Relationships Between GLP-2 and Markers of Bone Turnover Following Feeding
Condition: Obesity
MeSH terms: Obesity
Study type: Observational

Summary: 
      This study has been designed to study differences bone turnover in relation to glucagon-like
      peptide-2 (GLP-2) following feeding in lean and obese premenopausal women. Given the
      preliminary evidence that GLP-2 may act directly on osteoclasts, the investigators plan to
      determine whether GLP2 receptors are expressed in osteoclasts and the effect of GLP-2 on bone
      resorption.

      Hypotheses:

        1. Acute responses of GLP-2 and bone resorption markers following feeding are affected by
           body fat mass.

        2. Serum levels of GLP-2 are lower in obese pre-menopausal women and are associated with a
           reduction in trabecular and/or cortical bone mass

        3. GLP-2 has direct actions on osteoclast resorption via a functional receptor
    

Detailed description: 
      Study objectives:

        1. To determine if differences in baseline serum levels of GLP-2 are related to differences
           in bone microarchitecture, structure and strength at the distal tibia and distal radius
           between obese and lean premenopausal females.

        2. To determine whether obesity in premenopausal females influences levels of circulating
           GLP-2 following a standardised glucose meal with a resultant change in markers of bone
           formation and resorption

        3. To test whether GLP-2 directly affects osteoclast function via an identifiable receptor
    

Intervention name(s): Study visit procedures
Intervention type(s): Other
Intervention description(s): Anthropometric measurements to include:
Weight, height, and BMI.
Waist and hip circumference
Triceps skinfold thickness
Measurement of supine abdominal thickness A baseline blood sample (15ml)is taken before receiving a standard polycal drink (75g glucose load) Three further blood samples (15 ml) will be taken, at the time points 20, 60 and 120 minutes after glucose loading. In 10 subjects (5 lean and 5 obese) we will take an additional blood sample (up to 50 ml) at baseline into heparin to grow osteoclasts in culture. Visit duration - approximately 3-4 hours.
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        The investigators will recruit healthy pre-menopausal, Caucasian female participants 25-40
        years and divide them into two groups, obese and lean according to their Body Mass Index.
        Participants will be identified and approached from a study group of obese and lean
        participants previously recruited for the 'The Effects of Obesity on Bone Structure and
        Strength - Fat and Bone Study (FAB)' study (REC ref 10/H1308/61) conducted at the Academic
        Unit of Bone Metabolism (AUBM) in Sheffield. Participants from this study have been
        selected as some of the scan and neuromuscular function data generated from this study will
        be reused as explained below. Body Mass Index ≥30 kg/m2 will be used to define obesity with
        BMI for lean participants defined as 18.5-24.9 kg/m2. Thirty participants will be
        recruited, 15 obese and 15 lean. Participants will be matched for age, and where possible
        height.
      
Biospecimen description: 
      On completion of the study, serum and plasma aliquots will be moved to the Human Tissue
      Authority (HTA) licensed biorepository housed in the Centre for Biomedical Research.
    
Keywords: GLP2; Obesity; Premenopausal; Bone; Formation; Resorption