Postprandial Metabolites of Meal Challenge Test in Diabetes State

Study Overview
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Brief Summary
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Postprandial hyperglycemia is a hallmark feature of Type 2 Diabetes Mellitus (T2D), and persistent elevated glycemic level has shown to be strongly associated with oxidative stress, and a risk factor for cardiovascular disease (CVD). In Malaysia, the glycemic control is poor and patients with T2D commonly experiencing persistent postprandial hyperglycemia (12.7 mmol/L). A low glycemic index (GI) meal has been reported to reduce postprandial glycemia and insulin concentration in patients with T2D. Metabolomics technique can be used to identify comprehensive metabolites in response to different diet. Till date, local scientific data documented on the role and interaction between diet and metabolites for the Malaysian patients with T2D is unknown. This study is to determine the postprandial metabolomic effect of low and high GI meals in patients with T2D using the NMR-based metabolomics approach. Then, patients with T2D will be assigned for 14 days of chronic feeding trial intervention. This study will help to establish local baseline data and understand the impact of meal-patterns on metabolic and metabolite at postprandial responses.

Detailed Description
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Despite targeting to optimize fasting blood glucose and lowering HbA1c level, postprandial hyperglycemia needs to be highlighted in the management of Type 2 Diabetes Mellitus (T2D). Postprandial hyperglycemia is the rapid and significant rise in blood glucose level above 7.8 mmol/L 2 hour after meal ingestion. It is strongly associated with oxidative stress and a risk factor for cardiovascular disease (CVD). In Malaysia, the glycemic control is poor, and patients with T2D commonly experiencing persistent hyperglycemia (12.7 mmol/L), which is the highest concentration in South East Asia region. Nonetheless, a low glycemic index (GI) meal has been reported to reduce postprandial glycemia and insulin concentration in patients with T2D but the metabolite responsiveness following low GI meal is not studied yet. The study of the postprandial state is imperative as it reveals multiple aspects of metabolic health that would not be apparent from solely studying the fasting parameters. Hence, the objective of this study is to determine the postprandial metabolomic effects of low and high GI meals in patients with T2D using the NMR-based metabolomics approach. Then, the postprandial metabolic response and metabolomic profiles before and after the 14 days chronic feeding trial intervention will be determined and compared. The calculated sample size was 24 patients with T2D and 24 healthy individuals. The study design for meal challenge test (MCT) is a single-blinded, randomized crossover trial with 1-week washout period; whereas a case-control design will be used to compare metabolomic profiles of patients with T2D and healthy individuals. The MCT model is designed to be high GI (63) and low GI (46) with similar caloric value. During the test day, participants are required to consume the meal within 15 minutes and the blood sample will be taken at the following time points: 0min (fasting), 30, 60, 120, 180 and 240 min. Meanwhile, the urine sample will also be collected at 0, 60 and 240 min accordingly. The blood sample will be analyzed for blood glucose, insulin, GLP-1, and metabolites; while the urine sample will be analyzed for metabolites. The findings of this study are able to provide fundamental data on metabolic responsiveness of T2D patients following specific meal-plan tailored to Malaysian meal pattern using NMR-based metabolomics approach. Besides, this study is able to establish a local baseline data of postprandial metabolite profiles of patients with T2D following a specific meal plan. At the same time, this study contributes insight to improve diabetes meal-plan that is friendly to postprandial metabolic perturbations.

Official Title
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Metabolomics Determinant of Postprandial Metabolism Following Meal-Challenge Test in Diabetes State Using NMR-based Metabolomics Approach

Conditions
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Type2 Diabetes, Postprandial Hyperglycemia

Intervention / Treatment
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* Behavioral: Strategies to lower postprandial hyperglycemia in T2D patients
* Behavioral: Control group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI 18.5-35.0 kg/m² Glycemic control (HbA1c level 6.5 - 10.0%) On stabilised oral-antidiabetic drug (OAD) : metformin, sulphonylureas, SGLT2 inhibitors Estimated glomerular filtration rate (GFR) >60ml/min No clinically significant cardiovascular, renal or liver disease Exclusion Criteria: Smokers Pregnant and lactating women Food allergies or intolerances On weight loss diet On insulin therapy On OAD: DPP-4 inhibitors, GLP-1 receptor agonists, acarbose Anemia (Hb <10g/dL) On regular use of hormones or anti-inflammatory medication (aspirin, corticosteroid) Suggestive indicators for impaired thyroid (high T2H level) or liver function

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The meal challenge test (MCT) models are designed to be high glycemic index (GI) (GI=63, GL=25) and low GI meal (GI=46, GL=16), isocaloric (300kcal) with identical macronutrient distribution. The meals will be prepared on the morning of the test, portioned by weighing and served warm.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: T2D patients<br>T2D patients (n=24) will be randomized to high GI and low GI MCT randomly. | Behavioral: Strategies to lower postprandial hyperglycemia in T2D patients<br>* T2D patients will undergo a 14-day chronic feeding trial intervention where the strategies to lower postprandial hyperglycemia will be educated. For example, to control portion of carbohydrate, incorporate low GI food and diabetes-specific formula, promote physical activity and practice consistent meal timing. After that, patients will undergo MCT again to evaluate the difference before and after the intervention.<br>|
| Active Comparator: Healthy individuals<br>Healthy individuals (n=24) will be randomized to high GI MCT only. | Behavioral: Control group<br>* Assess nutritional status and no active intervention is conducted.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial glucose | Between low GI and high GI meal challenge measured by blood plasma using Abbott Architect c16000 analyser | Change from baseline and after 14-days intervention | 
| Postprandial insulin | Between low GI and high GI meal challenge measured by blood serum using COBAS e411 analyzer | Change from baseline and after 14-days intervention | 
| Postprandial GLP-1 | Between low GI and high GI meal challenge measured by blood plasma using total ELISA kit | Change from baseline and after 14-days intervention | 
| 1H-NMR metabolites | Between low GI and high GI meal challenge measured by blood plasma using 1H-NMR spectrometer | Change from baseline and after 14-days intervention | 
| Postprandial 1H-NMR metabolites | Between T2D and healthy individuals measured by blood plasma using 1H-NMR spectrometer | During the 4 hour meal challenge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body mass index (BMI) | Measured by weight change using Tanita digital weighing scale | Before and after the 14-days intervention | 
| Waist circumference | Using measuring tape | Before and after the 14-days intervention | 
| Lipid profile | Measured by blood plasma using Abbott Architect c16000 analyser | Before and after the 14-days intervention | 
| Dietary glycemic index (GI) | Between T2D and healthy individuals measured using Dietary History Questionnaire | Before and after the 14-days intervention | 
| Dietary Glycemic load(GL) | Between T2D and healthy individuals measured using Dietary History Questionnaire | Before and after the 14-days intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glycemic Index, NMR metabolomics, Postmeal glucose