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Effect of Short-Term Exercise Training on ATP Synthesis in Relatives of Type 2 Diabetic Humans (RECO1)

This study has been completed.
Hanusch Hospital
Karl-Landsteiner Institute for Endocrinology and Metabolism
Medical University of Vienna
Lund University Hospital
Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy
Information provided by:
Landsteiner Institut Identifier:
First received: June 30, 2008
Last updated: August 19, 2008
Last verified: July 2008
First degree relatives of type 2 diabetic patients (T2DM) suffer an increased risk of developing this disease themselves, starting with impaired insulin sensitivity. This risk can be minimized by lifestyle interventions such as regular exercise training. Until this day, little is known about the short-term effects of exercise training on insulin sensitivity and the lipid content of the liver and skeletal muscle.

Condition Intervention
Type 2 Diabetes Mellitus
Other: exercise training

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Effect of Short-Term Exercise Training on ATP Synthesis in Relatives of Type 2 Diabetic Humans

Resource links provided by NLM:

Further study details as provided by Landsteiner Institut:

Primary Outcome Measures:
  • ATP-Synthesis, liver lipid content, skeletal muscle lipid content

Enrollment: 26
Study Start Date: February 2006
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Other: exercise training
    3 bouts of exercise at 90%RCP during one week
Detailed Description:

Life style intervention including diet and exercise is the recommended strategy for the prevention of type 2 diabetes mellitus (T2DM). First-degree relatives of patients with type 2 diabetes mellitus (T2DM) have an increased risk of insulin resistance and T2DM. According to the current paradigm, inherited and environmental factors cause insulin resistance by increasing intramyocellular lipid metabolites and stimulation of inflammatory pathways which both interfere with insulin signal transduction leading to an impaired rise of glucose-6-phosphate (G6P) upon insulin stimulation indicating impaired glucose transport/phosphorylation. In sedentary humans, these alterations can coexist with excessive storage of triglycerides as intramyocellular or hepatocellular lipids (IMCL, HCL). This indicates reduction of the muscles´ oxidative capacity which has been confirmed by demonstration of decreased mitochondrial function and/or number in insulin resistant states such as aging, increased availability of plasma free fatty acids (FFA) and overt T2DM. Likewise, severely insulin resistant, but nondiabetic relatives present with elevated FFA, IMCL and HCL along with impaired mitochondrial ATP synthesis which most likely results from reduced mitochondrial contents. However, it is unclear whether these alterations are only due to inherited abnormalities of mitochondrial biogenesis or secondary to chronically impaired glucose tolerance, increased lipid availability or inflammatory processes which are controlled by cytokines such as adiponectin, visfatin and retinol binding protein-4 (RBP4).

Likewise it remains uncertain to which extent such abnormalities are reversible by physical exercise stimulation and/or occur independently of effects on insulin action.

Long-term endurance exercise training increases insulin sensitivity in sedentary young and elderly healthy, first degree relatives of type 2 diabetic patients, glucose intolerant and obese nondiabetic or type 2 diabetic humans. Exercise training for at least 4 weeks also enhances fat oxidation along with increased size, number and enzyme activities of mitochondria. However, little is known on the time course and onset of exercise-induced changes in glucose and energy metabolism independently of the acute exercise effects occurring within the first 24 hours. At 48 hours after one bout of aerobic exercise, insulin-stimulated glucose disposal and IMCL can be increased or unchanged. Effects of short-term exercise on the underlying energy generating pathways have not yet been reported in vivo in humans. Flux of inorganic phosphate (Pi) to ATP through ATP synthase (fATPase) provides a measure of mitochondrial ATP synthesis.

We use multinuclear magnetic resonance spectroscopy (MRS) to simultaneously measure fATP as well as G6P, IMCL and HCL before and after three bouts of cycling training. We will test the hypotheses that short-term exercise training simultaneously increases fATPase and insulin sensitivity in healthy humans (control) and in relatives. Furthermore, we will investigate whether baseline fATPase reflects whole-body oxidative capacity and whether post-exercise fATPase is influenced by lipid availability due to alterations in IMCL, HCL or circulating triglycerides or FFA.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • First degree relatives of type 2 diabetic patients
  • Age: 18-50 years
  • BMI <30 kg/m2 (due to limited MR diameter)
  • Normal routine lab tests (blood cell count, kidney, liver, pancreas, thyroid and neuromuscular function)
  • Availability within the local area throughout the study
  • Ability to understand and sign the consent forms

Exclusion Criteria:

  • Current smoking
  • Present drug treatment
  • Regular exercise training
  • Contraindications for MRS studies: claustrophobia and metalliferous implants
  • Pregnancy
  • HIV or Hepatitis
  • Acute disease 2 weeks previous to the examination
  • Heart disease
  • Hypertension (RR>140/95)
  • Liver disease
  • Kidney disease
  • Pulmonary disease
  • Thyroid disease
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Please refer to this study by its identifier: NCT00710008

Landsteiner Institute
Vienna, Austria, 1140
Sponsors and Collaborators
Landsteiner Institut
Hanusch Hospital
Karl-Landsteiner Institute for Endocrinology and Metabolism
Medical University of Vienna
Lund University Hospital
Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy
Study Director: Michael Roden, Prof.Dr. Landsteiner Institute
  More Information

Responsible Party: Landsteiner Institute Identifier: NCT00710008     History of Changes
Study First Received: June 30, 2008
Last Updated: August 19, 2008

Keywords provided by Landsteiner Institut:
type 2 diabetes,
exercise training,
intramyocellular lipids,
hepatocellular lipids
first degree relatives of

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases processed this record on April 27, 2017