Response of interleukin-6 during euglycaemic and hyperglycaemic exercise in patients with type 1 diabetes mellitus
Stefan Jenni1,2, Stephan Wueest3,4, Daniel Konrad3,4 & Christoph Stettler1
Background: Secretion of IL-6 during exercise is hypothesised to be regulated according to substrate availability within the working muscle. We have previously shown that energy supply in type 1 diabetes during aerobic exercise in hyperglycaemia strongly relies on carbohydrate oxidation whereas a physiological shift from carbohydrate to lipid oxidation occurs in euglycaemia. The present study investigated whether IL-6 response to exercise is different in euglycaemia compared with hyperglycaemia in patients with type 1 diabetes mellitus.
Methods: Seven male patients with type 1 diabetes were examined at two occasions in a randomized, single-blinded cross-over design. Glucose was clamped to eu- or hyperglycaemia (5 vs 11 mmol/l) with identical insulin levels. After clamp conditions were achieved the patients cycled at 5560% of their individual peak oxygen uptake over 120 min. The study was approved by the local ethics committee.
Results: Mean age±S.E.M. was 33.5±2.4 years and HbA1c was 6.7±0.2%. Before exercise levels of IL-6 were similar in euglycaemia and hyperglycaemia (2.1 pg/ml, 95% confidence interval 0.95.1, and 3.4 pg/ml, 95%CI 1.210.0, respectively). Over the entire study period levels of IL-6 significantly increased in euglycaemia (P for trend 0.014) but not in hyperglycaemia. After 2 h of euglycaemic exercise IL-6 increased by 2.0±1.3 pg/ml (mean±S.E.M.) but decreased by 2.6±1.6 pg/ml in hyperglycaemia (P for difference 0.058). Increments in IL-6 from baseline up to 2 hours post exercise were significantly higher in euglycaemia compared with hyperglycaemia (9.2±6.0 vs 3.3±4.4 pg/ml, P=0.047).
Conclusions: In patients with well controlled type 1 diabetes levels of IL-6 increased in response to prolonged aerobic exercise in euglycaemia, but not in hyperglycaemia. This finding is consistent with a regulation of IL-6 secretion by carbohydrate availability within the myocyte during exercise. Further studies are needed to better characterise the potential role of IL-6 in the regulation of fuel metabolism during aerobic exercise.