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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00481598
Recruitment Status : Completed
First Posted : June 4, 2007
Last Update Posted : September 12, 2008
University of Coimbra
Information provided by:
Landsteiner Institut

Brief Summary:

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 or disease Intervention/treatment Phase
Type 1 Diabetes Mellitus Procedure: magnet resonance spectroscopy Not Applicable

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Non Invasive Assessment of Liver Glycogen Kinetics and ATP Synthesis in Type1 Diabetics
Study Start Date : January 2006
Actual Primary Completion Date : July 2008
Actual Study Completion Date : September 2008

Resource links provided by the National Library of Medicine

Intervention Details:
  • Procedure: magnet resonance spectroscopy
    magnet resonance spectroscopy

Primary Outcome Measures :
  1. glycogen metabolism, gluconeogenesis, after 3 months of treatment; [ Time Frame: August 2008 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00481598

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

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Landsteiner Institute Identifier: NCT00481598     History of Changes
Other Study ID Numbers: JDRF Grant Number: 1-2006-74
First Posted: June 4, 2007    Key Record Dates
Last Update Posted: September 12, 2008
Last Verified: September 2008

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