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Low circulating insulin-like growth factor-1 levels are associated with high serum uric acid in nondiabetic adult subjects |
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| Institution: | 1. Department of Medical and Surgical Sciences, University “Magna Graecia” of Catanzaro, Italy;2. Department of Systems Medicine, University of Rome-Tor Vergata, Italy;1. Institute of Clinical Medicine, Family Medicine, University of Turku, Turku, Finland;2. Naantali Health Centre, Naantali, Finland;3. Härkätie Health Centre, Lieto, Finland;4. Unit of Family Medicine, Turku University Hospital, Turku, Finland;5. Institute of Clinical Medicine, Biostatistics, University of Turku, Turku, Finland;6. Mehiläinen Oy, Finland;7. Faculty of Pharmacy, Division of Social Pharmacy, University of Helsinki, Finland;8. Department of Internal Medicine, Turku City Hospital, Turku, Finland;1. Schulich Heart Center, Sunnybrook Health Sciences Center, Division of Cardiology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada;2. University Hospital of Copenhagen, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark;3. Department of Chemical and Biochemical Engineering, Center for Energy Resources Engineering (CERE), Technical University of Denmark (DTU), Kongens Lyngby, Denmark;4. Department of Clinical Physiology and Nuclear Medicine, University Hospital Hvidovre, Hvidovre, Denmark;5. Department of Family Medicine, University of Toronto, Toronto, Ontario, Canada;6. University Health Network, Division of Cardiology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada;7. Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada;8. Institute for Clinical Evaluative Sciences (ICES), Toronto, Ontario, Canada;9. Institute for Health Policy, Management and Evaluation (IHPME), University of Toronto, Toronto, Ontario, Canada;1. School of Information Science and Technology, University of Science and Technology of China, Hefei 230027, China;2. Centers for Biomedical Engineering, University of Science and Technology of China, Hefei 230027, China;1. Périnat-ARS-IDF, agence régionale de santé d’Île-de-France, 2, rue Saint-Martin, 75004 Paris, France;2. Observatoire régional de santé d’Île-de-France, Paris, France;3. Observatoire de la direction prévention santé, Conseil général du Val d’Oise, Cergy Pontoise, France;4. Inserm UMR 1153, équipe de recherche en épidémiologie obstétricale, périnatale et pédiatrique (EPOPé), centre de recherche épidémiologie et statistique, Sorbonne Paris Cité, DHU risques et grossesse, université Paris Descartes, 75006 Paris, France;5. CHI André-Grégoire, 93100 Montreuil, France;6. Hôpital Louis-Mourier, AP–HP, HUPNVS, 92700 Colombes, France;1. Intensive Care Units, Department of Anaesthesiology, Intensive Care and Pain Medicine, Helsinki University Hospital, Helsinki, Finland;2. Department of Clinical Chemistry, School Of Medicine, University of Eastern Finland and Eastern Finland Laboratory Centre, Kuopio, Finland;3. Department of Medical Sciences, Uppsala University, Uppsala, Sweden;4. Division of Medicine, Akershus University Hospital, Lørenskog, Norway and Institute for Clinical Medicine, University of Oslo, Oslo, Norway;5. Department of Anaesthesiology, South-Carelia Hospital, Lappeenranta, Finland;6. Department of Neurology, Helsinki University Hospital, Helsinki, Finland;7. Division of Intensive Care Medicine, Kuopio University Hospital, Kuopio, Finland |
| Abstract: | Background and aimsLow insulin-like growth factor-1 (IGF-1) levels and high uric acid concentrations are associated with cardio-metabolic disorders. Acute IGF-1 infusion decreases uric acid concentration in healthy individuals. In this study, we aimed to examine the relationship between IGF-1 and uric acid levels.Methods and results1430 adult non diabetic subjects were stratified into quartiles according to their circulating IGF-1 values. Significant differences in uric acid concentration, measured by the URICASE/POD method were observed between low (quartile 1), intermediate (quartile 2 and 3), and high (quartile 4) IGF-1 levels groups after adjusting for age, gender, and body mass index (P = 0.02). These differences remained significant after adjustment for blood pressure, total cholesterol, high density lipoprotein, triglycerides, fasting and 2 h post-load glucose levels, HOMA-IR index (P = 0.005), liver enzymes (P = 0.03), glucose tolerance status (P = 0.02), growth hormone levels (GH) (P = 0.05), anti-hypertensive treatments (P = 0.04) or diuretics use (P = 0.04)). To clarify the molecular links between IGF-1 and uric acid, we performed an in vitro study, incubating human hepatoma cells with uric acid for 24 or 48 h in the presence of GH and observed a 21% and 26% decrease, respectively, in GH-stimulated IGF-1 mRNA expression (P = 0.02 and P = 0.012, respectively). This effect appears to be mediated by uric acid ability to down regulate GH intracellular signaling; in fact we observed a significant decrease of GH activated JAK2 and Stat5 phosphorylation.ConclusionsThese data demonstrate an inverse relationship between IGF-1 and uric acid levels in adults and suggest that uric acid might affect hepatic IGF-1 synthesis. |
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