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

Completed

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

• Registration Number: NCT04031222
• Lead Sponsor: The Hospital for Sick Children

Brief Summary

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.

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 Timeline

• Study Start: 2017-05-19
• Primary Completion: 2019-02-15
• Study Completion: 2019-03-01
• Study First Submitted: 2019-07-10
• Study First Submitted QC: 2019-07-19
• Study First Posted: 2019-07-24
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-12
• Last Update Posted: 2022-09-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 52

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Whole body insulin sensitivity index	Through study completion, an average of 2 years.	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 / √ \[(fasting glucose x fasting insulin) x (mean glucose x mean insulin)\].
Microbiome Composition	Through study completion, an average of 3 years.	We will perform microbiome 16S ribosomal ribonucleic acid (rRNA) sequencing in fecal samples from study participants.
Inflammatory markers	Through study completion, an average of 3 years.	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.

Trial Locations

Locations (1)

The Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada