Acute effect of the renally excreted low-calorie sweetener, acesulfame potassium (Ace-K), on urinary glucose excretion in people with type 2 diabetes.

Following enrolment, each participant will be studied on 3 occasions, separated by at least 3 days, in a double-blinded, randomised, crossover design. On the evening preceding the study day (~1900h), participants will be given a standardised evening meal (McCain beef Lasagne 400g, 592 kcal with 66% carbohydrate, 17% protein and 17% fat). Following this meal, participants will be asked to fast from solids and liquids (other than water) until the following morning, when they will attend the CRF of the AHMS building at ~0800h. On each study day, participants will be instructed to defer any morning dose of prescribed medications until the end of the investigation, and an intravenous cannula will be placed into a vein of each forearm for IV dextrose infusion and blood sampling, respectively. A hyperglycaemic clamp will be maintained at 15 mmol/L from t = 0 to 210 min. This will be achieved by intravenous administration of an initial bolus of 25% dextrose (volume calculated to elevate blood glucose to 15 mmol/L from baseline as previously described), followed by a 25% dextrose infusion at a rate adjusted according to blood glucose concentrations measured every 5 min using a YSI analyser. Following an initial 30 min of stabilisation of the hyperglycaemic clamp, participants will be asked to empty their bladder at t = 30 min. Subsequently, participants will consume 400 mL water together with a gelatin capsule containing (i) 175 mg Ace-K, (ii) 58 mg sucralose (of equal sweetness to the dose of Ace-K) + 117 mg cellulose or (iii) 175 mg cellulose (placebo) at t = 30, 60, 90, 120, 150 and 180 min respectively, each within 5 min (the doses of Ace-K and sucralose are calculated based on ADI at 70 kg of body weight). Urine samples will be collected every 60 min between t = 30-210 min. The glucose levels in the urine will be measured immediately using a YSI analyser. “Arterialised” venous blood will be sampled every 30 min, kept warm with a heat pad, between t = 0 and 210 min for measurement of plasma insulin. Serum creatinine will be measured and used for calculating eGFR by the CKD-EPI formula. Renal artery blood flow will be measured using ultrasound at t = 30 and 210 min. After a final blood sample is collected, participants will be served a light lunch (a sandwich ordered from a Cafe within the building, approximately 350 kcal with 60% carbohydrate, 20% protein and 20% fat; a yoghurt, ~140 kcal with 60% carbohydrate, 30% protein and 10% fat) with water and once the blood concentration has stabilised above 5 mmol/L, they will be free to leave the laboratory.