METAPREDICT: Developing Predictors of the Health Benefits of Exercise for Individuals
Condition: Insulin Sensitivity; Physical Activity
MeSH terms: Insulin Resistance; Hypersensitivity
Study type: Interventional

Summary: 
      Physical activity is a powerful lifestyle factor that on average reduces risk for development
      of diabetes and cardiovascular disease. Nevertheless, investigators have demonstrated that
      following supervised endurance exercise training, 20% of subjects show no change in fitness
      and 30% demonstrate no improvement in insulin sensitivity.

      Our concept is that by using molecular profiling of blood/muscle samples investigators will
      develop personalised lifestyle intervention tools. Further, revealing the biological basis
      for a variable metabolic or cardiovascular response to exercise will enable us to propose new
      targets and biomarkers for drug discovery efforts directly in humans. Using our established
      OMICS approaches (RNA, DNA and Metabo-) investigators will generate classifiers that predict
      the responses to exercise-therapy (fitness and insulin sensitivity). Classifier generation is
      a statistical strategy for diagnosis or prognosis. Critically, investigators have a large
      human tissue biobank, including subjects with insulin-resistance; young to elderly males and
      females, as well as twins. Our SME partner has significant intellectual property and capacity
      in the field of bio-prediction, with a proven track-record of collaboration with the team and
      product development. Investigators will add to the diversity of our biobank by carrying-out
      an exercise intervention study using a novel time-efficient strategy that investigators have
      recently proven to be effective in reducing insulin resistance in sedentary young people and
      in middle aged obese subjects. A time-efficient protocol is a critical as lack-of-time is a
      key reason for not maintaining physical activity levels. Finally, investigators have a novel
      out-bred rodent model that replicates high and low exercise training responses and
      investigators will establish its suitability for future drug screening purposes. Because of
      these substantial pre-existing resources investigators believe that our project has a very
      high probability of delivering on its goals of improving the healthcare of European citizens.
    

Detailed description: 
      Aerobic exercise capacity, in prospective follow-up analyses, is a stronger a predictor of
      morbidity and mortality than other recognised risk factors such as hypertension. Furthermore,
      the most powerful lifestyle factor that on average reduces the risk for development of Type
      II diabetes is arguably increased physical activity. Investigators have clearly demonstrated
      that following many weeks of supervised aerobic exercise training ~20% of sedentary
      volunteers show almost no changes in gold standard measurements of fitness and many more
      demonstrate a poor response. Furthermore at least 25% of people demonstrate no improvement in
      insulin sensitivity in response to aerobic training. Critically, 15% of all subjects
      undergoing a supervised exercise intervention programme (with full compliance) actually
      demonstrated a decline in their insulin sensitivity after exercise training. Extensive
      citations were provided in the original grant application documents.

      A major aim of this project is to identify genomic or molecular predictors for this lack of
      positive benefit ('non-responder'), so that individualised health care strategies and life
      style changes can be produced to fight or prevent metabolic diseases such as obesity,
      diabetes and cardiovascular disease. Identification of 'high responders' to physical training
      forms an additional positive outcome from our research program. Understanding the biological
      basis for our 'highest-responders' will provide enormous insight into the molecular basis for
      positive exercise adaptation and a number of important health and industry related
      opportunities. For example, knowledge that a patient is a high-responder could be used to
      encourage cardiacfailure patients to remain motivated during their rehabilitation. Knowledge
      that a patient was a low responder would enable clinicians to set proper expectations during
      rehabilitation.

      Finally, as part of our research plan investigators will establish the utility of a novel
      time-efficient lifestyle strategy that has a high potential for being integrated into modern
      life.

      Investigators bring together leading EU and North American investigators to study life-style
      determinants of diabetes, obesity and cardiovascular disease. In particular, our workpackages
      are focused on boosting the capacity to diagnose, develop drug-screening solutions and enable
      the application of personalised medicine to the field of life-style determinants of diabetes,
      obesity and cardiovascular disease. Our deliverables include new validated products which can
      define higher risk populations. Investigators will achieve this through the identification
      and validation of molecular predictors that quantify the extent of the health benefits of
      increased physical activity. Optimisation of the prescription of physical activity for the
      treatment of insulin resistance, will contribute to the long term prevention of diabetic
      complications.
    

Intervention name(s): High Intensity Training (HIT); REHIT
Intervention type(s): Behavioral; Behavioral
Intervention description(s): 6 weeks of HIT, 3 times a week (3-5 1min on/off); 6 weeks 3 x week (20sec intervals)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: High Intensity Training; Insulin sensitivity; Fitness