**7. Conclusion**

ported evidence of endothelial dysfunction in patients with type 1 diabetes. In another study of 45 type 1 diabetic children, there was significantly lower peak brachial artery flowmediated dilation response and increased carotid artery intima-media thickness. This sug‐ gests that altered endothelium function in children with type 1 diabetes may predispose them to the development of early atherosclerosis (Jarvisalo et al., 2004). Furthermore, in a double-blind, placebo-controlled, randomized study of 41 young subjects with type I diabe‐ tes mellitus, vitamin E supplementation (1,000 IU for three months) had a positive effect on the endothelial function as evident by improved endothelial vasodilator function in both the

In addition to lipids and proteins, reactive oxygen species reacts with deoxyribonucleic acid resulting in various products, such as 8-hydroxydeoxyguanosine, that is excrete in urine ow‐ ing to deoxyribonucleic acid repair processes. Urinary 8-hydroxydeoxyguanosine has been proposed as an indicator of oxidative damage to deoxyribonucleic acid. Goodarzi and col‐ leagues (2010) evaluated the relationship between oxidative damage to deoxyribonucleic acid and protein glycation in 32 patients with type 1 diabetes. There were elevated levels of urinary 8-hydroxydeoxyguanosine, glycated hemoglobin, plasma malondialdehyde, and glycated serum protein in 32 patients with type 1 diabetes. There was a significant correla‐ tion between urinary 8-hydroxydeoxyguanosine and glycated hemoglobin. The findings in‐ dicate that that deoxyribonucleic acid is associated to glycemic control level (Goodarzi et al., 2010). In a study which investigated whether advanced glycation end product production and oxidative stress are augmented in young patients with type 1 diabetes at early clinical stages of the disease, advanced glycation end products, pentosidine, and 8-hydroxydeoxy‐ guanosine and acrolein-lysine were significantly higher in the patients with type 1 diabetes

Oxidative stress has been implicated in the major complications of diabetes mellitus, includ‐ ing retinopathy, nephropathy, neuropathy and accelerated coronary artery disease (Ceriello & Morocutti, 2000; Androne et al., 2000; Mackness et al., 2002). There is a clinical need for markers of oxidative stress which could potentially identify diabetic patients at increased risk for these complications. The introduction of breath microassays has enhanced the detec‐ tion of oxidative stress because reactive oxygen species oxidize polyunsaturated fatty acids in membranes to alkanes such as ethane and pentane. These are excreted in the breath as volatile organic compounds (Kneepkens & Lepage, 1994). Another marker of oxidative stress is the breath methylated alkane contour, comprising a three-dimensional display of C4 to C20 alkanes and monomethylated alkanes in the breath (Phillips et al., 2004). Phillips et al. (2004) reported significantly increased volatile organic compounds and breath methy‐ lated alkane contour in the breath of type 1 diabetic patients which was independent of gly‐ cemic as they did with blood glucose concentration or with glycation hemoglobin levels.

conduit and resistance vessels (Skyrme-Jones, 2000).

236 Type 1 Diabetes

compared with healthy control subjects (Tsukahara et al., 2003).

**6.3. Biomarkers of oxidative stress present in breath**

This review presented convincing experimental and clinical evidence that the aetiology of oxidative stress in diabetes mellitus arises from a number of mechanisms that includes ex‐ cessive reactive oxygen species production from the peroxidation of lipids, auto-oxidation of glucose, glycation of proteins, and glycation of antioxidative enzymes, which limit their ca‐ pacity to detoxify oxygen radicals. There is also evidence that supports the role of hypergly‐ cemia in producing oxidative stress and, eventually, severe endothelial dysfunction in blood vessels of individuals with type 1 diabetes mellitus. The induction of oxidative stress is a key process in the onset and development of diabetic complications, but the precise mecha‐ nisms has not been fully elucidated. A number of biomarkers of oxidative stress have been studied in type 1 diabetic patients such as malondialdehyde, F2-isoprostanes, advanced gly‐ cation end product and nitrotyrosine. The introduction of breath microassays has enhanced the detection of oxidative stress.

Type 1 diabetic patients have been found to have decreased amounts and efficiency of anti‐ oxidant defenses (both enzymatic and non-enzymatic) due to increased consumption of dis‐ tinct antioxidant components (e.g. intracellular glutathione) or to primarily low levels of antioxidant substances (flavonoids, carotenoids, vitamin E and C). This review also presents small clinical studies that have demonstrated improvements in a variety of oxidative stress biomarkers in type 1 diabetic patients who have received vitamin A, C or E supplements. However, the findings of key prospective randomized controlled antioxidant clinical trials have failed to demonstrate a significant benefit, in the prevention of cardiovascular events. There is a need for continued investigation of the association between reactive oxygen spe‐ cies, type 1 diabetes mellitus and its complications in order to clarify the molecular mecha‐ nisms by which increased oxidative stress accelerates the development of diabetic complications. This will have implication for the prevention and development of therapeutic choices for type 1 diabetic patients.
