Effects of Growth Hormone Supplementation to Adults With Growth Hormone Deficient on Metabolism and Adipose Tissue Molecular Phenotype
Condition: Growth Hormone Deficiency
Study type: Observational

Summary: 
      This study is designed as a follow up study to that performed in 2005.

      In the Baseline study (2005) extensive clinical whole body metabolic phenotyping was combined
      with in depth molecular and cellular biology analyses aimed at investigating the adipose
      tissue morphology as well as metabolic and inflammatory phenotypes in the adult GHD patients.
      Results published in (Ukropec et al., 2008)

      In this study identical endpoints will be investigated with the same methodology and within
      the same population; in order to seek relevant answers to questions on how the 6-yrs of rhGH
      therapy affects the

        -  whole body insulin sensitivity

        -  energy expenditure

        -  body fat distribution

        -  hepatic and skeletal muscle lipid content;

      as well as how it influences the adipose tissue

        -  endocrine,

        -  metabolic &

        -  inflammatory phenotypes.

      The strength of the planned study lies in the extensive whole body and adipose tissue
      phenotyping before and after the 6-year rhGH replacement therapy, that allows to determine
      the long-term effects of rhGH replacement therapy in GHD adults.

      Envisaged weakness is the limited size of the population; GHD adults (n=20); controls [age
      BMI and gender matched] (n=20). This, however, reflects [is limited by] the complexity of the
      study protocol as well as the stringency of the inclusion criteria.

      The clinical data obtained by methods of - integrated physiology would provide an excellent
      interpretation background for molecular-genetic studies at the tissue (adipose tissue) and
      cellular (adipocytes) level. Integration of the two could bring a new quality in the
      investigators understanding of metabolic derangements present in GHD, and will allow
      extending the investigators knowledge on the mechanisms of the long-term rhGH-therapy-induced
      improvement on body composition, metabolic health and the cardiovascular risk.
    


Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        Twenty growth hormone deficient adults, receiving supplementation with rhGH for 5 years
        (extensively examined in 2005-2006, prior to the start of rhGH therapy) and 20 age-,
        gender- and BMI- matched controls will enter the study. Both, GHD patients and controls
        will undergo an extensive clinical protocol, identical to that performed in 2005 (Ukropec
        et al., 2008a).

        The possibility of drop-out of patients needs to be taken into consideration. Possible
        lowering of the numbers of participants due to drop-out of individuals tested in the
        Baseline Study will be resolved by either (i) using biological material obtained in the
        Baseline Study which was originally not subjected to an extensive molecular genetic testing
        due to the limited capacity and high cost of these analyses and/or by (ii) recruiting
        necessary amount of new patients with history of 5 years rhGH therapy (initial examination
        is missing).
      
Biospecimen description: 
      plasma 2.5 ml, serum 5 ml, adipose tissue 300 mg taken by the percutaneous biopsy of
      abdominal subcutaneous adipose tissue, in local anaesthesia.
    
Keywords: Growth hormone deficiency; hrGH therapy; metabolic health; adipose tissue metabolism; adipose tissue inflammation; adipokines