Bone Health After Bariatric Surgery in Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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Background: Bone fragility is a complication of type 2 diabetes. Diabetes treatments may ameliorate or deteriorate bone fragility in this population. Bariatric surgery is gaining in popularity in people with type 2 diabetes and may impact bone health. Objectives: To evaluate the impact of the most popular bariatric procedure worldwide (sleeve gastrectomy (SG)) on vBMD by QCT in patients with type 2 diabetes; Secondary aims: (1) to identify the determinants of vBMD after bariatric surgery in patients with type 2 diabetes; (2) to compare vBMD and its potential determinants after bariatric surgery with obese controls without diabetes as well as with controls without obesity and normoglycemia.

Detailed Description
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This is a multicentre, prospective and observational study comprising a bariatric group with or without diabetes undergoing SG (n=70) and one control group (n=30). Outcome measures are assessed before and at 4 months, 8 months, one year and 3 years after surgery in the bariatric groups and at a single visit for the control group. Bariatric groups will include adult men and women with or without type 2 diabetes and obesity undergoing sleeve gastrectomy and followed at 0, 4 months, 8 months, 1 year and 3 years after surgery, and the control group will consist of 30 overweight individuals (10 men, 10 premenopausal women, 10 menopausal women) and without diabetes or prediabetes and assessed at a single visit.

Official Title
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Bone Health After Bariatric Surgery in Patients With Type 2 Diabetes

