Personalised antioxidant treatment for type 2 diabetes

This study will assess the effect of targeted and untargeted antioxidant treatments on glycaemic control in people with type 2 diabetes. Eighty individuals with type 2 diabetes will be enrolled in phase 1 of the study (antioxidant screening) to identify individuals with low vitamin C levels, low glutathione levels, and optimal levels of these two antioxidants. Once all 80 participants have been enrolled, blood collection for plasma vitamin C and erythrocyte glutathione measurement will be performed in all participants. Participants will then be allocated into three groups (n = 15 per group) based on their vitamin C and glutathione levels: 1) low vitamin C group (the 15 participants with the lowest vitamin C levels); 2) low glutathione group (the 15 participants with the lowest glutathione levels); 3) control antioxidant group (15 participants with vitamin C and glutathione levels in the top 50%). Participants who are identified as having low levels of both vitamin C and glutathione will be excluded and replaced by the participant with the next lowest antioxidant levels. If the number of participants with vitamin C and glutathione levels in the top 50% does not equal 15, the 15 participants with the highest composite score for these two antioxidants will be selected. Participants who do not fall into one of these three groups will be excluded from the remainder of the study. In phase 2 of the study (antioxidant treatment), participants in each of the three groups will consume tablets containing vitamin C (1000 mg/day) (arm 1) and N-acetylcysteine (1200 mg/day) (arm 2) for 90 days in a double-blind, randomised, crossover design with a 30-day washout period. N-acetylcysteine is converted to cysteine in the liver, which is used to produce glutathione. The order in which participants complete arms 1 and 2 will be randomised. Adherence to the intervention will be assessed using participant diaries and by oversupplying tablets and counting the tablets remaining at the end of the intervention. Glycaemic control (continuous glucose monitor; CGM and HbA1c), exercise capacity, vascular function, arterial stiffness, blood pressure, body composition (dual-energy x-ray absorptiometry), plasma vitamin C levels, erythrocyte glutathione levels, and oxidative stress (urine F2-isoprostanes) will be assessed before and after vitamin C and N-acetylcysteine supplementation over a 3-day testing period. On day 1, participants will provide a fasted blood and urine sample and have their blood pressure and body composition assessed. Participants will be fitted with a CGM and an activity monitor and will be provided with a standardised diet to consume over the 48-hour period of CGM recording. The standardised diet will include three main meals and two snacks per day. Continuous glucose data collected during the 24 hours commencing at midnight on day 2 will be used for subsequent analysis. On day 3, endothelium-dependent and -independent vascular function will be measured using brachial flow-mediated dilation and sub-lingual glyceryl trinitrate techniques. Arterial stiffness will be assessed non-invasively as carotid-femoral pulse wave velocity via applanation tonometry. Exercise capacity will be assessed determined during a graded exercise test on a stationary bike using open-circuit spirometry with concurrent electrocardiography and blood pressure measurements.