The Effects of TZD on Fat Metabolism and Insulin Sensitivity in GH-Replaced GHD Patients

April 12, 2007 updated by: University of Aarhus

"Can Growth Hormone's Lipolytic and Insulin-Antagonistic Effects be Modified by Peroxisome Proliferator-Activated Gamma Agonists?"

In the present double blind, placebo-controlled, parallel study we evaluated the impact of 12 weeks thiazolidinedione (TZD) administration on basal and insulin-stimulated substrate metabolism in growth hormone-replaced adults with growth hormone deficiency.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In human subjects GH (Growth Hormone) acutely antagonises the effects of insulin on glucose uptake in skeletal muscle and increases the hepatic glucose production of humans. This has clinical implications for patients with active acromegaly, in whom the prevalence of glucose intolerance and overt diabetes mellitus is increased. It is also of significance in relation to GH replacement therapy in GH-deficient adults not least when considering that a substantial proportion of these patients are insulin resistant in the GH-untreated state. There is evidence to indicate that the acute insulin antagonistic effects may be balanced with time by the favourable effects of GH on body composition and physical fitness, but the data are ambiguous. The mechanism underlying these effects of GH are not fully characterised, but there is experimental evidence of a causal linked to the concomitant stimulation of lipolysis, since GH-induced insulin resistance is partly abrogated when lipolysis is pharmacologically suppressed. This is noteworthy since elevated levels of free fatty acids (FFA) are also implicated in the pathogenesis of insulin resistance in patients with the metabolic syndrome and type 2 diabetes mellitus. Thiazolidinediones (TZDs) are insulin sensitizers which function as highaffinity agonists for the nuclear peroxisome-proliferator-activated receptor (PPAR) gamma, which improve insulin sensitivity in T2DM. PPAR gamma is a nuclear receptor expressed mainly in adipocytes, which activates the transcription of genes involved in lipid and glucose metabolism. Administration of TZD in T2DM enhances insulin-stimulated glucose uptake via mechanisms including a lowering of circulating FFA and a redistribution of fat away from hepatocytes and myocytes and into peripheral adipocytes. To our knowledge, the impact of TZDs on GH-induced insulin resistance has not previously been reported. Experimental data in human subjects on this issue are of potential importance not only in relation to patients with abnormal GH status, but also regarding our understanding of the pathogenesis of insulin resistance in general and the complex actions of PPAR gamma activation in particular.

Study Type

Interventional

Enrollment

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Aarhus C, Denmark, 8000
        • Medical Department M, The Medical Research Laboratories, Aarhus University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 71 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Growth hormone replaced (minimum 6 months) growth hormone deficient men
  • Age over 18 years

Exclusion Criteria:

  • Ischemic coronary disease, defined by EF<0.6, former myocardial infarction, angina pectoris or actual treatment of cardiac insufficiency
  • Actual or former malignancy, except intracranial neoplasia that caused the participants pituitary disease, provided that there was clinical evidence for permanent remission
  • Blood donation within 6 months
  • Excessive alcohol consumption
  • Known allergic reaction from contents of test drug
  • Radioactive radiation exposure in terms of treatment or study enrollment within one year
  • Liver insufficiency
  • Insulin treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Lipid oxidation
Circulating FFA level
FFA turnover

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Aarhus

Investigators

  • Principal Investigator: Jens OL Jorgensen, MD, University of Aarhus

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2004

Study Completion (Actual)

March 1, 2006

Study Registration Dates

First Submitted

April 12, 2007

First Submitted That Met QC Criteria

April 12, 2007

First Posted (Estimate)

April 13, 2007

Study Record Updates

Last Update Posted (Estimate)

April 13, 2007

Last Update Submitted That Met QC Criteria

April 12, 2007

Last Verified

April 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20030288

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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