hsCRP and E-Selectin as Markers of Endothelial Dysfunction in Children with Type 1 Diabetes Mellitus

Introduction: This study investigated the levels of inflammatory biomarkers in healthy children and those diagnosed with type 1 diabetes (T1DM), some of whom were affected by endothelial dysfunction (ED), characterized by increased inflammation and reduced vasodilatation. Methods: Thirty-one T1DM children showing no symptoms of vascular diseases and diagnosed by ultrasound techniques as ED-positive (T1DM-ED) or negative (T1DM), and 58 sex-age-matched healthy children were investigated for circulating levels of E-selectin, s-ICAM and s-VCAM, MMP-9, high-sensitivity C-reactive protein (hsCRP), and IL-6. Results: No differences were observed in s-ICAM, MMP-9, and IL-6 levels between case and control groups. Significantly higher levels of s-VCAM (p= 0.0001) were found in the T1DM (1359.1 ± 273 ng/mL) and T1DM-ED (1358.2 ± 112 ng/mL) groups; (control - 828.5 ± 212 ng/mL). Higher levels of E-selectin (p = 0.001) were found in the T1DM-ED group (331.2 ± 77 ng/mL); (control - 222.2 ± 74 ng/mL). The values of hsCRP were higher (p = 0.002) in the T1DM-ED group (0.36 ± 0.2 mg/L) relative to control (0.15 ± 0.1 mg/L) and T1DM (0.19 ± 0.2 mg/L). The results suggest that E-selectin and hsCRP can be useful markers of ED in children with T1DM.publishersversionpublishe

Associação de disfunção endotelial com alterações estruturais iniciais de aterosclerose e presença de marcadores séricos sugestivos de inflamação, disfunção endotelial e injúria vascular em crianças portadoras de Diabetes mellitus tipo 1

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Medicina, Programa de Pós-Graduação em Ciências Médicas, 2014.Diabetes mellitus tipo 1 (DM1) apresenta prevalência global crescente e cursa com complicações vasculares que constituem importantes fatores de risco para doenças de alta morbidade e mortalidade na vida adulta, como doenças cardiovasculares, cerebrovasculares e doença vascular periférica. As alterações estruturais típicas da aterosclerose são antecedidas por um processo de disfunção das células endoteliais que determina um estado sistêmico vasoconstrictor, pró-inflamatório e pró-trombótico que pode contribuir para o desenvolvimento das complicações vasculares diabéticas. Objetivo: verificar a presença de disfunção endotelial e alterações estruturais iniciais de aterosclerose em crianças portadoras de DM1. Métodos: a população do estudo foi constituída por 31 crianças diabéticas (separadas em subgrupo com tempo de diagnóstico menor que 5 anos e outro com 5 anos ou mais) e 58 crianças saudáveis, com idades entre 6 e 12 anos. Técnicas ultrassonográficas foram utilizadas para medir a dilatação fluxomediada (FMD) da artéria braquial e a espessura das camadas íntima-média das artérias carótidas (IMT). Os achados ultrassonográficos foram correlacionados com os níveis séricos de marcadores inflamatórios (IL-6, PCR-US), marcadores de disfunção endotelial (sE-selectina, sVCAM-1 e sICAM-1) e de injúria vascular (MMP-9). Resultados: crianças diabéticas com tempo maior de diagnóstico apresentaram percentagem de dilatação fluxo-mediada máxima significantemente menor que o grupo controle. Os níveis séricos de sVCAM-1 mostraram-se significantemente elevados nos dois subgrupos de diabéticos, em relação ao controle, e os níveis séricos de PCR-US e sE-selectina foram significantemente maiores, em relação a este grupo, apenas no subgrupo de diabéticos com maior tempo de diagnóstico. Não foram encontradas diferenças significativas entre os grupos quanto à espessura médio-intimal e aos níveis séricos de IL-6, sICAM-1 e MMP-9. A resposta vasodilatadora máxima apresentou correlação negativa com os níveis séricos de HbA1c e glicose de jejum. Conclusão: nossos achados sugerem que crianças diabéticas com 5 ou mais anos de diagnóstico já podem apresentar disfunção endotelial e um estado inflamatório sistêmico de baixa intensidade, embora sem alterações estruturais de aterosclerose.Type 1 Diabetes mellitus (DM1) displays an increasing global prevalence and its resultant cardiac, cerebral and peripheral vascular complications represent important risk factor for high morbidity and mortality in adult life. The development of DM1 vascular complications is preceded by endothelial dysfunction that result in systemic vasoconstriction and contribute to the progress to a pro-inflammatory and pro-thrombotic state. Objective: The purpose of this study was to verify the presence of endothelial dysfunction and initial structural changes of atherosclerosis in diabetic children. Methods: Thirty-one diabetic children aged 6-12 years, divided in two subgroups according to disease length composed the study group: subgroup 1, with less than five years and subgroup 2, with more than five years of disease span. Fifty-eight age-matched healthy children composed the control group. Ultrasonographic techniques were used to measure the flow-mediated dilatation of the brachial artery (FMD), and the intima-media thickness of carotid arteries (IMT). The ultrasonographic findings were correlated to plasmatic levels of inflammatory biomarkers (IL-6, hs-CRP), endothelial dysfunction (sE-selectin, sVCAM-1, sICAM-1) and vascular injury biomarkers (MMP-9). Results: Diabetic children with increased disease length disclosed flow-mediated dilatation maximum percentage mean values significantly decreased when compared with the values found in the control group. Levels of sVCAM-1 were significantly higher in both diabetic subgroups while the levels of hs-CRP and sE-selectin were significantly higher only in the subgroup with more than five years of disease length when compared to controls. Study groups and controls did not disclosed significant differences in relation to IMT, IL-6, sICAM-1 and MMP-9 levels. Vasodilator response was negatively correlated to disease length, plasmatic levels of HbA1c and fasting glucose. Conclusion: Our findings suggest that endothelial dysfunction and a low level of systemic inflammatory state may be already present in diabetic children with five more than years of disease length, in spite of absence of atherosclerotic structural changes

Endothelial dysfunction in children with type 1 diabetes mellitus

<div><p>ABSTRACT Objective The purpose of this study was to verify the presence of endothelial dysfunction and initial structural atherosclerotic changes in children with Type 1 diabetes mellitus (T1DM). Subjects and methods The study population comprised 31 diabetic children aged 6 to 12 years, divided into two subgroups according to the duration of the T1DM diagnosis: subgroup 1, with less than 5 years elapsed since diagnosis, and subgroup 2, with more than 5 years elapsed since diagnosis. The control group comprised 58 age-matched healthy children. Ultrasonographic techniques were used to measure the flow-mediated dilatation (FMD) of the brachial artery and the intima-media thickness (IMT) of the carotid arteries. Results Children with T1DM with longer disease duration showed significantly decreased mean values of FMD compared with those in the control group. No significant differences between the groups were found in relation to IMT. The FMD percentage presented a moderate negative correlation with glycated hemoglobin (HbA1c) and fasting glucose levels. Conclusion Our findings suggest that endothelial dysfunction may be already present in children with 5 years or more elapsed since diagnosis, even in the absence of atherosclerotic structural changes. The decreased vasodilation response correlated with hyperglycemia.</p></div