Aims/hypothesis To investigate exercise-related fuel metabolism in intermittent high-intensity (IHE) and continuous moderate intensity (CONT) exercise in individuals with type 1 diabetes mellitus. Methods In a prospective randomised open-label cross-over trial twelve male individuals with well-controlled type 1 diabetes underwent a 90 min iso-energetic cycling session at 50% maximal oxygen consumption (V ⋅ O 2max ), with (IHE) or without (CONT) interspersed 10 s sprints every 10 min without insulin adaptation. Euglycaemia was maintained using oral 13 C-labelled glucose. 13C Magnetic resonance spectroscopy (MRS) served to quantify hepatocellular and intramyocellular glycogen. Measurements of glucose kinetics (stable isotopes), hormones and metabolites complemented the investigation. Results Glucose and insulin levels were comparable between interventions. Exogenous glucose requirements during the last 30 min of exercise were significantly lower in IHE (p = 0.02). Hepatic glucose output did not differ significantly between interventions, but glucose disposal was significantly lower in IHE (p < 0.05). There was no significant difference in glycogen consumption. Growth hormone, catecholamine and lactate levels were significantly higher in IHE (p < 0.05). Conclusions/interpretation IHE in individuals with type 1 diabetes without insulin adaptation reduced exogenous glucose requirements compared with CONT. The difference was not related to increased hepatic glucose output, nor to enhanced muscle glycogen utilisation, but to decreased glucose uptake. The lower glucose disposal in IHE implies a shift towards consumption of alternative substrates. These findings indicate a high flexibility of exercise-related fuel metabolism in type 1 diabetes, and point towards a novel and potentially beneficial role of IHE in these individuals.

No abstract

Fructose metabolism is generally held to occur essentially in cells of the small bowel, the liver, and the kidneys expressing fructolytic enzymes (fructokinase, aldolase B and a triokinase). In these cells, fructose uptake and fructolysis are unregulated processes, resulting in the generation of intracellular triose phosphates proportionate to fructose intake. Triose phosphates are then processed into lactate, glucose and fatty acids to serve as metabolic substrates in other cells of the body. With small oral loads, fructose is mainly metabolized in the small bowel, while with larger loads fructose reaches the portal circulation and is largely extracted by the liver. A small portion, however, escapes liver extraction and is metabolized either in the kidneys or in other tissues through yet unspecified pathways. In sedentary subjects, consumption of a fructose‐rich diet for several days stimulates hepatic de novo lipogenesis, increases intrahepatic fat and blood triglyceride concentrations, and impairs insulin effects on hepatic glucose production. All these effects can be prevented when high fructose intake is associated with increased levels of physical activity. There is also evidence that, during exercise, fructose carbons are efficiently transferred to skeletal muscle as glucose and lactate to be used for energy production. Glucose and lactate formed from fructose can also contribute to the re‐synthesis of muscle glycogen after exercise. We therefore propose that the deleterious health effects of fructose are tightly related to an imbalance between fructose energy intake on one hand, and whole‐body energy output related to a low physical activity on the other hand.

Substantial amounts of fructose are present in our diet. Unlike glucose, this hexose cannot be metabolized by most cells and has first to be converted into glucose, lactate or fatty acids by enterocytes, hepatocytes and kidney proximal tubule cells, which all express specific fructose-metabolizing enzymes. This particular metabolism may then be detrimental in resting, sedentary subjects; however, this may also present some advantages for athletes. First, since fructose and glucose are absorbed through distinct, saturable gut transporters, co-ingestion of glucose and fructose may increase total carbohydrate absorption and oxidation. Second, fructose is largely metabolized into glucose and lactate, resulting in a net local lactate release from splanchnic organs (mostly the liver). This 'reverse Cori cycle' may be advantageous by providing lactate as an additional energy substrate to the working muscle. Following exercise, co-ingestion of glucose and fructose mutually enhance their own absorption and storage.

There is increasing concern that sugar consumption may be linked to the development of metabolic and cardiovascular diseases. There is indeed strong evidence that consumption of energy-dense sugary beverages and foods is associated with increased energy intake and body weight gain over time. It is further proposed that the fructose component of sugars may exert specific deleterious effects due to its propension to stimulate hepatic glucose production and de novo lipogenesis. Excess fructose and energy intake may be associated with visceral obesity, intrahepatic fat accumulation, and high fasting and postprandial blood triglyceride concentrations. Additional effects of fructose on blood uric acid and sympathetic nervous system activity have also been reported, but their link with metabolic and cardiovascular diseases remains hypothetical. There is growing evidence that fructose at physiologically consumed doses may exert important effects on kidney function. Whether this is related to the development of high blood pressure and cardiovascular diseases remains to be further assessed.