Assessment of biomarkers of inflammation and premature atherosclerosis in adolescents with type-1 diabetes mellitus
-
Ghufran Babar
,
Mark Clements
Abstract
Background
Type-1 diabetes mellitus (T1DM) causes endothelial dysfunction and early atherosclerosis, which can result in premature coronary artery disease. The aim of this study was to determine the impact of glycemic control, vascular oxidative stress and inflammation on vascular health in adolescents with T1DM.
Methods
This was a cross-sectional study in adolescents with age- and sex-matched T1DM who were ≥12 years and were at least 2 years post-diagnosis. Recruitment was balanced to include individuals with hemoglobin A1c (HbA1c) ≤8.5% (n=27) or with HbA1c ≥9.5% (n=25). Biomarkers of inflammation were measured in the blood including C-reactive protein (CRP), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), E-selectin, fibrinogen and tumor necrosis factor-α (TNF-α). Carotid intima media thickness (cIMT) and peripheral arterial tonometry (PAT) were assessed.
Results
Plasma E-selectin level was significantly different between the two groups with higher levels in the group with HbA1c ≥9.5% (65.0±27.7 ng/mL vs. 48.8±21.5 ng/mL, p=0.02). Though cIMT and PAT were not significantly different between the groups, Pearson correlation showed a significant direct relationship between rising HbA1c and mean right cIMT (p=0.02; r=0.37), PAT (p=0.03, r=0.31) and fibrinogen (p=0.03, r=0.03).
Conclusions
Elevated E-selectin level is an early marker of oxidative stress in T1DM patients with an elevated HbA1c level. Suboptimal glycemic control as evidenced by a rising HbA1c causes early atherosclerosis.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Singh TP, Groehn H, Kazmers A. Vascular function and carotid intimal-medial thickness in children with insulin-dependent diabetes mellitus. J Am Coll Cardiol 2003;41:661–5.10.1016/S0735-1097(02)02894-2Search in Google Scholar
2. Du XL, Edelstein D, Rossetti L, Fantus IG, Goldberg H, et al. Hyperglycemia-induced mitochondrial super oxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Proc Natl Acad Sci USA 2000;97:12222–6.10.1073/pnas.97.22.12222Search in Google Scholar PubMed PubMed Central
3. Giugliano D, Ceriello A, Paolisso G. Oxidative stress and diabetic vascular complications. Diabetes Care 1996;19:257–67.10.2337/diacare.19.3.257Search in Google Scholar PubMed
4. Holvoet P, Vanhaecke J, Janssens S, Van de Werf F, Collen D. Oxidized LDL and malondialdehyde-modified LDL in patients with acute coronary syndromes and stable coronary artery disease. Circulation 1998;98:1487–94.10.1161/01.CIR.98.15.1487Search in Google Scholar
5. McGill HC Jr, McMahan CA, Malcom GT, Oalmann MC, Strong JP. Effects of serum lipoproteins and smoking on atherosclerosis in young men and women. The PDAY Research Group. Pathobiological Determinants of Atherosclerosis in Youth. Arterioscler Thromb Vasc Biol 1997;17:95–106.10.1161/01.ATV.17.1.95Search in Google Scholar
6. Larsen J, Brekke M, Sandvik L, Arnesen H, Hanssen KF, et al. Silent coronary atheromatosis in type 1 diabetic patients and its relation to long-term glycemic control. Diabetes 2002;51:2637–41.10.2337/diabetes.51.8.2637Search in Google Scholar PubMed
7. Bevilacqua MP. Endothelial-leukocyte adhesion molecules. Ann Rev Immunol 1993;11:767–804.10.1146/annurev.iy.11.040193.004003Search in Google Scholar PubMed
8. Smith CW, Marlin SD, Rohlein R, Toman C, Anderson DC. Cooperative interaction of LFA and Mac-1 with intercellular adhesion molecule-1 in facilitating adherence and transendothelial migration of neutrophils in vitro. J Clin Invest 1989;83:2008–17.10.1172/JCI114111Search in Google Scholar PubMed PubMed Central
9. Libby P. Changing concepts of atherogenesis. J Intern Med 2000;247:349–58.10.1046/j.1365-2796.2000.00654.xSearch in Google Scholar PubMed
10. Targher G, Bertolin L, Zoppini G, Zenari L, Falezza G. Increased plasma markers of inflammation and endothelial dysfunction and their association with microvascular complications in type 1 diabetic patients without clinically manifest macroangiopathy. Diabet Med 2005;22:999–1004.10.1111/j.1464-5491.2005.01562.xSearch in Google Scholar PubMed
