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

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: NCT00459940
Recruitment Status : Completed
First Posted : April 13, 2007
Last Update Posted : April 13, 2007
Information provided by:
University of Aarhus

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Growth Hormone Deficiency Drug: Pioglitazone Not Applicable

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  (Clinical Trial)
Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: "Can Growth Hormone's Lipolytic and Insulin-Antagonistic Effects be Modified by Peroxisome Proliferator-Activated Gamma Agonists?"
Study Start Date : September 2004
Actual Study Completion Date : March 2006

Primary Outcome Measures :
  1. Circulating FFA level
  2. FFA turnover
  3. Lipid oxidation

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Ages Eligible for Study:   19 Years to 71 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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

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): NCT00459940

Medical Department M, The Medical Research Laboratories, Aarhus University Hospital
Aarhus C, Denmark, 8000
Sponsors and Collaborators
University of Aarhus
Principal Investigator: Jens OL Jorgensen, MD University of Aarhus

Publications: Identifier: NCT00459940     History of Changes
Other Study ID Numbers: 20030288
First Posted: April 13, 2007    Key Record Dates
Last Update Posted: April 13, 2007
Last Verified: April 2007

Keywords provided by University of Aarhus:
Growth hormone
Insulin resistance
Growth hormone replaced growth hormone deficient adults

Additional relevant MeSH terms:
Dwarfism, Pituitary
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Bone Diseases, Endocrine
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Endocrine System Diseases
Hypoglycemic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists