk Assessment, Department of Food Safety, Berlin, Germany. 4. Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. 5. German Center for Diabetes Research, Neuherberg, Germany. 6. German Center for Cardiovascular Research, partner site Berlin, Berlin, Germany. 7. Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, University of Tübingen, Tübingen, Germany. 8. Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. 9. Molecular Epidemiology Research Group, Max Delbrueck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany. 10. Charité-Universitätsmedizin Berlin, Berlin, Germany. 11. Berlin Institute of Health Biobank, Max Delbrueck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany. 12. Berlin Institute of Health, Berlin, Germany.
Abstract
CONTEXT: Adipocyte fatty acid-binding protein (FABP4) is expressed in adipose tissue and may impair glucose homeostasis and promote atherosclerotic processes. OBJECTIVE: We examined the association between serum FABP4 and risk of type 2 diabetes (T2D), myocardial infarction (MI), and stroke. DESIGN: Case-cohort study embedded within a sample of 27,548 participants of the EPIC-Potsdam cohort. PARTICIPANTS AND SETTING: A randomly selected subcohort (n = 2194) of participants who were free of cardiovascular disease and T2D at study baseline and 728 incident T2D cases, 206 incident stroke cases, and 185 incident MI cases with an average 8.2 (±1.7) years of follow-up. MAIN OUTCOME MEASURES: Incident T2D, MI, and stroke. RESULTS: In a multivariable-adjusted model, the hazard ratios (HRs) in the highest vs lowest quartile of FABP4 were 1.81 (95% CI, 1.21 to 2.70; Ptrend = 0.01) for T2D, 0.93 (95% CI, 0.55 to 1.55; Ptrend = 0.68) for MI, and 1.41 (95% CI, 0.80 to 2.49; Ptrend = 0.24) for stroke, respectively. In analyses stratified by sex, no statistically significant differences could be seen for associations between FABP4 and T2D and MI (Pinteraction by sex = 0.27 and 0.84, respectively), whereas a higher risk of stroke was observed in men (HR: 2.70, 95% CI 1.20 to 6.00; P = 0.04), but not in women (HR: 0.70, 95% CI 0.31 to 1.60; P = 0.53; Pinteraction = 0.02). CONCLUSIONS: These data support the hypothesis that elevated FABP4 levels may contribute to T2D risk. In contrast, our data did not support the hypothesis that circulating FABP4 may be relevant for MI, whereas the observed association with stroke in men may need further evaluation.
CONTEXT: Adipocyte fatty acid-binding protein (FABP4) is expressed in adipose tissue and may impair glucose homeostasis and promote atherosclerotic processes. OBJECTIVE: We examined the association between serum FABP4 and risk of type 2 diabetes (T2D), myocardial infarction (MI), and stroke. DESIGN: Case-cohort study embedded within a sample of 27,548 participants of the EPIC-Potsdam cohort. PARTICIPANTS AND SETTING: A randomly selected subcohort (n = 2194) of participants who were free of cardiovascular disease and T2D at study baseline and 728 incident T2D cases, 206 incident stroke cases, and 185 incident MI cases with an average 8.2 (±1.7) years of follow-up. MAIN OUTCOME MEASURES: Incident T2D, MI, and stroke. RESULTS: In a multivariable-adjusted model, the hazard ratios (HRs) in the highest vs lowest quartile of FABP4 were 1.81 (95% CI, 1.21 to 2.70; Ptrend = 0.01) for T2D, 0.93 (95% CI, 0.55 to 1.55; Ptrend = 0.68) for MI, and 1.41 (95% CI, 0.80 to 2.49; Ptrend = 0.24) for stroke, respectively. In analyses stratified by sex, no statistically significant differences could be seen for associations between FABP4 and T2D and MI (Pinteraction by sex = 0.27 and 0.84, respectively), whereas a higher risk of stroke was observed in men (HR: 2.70, 95% CI 1.20 to 6.00; P = 0.04), but not in women (HR: 0.70, 95% CI 0.31 to 1.60; P = 0.53; Pinteraction = 0.02). CONCLUSIONS: These data support the hypothesis that elevated FABP4 levels may contribute to T2D risk. In contrast, our data did not support the hypothesis that circulating FABP4 may be relevant for MI, whereas the observed association with stroke in men may need further evaluation.