Conditions
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Bariatric Surgery, Bone Health, Obesity, Morbid, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Procedure: Bariatric surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: bariatric groups: men and women; 18 to 60 years old; with a BMI >=35 kg/m2; with 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) (guidelines.diabetes.ca);) or without diabetes: HbA1c <6.5% AND fasting glucose <7.0 mM; who are awaiting bariatric surgery. Control group: BMI 25.0 to 29.9 kg/m2 (overweight group); without diabetes or prediabetes: HbA1c <6.0% AND fasting glucose <6.1 mM (Diabetes Canada criteria), with a stable weight for the last 3 months. Exclusion Criteria: bariatric groups: type 1 diabetes; disease (e.g. uncontrolled thyroid disease, malabsorptive or overt inflammatory disorder, metabolic bone disease, creatinine clearance <60 ml/min) or medication (e.g. glucocorticoids, anti-epileptic drugs, osteoporosis therapy and thiazolidinediones) affecting bone metabolism; BMI>60 kg/m2; CT scan impossible to perform (e.g. patient too large for the gantry aperture); pregnant women or women who plan to become pregnant during the study or women of childbearing age who do not agree to take an appropriate contraceptive method during the study; history of oesophageal, gastric or digestive surgery; history of bariatric surgery; cancer at risk of recurrence during the study; Prosthesis that could interfere with interpretation of imaging data; Chronic severe condition or illness precluding from participation in the project. Control group: Same criteria plus: >5% change in weight in the last 3 months; pregnancy or lactation in the last year.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sleeve gastrectomy diabetes<br>70 Men and women with or without type 2 diabetes and obesity undergoing sleeve gastrectomy | Procedure: Bariatric surgery<br>* Sleeve gastrectomy<br>|
| Control without obesity or diabetes<br>30 Men and women who are overweight (without obesity) and without diabetes | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in volumetric bone mineral density (vBMD) at lumbar spine, hip, tibia and radius | assessed by quantitative computed tomography (QCT) | before, 1 year after and 3 years after bariatric surgery | 
| Change in areal bone mineral density at lumbar spine, hip and radius | assessed by dual-energy X-ray absorptiometry (DXA) | before, 1 year after and 3 years after bariatric surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in N-terminal propeptide of type 1 procollagen (P1NP) | serum bone formation marker | before, 4 months after, 8 months after, 1 year after and 3 years after bariatric surgery | 
| Change in osteocalcin (total, gamma-carboxylated and and under-carboxylated) | serum bone formation marker | before, 4 months after, 8 months after, 1 year after and 3 years after bariatric surgery | 
| Change in bone alkaline phosphatase | serum bone formation marker | before, 4 months after, 8 months after, 1 year after and 3 years after bariatric surgery | 
| Change in C-telopeptide | serum bone resorption marker | before, 4 months after, 8 months after, 1 year after and 3 years after bariatric surgery | 
| Change in fasting glucose | diabetes control | before, 4 months after, 8 months after, 1 year after and 3 years after bariatric surgery | 
| Change in HbA1c | diabetes control | before, 4 months after, 8 months after, 1 year after and 3 years after bariatric surgery | 
| Change in fasting insulin | hormones involved in bone metabolism | before, 4 months after, 8 months after, 1 year after and 3 years after bariatric surgery | 
| Change in serum 25-hydroxyvitamin D | hormones involved in bone metabolism | before, 4 months after, 8 months after, 1 year after and 3 years after bariatric surgery | 
| Change in parathormone (PTH) | hormones involved in bone metabolism | before, 4 months after, 8 months after, 1 year after and 3 years after bariatric surgery | 
| Change in estradiol and estrone | hormones involved in bone metabolism | before, 4 months after, 8 months after, 1 year after and 3 years after bariatric surgery | 
| Change in insulin like growth factor (IGF)-1 | hormones involved in bone metabolism | before, 4 months after, 8 months after, 1 year after and 3 years after bariatric surgery | 
| Change in sclerostin | hormones involved in bone metabolism | before, 4 months after, 8 months after, 1 year after and 3 years after bariatric surgery | 
| Change in adiponectin | hormones involved in bone metabolism | before, 4 months after, 8 months after, 1 year after and 3 years after bariatric surgery | 
| Change in leptin | hormones involved in bone metabolism | before, 4 months after, 8 months after, 1 year after and 3 years after bariatric surgery | 
| Change in peptide YY (PYY) | hormones involved in bone metabolism | before, 4 months after, 8 months after, 1 year after and 3 years after bariatric surgery | 
| Change in ghrelin | hormones involved in bone metabolism | before, 4 months after, 8 months after, 1 year after and 3 years after bariatric surgery | 
| Change in oxidative stress markers | hormones involved in bone metabolism | before, 4 months after, 8 months after, 1 year after and 3 years after bariatric surgery | 
| Change in serum advanced glycation end products (AGEs) | hormones involved in bone metabolism | before, 4 months after, 8 months after, 1 year after and 3 years after bariatric surgery | 
| Change in Free fatty acids (FFA) | hormones involved in bone metabolism | before, 4 months after, 8 months after, 1 year after and 3 years after bariatric surgery | 
| Change in fat and lean mass | body composition assessed by bioimpedance and by DXA | before, 1 year after and 3 years after bariatric surgery | 
| Change in visceral and subcutaneous adipose tissue | body composition assessed by computed tomography (CT) | before, 1 year after and 3 years after bariatric surgery | 
| Change in muscle mass and fat content at mid-femur | assessed by computed tomography (CT) | before, 1 year after and 3 years after bariatric surgery | 
| Change in upper extremity muscle strength | assessed by hand grip strength | before, 1 year after and 3 years after bariatric surgery | 
| Change in lower extremity muscle strength | assessed by knee extensor strength | before, 1 year after and 3 years after bariatric surgery | 
| Change in muscle function | assessed by timed up and go test | before, 1 year after and 3 years after bariatric surgery | 
| Change in physical capacity | assessed by 6-minute walk test | before, 1 year after and 3 years after bariatric surgery | 
| Change in balance | assessed by Fullerton Advanced Balance (FAB) Scale | before and 1 year after bariatric surgery | 
| Change in sociodemographic factors | questionnaire | before, 1 year after and 3 years after bariatric surgery | 
| Change in nutrition | 3 web-based 24-h recalls | before, 4 months after, 8 months after, 1 year after and 3 years after bariatric surgery | 
| Change in self-reported physical activity level | by questionnaire | before, 4 months after, 8 months after, 1 year after and 3 years after bariatric surgery | 
| Change in measured physical activity level | by accelerometer | before, 1 year after and 3 years after bariatric surgery | 
| Change in gut microbiota | stool sample | before, 1 year after and 3 years after bariatric surgery | 
| Change in cutaneous Advanced glycation end products (AGEs) | skin autofluorescence | before, 4 months after, 8 months after, 1 year after and 3 years after bariatric surgery |