Abstract
Objective: To evaluate asymmetric dimethyl L-arginine (ADMA), nitric oxide (NO) and cardiovascular disease in adolescent type 1 diabetics.
Methods: The study included 62 type 1 diabetic patients and 30 healthy volunteers of the same age and sex. Blood samples were taken for assessment of ADMA, NO, oxidized low density lipoprotein (OxLDL), glycosylated hemoglobin, and lipid profile. Urine samples were taken for assessment of albumin/creatinine ratio. M mode echocardiography and flow mediated dilatation (FMD) via ultrasound were completed; t-test for independent variables, Pearson’s correlation, and stepwise multiple regression analysis were used.
Results: The mean age of patients was 16.3±1.5 years and mean duration of diabetes was 9.4±2.9 years. Nitric oxide, ADMA and FMD were significantly lower, while OxLDL and the albumin/creatinine ratio were significantly higher in diabetics. Nitric oxide had a significant negative correlation with left ventricular end-diastolic dimension, left ventricular end-systolic dimension, posterior wall thickness, left ventricular mass, albumin/creatinine ratio, and OxLDL, as well as a positive correlation with ADMA. Albumin/creatinine ratio had a significant positive correlation with OxLDL and negative correlation with ADMA. Stepwise multiple regression analysis revealed that ADMA is the only parameter related to NO, however, albumin/creatinine ratio and OxLDL are related to ADMA.
Conclusions: Type 1 diabetic patients had endothelial and diastolic dysfunction. The reduction in NO, ADMA, and elevation of OxLDL, and its relation to echocardiographic data and albumin/creatinine ratio, may reflect their role in cardiac and renal affection.
References
1. Sibal L, Agarwal SC, Schwedhelm E, Lüneburg N, Böger RH, et al. A study of endothelial function and circulating asymmetric dimethylarginine levels in people with Type 1 diabetes without macrovascular disease or microalbuminuria. Cardiovasc Diabetol 2009;8:27.10.1186/1475-2840-8-27Suche in Google Scholar
2. Cavusoglu E, Ruwende C, Chopra V, Poludasu S, Yanamadala S, et al. Relation of baseline plasma ADMA levels to cardiovascular morbidity and mortality at two years in men with diabetes mellitus referred for coronary angiography. Atherosclerosis 2010;210:226–31.10.1016/j.atherosclerosis.2009.10.034Suche in Google Scholar
3. Altinova AE, Arslan M, Sepici-Dincel A, Akturk M, Altan N, et al. Uncomplicated type 1 diabetes is associated with increased asymmetric dimethylarginine concentrations. J Clin Endocrinol Metabol 2007;92:1881–5.10.1210/jc.2006-2643Suche in Google Scholar
4. Heilman K, Zilmer M, Zilmer K, Kool P, Tillmann V. Elevated plasma adiponectin and decreased plasma homocysteine and asymmetric dimethylarginine in children with type 1 diabetes. Scand J Clin Lab Invest 2009;69:85–91.10.1080/00365510802419454Suche in Google Scholar
5. Cosson S, Kevorkian JP. Left ventricular diastolic dysfunction: an early sign of diabetic cardiomyopathy? Diabetes Metab 2003;29:455–66.10.1016/S1262-3636(07)70059-9Suche in Google Scholar
6. Fang ZY, Prins JB, Marwick TH. Diabetic cardiomyopathy: evidence, mechanisms and therapeutic implications. Endocr Rev 2004;25:543–67.10.1210/er.2003-0012Suche in Google Scholar PubMed
7. Abd El Dayem SM, Battah AA. Effect of glycemic control on the progress of left ventricular hypertrophy and diastolic dysfunction in children with type I diabetes mellitus. Anadolu Kardiyol Derg 2012;12:498–507.Suche in Google Scholar
