Open Access

Relation between carotid intima media thickness and oxidative stress markers in type 1 diabetic children and adolescents

  • Mona H El Samahy1,
  • Randa M Matter1,
  • Omneya I Youssef1Email author,
  • Manal A Shams El Din El Telbany2 and
  • Nermeen A Kamal1
Journal of Diabetes & Metabolic Disorders201312:50

DOI: 10.1186/2251-6581-12-50

Received: 1 February 2013

Accepted: 2 September 2013

Published: 19 December 2013

Abstract

Background

Carotid intima media thickness (CIMT) is a non invasive marker of subclinical atherosclerosis. Hyperglycemia, oxidatively modified atherogenic lipoproteins and advanced glycation end products are linked to increased oxidative stress in diabetes. We aimed to find out the relation between carotid intima media thickness in type 1 diabetic children and adolescents and plasma nitric oxide and total antioxidant capacity levels as markers of oxidative stress.

Methods

This study included 50 children and adolescents with type 1 diabetes mellitus with mean age (9.7 ± 3.4 years) and 50 healthy age and sex matched controls. They were subjected to assessment of hemoglobin A1c, total cholesterol and triglycerides, serum total antioxidant capacity, serum nitric oxide (NO) by colorimetric method and carotid intima media thickness by B-mode ultrasound.

Results

There was significant elevation in serum nitric oxide (17.07 ± 6.4 vs 12.6 ± 4.7 μmol/L; p < 0.001), CIMT (0.47 ± 0.04 vs 0.39 ± 0.02 mm; p < 0.001) and significant reduction in serum total antioxidant capacity (0.41 ± 0.29 vs 0.87 ± 0.23 mmol/L; p < 0.001) in diabetic patients compared to controls. Carotid intima media thickness was correlated positively with nitric oxide (r = 0.402, p = 0.01) and negatively with total antioxidant capacity (r = -0.341, p = 0.02). Carotid intima media thickness was also correlated positively with age, duration of diabetes but not correlated with glycemic control or lipid profile.

Conclusion

The significant elevation in nitric oxide and reduction in total antioxidant capacity in children and adolescents with type 1 diabetes mellitus with their correlation with carotid intima media thickness may reflect the role of oxidative stress in the development of atherosclerosis in young type 1 diabetic subjects.

Introduction

The atherogenicity of type 1 diabetes has been increasingly recognized [1]. Patients with diabetes show a 2- to 10-fold risk for developing atherosclerotic lesions compared with the normal population [2, 3]. Even if these complications become manifest in the adult diabetic patient, the process of vascular changes starts much earlier [4, 5]. The most significant changes in early subclinical period of atherosclerotic disease are endothelial dysfunction and increase in intima-media thickness observed in all arterial beds [6]. Common carotid artery intima-media thickness (CIMT), measured by high-resolution B-mode ultrasonography, is a noninvasive marker of subclinical atherosclerosis [79]. Normative values for CIMT are available for subjects aged 10 to 20 years [10, 11].

Mechanisms involved in the increased oxidative stress in diabetes include not only oxygen free radical generation due to nonenzymatic glycosylation (glycation), autooxidation of glycation products, but also changes in the tissue content and activity of antioxidant defense systems. Increased levels of the products of oxidative damage to lipids have been detected in serum of diabetic patients, and their presence correlates with the development of complications [1218].

Oxidative stress plays a pivotal role in the development of diabetes microvascular and cardiovascular complications [19].

In the diabetic macrovascular and in the heart, this appears to be a consequence of increased oxidation of fatty acids, resulting in part from pathway-specific insulin resistance [19].

Nitric oxide has cellular antioxidant and pro-oxidant actions [20]. The endothelial nitric oxide (NO) system plays a pivotal role in vascular physiology and pathology. NO is a potent vasodilator agent with anti-hypertensive, anti-thrombotic, anti-atherogenic, and anti-smooth muscle proliferative properties [21]. However, high amounts of NO produced by inducible NO synthase (iNOS) and/or peroxynitrite (ONOO-), a reactive intermediate of NO with superoxide anion are involved in pro-inflammatory reactions and tissue damage as well [22].

Total Antioxidant Capacity (TAC) is capable of serving as a parameter to monitor diabetes in patients with type 1 DM [23]. A depletion of the total antioxidant capacity is associated with a higher incidence of diabetic complications [24].

The relation between oxidative stress markers and carotid intima media thickness in type 1 diabetic children and adolescents was not extensively studied. Hence, this study aimed at assessment of carotid intima media thickness in children and adolescents with type1 diabetes mellitus in relation to plasma nitric oxide and plasma total antioxidant capacity levels and with diabetes duration, glycemic control and microvascular complications.

