The Effects of Growth Hormone (GH) on Lipid Depots

The Effect of Growth Hormone (GH) on Intramyocellular Lipids (IMCL), Intrahepatocellular Lipids (IHCL) and Visceral Fat Mass in Relation to Insulin Resistance

This study aims at investigating the effect of growth hormone on lipid-content of muscle and liver as well as visceral fat mass in relation to insulin sensitivity.

In addition, hormonal regulation and free fatty availability is assessed during a physical exercise at 50-60% VO2max.

Finally, the value of physical exercise in diagnosing growth hormone deficiency is investigated.

Hypothesis: 1) Lipid content of muscle and liver change with physical exercise and exercise capacity and free fatty availability will influence these changes. 2)Growth hormone replacement therapy will predominantly reduce visceral fat mass and increase free fatty availability.

3)Free fatty availability during exercise will be reduced in growth hormone deficient patients 4)Physical exercise may be an alternative way to diagnose growth hormone deficiency

Study Overview

• Status: Completed
• Conditions: Growth Hormone Deficiency
• Intervention / Treatment: Drug: Growth hormone replacement therapy in growth hormone deficient patients only.

Detailed Description

Using the two-step hyperinsulinaemic-euglycaemic clamp technique hepatic and peripheral insulin sensitivity is assessed.

Lipid depots (skeletal muscle and liver) are measured by MR-spectroscopy, visceral fat mass by MR-imaging.

Exercise capacity ist measured on a treadmill. Counterregulatory hormones, glucose and free fatty acids are measured during a 2h physical exercise at 50-60 VO2max Identical investigations are performed in adult growth hormone (GH) deficient patients before and after six months GH replacement therapy, in sedentary matched control subjects and in endurance trained athletes.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Abt. für Endokrinologie, Diabetologie und Klin. Ernährung, Inselspital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female patients with proven GH-deficiency defined as a peak GH of less than 3mU/l during an insulin provocation test with nadir plasma glucose less than 2.2 mmol/l and additionally, stable conventional replacement therapy including corticoids, thyroxin and gonadal hormones as needed.
• Ability to perform an exercise test on a treadmill or a walking band.
• Willingness to participate in the study and to give written informed consent.

Exclusion Criteria:

Active neoplasia

• Severe cardiovascular disease (unstable coronary heart disease, heart failure NYHA III-IV)
• Type 2 Diabetes mellitus
• Haemophilia or other coagulation disorder
• Inability to exercise
• Contraindications to exposure to a 3-T magnetic field (Pace-Makers, osteosynthetic material)
• Pregnant women
• Women in childbearing age unless on a continuous contraceptive therapy or surgically sterilised.
• Abnormal liver or renal function (Creatinine >130mmol/L, normal reference 45-93mmol/L; ASAT and ALAT > 3 times the upper reference limit).
• Major depression, psychosis and other severe personality disorders
• Excessive alcohol consumption (>60g/d) or drug-abuse
• Refusal to give written consent
• Patients, who are not suitable for the study according to the study physician

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Athletes, controls, patients; Sedentary controls: age, BMI, Gender and waist matched (to the growth hormone deficient patients) healthy control subjects Endurance trained athletes: minimal >50 mlO2/KG body weight	Drug: Growth hormone replacement therapy in growth hormone deficient patients only.; Genotropin once/daily sc., titration scheme according to the consensus guidelines of the GH and IGF-research society Duration: 6 months; Other Names: Genotropin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determination of visceral fat mass by MRI,Determination of IMCL and IHCL by MR Spectroscopy, Determination of peripheral and hepatic insulin sensitivity by two step hyperinsulinemic euglycemic clamp	2008 - 2009

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
maximal exercise capacity		2008 - 2009
Measurement of serum alphaKlothe by an ELISA	Measured in pg/mL	2008 - 2013

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Collaborators: Swiss National Science Foundation
• Investigators: Principal Investigator: Emanuel R Christ, Prof,MD,PhD, Abt. für Endokrinologie, Diabetologie und Klin. Ernährung, Inselspital, Berne

Publications and helpful links

General Publications

• Egger A, Kreis R, Allemann S, Stettler C, Diem P, Buehler T, Boesch C, Christ ER. The effect of aerobic exercise on intrahepatocellular and intramyocellular lipids in healthy subjects. PLoS One. 2013 Aug 14;8(8):e70865. doi: 10.1371/journal.pone.0070865. eCollection 2013.

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: June 25, 2007
• First Submitted That Met QC Criteria: June 25, 2007
• First Posted (Estimate): June 26, 2007

Study Record Updates

• Last Update Posted (Estimate): August 13, 2013
• Last Update Submitted That Met QC Criteria: August 12, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: 320000-109522/1