Microvascular Insulin Resistance and Mixed Meal Challenge

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Insulin Resistance
• Intervention / Treatment: Other: Mixed Meal Challenge; Other: Glucose Challenge

Detailed Description

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
• Enrollment (Anticipated): 45
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Menzies Institute for Medical Research
  • Victoria
    • Burwood, Victoria, Australia, 3125
      • Deakin University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mixed Meal Challenge; 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; Liquid mixed meal (300 calories - fat, carbohydrate, and protein).
Active Comparator: Glucose Challenge; 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; Glucose drink (50g glucose)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Menzies Institute for Medical Research
• Collaborators: Deakin University
• Investigators: Principal Investigator: Michelle A Keske, PhD, Menzies Institute for Medical Research

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2014
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: February 17, 2016
• First Submitted That Met QC Criteria: March 9, 2016
• First Posted (Estimate): March 15, 2016

Study Record Updates

• Last Update Posted (Actual): April 6, 2021
• Last Update Submitted That Met QC Criteria: April 4, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Insulin resistance; Microvascular; Glucose tolerance; Mixed Meal
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance
• Other Study ID Numbers: H14086

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO