Relationships Between GLP-2 and Markers of Bone Turnover Following Feeding (GLP-2)

Relationships Between GLP-2 and Markers of Bone Turnover Following Feeding: the Influence of Obesity and Cellular Mechanisms of Action

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

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Other: Study visit procedures

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

• Study Type: Observational
• Enrollment (Actual): 19

Contacts and Locations

Study Locations

• United Kingdom
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S5 7AU
      • Academic Unit of Bone Metabolism

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• 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.

Description

Inclusion Criteria:

• Age 25-40
• Caucasian
• Premenopausal
• Able and willing to consent
• BMI either 18.5-24.9 kg/m2 or ≥30 kg/m2
• Completion 'The Effects of Obesity on Bone Structure and Strength' study REC ref 10/H1308/61
• Consented to be approached for future research studies

Exclusion Criteria:

• Fracture less than twelve months prior to recruitment
• History of any long term immobilization (duration greater than three months)
• Current pregnancy or trying to conceive Pregnancy or breast feeding less than one year prior to recruitment
• Diabetes mellitus

• History of or current conditions known to affect bone metabolism, which may include:

  • Diagnosed skeletal disease or osteoarthritis
  • Chronic renal disease
  • Acute or chronic hepatic disease
  • Hyperparathyroidism or Hyperthyroidism
  • Malabsorption syndromes
  • Diagnosed endocrine disorders
  • Diagnosed diabetes mellitus
  • Clinically significant hypocalcemia or hypercalcemia
  • Diagnosed restrictive eating disorder

• Current or clinically significant previous use of medications or treatment known to affect bone metabolism, for example:

  • Depot medroxyprogesterone or the combined oral contraceptive pill
  • Glucocorticoid therapy
  • Anti-convulsant therapy
  • Bone treatments (e.g. Bisphosphonates)
• Alcohol intake of greater than 21 units per week
• Athlete, defined as an individual participating in competitive sport at amateur or professional level
• Monogenic and obesity syndromes
• History of cancer within the past 5 years excluding skin cancer non melanomas

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Obese; Premenopausal women, 25 - 40 years with BMI of ≥30kg/m2	Other: Study visit procedures; 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.
Lean; Premenopausal women, 25 - 40 years with BMI of 18.5-24.9 kg/m2	Other: Study visit procedures; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
GLP-2 levels	Change at 20, 60 and 120 minutes

Secondary Outcome Measures

Outcome Measure	Time Frame
Osteocalcin levels	Change at 20, 60 and 120 minutes
β Carboxy-terminal collagen crosslinks (β CTx)levels	Change at 20, 60 and 120 minutes
Procollagen 1 N-terminal propeptide (P1NP) levels	Change at 20, 60 and 120 minutes
High-resolution peripheral quantitative computed tomography (HRpQCT)	At baseline
Dual-emission X-ray absorptiometry (DXA)	At baseline

Collaborators and Investigators

• Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust
• Collaborators: University of Sheffield
• Investigators: Principal Investigator: Paul Dimitri, Dr, Sheffield Childrens Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2011
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: February 3, 2012
• First Submitted That Met QC Criteria: February 8, 2012
• First Posted (Estimate): February 13, 2012

Study Record Updates

• Last Update Posted (Actual): February 15, 2019
• Last Update Submitted That Met QC Criteria: February 12, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Obesity; Bone; Premenopausal; GLP2; Formation; Resorption
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: STH16160