Physical activity provides many health benefits to individuals with type 1 diabetes mellitus (T1DM), but poses high demands with regard to blood glucose control [1, 2, 3]. Adaptation of insulin therapy and/or ingestion of carbohydrates (CHO) are generally recommended to avoid exercise-related hypoglycemia. However, there is a paucity of data on the impact of different CHO types on exercise-associated blood glucose and fuel metabolism in T1DM. The purpose of the present study was to evaluate the metabolic effects of combined glucose-fructose and glucose-alone ingestion in exercising individuals with T1DM without pre-exercise insulin reduction.For this prospective, cross-over study evaluating metabolic response following two different ingestions of carbohydrate solutions (GLU, GLU-FRU) during a prolonged exercise 11 male complication-free individuals with T1DM (26±4y, BMI: 25.3±3.8 kg/m², mean HbA1c 7.0±0.6%, diabetes duration>5years) were recruited. A screening visit (assessment of anthropometrics, basic metabolic rate, and body composition) was performed prior to the trials, whereas for the exercise an incremental cardiopulmonary exercise test and a familiarization to the planned exercise intervention were carried out. All subjects followed a 2-day standardization protocol prior to the ¹³C-MRS glycogen examinations in liver and the right quadriceps muscle. Standardization involved a diet with a predefined daily carbohydrate intake (50% of daily energy requirements according to a metabolic assessment using indirect calorimetry, withdrawal from exercise, and avoidance of alcohol and caffeine). Patients injected their usual insulin dose and had a standardized breakfast before 7 am on the four separated test days involving two baseline glycogen measurements, an exercise intervention (following ingestion of either a GLU or GLU-FRU mixture) with hepatic and myocellular glycogen measurements afterwards. The isoenergetic exercise intervention consisted of a 90 min cycling session at 50% VO₂ max. Stable euglycemia was maintained using either oral glucose (100g glucose/L, 0.5% U-¹³C₆-glucose labelled) or glucose-fructose (100g glucose/L and 100g fructose/L, 0.5% U-¹³C₆-fructose labelled) solution following a pre-specified algorithm. MR localizer images and ¹H decoupled natural abundance ¹³C spectra (see Fig. 1) were recorded on a standard clinical 3.0 Tesla MR scanner (TRIO, Siemens Erlangen, Germany) using a transmit-receive ¹H/¹³C flexible surface coil (RAPID Biomedical GmbH, Rimpar, Germany). The metabolic assessment included a dual stable isotope approach (intravenous 6,6-²H₂-glucose, oral ¹³C-glucose/fructose) and measurements of whole body substrate oxidation using indirect calorimetry.Regarding the comparison between the two different ingestion schemes (GLU vs. GLU-FRU), mean±SEM of the total amount of required CHO immediately before and during exercise to maintain glycemia was comparable (34±4g vs. 31±3g; p=0.49). Mean±SEM levels of blood glucose (GLU: 7.7±0.3mM vs. GLU-FRU: 7.9±0.3mM; p=0.6) and insulin (GLU: 20.7±0.2mU/l vs. GLU-FRU: 20.5±0.2mU/l; p=1.00) were comparable between both interventions. Lactate concentrations were significantly higher during GLU-FRU (GLU: 2.1±0.2mM vs. GLU-FRU: 2.5±0.2mM, p=0.02). Counterregulatory hormones (adrenaline, noradrenaline, growth hormones, cortisol, and glucagon) did not differ between interventions. Rates of glucose appearance (Ra) and disappearance (Rd) were comparable (Ra 7.7±0.4 mg/kg*min and 7.5±0.5 mg/kg*min, p=0.7; Rd 8.3±0.4 mg/kg*min and 8.4±0.2 mg/kg*min, p=0.9 for GLU and GLU-FRU). In GLU-FRU the mean fructose ingestion rate was 2.1 mg/kg*min and the mean gluconeogenesis from fructose was 1.3 mg/kg*min. With regard to substrate oxidation fat oxidation was significantly higher (5.6±0.3mg/kg*min vs. 2.5±0.2mg/kg*min, p<0.001) and CHO oxidation was significantly lower (16.9±1.0mg/kg*min vs. 23.9±0.9mg/kg*min, p<0.001) in GLU-FRU compared to GLU. Mean change in hepatic glycogen content (see Fig. 2, 3) following GLU was -29%±8% compared to -19%±11% following GLU-FRU (p=0.76). Regarding myocellular glycogen consumption, GLU lead to a mean change in glycogen content of -42%±5%, whereas mean change following GLU-FRU was -42% ±4% (p=0.66). Combined tracer and indirect calorimetry data however suggest peripheral glycogen sparing in GLU-FRU giving the comparable rates of plasma glucose oxidation and significantly lower net carbohydrate oxidation.Mixed ingestion of a glucose-fructose solution in exercising volunteers with T1DM without prior insulin adaption appears to induce a shift towards increased fat oxidation and potential glycogen sparing effects when compared to glucose alone.