Patients and methods

This case control study was conducted at the Pediatric Diabetes Clinic, Children’s Hospital, Ain Shams University, Cairo, Egypt in the period from April 2011 to February 2012.It included 50 patients with type 1 diabetes mellitus(DM) regularly attending the clinic. They were 37 females (74%) and 13 males (36%). Their ages ranged from 6–16 years with a mean age of 9.7 ± 3.4 years. Their duration of illness ranged from 1–13 years with mean diabetes duration of 4.5 ± 3.5 years. Patients were further subdivided into two groups according to the duration of diabetes: (Group I) included 22 children and adolescents with diabetes duration of 5 years or more, (Group II) included 28 children and adolescents with diabetes duration of less than 5 years. Fifty age and sex matched healthy individuals were included as a control group. They were 14 males and 36 females. Their age ranged from 2–14 years with mean age of 9.8 ± 3.14 years.

The study was approved by the Ethical Committee of Ain Shams University Faculty of Medicine.

Inclusion criteria

Patients were included in the study only if they have type 1 diabetes mellitus on regular insulin therapy regularly visiting the Clinic.

Exclusion criteria

Included Type 2 diabetes mellitus, hypertension, patients with malignancy, connective tissue diseases, liver dysfunction, renal dysfunction (serum creatinine > 1.2 mg/dl), congenital or acquired cardiovascular disorders, administration of drugs other than insulin (such as oral hypoglycemics, antihypertensives, antiplatelets or lipid lowering medications, aspirin, or vitamin supplements) at the time of the study and none of them was cigarette smoker.

All patients were subjected to detailed history taking, thorough clinical examination, measurement of Glycosylated Hb (HbA1c) by HPLC (high performance liquid Chromatography). Patients were considered under optimal glycemic control when their HbA1c was < 7.5% [25]. Microalbuminuria was assayed using SERA-PAK immuno-microalbumin Kit (Bayer Corporation, Benedict Ave, Tarry town, NY, USA). Persistent microalbuminuria was defined when two of three samples showed urinary albumin excretion rate of 30–300 μg/mg creatinine [26] fasting serum triglycerides, serum cholesterol using Synchron CX7 (Brea, California, USA) [27]. Serum total antioxidant capacity by colorimetric method [28], serum NO by colorimetric method [29] and Carotid intimal –media thickness (CIMT) assessment using B mode ultrasonography [30].

Measurment of serum Total Antioxidant Capacity (TAC) by colorimetric method.

The determination of antioxidative capacity was performed by the reaction of antioxidants in the sample with a defined amount of exogenously provide hydrogen peroxide (H2O2) the antioxidants in the sample eliminate a certain amount of the provided hydrogen peroxide. The residual H2O2 was determined clorometrically by an enzymatic reaction which Involves the conversion of 3,5,dichloro _2_ hydroxyl benzensulphonate to a colored product [28].

Measurement of serum Nitric oxide (NO) was done using colorimetric method. This assay determines nitric oxide concentrations based on the enzymatic conversion of nitrate to nitrite by nitrate reductase. The reaction is followed by colorimetric detection of nitrite as an azo dye product of the Griess Reaction. The Griess Reaction is based on the two-step diazotization reaction in which acidified NO2- produces a nitrosating agent, which reacts with sulfanilic acid to produce the diazonium ion. This ion is then coupled to N-(1-naphthyl) ethylenediamine to form the chromophoric azo-dervative which absorbs light at 540–570 nm [29].

Statistical analysis

Demographic and clinical data are presented as means ± SD or proportions. Differences in continuous variables between males and females were tested with the Student t test for normally distributed data and the Mann–Whitney U test for non-normally distributed data. The χ2 test for contingency tables with different degrees of freedom was obtained to detect associations between categorical independent variables. Adjustment for multiple confounding was done using linear regression analysis with a manual backward procedure. Multivariate analyses were preceded by estimation of the correlation between potential confounders. A significance level of < 0.05 was used. All statistical analysis was done using the SPSS software package for Windows, version 15.0 (SPSS, Chicago, IL).

Results

  • Patients mean systolic blood pressure (SBP) was103.500 ± 18.077 mmHg and mean diastolic blood pressure (DBP) was 68 ± 10.302 mmHg. Three (6%) of our patients had SBP and DBP > 95% percentile while 97% were within the normal ranges.

  • Diabetic patients showed significant increase in nitric oxide and decrease in total antioxidant capacity level than controls (P value < 0.001)] (Table 1), Figure 1.

