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

NCT04031222 | Completed

• 1 other identifier: 1000055159
• Study Type: observational
• Target: 52
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• 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.

Eligibility Criteria

• Age: 12 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Adolescents with obesity

You may qualify if:

• \. 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)

You may not qualify if:

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

Sponsors & Collaborators

• The Hospital for Sick Children: lead
• University of Toronto: collaborator
• University of Guelph: collaborator
• Sunnybrook Health Sciences Centre: collaborator

Study Sites (1)

The Hospital for Sick Children

Toronto, Ontario, M5G1X8, Canada

Location

MeSH Terms

Conditions

Obesity; Prediabetic State; Pediatric Obesity; Inflammation; Insulin Resistance

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Pathologic Processes; Hyperinsulinism

Study Officials

• Jill K Hamilton, MD

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Endocrinologist, Division Head, Endrocrinology

Study Record Dates

• First Submitted: July 10, 2019
• First Posted: July 24, 2019
• Study Start: May 19, 2017
• Primary Completion: February 15, 2019
• Study Completion: March 1, 2019
• Last Updated: September 13, 2022

Record last verified: 2022-09

Locations

CA (1)