8. Flegg HM. An investigation for the determination of serum cholesterol by an enzymatic method. Ann Clin Biochem 1973;10:79–84.10.1177/000456327301000125Suche in Google Scholar
9. Friedwald WT, Levy RI, Fredrickson DS. Estimation of low density cholesterol in plasma without use of the preparative ultracentrifugation. Clin Chem 1972;18:499–502.10.1093/clinchem/18.6.499Suche in Google Scholar
10. Wahlefeld AW. Triglyceride determination after enzymatic hydrolysis. In: Berger HU, editor. Methods of enzymatic analysis, 2nd English Ed. (translated from third German Ed.). Weinheim: Verlag Chemie and NY and London: Academic Press, Inc.,1974:1813–35.Suche in Google Scholar
11. Danilova LA, Lopatina NI. Colorimetric method of determining glycosylated haemoglobin. Lab Delo 1986;5:282–3.Suche in Google Scholar
12. Mogensen CE. Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Eng J Med1984;310:356–60.10.1056/NEJM198402093100605Suche in Google Scholar PubMed
13. Schulze F, Wesemann R, Schwedhelm E, Sydow K, Albsmeier J, et al. Determination of asymmetric dimethylarginine (ADMA) using a novel ELISA assay. Clin Chem Lab Med 2004;42:1377–83.10.1515/CCLM.2004.257Suche in Google Scholar PubMed
14. Craig WY, Poulin SE, Nelson CP, Ritchie RF. An ELISA method for detection and quantitation of IgG antibody against oxidized low density lipoprotein: the effect of blocking buffer and the method of data expression on experimental findings. Clin Chem 1994;40:882–8.10.1093/clinchem/40.6.882Suche in Google Scholar
15. Pettersen MD, Du W, Skeens ME, Humes RA. Regression equations for calculation of z scores of cardiac structures in a large cohort of healthy infants, children, and adolescents: an echocardiographic study. J Am Soc Echocardiogr 2008;21:922–34.10.1016/j.echo.2008.02.006Suche in Google Scholar
16. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, et al. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 1986;57:450–8.10.1016/0002-9149(86)90771-XSuche in Google Scholar
17. Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilatation of the brachial artery. J Am Coll Cardiol 2002;39:257–65.10.1016/S0735-1097(01)01746-6Suche in Google Scholar
18. Ferrara LA, Palmieri V, Limauro S, Viola S, Palmieri EA, et al. Association between post-ischemic forearm blood flow and blood pressure response to maximal exercise in well trained healthy young men. Int J Cardiol 2006;111:394–8.10.1016/j.ijcard.2005.08.011Suche in Google Scholar
19. Kuvin JT, Patel AR, Sliney KA, Pandian NG, Rand WM, et al. Peripheral vascular endothelial function testing as a non invasive indicator of coronary artery disease. J Am Coll Cardiol 2001;38:1843–9.10.1016/S0735-1097(01)01657-6Suche in Google Scholar
20. Palmieri V, Migliaresi P, Orefice M, Lupo T, Di Minno MN, et al. High prevalence of subclinical cardiovascular abnormalities in patients with systemic lupus erythematosus in spite of a very low clinical damage index. Nutr Metab Cardiovasc Dis 2009;19:234–40.10.1016/j.numecd.2008.09.009Suche in Google Scholar PubMed
21. Di Cori A, Di Bello V, Miccoli R, Talini E, Palagi C, et al. Left ventricular function in normotensive young adults with well controlled type 1 diabetes mellitus. Am J Cardiol 2007;99: 84–90.10.1016/j.amjcard.2006.07.063Suche in Google Scholar PubMed
22. Palmieri V, Capaldo B, Russo C, Laccarino M, Pezzullo S, et al. Uncomplicated type 1 diabetes and preclinical left ventricular myocardial dysfunction: insights from echocardiography and exercise cardiac performance evaluation. Diabetes Res Clin Pract 2008;79:262–8.10.1016/j.diabres.2007.09.014Suche in Google Scholar PubMed
