Martin Heier1, Hanna Dis Margeirsdottir2, Cathrine Brunborg3, Kristian F Hanssen4, Knut Dahl-Jørgensen5, Ingebjørg Seljeflot6. 1. Pediatric Department Ullevål, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway; Oslo Diabetes Research Centre, Oslo, Norway. Electronic address: 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. Department of Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway. 4. Faculty of Medicine, University of Oslo, Oslo, Norway; Oslo Diabetes Research Centre, Oslo, Norway; Department of Endocrinology, Oslo University Hospital, Oslo, Norway. 5. Pediatric Department Ullevål, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway; Oslo Diabetes Research Centre, Oslo, Norway. 6. Faculty of Medicine, University of Oslo, Oslo, Norway; Center for Clinical Heart Research and Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway.
Abstract
OBJECTIVE: Patients with type 1 diabetes have increased mortality from cardiovascular disease, and inflammation is important in the development of atherosclerosis. Our aim was to evaluate the extent of inflammation and the influence of glycemic control in the early phases of atherosclerosis in childhood type 1 diabetes. MATERIALS AND METHODS: A population based cohort representative of all children with type 1 diabetes in Norway was studied. Diabetes patients (n = 314) were compared to healthy controls (n = 120), aged 8-18 years. Circulating levels of VCAM-1, ICAM-1, E-selectin, P-selectin, TNFα, IL-6, CRP, MCP-1, IL-18, MMP-9 and TIMP-1 were measured by immunoassays. RESULTS: The diabetes patients had a mean age of 13.7 (SD = 2.8) years, disease duration of 5.5 (SD = 3.4) years and HbA1c of 8.4 (SD = 1.2) % (68 mmol/mol, SD = 13.1). The levels of most of the measured markers were significantly increased in the diabetes group compared to controls. In the diabetes group, all except MCP-1 and MMP-9 were significantly correlated to HbA1c, albeit the relation to VCAM-1 was inverse. There were no significant correlations in the control group. The measured markers were only to a limited degree associated with traditional risk factors. CRP showed the most pronounced difference between diabetes patients and controls and the strongest correlation with HbA1c. The use of oral contraceptives profoundly increased CRP levels, independent of the presence of diabetes. CONCLUSIONS: Our results indicate that inflammation may play an important role in the accelerated atherosclerosis in early type 1 diabetes, and that this process seems primarily driven by hyperglycemia.
OBJECTIVE:Patients with type 1 diabetes have increased mortality from cardiovascular disease, and inflammation is important in the development of atherosclerosis. Our aim was to evaluate the extent of inflammation and the influence of glycemic control in the early phases of atherosclerosis in childhood type 1 diabetes. MATERIALS AND METHODS: A population based cohort representative of all children with type 1 diabetes in Norway was studied. Diabetespatients (n = 314) were compared to healthy controls (n = 120), aged 8-18 years. Circulating levels of VCAM-1, ICAM-1, E-selectin, P-selectin, TNFα, IL-6, CRP, MCP-1, IL-18, MMP-9 and TIMP-1 were measured by immunoassays. RESULTS: The diabetespatients had a mean age of 13.7 (SD = 2.8) years, disease duration of 5.5 (SD = 3.4) years and HbA1c of 8.4 (SD = 1.2) % (68 mmol/mol, SD = 13.1). The levels of most of the measured markers were significantly increased in the diabetes group compared to controls. In the diabetes group, all except MCP-1 and MMP-9 were significantly correlated to HbA1c, albeit the relation to VCAM-1 was inverse. There were no significant correlations in the control group. The measured markers were only to a limited degree associated with traditional risk factors. CRP showed the most pronounced difference between diabetespatients and controls and the strongest correlation with HbA1c. The use of oral contraceptives profoundly increased CRP levels, independent of the presence of diabetes. CONCLUSIONS: Our results indicate that inflammation may play an important role in the accelerated atherosclerosis in early type 1 diabetes, and that this process seems primarily driven by hyperglycemia.
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