11. Aggoun Y, Szezepanski I, Bonnet D. Noninvasive assessment of arterial stiffness and risk of atherosclerotic events in children. Pediatr Res 2005;58:173–8.10.1203/01.PDR.0000170900.35571.CBSearch in Google Scholar
12. Crouse III JR, Craven TE, Hagaman AP, Bond MG. Association of coronary disease with segment-specific intimal-medial thickening of the extracranial carotid artery. Circulation 1995;92:1141–7.10.1161/01.CIR.92.5.1141Search in Google Scholar
13. Babar GS, Zidan H, Widlansky ME, Das E, Hoffmann RG, et al. Impaired endothelial function in preadolescent children with type 1 diabetes. Diabetes Care 2011;34:681–5.10.2337/dc10-2134Search in Google Scholar
14. Jarvisalo MJ, Raitakari M. Endothelial dysfunction and increased arterial intima-media thickness in children with type 1 diabetes. Circulation 2004;109:1750–5.10.1161/01.CIR.0000124725.46165.2CSearch in Google Scholar
15. Haller MJ, Samyn M, Nichols WW, Brusko T, Wasserfall C, et al. Radial artery tonometry demonstrates arterial stiffness in children with type 1 diabetes. Diabetes Care 2004;27:2911–7.10.2337/diacare.27.12.2911Search in Google Scholar
16. Laurent J, Cockcroft L, Van Bortel P, Boutouyrie C, Giannattasio D, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J 2006;27:2588–605.10.1093/eurheartj/ehl254Search in Google Scholar
17. Wilkinson IB, Fuchs SA, Jansen IM, Spratt JC, Murray GD, et al. Reproducibility of pulse wave velocity and augmentation index measured by pulse wave analysis. J Hypertens 1998;16:2079–84.10.1097/00004872-199816121-00033Search in Google Scholar
18. Rolo AP, Palmeira CM. Diabetes and mitochondrial function: role of hyperglycemia and oxidative stress. Toxicol Appl Pharmacol 2006;212:167–78.10.1016/j.taap.2006.01.003Search in Google Scholar
19. Walzog B, Gaehtgens P. Adhesion molecules: the path to a new understanding of acute inflammation. News Physiol Sci 2000;15:107–13.10.1152/physiologyonline.2000.15.3.107Search in Google Scholar
20. Elhadd TA, Kennedy G, Hill A, McLaren M, Newton RW, et al. Abnormal markers of endothelial cell activation and oxidative stress in children, adolescents and young adults with type 1 diabetes with no clinical vascular disease. Diabetes Metab Res Rev 1999;15:405–11.10.1002/(SICI)1520-7560(199911/12)15:6<405::AID-DMRR69>3.0.CO;2-HSearch in Google Scholar
21. Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, et al. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group: intensive diabetes therapy and carotid intima-media thickness in type 1 diabetes mellitus. N Engl J Med 2003;348:2294–303.10.1056/NEJMoa022314Search in Google Scholar PubMed PubMed Central
22. Polak JF, Backlund JY, Cleary PA, Harrington AP, O’Leary DH, et al. Progression of carotid artery intima-media thickness during 12 years in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. Diabetes 2011;60:607–13.10.2337/db10-0296Search in Google Scholar PubMed PubMed Central
23. Dalla Pozza R, Netz H, Schwarz H-P, Bechtold S. Subclinical atherosclerosis in diabetic children: results of a longitudinal study. Pediatr Diabetes 2010;11:129–33.10.1111/j.1399-5448.2009.00540.xSearch in Google Scholar PubMed
24. Jensen-Urstad KJ, Reichard PG, Rosfors JS, Lindblad LE, Jensen-Urstad MT. Early atherosclerosis is retarded by improved long-term blood glucose control in patients with IDDM. Diabetes 1996;45:1253–8.10.2337/diab.45.9.1253Search in Google Scholar PubMed
25. Snell-Bergeon JK, West NA, Mayer-Davis EJ. Inflammatory markers are increased in youth with type 1 diabetes: the SEARCH Case-Control study. J Clin Endocrinol Metab 2010;95:2868–76.10.1210/jc.2009-1993Search in Google Scholar PubMed PubMed Central
26. Wilkinson IB, MacCallum H, Rooijmans DF, Murray GD, Cockcroft JR, et al. Increased augmentation index and systolic stress in type 1 diabetes mellitus. Q J Med 2000;93:441–8.10.1093/qjmed/93.7.441Search in Google Scholar PubMed
27. Sims TJ, Rasmussen LM, Oxlund H, Bailey AJ. The role of glycation cross-links in diabetic vascular stiffening. Diabetologia 1996;39:946–51.10.1007/BF00403914Search in Google Scholar PubMed
28. Giannattasio C, Failla M, Piperno A, Grappiolo A, Gamba P, et al. Early impairment of large artery structure and function in type I diabetes mellitus. Diabetologia 1999;42:987–94.10.1007/s001250051257Search in Google Scholar PubMed