Figure 1

Comparison between patients and controls regarding values of nitric oxide and total antioxidant capacity.

  • NO level was higher in patients with suboptimal glycemic control than those with optimal glycemic control [(23.38 ± 6.7 μmol/L) vs (16.33 ± 5.6 μmol/L)] (P value = 0.017) and in patients with nephropathy than patients without nephropathy [(22.00 ± 4.14 μmol/L) vs (16.67 ± 6.5 μmol/L)] (P value = 0.033).

  • No statistically significant difference was found in TAC level between diabetic patients with and without nephropathy or between patients with suboptimal and optimal glycemic control (p value >0.05)

  • Serum total cholesterol and triglycerides were significantly higher in studied patients than control group, although within normal range.

  • Carotid intima media thickness was significantly increased in diabetic patients compared to normal controls [(mean 0.46 ± 0.04 mm) vs (mean 0.39 ±0.02 mm)] (P < 0.001) (Table 1), Figure 1.

  • Carotid intima media thickness was significantly increased in diabetic patients with suboptimal than those with optimal glycemic control [(0.46 ± 0.04 cm) vs (0.40 ± 0.02 cm)] (P value 0.04), in patients with diabetes duration > 5 years than those with diabetes duration < 5 years [(0.50 ± 0.03 mm) vs (0.43 ± 0.02 mm)] (P value <0.001)] (Table 2) and in diabetic patients with than patients without nephropathy [ (0.49 ± 0.02) vs (0.40 ± 0.04)] (P value = 0.009).

  • A statistically significant positive correlation was found between carotid intima media thickness and age, duration of diabetes mellitus, systolic and diastolic blood pressure and nitric oxide (P value < 0.001 and <0.001, 0.002, 0.007 and 0.01 respectively) and a significant negative correlation was found between carotid intima media thickness and total antioxidant capacity (P value = 0.02) (Table 3). No significant correlation was found between carotid intima media thickness and mean HbA1c, cholesterol or triglycerides (P value >0.05).

Table 1

Comparison between diabetic patients and control group regarding studied parameters

Groups

 

t-test

Patients(n50) Mean ± SD

Controls(n50) Mean ± SD

t

P-value

Age (years)

9.78 ± 3.45

9.86 ± 3.14

-0.12

0.90

BMI(kg/m2)

20.120 ± 4.155

18.740 ± 3.87

t = 1.72

0.09

Cholesterol (mg/dl)

147.35 ± 38.92

120.68 ± 35.26

t = 3.5

0.0005*

Triglycerides (mg/dl)

80.86 ± 25.10

62.40 ± 20.50

t = 4.03

0.0001*

NO (μmol/L)

17.07 ± 6.36

12.57 ± 4.74

3.98

<0.001*

TAC (mmol/L)

0.41 ± 0.29

0.87 ± 0.23

-8.87

<0.001*

CIMT (mm)

0.47 ± 0.04

0.40 ± 0.02

9.66

<0.001*

Gender

37/13

36/14

0.437#

0.509

NO nitric oxide, TAC Total antioxidant capacity, CIMT carotid intima media thickness; #= Chi-Square.

*Indicate statistical significance.

Table 2

Comparison between patients with diabetes duration <5 years and >5 years regarding studied parameters

 

Patients with diabetes duration ≤ 5 years(n = 28)

Patients with diabetes duration > 5 years(n = 22)

T-test

Mean ± SD

Mean ± SD

t

P-value

Age (years)

7.64 ± 2.80

12.50 ± 1.946

-6.92

<0.001*

Mean HbA1c%

8.47 ± 1.98

9.73 ± 2.07

-2.19

0.03*

Cholesterol (mg/dl)

134.36 ± 38.34

162.50 ± 35.23

-1.94

0.07

Triglycerides (mg/dl)

79.13 ± 24.74

81.86 ± 25.54

0.38

0.7

NO (μmol/L)

16.27 ± 6.70

18.09 ± 5.89

-1.01

0.32

TAC (mmol/L)

0.45 ± 0.31

0.36 ± 0.25

1.18

0.25

CIMT (mm)

0.44 ± 0.03

0.50 ± 0.03

-7.09

<0.001*

NO nitric oxide, TAC Total antioxidant capacity, CIMT carotid intima media thickness.

*Indicate statistical significance.

