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Non Invasive Assessment of Liver Glycogen Kinetics and ATP Synthesis in Type1 Diabetics

This study has been completed.
Sponsor:
Collaborator:
University of Coimbra
Information provided by:
Landsteiner Institut
ClinicalTrials.gov Identifier:
NCT00481598
First received: June 1, 2007
Last updated: September 11, 2008
Last verified: September 2008
  Purpose

Patients with Type 1 diabetes (T1DM) suffer from impaired postprandial hepatic glycogen storage and breakdown, if they are under poor glycaemic control. Poor glycogen storage in the liver puts these patients at risk of fasting hypoglycaemia. Amelioration of glycaemic control could improve these abnormalities and thereby reduce the risk of hypoglycaemia in these patients. The "gold standard" technique for the assessment of hepatic glycogen metabolism in humans, 13 C magnetic resonance spectroscopy (13C-MRS), is expensive and limited to a few centers worldwide. Furthermore, treated type 1 diabetic patients exhibit skeletal muscle insulin resistance when treated insufficiently. This condition can also be reversed by improvement of glycaemic control. Recent studies link skeletal muscle insulin resistance to impaired mitochondrial function. Up to date, the impact of glycaemic control on skeletal muscle mitochondrial function has not yet been assessed.

Aim 1 of our project is to establish a new assessment method for glycogen metabolism. This new method is based on oral administration of 2H2O and acetaminophen.

Our second aim is to examine the impact of improvements of glycaemic control on skeletal muscle mitochondrial function in type 1 diabetic patients.

Our third aim is to assess the ATP-synthesis in T1DM.

We will conduct a prospective study on 14 patients with type 1 diabetes and 14 healthy controls.

On the respective study day, participants will be served three standardized meals, blood sugar will be controlled hourly and blood samples will be drawn at timed intervals to determine glucoregulatory hormones, metabolites and enrichments of [6,6-2H2]glucose.

During the night, four 13C-MRS-measurements will be performed in combination with [6,6-2H2]glucose infusion to assess glucose production, glycogen breakdown and gluconeogenesis.

In addition, patients will drink 3g/kg bodyweight 2H2O and acetaminophen will be administered. Thus the new 2H2O-acetaminophen method will be applied simultaneously with the "gold standard" method.

The following morning, mitochondrial function will be assessed in skeletal muscle from unidirectional flux through ATP synthase by 31P MRS.

TIDM patients will be studied twice. First, under conditions of insufficient glycaemic control and the second time after three months of intensified insulin treatment using CSII pumps aiming at optimized metabolic control. Healthy controls will be studied only once.

To assess muscular mitochondrial function in T1DM we will measure ATP synthesis in a calf muscle with magnetic resonance spectroscopy. First, we will conduct a basal measurement. Thereafter, we will start a hyperinsulinaemic euglycemic calmp to stimulate the ATP synthesis and measure again.

This study will provide information on rates of post absorptive glycogen breakdown, gluconeogenesis, and postprandial glycogen storage in the liver and on the skeletal muscle mitochondrial function under conditions of optimized glycaemic control for 3 months.

Finally, this study will demonstrate whether or not poorly controlled type 1 diabetic patients exhibit abnormalities in muscle mitochondrial function and to what extent those alterations can be reversed by optimized glycaemic control. We expect to validate the 2H2O-acetaminophen method, which will provide justification for a broad scale in clinical studies.


Condition Intervention
Type 1 Diabetes Mellitus
Procedure: magnet resonance spectroscopy

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Non Invasive Assessment of Liver Glycogen Kinetics and ATP Synthesis in Type1 Diabetics

Resource links provided by NLM:


Further study details as provided by Landsteiner Institut:

Primary Outcome Measures:
  • glycogen metabolism, gluconeogenesis, after 3 months of treatment; [ Time Frame: August 2008 ] [ Designated as safety issue: No ]

Estimated Enrollment: 28
Study Start Date: January 2006
Study Completion Date: September 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Procedure: magnet resonance spectroscopy
    magnet resonance spectroscopy
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Type 1 Diabetes Mellitus
  • HbA1c at the beginning of the trial between 8,5% and 10%
  • 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00481598

Locations
Austria
Landsteiner Institute for Endocrinology and Metabolic Diseases, Hanusch Hospital Heinrich Collin Straße 30
Vienna, Austria, 1140
Sponsors and Collaborators
Landsteiner Institut
University of Coimbra
Investigators
Study Director: Michael Roden, Professor Dr. Landsteiner Institute
  More Information

No publications provided

Responsible Party: Landsteiner Institute
ClinicalTrials.gov Identifier: NCT00481598     History of Changes
Other Study ID Numbers: JDRF Grant Number: 1-2006-74
Study First Received: June 1, 2007
Last Updated: September 11, 2008
Health Authority: Austria: Ethikkommission

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases

ClinicalTrials.gov processed this record on November 20, 2014