Microvascular Insulin Resistance and Mixed Meal Challenge

Menzies Institute for Medical Research45 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

SCREENING

Masking

NONE

Enrollment

Conditions

Insulin Resistance

Interventions

Mixed Meal ChallengeOTHER

Liquid mixed meal (300 calories - fat, carbohydrate, and protein).

Glucose ChallengeOTHER

Glucose drink (50g glucose)

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (2)

Menzies Institute for Medical Research

Hobart, Tasmania, Australia

Deakin University

Burwood, Victoria, Australia

Outcomes

Primary Outcomes

Change from baseline in muscle microvascular blood flow

Microvascular responses will be measured by contrast enhanced ultrasound before and 1hr after each challenge.

Time frame: 1 hr

Secondary Outcomes

Changes in blood glucose levels

Blood glucose levels will be measured at 0, 15, 30, 60, 90 and 120 min following each challenge.

Time frame: 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.

Time frame: 2hr

Changes in the respiratory exchange ratio (RER)

Changes in RER will be measured by metabolic cart during each challenge.

Time frame: 1 hr

Data from ClinicalTrials.gov

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