Ts collected at the in-person visits will be recorded using a standardized, electronic proforma. Dietary intake and patterns will be evaluated using a 3-day food diary to assess components of the usual diet (Dietplan 6, Forestfield Software Ltd, Horsham, West Sussex, UK). Methods Anthropometric measures will include height in metres, weight in kilogrammes, and waist circumference in centimetres. Body mass index will be calculated from the weight in kilogrammes divided by the height in metres squared. Sitting blood pressure will be measured by digital oscillometry (Omron 705IT, OMRON HealthcareEarle et al. J Transl Med (2016) 14:Page 3 ofDiabetes Registers of General Practices in South West London, UKelectrocardiography (Seca CardioConcept 5.6, Seca UK) performed and read using Novacode criteria [18].Arterial stiffnessPatients with Type 2 Diabetes with an increased risk of progressive CKDEligible patients from different heritage groups screened and consentedFinger plethysmography is a non-invasive method to assess changes in finger blood flow that will be used as a proxy measure of arterial stiffness. The pulse wave amplitude will be measured from the finger-tip using infra-red light (PulseTrace PCA2, CareFusion UK 232 Ltd, Basingstoke). The contour of the finger pulse will then PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28893839 be automatically analysed to determine a stiffness index which has been shown to be correlate with pulse wave velocity after adjustment age, sex, height, and weight [19].Biochemical assessmentsWhite CaucasianAfrican and Indo-AsianEligible patients from each heritage group randomized to one of 4 possible interventions for 24 monthsPlacebo vitamin E Placebo TAPI-2MedChemExpress TAPI-2 selenium Placebo vitamin E Active seleniumActive vitamin E Active selenium Placebo selenium Active vitamin EFig. 1 Flow diagram of the recruitment, randomization and followup of eligible patients double-blind, randomized placebo controlled trial into the 2 ?2 factorial, to achieve balanced representation of non-Caucasian and Caucasian heritage groupsEurope, The Netherlands) according to the National Institutes of Synergisidin structure Health and Care Excellence guidance (http:// www.nice.org.uk/guidance/cg127). Patients will undergo routine clinical assessments for the complications of diabetes. The presence or absence of retinopathy will be reviewed on an annual basis by standardized, digital retinal fundal photography which will be reported according to National Health Service guidelines by retinal screeners who are unaware of the patient’s participation in the study (http://www.diabeticeye.screening.nhs.uk/gradingcriteria). Peripheral neuropathy will be assessed according to responses to testing with a 10 g monofilament. Peripheral vascular disease will be assessed by the appreciation of the dorsalis pedis and posterior tibial artery pulsation by digital examination. Patients will also be screened for ischaemic heart disease in response to modified questions from the Rose questionnaire [17] and have 12-lead restingVenous blood will be sampled after a 12 h fast. Measurements will be performed to allow several domains of the study to be addressed, including lipids, systemic inflammation, oxidative damage and stress, diabetes control and nutrition. Deoxyribonucleic acid (DNA) will be extracted from whole blood using a salting-out method as described by Miller et al. [20] for the subsequent analysis of genetic polymorphisms of the antioxidant enzymes being investigated. Plasma creatinine will be used to estimate renal function–usin.Ts collected at the in-person visits will be recorded using a standardized, electronic proforma. Dietary intake and patterns will be evaluated using a 3-day food diary to assess components of the usual diet (Dietplan 6, Forestfield Software Ltd, Horsham, West Sussex, UK). Methods Anthropometric measures will include height in metres, weight in kilogrammes, and waist circumference in centimetres. Body mass index will be calculated from the weight in kilogrammes divided by the height in metres squared. Sitting blood pressure will be measured by digital oscillometry (Omron 705IT, OMRON HealthcareEarle et al. J Transl Med (2016) 14:Page 3 ofDiabetes Registers of General Practices in South West London, UKelectrocardiography (Seca CardioConcept 5.6, Seca UK) performed and read using Novacode criteria [18].Arterial stiffnessPatients with Type 2 Diabetes with an increased risk of progressive CKDEligible patients from different heritage groups screened and consentedFinger plethysmography is a non-invasive method to assess changes in finger blood flow that will be used as a proxy measure of arterial stiffness. The pulse wave amplitude will be measured from the finger-tip using infra-red light (PulseTrace PCA2, CareFusion UK 232 Ltd, Basingstoke). The contour of the finger pulse will then PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28893839 be automatically analysed to determine a stiffness index which has been shown to be correlate with pulse wave velocity after adjustment age, sex, height, and weight [19].Biochemical assessmentsWhite CaucasianAfrican and Indo-AsianEligible patients from each heritage group randomized to one of 4 possible interventions for 24 monthsPlacebo vitamin E Placebo selenium Placebo vitamin E Active seleniumActive vitamin E Active selenium Placebo selenium Active vitamin EFig. 1 Flow diagram of the recruitment, randomization and followup of eligible patients double-blind, randomized placebo controlled trial into the 2 ?2 factorial, to achieve balanced representation of non-Caucasian and Caucasian heritage groupsEurope, The Netherlands) according to the National Institutes of Health and Care Excellence guidance (http:// www.nice.org.uk/guidance/cg127). Patients will undergo routine clinical assessments for the complications of diabetes. The presence or absence of retinopathy will be reviewed on an annual basis by standardized, digital retinal fundal photography which will be reported according to National Health Service guidelines by retinal screeners who are unaware of the patient’s participation in the study (http://www.diabeticeye.screening.nhs.uk/gradingcriteria). Peripheral neuropathy will be assessed according to responses to testing with a 10 g monofilament. Peripheral vascular disease will be assessed by the appreciation of the dorsalis pedis and posterior tibial artery pulsation by digital examination. Patients will also be screened for ischaemic heart disease in response to modified questions from the Rose questionnaire [17] and have 12-lead restingVenous blood will be sampled after a 12 h fast. Measurements will be performed to allow several domains of the study to be addressed, including lipids, systemic inflammation, oxidative damage and stress, diabetes control and nutrition. Deoxyribonucleic acid (DNA) will be extracted from whole blood using a salting-out method as described by Miller et al. [20] for the subsequent analysis of genetic polymorphisms of the antioxidant enzymes being investigated. Plasma creatinine will be used to estimate renal function–usin.