Microvascular Insulin Resistance and Mixed Meal Challenge

Study Overview
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Brief Summary
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Insulin resistance (or pre-diabetes) is diagnosed using the oral glucose tolerance test. However, high blood glucose levels during this test may adversely impact on microvascular function. Investigators will determine whether a liquid mixed meal challenge (from carbohydrate, protein and fat) is a more appropriate test for assessing microvascular-derived insulin resistance.

Detailed Description
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After consuming a meal, 80% of glucose is disposed in skeletal muscle. Our research group has demonstrated that microvascular blood flow in skeletal muscle plays an integral role in this process. Physiological doses of insulin stimulate microvascular blood flow, and that this increase is associated with enhanced glucose uptake by muscle. This microvascular action of insulin is lost during insulin resistance and type 2 diabetes. The oral glucose tolerance test (GTT) is the gold standard for assessing insulin resistance and pre-diabetes and is used world-wide. However high blood glucose levels following a glucose load may adversely impact on microvascular function. The aim of this project is to determine whether a mixed meal challenge (liquid drink consisting of carbohydrate, fat and protein) is a better test for assessing microvascular-derived insulin resistance.

Official Title
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Microvascular Insulin Resistance and Mixed Meal Challenge

Conditions
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Insulin Resistance

Intervention / Treatment
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* Other: Mixed Meal Challenge
* Other: Glucose Challenge


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-70 years. Normal to overweight (BMI 19-35 kg/m2). Normotensive (Seated brachial blood pressure <160/100 mmHg). Considered healthy (HbA1c <6.5 %) or have clinically diagnosed type 2 diabetes. Either have a parent with T2D, or no family history of type 2 diabetes for two generations. Have given signed informed consent to participate in the study Exclusion Criteria: Age <18 yrs or >70 yrs Morbidly obese with a BMI ≥36 kg/m2 History of myocardial infarction or stroke History of malignancy within past 5 years (except for non-melanoma skin cancers) Current smoker History of severe liver disease History of drug or alcohol abuse Elective major surgery during the course of the study Pregnancy/lactation Participation or intention to participate in another clinical research study during the study period.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mixed Meal Challenge<br>Participants will consume a liquid mixed meal ( 300 calories - fat, carbohydrate, and protein) for monitoring changes in glucose metabolism, plasma insulin and microvascular responses in skeletal muscle over 2 hours. | Other: Mixed Meal Challenge<br>* Liquid mixed meal (300 calories - fat, carbohydrate, and protein).<br>|
| Active Comparator: Glucose Challenge<br>Participants will consume a glucose challenge (50g glucose) for monitoring changes in glucose metabolism, plasma insulin and microvascular responses in skeletal muscle over 2 hours. | Other: Glucose Challenge<br>* Glucose drink (50g glucose)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in muscle microvascular blood flow | Microvascular responses will be measured by contrast enhanced ultrasound before and 1hr after each challenge. | 1 hr | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in blood glucose levels | Blood glucose levels will be measured at 0, 15, 30, 60, 90 and 120 min following each challenge. | 2 hr | 
| Changes in plasma insulin levels | Plasma insulin levels will be measured at 0, 15, 30, 60, 90 and 120 min following each challenge. | 2hr | 
| Changes in the respiratory exchange ratio (RER) | Changes in RER will be measured by metabolic cart during each challenge. | 1 hr | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Microvascular, Insulin resistance, Mixed Meal, Glucose tolerance