Impact of Physical Activity on Blood Glucose Stability and Energy Stores in Individuals With Type 1 Diabetes
Condition: Type 1 Diabetes Mellitus; Exercise; Hypoglycemia; Carbohydrate Metabolism
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia
Study type: Interventional

Summary: 
      Whereas physical activity clearly results in improvements in glycemic control in type 2
      diabetes, in individuals with type 1 diabetes (T1DM) the impact of exercise on blood sugar
      control is more complex. In type 1 diabetes T1DM the inability to reduce exogenous insulin
      levels during exercise is a key factor that contributes to an increased risk of
      exercise-induced hypoglycemia. Since rapid adaptation of insulin dosage may be especially
      difficult in patients on a multiple daily injection regimen, alternative strategies are
      required to improve exercise-associated glucose stability. There is increasing evidence that
      the combination of steady state continuous low to moderate intensity exercise with short
      bursts of high intensity exertion (eg in the form of sprints) is an effective, well
      tolerated, novel strategy to prevent exercise-related hypoglycemia. A further promising
      option to stabilize blood sugar levels during and after exercise may be the ingestion of
      fructose in addition to glucose in form of a sport drink.
    

Detailed description: 
      Background

      Regular physical activity enhances insulin sensitivity in both healthy subjects and patients
      with diabetes mellitus. However, while the effects of physical activity on glucose control
      are undoubtedly beneficial in patients with type 2 diabetes, exercise can cause major
      disturbances in blood glucose levels in type 1 diabetic individuals. Hypoglycemia is a common
      complication in patients with T1DM engaging in endurance activities such as running and
      cycling. So far there are limited strategies suggested to improve exercise-related blood
      sugar self-management. Current recommendations focus on variation in timing and dosage of
      insulin administration and adjustments in carbohydrate intake. Since rapid adaptation of
      insulin dosage may be difficult, alternative strategies to improve exercise-related glucose
      stability are required. Increasing evidence suggests that intermittent high intensity
      exercise (IHE), by triggering a counterregulatory hormone response, may counter-balance the
      risk of exercise-associated hypoglycemia. However, previous studies investigating IHE in T1DM
      were limited by heterogeneous study populations, comparably short exercise protocols, and
      deficits in standardization procedures. In addition, a comprehensive assessment of the
      underlying fuel metabolism has not been performed so far. As a consequence, the results
      remain controversial and their interpretation as well as applicability are restricted.

      A further alternative strategy to maintain stable glycemia during exercise may be deduced
      from recent studies in non-diabetic individuals suggesting that the combined ingestion of
      fructose and glucose during exercise provides the liver with an increased amount of
      gluconeogenic precursors, thereby reducing consumption of endogenous glycogen
      stores.Moreover, conversion of fructose into glucose and lactate may provide constant and
      efficient fuel for working muscles. However, studies assessing the impact of fructose
      ingestion during exercise in patients with T1DM have not been performed so far.

      Objective

      The investigators aim to assess the impact of two novel non-pharmaceutical and easily
      feasible approaches on exercise-related blood glucose stability and its underlying
      exercise-related fuel metabolism in patients with T1DM.

      Substudy A will assess the influence on exercise-related glycemia and fuel metabolism of an
      IHE protocol compared to an iso-energetic continuous exercise (CONT). It will be investigated
      whether individuals reach more stable blood glucose levels when engaging in IHE compared to
      CONT.

      Substudy B will investigate whether fueling the patients with a mixed oral 1:1
      glucose-fructose carbohydrate solution will maintain glucose values within a more stable
      range when compared to carbohydrate supplementation by glucose alone.

      Methods

      Blood glucose levels, counterregulatory hormones, metabolites such as lactate and free fatty
      acids as well as inflammatory biomarkers will be assessed by regular blood samplings. By
      means of oral and intravenously given stable isotopes (U-13 C glucose and 2H glucose)
      exercise-related glucose kinetics will be investigated. Exercise-induced glycogen consumption
      will be measured using magnetic resonance spectroscopy technology. Late glycemic excursions
      will be recorded by continuous glucose monitoring systems.

      In order to validate 13C magnetic resonance spectroscopy (MRS) measurement of hepatic and
      myocellular glycogen content a pre-study involving 10 patients and an equal number of matched
      healthy controls will be performed (validation and reproducibility study).
    

Intervention name(s): IHE first, CONT second; CONT first, IHE second; GLU first, GLU-FRU second; GLU-FRU first, GLU second
Intervention type(s): Procedure; Procedure; Procedure; Procedure
Intervention description(s): IHE: intermittent high intensity exercise: integration of 10 s maximal sprints every 10 minutes in a continuous low to moderate intensity exercise of 90 minutes. CONT (occurring after a washout period of 2-8 weeks): continuous moderate intensity exercise of 90 minutes; CONT: continuous moderate intensity exercise of 90 minutes. IHE (occurring after a washout period of 2-8 weeks): intermittent high intensity exercise: integration of 10 s maximal sprints every 10 minutes in a continuous low to moderate intensity exercise of 90 minutes; : ingestion of a 6% carbohydrate solution (consisting of 90 g glucose dissolved in 1500 ml tap water) over a continuous moderate exercise of 90 minutes. GLU FRU (occurring after a washout period of 2-8 weeks): ingestion of a 12% carbohydrate solution (consisting of 90 g glucose + 90 g fructose dissolved in 1500 ml tap water) over a continuous moderate exercise of 90 minutes; GLU-FRU : ingestion of a 12% carbohydrate solution (consisting of 90 g glucose + 90 g fructose dissolved in 1500 ml tap water) over a continuous moderate exercise of 90 minutes. GLU (occurring after a washout period of 2-8 weeks): : ingestion of a 6% carbohydrate solution (consisting of 90 g glucose dissolved in 1500 ml tap water) over a continuous moderate exercise of 90 minutes.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care
Keywords: exercise; isotope labeling, stable; spectroscopy, magnetic resonance; monitoring, home blood glucose; hormones