Caffeine Ingestion to Counter the Exercise-mediated Fall in Glycaemia in Type 1 Diabetes
Condition: Caffeine and Carbohydrate; Carbohydrate Only; Placebo
MeSH terms: Diabetes Mellitus, Type 1
Study type: Interventional

Summary: 
      This project will aim to investigate the clinical efficacy and metabolic effects of a
      pre-exercise dose of caffeine with a low (10g) dose of carbohydrate (CAF+lowCHO) without
      modification of insulin degludec on exercise metabolism in people with T1D.
    

Detailed description: 
      Treatment of type 1 diabetes (T1D) involves lifelong use of exogenous insulin to manage blood
      glucose concentration. As with the rest of the population, people living with T1D are
      recommended to engage in regular exercise for a variety of health and fitness reasons .
      However, glycaemic control during exercise remains a particular challenge for this population
      due to rapid changes in insulin sensitivity and the impact of additional hormones which
      increase the risk of exercise-related hypoglycaemia. Current guidelines to prevent
      exercise-induced hypoglycaemia suggest insulin dose reduction and/or ingestion of
      carbohydrates in the context of the exercise bout. However, these adaptations are often
      difficult to apply, as insulin dose adjustments require knowledge of insulin pharmacokinetics
      and advanced planning which is not always possible. None of these strategies provide complete
      assurance that hypoglycaemia will not occur and high carbohydrate intake can be
      counterproductive if weight management is the target. Furthermore, modern very long-acting
      insulin analogues, which are favoured by many people with T1D, do not offer the option to
      rapidly or transiently reduce insulin before exercise. When using such insulins, dose
      reductions may take two to three days to achieve an adapted steady state, increasing the risk
      of inadequate insulin following exercise. Collectively, these factors increase the risk of
      further deterring patients from exercise. Simple, alternative strategies to reduce the risk
      of hypoglycaemia, both during and after exercise are needed.

      Caffeine (1,3,7-trimethylxanthine) is the most commonly consumed chemical stimulant in the
      world that is naturally found in many foods and is frequently added to sports supplements due
      to its ergogenic effects in a range of sporting events. Caffeine has numerous physiological
      effects throughout the body including increased lipolysis in adipose tissues and hepatic
      glucose production in the liver alongside a decrease in glucose uptake in skeletal muscle.
      These responses have led to the suggestion that acute caffeine intake may attenuate
      exercise-associated hypoglycaemia in people with T1D. Ingestion of modest amounts of caffeine
      (200-250 mg, equivalent to 3-4 cups of coffee each day) has been shown to augment the
      symptomatic and hormonal responses to hypoglycaemia in participants with and without T1D.
      Caffeine has also been shown to reduce the frequency of moderate episodes of hypoglycaemia
      occurring overnight. The paucity of data on caffeine and exercise in individuals with T1D, in
      conjunction with caffeine's popularity both socially and as a sports supplement, suggests
      this deserves further attention.

      A clear example whereby caffeine supplementation may be of use is in patients using an
      ultra-long acting basal insulin analogue such as insulin degludec. The administration is via
      subcutaneous injection once daily, and it has a duration of action that lasts up to 42 hours
      (compared to 18 to 26 hours provided by other marketed long-acting insulins such as insulin
      glargine and insulin detemir). On average, the half-life at steady state is approximately 25
      hours independent of dose. Compared to the other basal insulin analogues, the risk of
      hypoglycaemia appears to be lower with insulin degludec, however, hypoglycaemia still occurs.
      In the case of physical exercise, the inability of the patient using such long-acting
      insulins to make rapid adjustments can translate to the occurrence of exercise-related
      hypoglycaemia due to an inability to reduce insulin already onboard, hence the need for new
      strategies to prevent this undesired phenomenon. When using such insulins, dose reductions
      may take two to three days to achieve an adapted steady state, increasing the risk of
      inadequate insulin following exercise. Applying a novel in-house developed lipid
      chromatography-mass spectrometry (LC-MS) assay, members of our research group observed that a
      single bout of aerobic exercise increases systemic insulin degludec concentrations in adults
      on stable basal insulin degludec regimens. Therefore, if these individuals wish to engage in
      regular exercise, as recommended in international guidelines, current treatment strategies
      may not be sufficient. For patients treated with modern basal insulin analogues, it seems
      more adequate not to modify the ultra-long acting insulin doses, as this can often result in
      more confusion than improvement, but to apply alternative strategies for recreational
      exercise. Caffeine ingestion pre or post exercise may offer a simple means to better manage
      glycaemia in the context of exercise in patients using these insulins and have the added
      benefit of reducing carbohydrate requirements in the context of exercise.
    

Intervention name(s): Caffeine and glucose; Glucose alone; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): Caffeine and glucose powder dissolved in water; Glucose powder dissolved in water; Artificial sweetener dissolved in water
Intervention MeSH terms: Caffeine
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Single-centre, randomised, double-blind crossover design
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: caffeine; type 1 diabetes; exercise; hypoglycemia; glucose