Martin Heier1, Hanna Dis Margeirsdottir2, Peter Abusdal Torjesen3, Ingebjørg Seljeflot4, Knut Haakon Stensæth5, Mario Gaarder6, Cathrine Brunborg7, Kristian Folkvord Hanssen8, Knut Dahl-Jørgensen9. 1. Department of Pediatrics, Oslo University Hospital, Oslo, Norway Faculty of Medicine, University of Oslo, Oslo, Norway Oslo Diabetes Research Centre, Oslo, Norway martin.heier@medisin.uio.no. 2. Faculty of Medicine, University of Oslo, Oslo, Norway Oslo Diabetes Research Centre, Oslo, Norway Akershus University Hospital, Lørenskog, Norway. 3. Faculty of Medicine, University of Oslo, Oslo, Norway Hormone Laboratory, Oslo University Hospital, Oslo, Norway. 4. Faculty of Medicine, University of Oslo, Oslo, Norway Center for Clinical Heart Research and Department of Cardiology, Oslo University Hospital, Oslo, Norway. 5. Faculty of Medicine, University of Oslo, Oslo, Norway Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway. 6. Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway. 7. Department of Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway. 8. Faculty of Medicine, University of Oslo, Oslo, Norway Oslo Diabetes Research Centre, Oslo, Norway Department of Endocrinology, Oslo University Hospital, Oslo, Norway. 9. Department of Pediatrics, Oslo University Hospital, Oslo, Norway Faculty of Medicine, University of Oslo, Oslo, Norway Oslo Diabetes Research Centre, Oslo, Norway.
Abstract
BACKGROUND: Advanced protein glycation is an important mechanism for the development of late diabetic complications including atherosclerosis. Methylglyoxal-derived hydroimidazolone-1 is the most abundant advanced glycation end product in human plasma. AIM: To investigate the relationship between methylglyoxal-derived hydroimidazolone-1 and early signs of atherosclerosis in children and adolescents with type 1 diabetes and healthy controls. METHODS: A total of 314 diabetes patients aged 8-18 years were compared with 120 healthy controls. Serum methylglyoxal-derived hydroimidazolone-1 was measured by immunoassay. Atherosclerosis was evaluated by assessing carotid intima-media thickness by ultrasound, arterial stiffness by Young's modulus and inflammation by C-reactive protein. RESULTS: Methylglyoxal-derived hydroimidazolone-1 was significantly increased in the diabetes group compared with controls, 155.3 (standard deviation (SD) = 41.0) versus 143.0 (SD = 35.1) U/mL, p = 0.003, as was C-reactive protein, median 0.51 (0.27, 1.83) versus 0.31 (0.19, 0.67) mg/L, p < 0.001. There was no significant difference between the groups regarding carotid intima-media thickness or Young's modulus. Multiple regression analysis showed a significant positive association between methylglyoxal-derived hydroimidazolone-1 and C-reactive protein in the diabetes group. CONCLUSION: Serum levels of methylglyoxal-derived hydroimidazolone-1 in diabetes patients are increased and associated with low-grade inflammation, but not yet arterial stiffness or wall thickness. This indicates that methylglyoxal-derived hydroimidazolone-1 may be important in the early phase of the accelerated atherosclerotic process in diabetes.
BACKGROUND: Advanced protein glycation is an important mechanism for the development of late diabetic complications including atherosclerosis. Methylglyoxal-derived hydroimidazolone-1 is the most abundant advanced glycation end product in human plasma. AIM: To investigate the relationship between methylglyoxal-derived hydroimidazolone-1 and early signs of atherosclerosis in children and adolescents with type 1 diabetes and healthy controls. METHODS: A total of 314 diabetespatients aged 8-18 years were compared with 120 healthy controls. Serum methylglyoxal-derived hydroimidazolone-1 was measured by immunoassay. Atherosclerosis was evaluated by assessing carotid intima-media thickness by ultrasound, arterial stiffness by Young's modulus and inflammation by C-reactive protein. RESULTS:Methylglyoxal-derived hydroimidazolone-1 was significantly increased in the diabetes group compared with controls, 155.3 (standard deviation (SD) = 41.0) versus 143.0 (SD = 35.1) U/mL, p = 0.003, as was C-reactive protein, median 0.51 (0.27, 1.83) versus 0.31 (0.19, 0.67) mg/L, p < 0.001. There was no significant difference between the groups regarding carotid intima-media thickness or Young's modulus. Multiple regression analysis showed a significant positive association between methylglyoxal-derived hydroimidazolone-1 and C-reactive protein in the diabetes group. CONCLUSION: Serum levels of methylglyoxal-derived hydroimidazolone-1 in diabetespatients are increased and associated with low-grade inflammation, but not yet arterial stiffness or wall thickness. This indicates that methylglyoxal-derived hydroimidazolone-1 may be important in the early phase of the accelerated atherosclerotic process in diabetes.
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