Table 3

Correlation between CIMT, serum NO and serum TAC in diabetic patients

  

CIMT (mm)

NO (μmol/L)

Age (years)

r

0.741

 

P-value

<0.001*

Duration of diabetes (years)

r

0.656

P-value

<0.001*

SBP (mmHg)

r

0.126

P-value

0.002*

DBP (mmHg)

r

0.379

P-value

0.007*

NO (μmol/L)

r

0.40

P-value

0.01*

TAC(mmol/L)

r

-0.34

-0.53

P-value

0.02*

<0.001*

CIMT carotid intima media thickness, SBP systolic blood pressure, DBP diastolic blood pressure, NO nitric oxide, TAC Total antioxidant capacity.

*Indicate statistical significance.

Discussion

The present study showed a significant increase in serum nitric oxide (NO) level in diabetic patients than controls which came in agreement with many studies [3133]. Pitocco et al. [34] suggested a reduced asymmetric dimethyl arginine (ADMA) inhibition of NOS as possible mechanism involved in the pathogenesis of oxidative stress in female subjects with a short duration and uncomplicated type 1 diabetes.

Serum NO level was significantly increased in diabetic patients with than those without nephropathy which came in accordance to previous studies [35, 36]. Prabhakar, [37] reported that the enhanced NO production may contribute to hyperfiltration and microalbuminuia at early diabetic nephropathy. NO level was significantly higher in patients with suboptimal than optimal glycemic control which came in agreement with others [38].

A significant decrease in total antioxidant capacity level was found in patients than controls which came in agreement with several studies [3942]. Lack of difference in TAC level between our studied patients with and without nephropathy is concordant with El-desoky et al. [43] who found that plasma TAC in patients of diabetes mellitus type I with nephropathy was not significantly decreased as compared with diabetes mellitus type 1 with no nephropathy and they concluded that TAC cannot be used to differentiate between diabetes mellitus type 1 with and without nephropathy.

Serum total cholesterol and triglycerides were significantly higher in studied diabetic patients compared to control group although within the normal range. This agreed with Margeisdottir et al. [44] who attributed those findings to the young age of the patients.

Diabetic patients showed a significant increase in CIMT mean values compared to controls. Those results came in accordance to several studies [4547]. A significant increase in CIMT in patients with nephropathy compared to patients without nephropathy came in concordance with Gul et al. [47] suggesting that diabetic microangiopathy is related with macroangiopathy and in patients with suboptimal glycemic control compared to patients with optimal glycemic control which came in concordance with Abdelghaffar et al. [46].

CIMT was directly correlated with age in studied diabetic patients which agreed with many studies [4648]. A strong direct correlation was found between mean CIMT and patients systolic and diastolic blood pressure which agreed with several studies [46, 48, 49]. The relationship between increased CIMT and blood pressure suggests that smooth muscle proliferation plays a role in the early diffuse thickening of the arterial wall [49].

No significant correlation was found between mean CIMT and metabolic control parameter HbA1c, this agreed with many studies [47, 50]. Data from the literature indicated that, in contrast to the functional impairment of the endothelium, structural changes are not correlated to single parameter such as the HbA1c at a young age [50].

A statistically significant positive correlation was found between carotid intima media thickness and nitric oxide level which agreed with Dursun et al. [51] who explored the relation between CIMT and oxidative stress markers in type 2 diabetic patients on maintenance hemodialysis. Zineh et al. [52] reported the association between NOS3 polymorphisms and arterial stiffness in children with type 1 diabetes. Insulin acts by modulating the release of vasodilator substances, such as nitric oxide and prostaglandins, from vascular endothelium, by both stimulating and inhibiting the sympathetic nervous system and by protecting smooth muscle cells in blood vessel from apoptosis induced by oxidative stress [53]. Thus the vasodilatory and antioxidant effects of insulin are depressed in case of insulin deficiency (i.e. type 1 diabetes) [54].

A negative correlation was found between CIMT and total antioxidant capacity level. Lower serum TAC levels were observed in atherosclerotic coronary artery disease patients with an inverse association with number of damaged coronary vessels [55]. Other research reported increased DNA damage in the nucleus of coronary cells and decreased plasma TAC level in coronary artery disease patients [56].

Conclusion

The significant elevation in nitric oxide and reduction in total antioxidant capacity in children and adolescents with type 1 diabetes mellitus together with their correlation with carotid intima media thickness may reflect the role of oxidative stress in the development of atherosclerosis in young type 1 diabetic subject. Further studies to measure other antioxidant markers like glutathione or antioxidants or markers of oxidative stress like malondialdehyde in relation to carotid intima media thickness are warranted.

Abbreviations

CIMT: 

Carotid intima media thickness

DM: 

Diabetes mellitus

HbA1c: 

Glycosylated hemoglobin

NO: 

Nitric oxide

TAC: 

Total antioxidant capacity

SBP: 

Systolic blood pressure

DBP: 

Diastolic blood pressure

ELISA: 

Enzyme linked immune sorbent assay.

Declarations

Acknowledgements

We are grateful to the staff of the Diabetes Clinic and echocardiography unit, Children's Hospital, Ain Shams University, Cairo Egypt.

Authors’ Affiliations

(1)
Departments of Pediatrics, Faculty of Medicine, Ain Shams University
(2)
Clinical Pathology, Faculty of Medicine, Ain Shams University

References

  1. Rabago Rodriguez R, Gómez-Díaz RA, Tanus Haj J, Avelar Garnica FJ, Ramirez Soriano E, Nishimura Meguro E, Aguilar-Salinas CA, Wacher NH: Carotid intima-media thickness in pediatric type 1 diabetic patients. Diabetes Care 2007,30(suppl 10):2599–2602.View ArticlePubMedGoogle Scholar
  2. Pyörälä K, Laakso M, Uusitupa M: Diabetes and atherosclerosis: an epidemiologic view. Diabetes Metab Rev 1987, 3: 463–524. 10.1002/dmr.5610030206View ArticlePubMedGoogle Scholar
  3. Daneman D: Type 1 diabetes. Lancet 2006, 367: 847–858. 10.1016/S0140-6736(06)68341-4View ArticlePubMedGoogle Scholar
  4. Garcia MJ, McNamara PM, Gordon T, Kannell WB: Morbidity and mortality in diabetics in the Framingham population: sixteen year follow-up study. Diabetes 1974, 23: 105–111.View ArticlePubMedGoogle Scholar
  5. Järvisalo MJ, Jartti L, Näntö-Salonen K, Irjala K, Rönnemaa T, Hartiala JJ, Celermajer DS, Raitakari OT: Increased aortic intima-media thickness. A marker of preclinical atherosclerosis in high-risk children. Circulation 2001, 104: 2943–2947. 10.1161/hc4901.100522View ArticlePubMedGoogle Scholar
  6. Glagov S, Weisenberg E, Zarins CK, Stankonavicius R, Kolettis GJ: Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 1987, 316: 1371–1375. 10.1056/NEJM198705283162204View ArticlePubMedGoogle Scholar
  7. Parikh A, Danemann D: Is carotid ultrasound a useful tool in assessing cardiovascular disease in individuals with diabetes? Diabetes Technol Ther 2004, 6: 65–69. 10.1089/152091504322783440View ArticlePubMedGoogle Scholar
  8. De Groot E, Hovingh K, Wiegman A, Duriez P, Smit AJ, Fruchart JC, Kastelein JJP: Measurement of arterial wall thickness as a surrogate marker for atherosclerosis. Circulation 2004, 109: 33–38. 10.1161/01.CIR.0000115209.47022.9BView ArticleGoogle Scholar
  9. Stabouli S, Kotsis V, Papamichael C, Constantinopoulos A, Zakopoulos N: Adolescent obesity is associated with high ambulatory blood pressure and increased carotid intimal-medial thickness. J Pediatr 2005, 147: 651–656. 10.1016/j.jpeds.2005.06.008View ArticlePubMedGoogle Scholar
  10. Jourdan C, Wuhl E, Litwin M, Fahr K, Trelewicz J, Jobs K, Schenk JP, Grenda R, Mehls O, Troger J, Schaefer F: Normative values for intima-media thickness and distensibility of large arteries in healthy adolescents. J Hypertens 2005, 23: 1707–1715. 10.1097/01.hjh.0000178834.26353.d5View ArticlePubMedGoogle Scholar
  11. Litwin M, Wuhl E, Jourdan C, Trelewicz J, Niemirska A, Fahr K, Jobs K, Grenda R, Wawer ZT, Rajszys P, Troger J, Mehls O, Schaefer F: Altered morphologic properties of large arteries in children with chronic renal failure and after renal transplantation. J Am Soc Nephrol 2005, 16: 1494–1500. 10.1681/ASN.2004110932View ArticlePubMedGoogle Scholar
  12. Maritim AC, Sanders RA, Watkins JB: Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol 2003, 17: 24–38. 10.1002/jbt.10058View ArticlePubMedGoogle Scholar
  13. Guillermo Z, Fortuño A, Díez J: Oxidative stress and atherosclerosis in early chronic kidney disease. Nephrol Dial Transplant 2006, 21: 2686–2690. 10.1093/ndt/gfl398View ArticleGoogle Scholar
  14. Wolff SP: Diabetes mellitus and free radicals. Free radicals, transition metals and oxidative stress in the etiology of diabetes mellitus and complications. Br Med Bull 1993, 49: 642–652.PubMedGoogle Scholar
  15. Brownlee M: Biochemistry and molecular cell biology of diabetic complications. Nature 2001, 414: 813–820. 10.1038/414813aView ArticlePubMedGoogle Scholar
  16. Wieruszwysocka B, Wysocki H, Byks H, Zozulinska D, Wykretowicz A, Kazierczak M: Metabolic control quality and free radical activity in diabetic patients. Diabetes Res Clin Pract 1995, 27: 193–197. 10.1016/0168-8227(95)01043-DView ArticleGoogle Scholar
  17. Heistad Donald D: Oxidative Stress and VascularDisease. Arterioscler Thromb Vasc Biol 2005, 26: 689–695.View ArticleGoogle Scholar
  18. Liu Shang X, Hou Fan F, Guo Zhi J, Nagai R, Zhang Wei R, Liu Zhi Q, Zhou Zhan M, Zhou M, Di X, Wang Guo B, Zhang X: Advanced oxidation protein products accelerate atherosclerosis through promoting oxidative stress and inflammation. Arterioscler Thromb Vasc Biol 2006, 26: 1156–1162. 10.1161/01.ATV.0000214960.85469.68View ArticlePubMedGoogle Scholar
  19. Giacco F, Brownlee M: Oxidative stress and diabetic complications. Circ Res 2010, 107: 1058–1070. 10.1161/CIRCRESAHA.110.223545PubMed CentralView ArticlePubMedGoogle Scholar
  20. Joshi MS, Ponthier JL, Lancaster JR: Cellular antioxidant and pro-oxidant actions of nitric oxide. Free Radic Biol Med 1999, 27: 1357–1366. 10.1016/S0891-5849(99)00179-3View ArticlePubMedGoogle Scholar
  21. Vallence P: Vascular nitric oxide in health and disease. In Nitric Oxide Biology andPathobiology. Edited by: Ignarro L. San Diego, CA: Academic; 2000:921–930.View ArticleGoogle Scholar
  22. Yamagishi S, Matsui T: Nitric oxide, a janus-faced therapeutic target for diabetic microangiopathy-Friend or foe? Pharmacol Res 2011,64(3):187–194. 10.1016/j.phrs.2011.05.009View ArticlePubMedGoogle Scholar
  23. Celik S, Akkaya H: Total antioxidant capacity, catalase and superoxide dismutase on rats before and after diabetes. J Anim Vet Adv 2009, 8: 1503–1508.Google Scholar
  24. Opara EC, Abdel-Rahman E, Soliman S, Kamel WA, Souka S, Lowe JE, Abdel-Aleem S: Depletion of total antioxidant capacity in type 2 diabetes. Metabolism 1999, 48: 1414–1417. 10.1016/S0026-0495(99)90152-XView ArticlePubMedGoogle Scholar
  25. Rewers M, Pihoker C, Donaghue K, Hanas R, Swift P, Klingensmith GJ: International Society for Pediatric and Adolescent Diabetes (ISBAD) Assessment and monitoring of glycemic control in children and adolescents with diabetes. Pediatr Diabetes 2007, 8: 408–418. 10.1111/j.1399-5448.2007.00352.xView ArticlePubMedGoogle Scholar
  26. Mogensen CE, Keane WF, Bennett PH, Jerums G, Parving HH, Passa P, Steffes MW, Striker GE, Viberti GC: Prevention of diabetic renal disease with special reference to microalbuminuria. Lancet 1995, 346: 1080–1084. 10.1016/S0140-6736(95)91747-0View ArticlePubMedGoogle Scholar
  27. Warnick GR, Wood PD: National Cholesterol Education Program recommendations for measurement of high-density lipoprotein cholesterol: executive summary. The National Cholesterol Education Program Working Group on Lipoprotein Measurement. Clin Chem 1995, 41: 1427–1433.PubMedGoogle Scholar
  28. Koracevic D, Koracevic G, Djordjevic V, Andrejevic S, Cosic V: Method for the measurement of antioxidant activity in human fluids. J Clin Pathol 2001, 54: 356–361. 10.1136/jcp.54.5.356PubMed CentralView ArticlePubMedGoogle Scholar
  29. Miles AM, Wink DA, Cook JC, Grisham MB: Determination of nitric oxide using fluorescence spectroscopy. Methods Enzymol 1996, 268: 105–120.View ArticlePubMedGoogle Scholar
  30. Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R: Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging. Circulation 1986, 74: 1399–1406. 10.1161/01.CIR.74.6.1399View ArticlePubMedGoogle Scholar
