Obstructive Sleep Apnea-induced Changes in Adipose and Liver Tissue and Effects of Massive Weight Loss on Inflammation
Condition: Obesity; Obstructive Sleep Apnea
MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Inflammation; Weight Loss
Study type: Observational

Summary: 
      UPDATED May 2016:

      Originally the study design included investigation of the effects of the bioactive compound
      resveratrol compared to placebo tablets and to CPAP treatment. Due to fewer subjects having
      OSA than estimated by pre-study and, therefore, difficulties in the recruiting process the
      investigators have found it necessary to descale the study design. Hence, we have
      discontinued the resveratrol and CPAP intervention and will focus on the cross-sectional
      investigation of metabolic changes in subjects with and without OSA and the effect of weight
      loss after bariatric surgery on inflammation, OSA severity, metabolism and arterial
      stiffness.

      Obstructive sleep apnea (OSA) is a common disorder especially among obese individuals and
      patients with type 2 diabetes. OSA is associated with an increased morbidity and mortality.

      Continuous positive airway pressure (CPAP) is the standard treatment. Also weight loss is
      known to reduce the severity of OSA, especially bariatric surgery has proven effective
      because of the massive weight loss.

      The investigators hypothesize that OSA via pro-inflammatory responses in various tissues
      causes low-grade inflammation which ultimately induce the associated co-morbidities. The
      investigators hypothesize that massive weight loss after bariatric surgery have beneficial
      effects on severity of OSA, inflammatory status and improves insulin sensitivity.
    

Detailed description: 
      UPDATED May 2016:

      Originally the study design included investigation of the effects of the bioactive compound
      resveratrol compared to placebo tablets and to CPAP treatment. Due to fewer subjects having
      OSA than estimated by pre-study and, therefore, difficulties in the recruiting process the
      investigators have found it necessary to descale the study design. Hence, we have
      discontinued the resveratrol and CPAP intervention and will focus on the cross-sectional
      investigation of metabolic changes in subjects with and without OSA and the effect of weight
      loss after bariatric surgery on inflammation, OSA severity, metabolism and arterial
      stiffness.

      OSA causes insulin resistance and seems to aggravate obesity related comorbidities such as
      hypertension, dyslipidemia and increase the risk of development of type 2 diabetes and
      non-alcoholic fatty liver disease.

      More mechanisms may be involved in the pathogenesis of these negative effects from OSA but
      hypoxia-induced low-grade inflammation may play a central role since the levels of
      inflammatory markers generally are elevated in OSA. The tissues which are responsible for
      these systemic alterations are not known, however, adipose tissue might be a good candidate
      since it is known from studies that human adipose tissue can influence systemic inflammation.

      Some studies even describe a small but significant anti-inflammatory effect and a beneficial
      effect on glucose metabolism following CPAP treatment. In addition, weight loss in patients
      with OSA is known to reduce the severity of or completely eliminate OSA.

      The purpose of this study is primarily to investigate:

        1. the metabolic changes in adipose and liver tissue induced by OSA in order to better
           understand how OSA negatively affects whole-body metabolism

        2. the effect of weight loss after bariatric surgery on systemic inflammation, metabolism
           and the severity of OSA

      24 subjects scheduled to undergo bariatric surgery will be recruited. They will all be
      screened for OSA. 12 subjects without OSA and 12 subjects with OSA will be included and
      examined before surgery and 6 months post-surgery.

      The investigators will look at changes in:

        -  Inflammation-markers

        -  Biochemical markers of fat and sugar-metabolism

        -  Gene-expression in adipose and liver-tissue

        -  Severity of OSA

        -  Pulse-wave velocity
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Study groups will be selected from subjects referred to the outpatient clinics in Central
        Denmark Region and who meet the national guideline criteria for bariatric surgery.
      
Biospecimen description: 
      Blood samples, urine, subcutaneous adipose tissue, visceral adipose tissue and liver tissue.
    
Keywords: Inflammation; Insulin resistance; Bariatric surgery