T of diabetic kidney lesions which can be ameliorated with antioxidant treatment. In a rodent model of type 2 diabetes and kidney disease, vitamin E given as an antioxidant therapy, restored antioxidant enzyme activity and reduced oxidative damage of renal tissue [6]. This has led to suggestions that strategies to enhance endogenous antioxidant mechanisms could help prevent microvascular diabetic complications [7]. Markers of oxidative stress are increased in the circulation and renal tissue of patients with diabetes compared with control patients without diabetes [8, 9]. Patients of African origin have been found to have higher circulating levels of lipid peroxide, lower concentrations of vitamin E and faster rates of decline in renal function compared with those of Caucasian heritage [10, 11]. Relatively low levels of serum selenium have been reported in people of Asian origin [12]. Selenium is a co-factor for the antioxidant enzyme GPx, and low levels are associated with an upregulation of inflammatory chemokines. Selenium supplementation attenuates the inflammatory response and in systemic inflammatory disease states may improve clinical outcomes [13, 14]. The activity of GPx in plasma is largely derived from renal tubular epithelium and is reduced in the presence of renal disease [15, 16]. It is unclear whether the level of activity of GPx contributes to the susceptibility to progressive renal disease. In this study, we will comparethe effect over time of antioxidant therapy with vitamin E and/or selenium in patients with type PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28854080 2 diabetes and early CKD, on measures of systemic inflammation, antioxidant enzyme activity and changes in eGFR.Subjects We plan to recruit a total of 200 adult patients with type 2 diabetes of white, Caucasian and non-Caucasian (African, Caribbean or Indo-Asian) heritage from general practices in South West London, UK. An equal number of eligible patients will be randomized to receive, either, active selenium (200 g once daily) or its placebo and/ or vitamin E (400 IU once daily) or its placebo in a 2 ?2 factorial design (Fig. 1). Treatment allocation will be according to a computer generated code for each group to which the patients and researchers will be blinded. Type 2 diabetes mellitus will be diagnosed according to WHO criteria. Eligible patients will have hypertension (3 consecutive sitting blood pressure readings >140 systolic and/or diastolic 90 mmHg without treatment or receiving treatment for known hypertension) and early CKD PD173074MedChemExpress PD173074 defined as an eGFR > 45 and <90 mL/min/1.73 m2 and/or urinary albumin:creatinine ratio >3 mg/mmol. Patients will be excluded if they have any of the following: a history of cardiovascular disease, defined as having a clinical record of ischaemic heart disease (angina, myocardial infarction, coronary artery revascularization and or heart failure), peripheral vascular disease (intermittent claudication or peripheral artery revascularization) or cerebrovascular disease (transient ischaemic episodes or stroke), a history of malignancy or any other life threatening illness, current pregnancy, systolic blood pressure >200 mmHg, diastolic blood pressure >160 mmHg, haemoglobin A1c > 86 mmol/mol (10 ), significant renal impairment (eGFR < 45 mL/min 1.73 m2) and nephrotic range urine protein excretion (total protein excretion rate >3 g/day or albumin:creatinine ratio >300 mg/ mmol). The medical, family, social and treatment histories, and the clinical and biochemical measuremen.
