Mechanisms of Inflammation, Immunity, Islet Cell and Intestinal Hormone Changes in Youth at Risk for Diabetes (MI4D)

Mechanisms of Inflammation, Immunity, Islet Cell and Intestinal Hormone Changes in Youth at Risk for Diabetes (MI4D)

This study intends to assess the role of inflammation in insulin resistant conditions (i.e., obesity and pre-diabetes) and the subsequent development of disease, such as type 2 diabetes (T2D) and cardiovascular disease (CVD), in the adolescent population.

Study Overview

• Status: Completed
• Conditions: Inflammation; Obesity; Insulin Resistance; PreDiabetes; Adolescent Obesity; Immunity; Gut Microbiome; Gut Hormones; Beta Cell Dysfunction; Metabolic Problems

Detailed Description

This study proposes to characterize inflammatory biomarkers, insulin resistance and fecal microbiome composition in obese/pre-diabetic adolescents after glucose ingestion, followed by an oral fat tolerance test on a separate visit. Lipoprotein abnormalities and intestinal biomarkers, post-lipid ingestion, will also be evaluated. The primary aim is to assess the role of inflammation in insulin resistant conditions (i.e., obesity and pre-diabetes) and the subsequent development of disease, such as type 2 diabetes (T2D) and cardiovascular disease (CVD), in the adolescent population.

• Study Type: Observational
• Enrollment (Actual): 52

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G1X8
      • The Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adolescents with obesity

Description

Inclusion Criteria:

1. Adolescents aged 12 - 18 years old with obesity (defined as body mass index (BMI) >97th percentile based on their age- and sex-specific World Health Organization growth chart)

Exclusion Criteria:

1. Known type 2 diabetes
2. Diabetes secondary to medication or surgery
3. Antibodies suggestive of type 1 diabetes
4. Pregnancy
5. Were born by C-section
6. Developmental delay precluding assent/consent
7. Acute illness within the past 3 days (chills, fever, vomiting > 1x, or diarrhea > 3x)
8. Taking medications that influence glucose (e.g., steroids, metformin) or lipids (e.g., statins)
9. Have taken prescribed medicine/antibiotics in the three months prior to clinic or study visit
10. Significant chronic illness (e.g., Cushing's Disease, Craniopharyngioma, Hypothalamic Obesity, etc.)
11. Lactose intolerance and/or milk allergy (Study Visit Day 2 Only)
12. Bariatric surgery

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Whole body insulin sensitivity index	Multiple measurements from a 2-hour oral glucose tolerance will be aggregated to arrive at one reported value (ie., insulin in uU/mL units and glucose values in mg/dL units which are measured at baseline, 30 min, 60 min, 90 min, and 120 min during the oral glucose tolerance test will be combined to calculate whole body insulin sensitivity index). There is no unit of measure for whole body insulin sensitivity index. Whole body insulin sensitivity index will be calculated using the following equation: whole body insulin sensitivity index = 10,000 / √ [(fasting glucose x fasting insulin) x (mean glucose x mean insulin)].	Through study completion, an average of 2 years.
Microbiome Composition	We will perform microbiome 16S ribosomal ribonucleic acid (rRNA) sequencing in fecal samples from study participants.	Through study completion, an average of 3 years.
Inflammatory markers	Cytokines will be measured in plasma and fecal water with Bio-PlexTM arrays providing biomarkers of type 1 diabetes and/or type 2 diabetes progression. As indices of gut microbial translocation, serum lipopolysaccharides (LPS), macrophage secreted cluster of differentiation 14 (CD14) that binds LPS and LPS binding protein (LBP) will be examined.	Through study completion, an average of 3 years.

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Collaborators: Sunnybrook Health Sciences Centre; University of Toronto; University of Guelph
• Investigators: Principal Investigator: Jill K Hamilton, MD, The Hospital for Sick Children

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2017
• Primary Completion (Actual): February 15, 2019
• Study Completion (Actual): March 1, 2019

Study Registration Dates

• First Submitted: July 10, 2019
• First Submitted That Met QC Criteria: July 19, 2019
• First Posted (Actual): July 24, 2019

Study Record Updates

• Last Update Posted (Actual): September 13, 2022
• Last Update Submitted That Met QC Criteria: September 12, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Hyperinsulinism; Obesity; Inflammation; Pediatric Obesity; Insulin Resistance
• Other Study ID Numbers: 1000055159

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No