  31. Abou-Seif MA, Youssef AA: Evaluation of some biochemical changes in diabetic patients. Clin Chim Acta 2004, 346: 161–170. 10.1016/j.cccn.2004.03.030View ArticlePubMedGoogle Scholar
  32. Astaneie F, Afshari M, Mojtahedi A, Mostafalou S, Zamani MJ, Larijani B, Abdollahi M: Total antioxidant capacity and levels of epidermal growth factor and nitric oxide in blood and saliva of insulin-dependent diabetic patients. Arch Med Res 2005,36(4):376–381. 10.1016/j.arcmed.2005.03.007View ArticlePubMedGoogle Scholar
  33. Di Nardo W, Pitocco D, Di Leo MA, Picciotti PM, Di Stasio E, Collina C, Santini S, Scarano E, Ghirlanda G: Modifications in nasal function and nitric oxide serum level in type 1 diabetes. J Otolaryngol Head Neck Surg 2008, 37: 611–615.PubMedGoogle Scholar
  34. Pitocco D, Zaccardi F, Di Stasio E, Romitelli F, Martini F, Scaglione GL, Speranza D, Santini S, Zuppi C, Ghirlanda G: Role of asymmetric-dimethyl-L-arginine (ADMA) and nitrite/nitrate (NOx) in the pathogenesis of oxidative stress in female subjects with uncomplicated type 1 diabetes mellitus. Diabetes Res Clin Pract 2009, 86: 173–176. 10.1016/j.diabres.2009.09.019View ArticlePubMedGoogle Scholar
  35. Horoz OO, Yuksel B, Bayazit AK, Attila G, Sertdemir Y, Mungan NO, Topaloglu AK, Ozer G: Ambulatory blood pressure monitoring and serum nitric oxide concentration in type 1 diabetic children. Endocr J 2009, 56: 477–485. 10.1507/endocrj.K08E-338View ArticlePubMedGoogle Scholar
  36. Chiarelli F, Cipollone F, Romano F, Tumini S, Costantini F, di Ricco L, Pomilio M, Pierdomenico SD, Marini M, Cuccurullo F, Mezzetti A: Increased circulating nitric oxide in young patients with type 1 diabetes and persistent microalbuminuria: relation to glomerular hyperfiltration. Diabetes 2000, 49: 1258–1263. 10.2337/diabetes.49.7.1258View ArticlePubMedGoogle Scholar
  37. Prabhakar SS: Role of nitric oxide in diabetic nephropathy. Semin Nephrol 2004, 24: 333–344. 10.1016/j.semnephrol.2004.04.005View ArticlePubMedGoogle Scholar
  38. Iwanicka Z, Lewandowicz-Uszy.ska A, G.ab E, Kotschy B: Relationship between nitrogen oxide and the degree of metabolic control of diabetes mellitus type 1 in children and adolescents. Wiad Lek 2006, 59: 27–31.PubMedGoogle Scholar
  39. Telci A, Cakatay U, Salman S, Satman I, Sivas A: Oxidative protein damage in early stage Type 1 diabetic patients. Diabetes Res Clin Pract 2000, 50: 213–223.View ArticlePubMedGoogle Scholar
  40. Marra G, Cotroneo P, Pitocco D, Manto A, Di Leo MA, Ruotolo V, Caputo S, Giardina B, Ghirlanda G, Santini SA: Early increase of oxidative stress and reduced antioxidant defenses in patients with uncomplicated type 1 diabetes: a case for gender difference. Diabetes Care 2002, 25: 370–375. 10.2337/diacare.25.2.370View ArticlePubMedGoogle Scholar
  41. Varvarovska J, Racek J, Stozicky F, Soucek J, Trefil L, Pomahacova R: Parameters of oxidative stress in children with type 1 diabetes mellitus and their relatives. J Diab Complicat 2003, 17: 7–10. 10.1016/S1056-8727(01)00228-8View ArticleGoogle Scholar
  42. Suys B, de Beeck LO, Rooman R, Kransfeld S, Heuten H, Goovaerts I, Vrints C, de Wolf D, Matthys D, Manuel-y-Keenoy B: Impact of oxidative stress on the endothelial dysfunction of children and adolescents with type 1 diabetes mellitus: protection by superoxide dismutase? Pediatr Res 2007, 62: 456–461. 10.1203/PDR.0b013e318142581aView ArticlePubMedGoogle Scholar
  43. El-desoky MA, Amin AE, El-refai MO, Farid RJ, Labib AA: Evaluation of Some Biochemical Changes in Diabetic Patients. The Egyptian Journal of Hospital Medicine 2013, 50: 150–155.View ArticleGoogle Scholar
