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

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.

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Key information

Conditions

Obesity Adolescent Obesity Beta Cell Dysfunction Body Weight Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Gut Hormones Gut Microbiome Hyperinsulinism Immunity Inflammation Insulin Resistance Metabolic Diseases Metabolic Problems Nutrition Disorders Nutritional and Metabolic Diseases Overnutrition Overweight Pathologic Processes Pathological Conditions, Signs and Symptoms Pediatric Obesity PreDiabetes Prediabetic State Signs and Symptoms

Age range

12 year–18 year

Sex eligibility

All sexes

Study type

Observational

Primary location

The Hospital for Sick Children

Toronto, Ontario, M5G1X8, Canada

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

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

Treatment and study plan

Primary outcomes

Whole body insulin sensitivity index

Time frame: 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

Time frame: 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

Time frame: 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.

Sponsors and collaborators

Lead sponsor

The Hospital for Sick Children

Other

Collaborators

Sunnybrook Health Sciences Centre
University of Guelph
University of Toronto

Registry information

Official study title

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

Acronym: MI4D

Important dates

Study start: 2017
Primary completion: 2019
Study completion: 2019
First posted: Jul 24, 2019
Registry last updated: Sep 13, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed