Adolescent Obesity, Beta Cell Dysfunction, Gut Hormones, Gut Microbiome, Immunity, Inflammation, Insulin Resistance, Metabolic Problems, Obesity, PreDiabetes
Conditions
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.
Interventions
None listed
Sponsors
University of Toronto
University of Guelph
Sunnybrook Health Sciences Centre
The Hospital for Sick Children
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
12 Years to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Canada
Outcome results
None listed