Determining the Minimal Amount of Exercise to Improve Glycaemic Control
Condition: Type 2 Diabetes
Study type: Interventional

Summary: 
      In 2015, there were 415 million adults worldwide with type II diabetes and by 2040, typeII
      diabetes will affect one in ten adults worldwide. Type II diabetes reduces quality of life
      and total lifespan, and two of the best countermeasures to type II diabetes are not drugs,
      but diet and exercise. Several studies have investigated the effects of exercise modality
      (aerobic, resistance, or concurrent) on glycaemic control and the mechanisms of these
      benefits. However, the minimal 'dose' of exercise required to increase insulin sensitivity
      and improve glycaemic control has never been established. Secondly, there is a progressive
      loss of muscle structure and function with age, which is known as sarcopenia. This study will
      also investigate whether the minimal amount of exercise is influenced by biological age and
      muscle mass by comparing physiological and biochemical responses in BMI-matched young and old
      volunteers. This study will therefore provide pilot data on the effect of age on
      exercise-mediated glycaemic control.
    

Detailed description: 
      Background Information and rationale Overarching aim: The purpose of this study is to
      identify the minimum number of calories that must be expended to improve the control of blood
      glucose in young and older overweight males, and in those with type II diabetes.

      Why is this important? In 2015, there were 415 million adults worldwide with type II diabetes
      and by 2040, type II diabetes will affect one in ten adults worldwide. If the minimal volume
      of exercise to improve glycaemic control can be established, this could increase exercise
      compliance and population health.

      Current knowledge and preliminary data Acute exercise improves glycaemic control by promoting
      the translocation of the glucose transporter GLUT-4 in an insulin-independent pathway. This
      mechanism is intact even in patients with type II diabetes. An acute bout of exercise for ~70
      mins at 65% VO2max (energy expenditure of 350kcal) improves insulin sensitivity by ~15% 1h
      after exercise, and ~30% the day following exercise in obese adults. This improved insulin
      sensitivity is also associated with a 17% reduction in circulating free fatty acids, which
      chronically might benefit both type II diabetes and cardiovascular disease - a major
      secondary complication of type II diabetes. Several studies have investigated the effects of
      exercise modality (aerobic, resistance, or concurrent) on glycaemic control and the
      mechanisms of these benefits (8). However, the minimal 'dose' of exercise required to
      increase insulin sensitivity and improve glycaemic control has never been established.
      Secondly, there is a progressive loss of muscle structure and function with age, which is
      known as sarcopenia. This study will also investigate whether the minimal amount of exercise
      is influenced by biological age and muscle mass by comparing physiological and biochemical
      responses in BMI-matched young and old volunteers. Establishing the dose-response
      relationship for exercise and glycaemic control. It is important to establish the optimal
      dose-response relationship for exercise and glycaemic control in order to maximise the health
      benefits and minimize side-effects of the exercise intervention. Whilst the risks of exercise
      are low unless undertaking athlete-level training for several years, establishing the minimum
      exercise required for glycaemic control would improve exercise adherence. Indeed, lower
      volumes of exercise are easier to maintain than larger volumes, and this has led to the
      adoption of short-duration exercise strategies for glycaemic control, such as high intensity
      interval training.

      Previous work has shown that an acute bout of cycling expending 350kcal can increase insulin
      sensitivity by ~30% the day following exercise in obese adults. On this basis, the proposed
      study will test three levels of kcal expenditure: 1) a 350kcal intervention, which is
      predicted to increase insulin sensitivity in line with; 2) a 700kcal intervention, to deliver
      a profound (doubling) stimulus to increase insulin sensitivity; and 3) 175kcal intervention,
      to examine the efficacy of a halved stimulus on insulin sensitivity. These three intervention
      points are necessary in order to accurately model the dose response relationship between
      amount of exercise and insulin sensitivity, which is currently unknown. There will also be a
      no exercise trial where the same data are collected and used to calculate baseline glycaemic
      control/insulin sensitivity from which any increase prompted by exercise can be determined.
      If the minimal volume of exercise to improve glycaemic control can be established, this could
      increase exercise compliance and population health. This minimal amount of exercise may
      increase in older subjects where muscle mass and quality is reduced. This study will
      therefore provide pilot data on the effect of age on exercise-mediated glycaemic control.

      Objectives of the study Recruitment and testing will take place throughout the first 15
      months of the study, allowing 3 months at the end of the study for data analysis. The
      investigators will use a randomised, crossover design study, where all subjects will complete
      (i) no exercise; (ii) 175kcal exercise; (iii) 350kcal exercise; and (iv) 700kcal exercise
      trials the day before an oral glucose tolerance test (OGTT). An acute bout of 350kcal
      exercise can improve insulin sensitivity by ~30% the following day; the trials in the
      proposed study intend to result in: (i) baseline glycaemic control; (ii) small improvements
      in glycaemic control; (iii) ~30% improvement in glycaemic control; and (iv) large >30%
      improvement in glycaemic control. The OGTT, continuous glucose monitoring (CGM), measurement
      of insulin, and FFA will be used to calculate dose response curves in each of these
      individual variables, where the minimum amount of exercise to improve glycaemic control can
      be ascertained.
    

Intervention name(s): Cycle ergometry exercise at 60% VO2max
Intervention type(s): Other
Intervention description(s): Participants visit the lab on four occasions to complete (i) no exercise; (ii) 175kcal exercise; (iii) 350kcal exercise; (iv) or 700kcal exercise (randomised).
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science