23. Wiltshire EJ, Gent R, Hirte C, Pena A, Thomas DW, et al. Endothelial dysfunction relates to folate status in children and adolescents with type 1 diabetes. Diabetes 2002;51:2282–6.10.2337/diabetes.51.7.2282Suche in Google Scholar PubMed
24. 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)02894-2Suche in Google Scholar
25. Donaghue KC, Robinson J, McCredie R, Fung A, Silink M, et al. Large vessel dysfunction in diabetic adolescents and its relationship to small vessel complications. J Pediatr Endocrinol Metab 1997;10:593–8.10.1515/JPEM.1997.10.6.593Suche in Google Scholar
26. Paiva H, Lehtimaki T, Laakso J, Ruokonen I, Rantalaiho V, et al. Plasma concentrations of asymmetric- dimethyl-arginine in type 2 diabetes associate with glycemic control and glomerular filtration rate but not with risk factors of vasculopathy. Metabolism. 2003;52:303–7.10.1053/meta.2003.50048Suche in Google Scholar
27. Kawano H, Motoyama T, Hirashima O, Hirai N, Miyao Y, et al. Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilation of brachial artery. J Am Coll Cardiol 1999;34:146–54.10.1016/S0735-1097(99)00168-0Suche in Google Scholar
28. Cosentino F, Hishikawa K, Katusic ZS, Luscher TF. High glucose increases nitric oxide synthase expression and superoxide anion generation in human aortic endothelial cells. Circulation 1997;96:25–8.10.1161/01.CIR.96.1.25Suche in Google Scholar
29. Valkonen VP, Paiva H, Salonen JT, Lakka TA, Lehtimaki T, et al. Risk of acute coronary events and serum concentration of asymmetrical dimethylarginine. Lancet 2001;358:2127–8.10.1016/S0140-6736(01)07184-7Suche in Google Scholar
30. Huemer M, Simma B, Mayr D, Muhl A, Rami B, et al. Low levels of asymmetric dimethylarginine in children with diabetes mellitus type 1 compared with healthy children. J Pediatric 2011;158:602–6.10.1016/j.jpeds.2010.09.058Suche in Google Scholar
31. Boger RH, Zoccali C. ADMA: a novel risk factor that explains excess cardiovascular event rate in patients with end-stage renal disease. Atherosclerosis 2003;4:23–8.10.1016/S1567-5688(03)00030-8Suche in Google Scholar
32. McDermott JR. Studies on the catabolism of Ng-methylarginine, Ng, Ng-dimethylarginine and Ng, Ng-dimethylarginine in the rabbit. Biochem J 1976;154:179–84.10.1042/bj1540179Suche in Google Scholar PubMed PubMed Central
33. Kimoto M, Whitley GS, Tsuji H, Ogawa T. Detection of NG, NG dimethylarginine dimethylaminohydrolase in human tissues using a monoclonal antibody. J Biochem 1995;117:237–8.10.1093/jb/117.2.237Suche in Google Scholar PubMed
34. Achan V, Broadhead M, Malaki M, Whitley G, Leiper J, et al. Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humans and is actively metabolized by dimethylarginine dimethylaminohydrolase. Arterioscler Thromb Vasc Biol 2003;23:1455–9.10.1161/01.ATV.0000081742.92006.59Suche in Google Scholar
35. Tarnow L, Hovind P, Teerlink T, Stehouwer CD, Parving HH. Elevated plasma asymmetric dimethylarginine as a marker of cardiovascular morbidity in early diabetic nephropathy in type 1 diabetes. Diabetes Care 2004;27:765–9.10.2337/diacare.27.3.765Suche in Google Scholar
36. Dixon LJ, Hughes SM, Rooney K, Madden A, Devine A, et al. Increased superoxide production in hypertensive patients with diabetes mellitus: role of nitric oxide synthase. Am J Hypertens 2005;18:839–43.10.1016/j.amjhyper.2005.01.004Suche in Google Scholar
