Determinants of Bone and Muscle Quality and Strength in Obesity With and Without Diabetes (BODI2)

Background: Osteoporotic fractures are a major public health issue. They cause substantial disability, loss of autonomy, morbidity and excess mortality. Diabetes is also associated with increased risk for falls and fractures through a direct impact of elevated blood glucose on the skeleton and on muscles.

Research project overview: The investigators propose a cross-sectional study that will involve 2 research centers in the province of Quebec. The investigators will recruit 20 obese participants, without diabetes, who have not undergone bariatric surgery, for one-time measurements to be compared with baseline measurements (pre-surgery) from participants in the bariatric obese diabetic groups with type II diabetes mellitus from the ongoing study BODI study (NCT03455868). Bone Mineral Density as well as muscle quality, strength and function will be evaluated at a single study visit.

Relevance: This data will permit the evaluation of the bone-muscle unit in patients with obesity with and without diabetes, and assess whether the presence and duration of diabetes impacts further on clinical and functional musculoskeletal outcomes (falls, fractures and mobility and strength) in this population. AGEs, if associated with muscle and bone deterioration, might become an easily accessible biomarker of musculoskeletal health in the clinical setting.

Study Overview

• Status: Completed
• Conditions: Quality of Life; Obesity; Fractures, Bone; Diabetes Mellitus, Type 2; Diabetes Mellitus; Body Weight; Musculoskeletal Diseases; Osteoporosis; Bone Diseases, Metabolic; Fall; Osteoporotic Fractures

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada, G1V 4G5
    • Centre de recherche de l'IUCPQ
  • Quebec
    • Montréal, Quebec, Canada, H3H 2R9
      • Research Institute of the McGill University Health Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

This is a multi-center, cross-sectional, observational study comprising of two groups of participants with obesity either with or without diabetes (n=20/group). The diabetic groups will include 20 adult men and women with obesity and type 2 diabetes, and the non-diabetic group will consist of 20 age- and sex- matched individuals with obesity and normoglycemia.

Description

Inclusion Criteria:

A) Diabetic group

• BMI >=35 kg/m2
• Clinical diagnosis of type 2 diabetes
• Use of oral hypoglycemic agents or insulin or 2 of the following tests confirming type 2 diabetes: HbA1c >=6.5%; fasting glucose >=7.0 mM; 2-h glucose post 75g oral glucose tolerance test (OGTT) >=11.1 mM)

B) Non-diabetic group:

• BMI >=35 kg/m2
• Normoglycemia (HgbA1c <5.7% and Fasting glucose <5.6 nM)

Exclusion Criteria:

• BMI >60 kg/m2
• Clinical diagnosis of type 1 diabetes
• Disease (e.g. uncontrolled thyroid disease, malabsorptive or overt inflammatory disorder, metabolic bone disease, creatinine clearance <60 ml/min)
• Medication (e.g. gluccocorticoids, anti-epileptic drugs, osteoporosis therapy and thiazolidinediones) affecting bone metabolism
• Pregnancy
• History of oesophageal, gastric, digestive or bariatric surgery
• Prosthesis that could interfere with interpretation of imaging data
• Chronic severe condition or illness precluding from participation in the project.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Diabetic; 20 men and women with type 2 diabetes and obesity
Non-diabetic; 20 normoglycemic men and women with obesity matched for age and sex with diabetic group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle size measured as cross-sectional muscle area at the proximal femur	Measured by quantitative computed tomography (QCT)	Baseline
Muscle composition measured as muscle fat content at the proximal femur	Measured by quantitative computed tomography (QCT)	Baseline
Volumetric bone mineral density (vBMD) at the spine, hip, radius and tibia	Measured by quantitative computed tomography (QCT)	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
N-terminal propeptide of type 1 procollagen concentration	Serum bone formation marker	Baseline
Osteocalcin (total and decarboxylated) concentration	Serum bone formation marker	Baseline
Bone specific alkaline phosphatase concentration	Serum bone formation marker	Baseline
C-telopeptide concentration	Serum bone resorption marker	Baseline
Fasting glucose concentration	Diabetes control	Baseline
Fasting Hemoglobin A1c concentration	Diabetes control	Baseline
Insulin concentration	Hormone involved in bone metabolism	Baseline
Serum 25-hydroxyvitamin D concentration	Hormone involved in bone metabolism	Baseline
Parathormone concentration	Hormone involved in bone metabolism	Baseline
Estradiol concentration	Hormone involved in bone metabolism	Baseline
Insulin like growth factor-1 concentration	Hormone involved in bone metabolism	Baseline
Sclerostin concentration	Hormone involved in bone metabolism	Baseline
Adiponectin concentration	Hormone involved in bone metabolism	Baseline
Leptin concentration	Hormone involved in bone metabolism	Baseline
Body composition measured as visceral and subcutaneous adipose tissue	Measured by computed tomography (CT)	Baseline
Body composition measured by fat and lean mass	Measured using dual-energy X-ray absorptiometry (DXA)	Baseline
Bone marrow adiposity	Measured by computed tomography (CT)	Baseline
Upper extremity muscle strength measured by grip force in kg	Measured using Jamar Hydraulic Hand Dynamometer	Baseline
Lower extremity muscle strength measured by peak torque generated by knee extension	Measured using Biodex isokinetic dynamometer	Baseline
Functional mobility measured by time that a person takes to rise from a chair, walk three meters, turn around, walk back to the chair, and sit down.	Measured using Timed Up and Go test.	Baseline
Functional exercise capacity measured by total distance ambulated during a 6 minute time period	Measured using Six Minute Walk Test	Baseline
Self-reported physical activity measured in metabolic equivalents (MET)	Measured using the International Physical Activity Questionnaire	Baseline
Cutaneous Advanced glycation end products (AGEs) measurement	Measured by measured by AGE Reader	Baseline
Physical activity measured by total activity and time spent in different intensities of exercise measured over 7 consecutive days	Actigraph GT3X+ Accelerometer	Baseline
Functional balance score obtained using multidimensional balance assessment. Higher scores indicate better balance abilities	Fullerton Advanced Balance (FAB) Scale	Baseline
Physical health	SF-12	Baseline
Community Participation Restriction	Life-space mobility assessment	Baseline
Health-related quality of life	How are you today? Visual analogue scale	Baseline

Collaborators and Investigators

• Sponsor: Suzanne Morin
• Collaborators: CHU de Quebec-Universite Laval

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2020
• Primary Completion (Actual): June 14, 2021
• Study Completion (Actual): June 14, 2021

Study Registration Dates

• First Submitted: September 10, 2019
• First Submitted That Met QC Criteria: September 13, 2019
• First Posted (Actual): September 18, 2019

Study Record Updates

• Last Update Posted (Actual): September 1, 2021
• Last Update Submitted That Met QC Criteria: August 30, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Mobility; Strength; Advanced glycation end products; Advanced imaging
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Wounds and Injuries; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Overweight; Diabetes Mellitus; Diabetes Mellitus, Type 2; Obesity; Body Weight; Fractures, Bone; Osteoporosis; Bone Diseases; Musculoskeletal Diseases; Bone Diseases, Metabolic; Metabolic Diseases; Osteoporotic Fractures
• Other Study ID Numbers: MP-37-2020-5872

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No