29. McGill HC Jr, McMahan CA. Starting earlier to prevent heart disease. J Am Med Assoc 2003;290:2320–2.10.1001/jama.290.17.2320Search in Google Scholar PubMed
©2019 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Mini Review
- Clinical, biochemical, and molecular spectrum of short/branched-chain acyl-CoA dehydrogenase deficiency: two new cases and review of literature
- Original Articles
- Assessment of biomarkers of inflammation and premature atherosclerosis in adolescents with type-1 diabetes mellitus
- Frequency, clinical characteristics, biochemical findings and outcomes of DKA at the onset of type-1 DM in young children and adolescents living in a developing country – an experience from a pediatric emergency department
- Hepatopathies in children and adolescents with type 1 diabetes
- Comparative evaluation of neuroendocrine dysfunction in children with craniopharyngiomas before and after mass effects are removed
- Functional and endocrine-metabolic oligomenorrhea: proposal of a new diagnostic assessment tool for differential diagnosis in adolescence
- Socioeconomic status of the population – a prime determinant in evaluating iodine nutritional status even in a post salt iodization scenario
- Long-term outcome of hyperthyroidism diagnosed in childhood and adolescence: a single-centre experience
- Thyroid function in patients with Prader-Willi syndrome: an Italian multicenter study of 339 patients
- Maternal factors associated with neonatal vitamin D deficiency
- IGF-1 assessed by pubertal status has the best positive predictive power for GH deficiency diagnosis in peripubertal children
- One-year treatment with gonadotropin-releasing hormone analogues does not affect body mass index, insulin sensitivity or lipid profile in girls with central precocious puberty
- Letter to the Editor
- Prediabetes in children and adolescents in the United States: prevalence estimates and comorbidities – a population analysis
- Case Reports
- Severe in utero under-virilization in a 46,XY patient with Silver-Russell syndrome with 11p15 loss of methylation
- Carney complex due to a novel pathogenic variant in the PRKAR1A gene – a case report
- Challenging diagnosis of thyroid hormone resistance initially as Hashimoto’s thyroiditis
Articles in the same Issue
- Frontmatter
- Mini Review
- Clinical, biochemical, and molecular spectrum of short/branched-chain acyl-CoA dehydrogenase deficiency: two new cases and review of literature
- Original Articles
- Assessment of biomarkers of inflammation and premature atherosclerosis in adolescents with type-1 diabetes mellitus
- Frequency, clinical characteristics, biochemical findings and outcomes of DKA at the onset of type-1 DM in young children and adolescents living in a developing country – an experience from a pediatric emergency department
- Hepatopathies in children and adolescents with type 1 diabetes
- Comparative evaluation of neuroendocrine dysfunction in children with craniopharyngiomas before and after mass effects are removed
- Functional and endocrine-metabolic oligomenorrhea: proposal of a new diagnostic assessment tool for differential diagnosis in adolescence
- Socioeconomic status of the population – a prime determinant in evaluating iodine nutritional status even in a post salt iodization scenario
- Long-term outcome of hyperthyroidism diagnosed in childhood and adolescence: a single-centre experience
- Thyroid function in patients with Prader-Willi syndrome: an Italian multicenter study of 339 patients
- Maternal factors associated with neonatal vitamin D deficiency
- IGF-1 assessed by pubertal status has the best positive predictive power for GH deficiency diagnosis in peripubertal children
- One-year treatment with gonadotropin-releasing hormone analogues does not affect body mass index, insulin sensitivity or lipid profile in girls with central precocious puberty
- Letter to the Editor
- Prediabetes in children and adolescents in the United States: prevalence estimates and comorbidities – a population analysis
- Case Reports
- Severe in utero under-virilization in a 46,XY patient with Silver-Russell syndrome with 11p15 loss of methylation
- Carney complex due to a novel pathogenic variant in the PRKAR1A gene – a case report
- Challenging diagnosis of thyroid hormone resistance initially as Hashimoto’s thyroiditis