  44. Margeirsdottir HD, Stensaeth KH, Larsen JR, Brunborg C, Dahl-Jorgensen K: Early signs of atherosclerosis in diabetic children on intensive insulin treatment: a population-basedstudy. Diabetes Care 2010, 33: 2043–2048. 10.2337/dc10-0505PubMed CentralView ArticlePubMedGoogle Scholar
  45. Jarvisalo MJ, Raitakari M, Toikka JO, Putto-Laurila A, Rontu R, Laine S, Lehtimaki T, Ronnemaa T, Viikari J, Raitakari OT: Endothelial dysfunction and increased arterial intima media thickness in children with type 1 diabetes. Circulation 2004, 109: 1750–1755. 10.1161/01.CIR.0000124725.46165.2CView ArticlePubMedGoogle Scholar
  46. Abdelghaffar S, El Amir M, El Hadidi A, El Mougi F: Carotid intima-media thickness: an index for subclinical atherosclerosis in type 1 diabetes. J Trop Pediatr 2006, 52: 39–45. 10.1093/tropej/fmi071View ArticlePubMedGoogle Scholar
  47. Gul K, Ustun I, Aydin Y, Berker D, Erol K, Unal M, Barazi AO, Deliba.i T, Guler S: Carotid intima-media thickness and its relations with the complications in patients with type 1 diabetes mellitus. Anadolu Kardiyol Derg 2010, 10: 52–58.View ArticlePubMedGoogle Scholar
  48. Nathan DM, Lachin J, Cleary P, Orchard T, Brillon DJ, Backlund JY, O’Leary DH, Genuth S, Diabetes Control and Complications Trial; Epidemiology of Diabetes Interventions and Complications Research Group: Intensive diabetes therapy and carotid intima-mediathickness in type 1 diabetes mellitus. N Engl J Med 2003, 348: 2294–2303.View ArticlePubMedGoogle Scholar
  49. Jarvisalo MJ, Putto-Laurila A, Jartti L, Lehtimaki T, Solakivi T, Ronnemaa T, Raitakari OT: Carotid Artery Intima-Media Thickness in Children with Type 1 Diabetes. Diabetes 2002, 51: 493–498. 10.2337/diabetes.51.2.493View ArticlePubMedGoogle Scholar
  50. Dalla Pozza R, Bechtold S, Bonfig W, Putzker S, Kozlik-Feldmann R, Netz H, Schwarz HP: Age of onset of type 1 diabetes in children and carotid intima medial thickness. J Clin Endocrinol Metab 2007, 92: 2053–2057. 10.1210/jc.2006-2868View ArticlePubMedGoogle Scholar
  51. Dursun B, Dursun E, Suleymanlar G, Ozben B, Capraz I, Apaydin A, Ozben T: The effect of hemodialysis on accelerated atherosclerosis in diabetic patients: correlation of carotidartery intima-media thickness with oxidative stress. J Diabetes Complications 2009, 23: 257–264. 10.1016/j.jdiacomp.2007.12.007View ArticlePubMedGoogle Scholar
  52. Zineh I, Beitelshees AL, Haller MJ: NOS3 polymorphisms are associated with arterial stiffness in children with type 1 diabetes. Diabetes Care 2007, 30: 689–693. 10.2337/dc06-1697View ArticlePubMedGoogle Scholar
  53. Muniyappa R, Quon MJ: Insulin action and insulin resistance in vascular endothelium. Curr Opin Clin Nutr Metab Care 2007,10(4):523–530. 10.1097/MCO.0b013e32819f8ecdView ArticlePubMedGoogle Scholar
  54. Faienza MF, Acquafredda A, Tesse R, Luce V, Ventura A, Maggialetti N, Monteduro M, Giordano P, Cavallo L: Risk factors for subclinical atherosclerosis in diabetic and obese children. Int J Med Sci 2013,10(3):338–343. 10.7150/ijms.5181PubMed CentralView ArticlePubMedGoogle Scholar
  55. Nojiri S, Daida H, Mokuno H, Iwama Y, Mae K, Ushio F, Ueki T: Association of serum antioxidant capacity with coronary artery disease in middle-aged men. Jpn Heart J 2001, 42: 677–690. 10.1536/jhj.42.677View ArticlePubMedGoogle Scholar
  56. Demirbag R, Yilmaz R, Kocyigit A: Relationship between DNA damage, total antioxidant capacity and coronary artery disease. Mutat Res 2005, 570: 197–203. 10.1016/j.mrfmmm.2004.11.003View ArticlePubMedGoogle Scholar

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© El Samahy et al.; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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