Identification of Biometric Marker(s) Capable of Detecting Early Prediabetes: Clinical Trial 1: Antagonism of Hepatic Muscarinic Receptors Attenuates the Postprandial Actions of Hepatic Insulin Sensitizing Substance (HISS)
Overview
- Phase
- Not Applicable
- Intervention
- Standardized liquid test meal
- Conditions
- Healthy
- Sponsor
- SciMar Ltd.
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Time course change in serum glucose
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The proposed clinical trial is a controlled study of n=24 healthy adult individuals tested in both the Meal-Induced Insulin Sensitization (MIS) state and, following atropine blockade, Absence of Meal-Induced Insulin Sensitization (AMIS) state to differentiate the postprandial glycemia, insulinemia, triglyceride and Hepatic Insulin Sensitizing Substance (HISS) levels in the two states.
The purpose of this study is the identification and development of biometric markers which incorporate the actions and interplay between insulin and HISS. Overall, the study aims to:
- Utilize a standardized test meal to detect one of the earliest pathologies present during the development of insulin resistance, pre-diabetes and obesity.
- Compare the control (HISS positive) and post-atropine (HISS negative) tests with the acute consequences of absence of MIS (AMIS) being graphically shown over 4 hours of postprandial nutrient partitioning, tracking the full metabolomic dynamic pattern.
- To establish values for potential indices (bio-impedance, hand-grip strength, spirometry) in young, fit, lean individuals. These values will be used as baselines for comparative analysis in future clinical trials employing individuals with various degrees of insulin resistance to full Type 2 Diabetes.
- Demonstrate that these biometric markers can differentiate between the HISS positive and HISS negative post-meal state with the future aim of using the biomarkers for the detection of early prediabetes.
The study will involve 4 study visits: Visit 1 - Prescreening; Visit 2 - Screening; Visit 3 - Liquid test meal administration and postprandial blood collection; Visit 4 - Atropine administration + Liquid test meal administration and postprandial blood collection.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy (absence of disease)
- •Not on any prescribed medications
- •Male and female (in follicular phase)
- •20-40 years of age
- •Normal BMI range (18.5-24.9)
- •Able to understand and communicate in English
- •Comfortable having blood drawn
- •Willing to provide urine and blood samples
- •Normal urinalysis, Complete Blood Count (CBC) and blood chemistry laboratory test results
- •Willingness to undergo bioimpedance testing, handgrip dynamometry (strength) testing, and pulmonary function test (spirometry).
Exclusion Criteria
- •Glaucoma, Pyloric Stenosis
- •Obstructive Uropathy, Urinary Incontinence
- •Diabetes, Cardiovascular Disease, including Heart Murmurs
- •Diagnosed or with history (last 6 months) and receiving pharma or professional therapy for Psychological/Psychiatric issues
- •Inflammatory conditions, including IBD
- •Subject on any hormone treatment, including thyroid hormone
- •Subject on any steroid therapy including cortisol, or any anti-inflammatory agent
- •Sensitivity to anti-cholinergic drugs
- •Allergic or have sensitivities to rubbing alcohol during blood draw
- •Allergy/sensitivity to any component of the standardized test meal (dextrose, lecithin, soy protein)
Arms & Interventions
Standardized liquid test meal
Intervention: Standardized liquid test meal
Atropine + Standardized liquid Test meal
Intervention: Atropine + Standardized liquid test meal
Outcomes
Primary Outcomes
Time course change in serum glucose
Time Frame: Control: Baseline, and every 30 minutes up to 4 hours after test meal administration; Test: Baseline, 15 mins post atropine and every 30 minutes up to 4 hours after test meal administration
Time course and curve analysis of serum glucose response after the test meal administration with and without atropine pre-treatment.
Time course change in serum insulin
Time Frame: Time Frame: Control: Baseline, and every 30 minutes up to 4 hours after test meal administration; Test: Baseline, 15 mins post atropine and every 30 minutes up to 4 hours after test meal administration
Time course and curve analysis of serum insulin response after the test meal administration with and without atropine pre-treatment
Time course change in serum triglycerides
Time Frame: Control: Baseline, and every 30 minutes up to 4 hours after test meal administration; Test: Baseline, 15 mins post atropine and every 30 minutes up to 4 hours after test meal administration
Time course and curve analysis of serum triglycerides response after the test meal administration with and without atropine pre-treatment
Time course change in plasma HISS levels
Time Frame: Time Frame: Control: Baseline, and every 30 minutes up to 4 hours after test meal administration; Test: Baseline, 15 mins post atropine and every 30 minutes up to 4 hours after test meal administration
Time course and curve analysis of plasma HISS response after the test meal administration with and without atropine pre-treatment
Secondary Outcomes
- Time course change in serum free fatty acids(Control: Baseline, and every 30 minutes up to 4 hours after test meal administration; Test: Baseline, 15 mins post atropine and every 30 minutes up to 4 hours after test meal administration)
- Time course change in plasma lactate(Control: Baseline, and every 30 minutes up to 4 hours after test meal administration; Test: Baseline, 15 mins post atropine and every 30 minutes up to 4 hours after test meal administration)
- Time frame fasted HOMA-IR (Molar Units)(Control: Baseline fasted Test: 15 mins post atropine)
- Time course change in Meal Induced Glycemia (MIG) scores (Molar Units)(Control: Every 30 minutes up to 4 hours after test meal administration; Test: Every 30 minutes up to 4 hours after test meal administration)