Mechanisms by Which Strength Training Ameliorates the Metabolic Syndrome
Condition: Metabolic Syndrome
MeSH terms: Metabolic Syndrome; Syndrome
Study type: Interventional

Summary: 
      Prevention and treatment strategies for diabetes use exercise as the cornerstone. Even though
      endurance training and strength training both improve insulin resistance, strength training
      may be better suited for persons at risk for type 2 diabetes. We will expand our pilot
      studies of muscle adaptation induced by resistance exercise training to determine the
      biochemical mechanisms that will cause people with the Metabolic Syndrome to secure major
      benefit from intense strength training.
    

Detailed description: 
      Life style alterations can be powerful deterrents to developing type 2 diabetes and are
      cornerstones of the treatment of this condition. Both aerobic and resistance exercise improve
      diabetes blood glucose control and insulin resistance. These two types of exercise appear to
      exert their effects on different muscle fiber types - red for endurance and white for
      strength. Similar to the effects of endurance exercise training, strength training increases
      muscle glucose transporter isoform 4 (GLUT4), but in contrast, mitochondria numbers do not
      increase. We hypothesize (1) that strength training in persons with pre-diabetes may be
      effective in reversing insulin resistance by novel mechanisms that are distinct from the
      endurance training-induced mitochondrial biogenesis. We further hypothesize (2) that
      resistance exercise training enhances whole body insulin action primarily by increasing the
      white fiber size via the protein kinase mammalian target of rapamycin (mTOR) and improves
      insulin-stimulated glucose uptake by increased GLUT4 expression primarily in white fibers of
      the trained muscles. In this proposal, we will perform eight weeks of progressive strength
      training on ten subjects with the Metabolic Syndrome who are at high risk for developing type
      2 diabetes and on ten sedentary control subjects. This project builds on our experience with
      a study of focused resistance training whose results are presented in this application. In
      this pilot study, subjects exercised on stationary bicycles for six weeks causing muscle
      GLUT4 and phopho-mTOR to increase substantially, but maximal oxygen uptake (VO2max),
      phospho-AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-γ
      co-activator (PGC-1α), and mitochondrial markers did not change. Our hypotheses will be
      tested by two Specific Aims. (1) Subjects at high risk for diabetes will undergo
      progressively increasing intensity resistance exercise training and increased strength and
      improved insulin responsiveness will both be quantified to demonstrate significant benefit,
      and (2) quantify the effect of resistance exercise training on anatomic and functional
      adaptation in muscle. We will characterize fiber type, fiber size, fiber-specific changes in
      mitochondrial DNA and enzymes, fiber-specific changes in the principle glucose transporters
      in muscle (GLUT4, GLUT5, and GLUT12), and evaluate changes in two distinct intramuscular
      pathways (AMPK, mTOR) and regulatory factors (PGC-1α, PPARγ, PPARδ) using immunoblots of
      muscle subcellular fractions and immunohistochemical techniques. These evaluations of
      molecular mechanisms will also include assessing changes in full human Affymetrix gene array
      data that may move us to new potential resistance training-regulated gene targets. It is the
      long-term goal of this team of investigators to understand the interplay between life style
      changes and pharmacological agents in the prevention and treatment of diabetes. Our results
      will facilitate the development of more effective clinical options to turn back the epidemic
      of obesity and diabetes in the United States.
    

Intervention name(s): strength training
Intervention type(s): Behavioral
Intervention description(s): eight weeks of progressively increasing resistance training will be done in both groups side-by-side
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: diabetes, metabolic syndrome, type 2 diabetes