37. Vaarala O. Antibodies to oxidized LDL. Lupus 2000;9:202–5.10.1191/096120300678828280Suche in Google Scholar
38. Berliner JA, Heinecke JW. The role of oxidized lipoproteins in atherogenesis. Free Radic Biol Med 1996;20:707–27.10.1016/0891-5849(95)02173-6Suche in Google Scholar
39. Steiberg D. Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem 1997;272:20963–6.10.1074/jbc.272.34.20963Suche in Google Scholar
40. Wolff SP, Jiang ZY, Hunt JV. Protein glycation and oxidative stress in diabetes mellitus and ageing. Free Radic Biol Med 1991;10:339–52.10.1016/0891-5849(91)90040-ASuche in Google Scholar
41. Nourooz-Zadeh J, Tajaddini-Sarmadi J, McCarthy S, Betteridge DJ, Wolff SP. Elevated levels of authentic plasma hydroperoxides in NIDDM. Diabetes 1995;44:1054–8.10.2337/diab.44.9.1054Suche in Google Scholar
42. Berliner JA, Navab M, Fogelman AM, Frank JS, Demer LL, et al. Atherosclerosis: basic mechanism of oxidation, inflammation and genetics. Circulation 1995;91:2488–96.10.1161/01.CIR.91.9.2488Suche in Google Scholar
43. Bowie A, Owens D, Collin P, Johnson A, Tomkin GH. Glycosylated low density lipoprotein is more sensitive to oxidation: implications for the diabetic patients? Atherosclerosis 1993;102:63–7.10.1016/0021-9150(93)90084-8Suche in Google Scholar
44. Palinski W, Rosenfeld ME, Yla-Herttuala S, Gurtner GC, Socher SS, et al. Low density lipoprotein undergoes oxidative modification in vivo. Proc Natl Acad Sci 1989;86:1372–6.10.1073/pnas.86.4.1372Suche in Google Scholar
45. Steinerová A, Racek J, Stozický F, Zima T, Fialová L, et al. Antibodies against oxidized LDL–theory and clinical use. Physiol Res 2001;50:131–41.Suche in Google Scholar
46. Salonen JT, Ylä-Herttuala S, Yamamoto R, Butler S, Korpela H, et al. Antibody against oxidized LDL and progression of carotid atherosclerosis. Lancet 1992;339:883–7.10.1016/0140-6736(92)90926-TSuche in Google Scholar
©2014 by Walter de Gruyter Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Original articles
- Assessment of hearing in children with type 1 diabetes mellitus
- Insulin resistance and lipid profiles in HIV-infected Thai children receiving lopinavir/ritonavir-based highly active antiretroviral therapy
- Increased hunger and speed of eating in obese children and adolescents
- Glucagon and insulin cord blood levels in very preterm, late preterm and full-term infants
- Thyroid function in late preterm infants in relation to mode of delivery and respiratory support
- Prevalence of vitamin D deficiency and its related factors in children and adolescents living in North Khorasan, Iran
- Asymmetric dimethyl L-arginine, nitric oxide and cardiovascular disease in adolescent type 1 diabetics
- A combined nutritional-behavioral-physical activity intervention for the treatment of childhood obesity – a 7-year summary
- The effect of earlier puberty on cardiometabolic risk factors in Afro-Caribbean children
- Prevalence of risk of deficiency and inadequacy of 25-hydroxyvitamin D in US children: NHANES 2003–2006
- Serum uric acid: relationships with biomarkers in adolescents and changes over 1 year
- Psychological impact on parents of children with congenital adrenal hyperplasia: a study from Sri Lanka
- Investigation of adropin and leptin levels in pediatric obesity-related nonalcoholic fatty liver disease
- Diseases accompanying congenital hypothyroidism
- Molecular diagnosis of a Chinese pedigree with α-mannosidosis and identification of a novel missense mutation
- Are the characteristics of thyroid cancer different in young patients?
- Unsaturated fatty acids and insulin resistance in childhood obesity
- Effect of genetic subtypes and growth hormone treatment on bone mineral density in Prader-Willi syndrome
- KCNJ11 gene mutation analysis on nine Chinese patients with type 1B diabetes diagnosed before 3 years of age
- Prevalence and risk factors of metabolic syndrome in school adolescents of northeast China
- Patient reports
- A novel activating ABCC8 mutation underlying neonatal diabetes mellitus in an infant presenting with cerebral sinovenous thrombosis
- Endocrinological anomalies in a patient with 12q14 microdeletion syndrome. Completing phenotype of this exceptional short stature condition
- Acute mental status change as the presenting feature of adrenal insufficiency in a patient with autoimmune polyglandular syndrome type II and stroke
- Effect of ethosuximide on cortisol metabolism in the treatment of congenital adrenal hyperplasia
- Absence of WNT4 gene mutation in a patient with MURCS association
- Identification of a novel insulin receptor gene heterozygous mutation in a patient with type A insulin resistance syndrome
- Adrenal insufficiency in association with congenital nephrotic syndrome: a case report
- Diabetic lipemia presenting as eruptive xanthomas in a child with autoimmune polyglandular syndrome type IIIa
- A case report of nephrogenic diabetes insipidus with idiopathic Fanconi syndrome in a child who presented with vitamin D resistant rickets
- Letter to the Editor
- Hyperbilirubinemia in neonates of diabetic mothers: an indirect biomarker of organ damage?
Artikel in diesem Heft
- Frontmatter
- Original articles
- Assessment of hearing in children with type 1 diabetes mellitus
- Insulin resistance and lipid profiles in HIV-infected Thai children receiving lopinavir/ritonavir-based highly active antiretroviral therapy
- Increased hunger and speed of eating in obese children and adolescents
- Glucagon and insulin cord blood levels in very preterm, late preterm and full-term infants
- Thyroid function in late preterm infants in relation to mode of delivery and respiratory support
- Prevalence of vitamin D deficiency and its related factors in children and adolescents living in North Khorasan, Iran
- Asymmetric dimethyl L-arginine, nitric oxide and cardiovascular disease in adolescent type 1 diabetics
- A combined nutritional-behavioral-physical activity intervention for the treatment of childhood obesity – a 7-year summary
- The effect of earlier puberty on cardiometabolic risk factors in Afro-Caribbean children
- Prevalence of risk of deficiency and inadequacy of 25-hydroxyvitamin D in US children: NHANES 2003–2006
- Serum uric acid: relationships with biomarkers in adolescents and changes over 1 year
- Psychological impact on parents of children with congenital adrenal hyperplasia: a study from Sri Lanka
- Investigation of adropin and leptin levels in pediatric obesity-related nonalcoholic fatty liver disease
- Diseases accompanying congenital hypothyroidism
- Molecular diagnosis of a Chinese pedigree with α-mannosidosis and identification of a novel missense mutation
- Are the characteristics of thyroid cancer different in young patients?
- Unsaturated fatty acids and insulin resistance in childhood obesity
- Effect of genetic subtypes and growth hormone treatment on bone mineral density in Prader-Willi syndrome
- KCNJ11 gene mutation analysis on nine Chinese patients with type 1B diabetes diagnosed before 3 years of age
- Prevalence and risk factors of metabolic syndrome in school adolescents of northeast China
- Patient reports
- A novel activating ABCC8 mutation underlying neonatal diabetes mellitus in an infant presenting with cerebral sinovenous thrombosis
- Endocrinological anomalies in a patient with 12q14 microdeletion syndrome. Completing phenotype of this exceptional short stature condition
- Acute mental status change as the presenting feature of adrenal insufficiency in a patient with autoimmune polyglandular syndrome type II and stroke
- Effect of ethosuximide on cortisol metabolism in the treatment of congenital adrenal hyperplasia
- Absence of WNT4 gene mutation in a patient with MURCS association
- Identification of a novel insulin receptor gene heterozygous mutation in a patient with type A insulin resistance syndrome
- Adrenal insufficiency in association with congenital nephrotic syndrome: a case report
- Diabetic lipemia presenting as eruptive xanthomas in a child with autoimmune polyglandular syndrome type IIIa
- A case report of nephrogenic diabetes insipidus with idiopathic Fanconi syndrome in a child who presented with vitamin D resistant rickets
- Letter to the Editor
- Hyperbilirubinemia in neonates of diabetic mothers: an indirect biomarker of organ damage?