Molecular, Metabolomic and Nutritional Changes After Metabolic Surgery

Study Overview
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Brief Summary
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Obesity is a major risk factor for Type 2 Diabetes (T2D) and cardiovascular diseases, such as hypertension and dyslipidemia. Recently, weight loss surgery (i.e., metabolic or bariatric surgery) has been shown to result in very good long-term glycemic control in patients with T2D and obesity. However, knowledge and data on molecular levels and metabolomics are still limited. This study will fill in these gaps and provide potential biomarkers for T2D. Lifestyle and dietary practices (LDP) influence the clinical outcome and metabolites in T2D. Although the roles of LDP is critical in ensuring optimal clinical outcomes, data is still limited especially on relating the LDP and metabolomics in T2D.

Detailed Description
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Study design This is a prospective single centre study to explore molecular aspects and metabolomic changes among 102 obese individuals of different diabetes status, undergoing metabolic surgery, which is currently performed in Hospital Kuala Lumpur, Malaysia. Serial measurements of the selected markers will be made pre-operative (baseline), at 6 and 12 months follow up after surgery. Twenty (20) healthy individuals will be recruited as controls. Study population All subjects with obesity (Body Mass Index ≥ 30kg/m^2 [WHO classification])) and diagnosed with pre-diabetes, T2D and non-diabetic (healthy) who are undergoing metabolic surgery at Hospital Kuala Lumpur will be recruited. All patients referred by endocrinologists who are eligible and fulfill the inclusion and exclusion criteria for metabolic surgery will be included in the study until the sample size is achieved. Routinely, all patients will need to pay a visit to the clinic at 1, 2, 4 weeks after surgery, then 3, 6, 9, 12, 18, 24 months and after that, a life-long annual visit. Therefore, visit 6- and 12-month will be utilized for study follow-ups. Metabolic surgery The two most standard metabolic surgical procedures performed at Hospital Kuala Lumpur are laparoscopic sleeve gastrectomy and laparoscopic Roux en Y gastric bypass (RYGB). All the procedures are performed laparoscopically using 5-ports technique.

Official Title
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Molecular, Metabolomic and Nutritional Changes After Metabolic Surgery Among Obese Diabetic Patients and Biomarkers of Different Diabetes Status.

Conditions
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Obesity; Endocrine, Diabete Type 2, PreDiabetes

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients' Inclusion Criteria BMI > 30kg/m2 Men and women Ages 18-65 years old Diabetes status (non diabetic, pre diabetes and diabetes) Patients who will undergo metabolic surgery Healthy individuals' Inclusion Criteria BMI < 30kg/m2, Men and women Ages 18-65 years old No diabetes No pre diabetes No other co-morbidities (high total cholesterol, high triglycerides, high blood pressure) Exclusion Criteria: Patients' Exclusion Criteria BMI <30 kg/m2 Use of medications that may affect body weight at screening or during a 3 month period prior Other medical conditions like Cushing's, acromegaly, Heart failure, Crohn's disease, etc Alcohol dependence Healthy Individuals' Exclusion Criteria BMI > 30 kg/m2 (obese) BMI < 18.5 kg/m2 (underweight) Diabetes status (pre diabetes and diabetes) Use of medications that may affect body weight at screening or during a 3 month period prior Other co-morbidities (high total cholesterol, high triglycerides, high blood pressure, cancer) Other medical conditions like Cushing's, acromegaly, Heart failure, Crohn's disease, etc Alcohol dependence

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| Obese only<br>Definition of Obese: Body Mass Index ≥ 30kg/m^2 (WHO classification) Definition of Non Diabetes: Fasting Plasma Glucose (FPG) < FPG 100 mg/dL (5.6 mmol/L) | |
| Obese with prediabetes<br>Definition of Obese: Body Mass Index ≥ 30kg/m^2 (WHO classification) Definition of Prediabetes: FPG 100 mg/dL (5.6 mmol/L) to 125 mg/dL (6.9 mmol/L) (IFG) OR A1C 5.7-6.4% (39-47 mmol/mol) | |
| Obese with diabetes<br>Definition of Obese: Body Mass Index ≥ 30kg/m^2 (WHO classification) Definition of Diabetes: (American Diabetes Association, 2020) FPG ≥126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 h.* OR A1C ≥6.5% (48 mmol/mol). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body weight changes | Body weight changes | 6 months | 
| Body weight changes | Body weight changes | 12 months | 
| Body mass index (BMI) changes | Body mass index changes measured in kg/m^2 (weight in kilograms, height in meters) | 6 months | 
| Body mass index (BMI) changes | Body mass index changes measured in kg/m^2 (weight in kilograms, height in meters) | 12 months | 
| Body Fat Percentage changes | Body Fat Percentage changes measured in percentage | 6 months | 
| Body Fat Percentage changes | Body Fat Percentage changes measured in percentage | 12 months | 
| Fasting Blood Glucose changes | Fasting Blood Glucose changes measured in mmol/L | 6 months | 
| Fasting Blood Glucose changes | Fasting Blood Glucose changes measured in mmol/L | 12 months | 
| HbA1c changes | HbA1c changes measured in percentage | 6 months | 
| HbA1c changes | HbA1c changes measured in percentage | 12 months | 
| Changes of metabolites profile | Changes of serum diabetes-related metabolites using Nuclear Magnetic Resonance (NMR) | 6 months | 
| Changes of metabolites profile | Changes of serum diabetes-related metabolites using Nuclear Magnetic Resonance (NMR) | 12 months | 
| Changes in lipid related biochemical parameters | Changes in triglyceride, total cholesterol, LDL cholesterol, HDL cholesterol levels in mmol/L | 6 months | 
| Changes in lipid related biochemical parameters | Changes in triglyceride, total cholesterol, LDL cholesterol, HDL cholesterol levels in mmol/L | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life changes | Quality of Life score measured by Obesity and Weight-Loss Quality of Life (OWLQOL ) questionnaire | At baseline, month 6 and month 12 | 
| Dietary Intake changes | Dietary intake changes measured by Food Frequency Questionnaire (FFQ) | At baseline, month 6 and month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bariatric surgery, Metabolic surgery