DRA: Exploring the Molecular Basis to Healthy Obesity: The Diabetes Risk Assessment Study
Study Details
Study Description
Brief Summary
The purpose of this study is to better understand the genetic and metabolic differences in obese individuals with and without type 2 diabetes. It is expected that this research will help improve our understanding of the variability observed between obese and diabetic individuals.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Detailed Description
PURPOSE: Diabetes is one of the fastest growing diseases in Canada; however, lifestyle changes (e.g. changes in diet and physical activity) can prevent or postpone the development of this metabolic disease. The proposed research project hypothesizes that knowledge of the diabetic and obese metabolic phenotype (i.e. the metabotype) has value in predicting these diseases, preventing their downstream complications, and personalizing therapeutic and lifestyle interventions to improve diabetes and obesity management. The overall purpose of this research is to identify biomarkers that uniquely reflect the metabolic perturbations associated with type 2 diabetes and obesity. This information will be invaluable in the design of more personalized interventions to manage these disease states
RATIONALE: Type-2 diabetes is a disease state that affects multiple organs of the biological system, including alterations in adipocyte and muscle insulin signalling, hepatic glucose production, glucose absorption from the gastrointestinal tract, and pancreatic insulin deficiency caused by the loss of β-cell mass and function. Understanding the molecular communication taking place both within and between these tissues is paramount to unravel the metabolic regulatory networks and mechanisms underlying diabetes. Global gene expression profiling (i.e. transcriptomics) and metabolite profiling (i.e. metabolomics) offer powerful approaches to understand the biological processes associated with diabetes and obesity. The analysis of gene expression profiles provides an opportunity to identify early markers of metabolic dysregulation. In contrast, metabolites represent an endpoint of gene and protein function; thus metabolomics is ideally suited for the identification of biomarkers that reflect the biochemical processes underlying a physiological state. By integrating gene expression profiling with metabolite profiling, we will have the opportunity to improve our understanding of the metabolic perturbations related to obesity and/or type-2 diabetes.
OBJECTIVES: The specific goals of this project are to:
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Recruit a sample of lean, lean/diabetic, obese, and obese/diabetic research participants from the Guelph community.
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Assess blood glucose and insulin levels in these 4 groups both at baseline and after the consumption of a standardized high fat/high calorie meal.
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Define the metabotype of these 4 groups by profiling plasma metabolites with mass spectrometry. The current study will examine only blood metabolites.
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Define subcutaneous adipose tissue gene expression profiles of these 4 groups using microarray technology.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: High fat/high calorie meal All subjects are provided a high calorie (~1300kcal) and high fat (~60g fat) breakfast meal. |
Other: High fat/high calorie meal
All subjects are provided a high calorie (~1300kcal) and high fat (~60g fat) breakfast meal.
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Outcome Measures
Primary Outcome Measures
- Measure circulating inflammatory markers and fatty acids associated with obesity and diabetes. [baseline]
Common inflammatory markers (e.g. IL-6, TNFalpha, adiponection) will be measured using either standard ELISA and multiplex bead technology. Serum fatty acids will be measured using gas chromatography.
Secondary Outcome Measures
- Analyze adipose tissue gene expression in obese and diabetic subjects [baseline]
Gene expression analyzed using microarrays
- Measure standard clinical and anthropometric markers associated with obesity and diabetes. [baseline]
Standard clinical parameters (e.g. triglycerides, cholesterol, glucose, insulin, etc) and anthropometric measurements (e.g. body mass index, waist circumference, etc) will be determined.
- Examine global serum metabolite profiles associated with obesity and diabetes. [baseline]
Serum metabolites will be measured using gas chromatography coupled with mass spectrometry.
- Measure standard clinical and anthropometric parameters in obese and diabetic participants following a standardized meal. [2 hours after consuming a standardized meal]
All subjects will be provided a standardized meal and after 2 hours standard clinical parameters (e.g. triglycerides, cholesterol, glucose, insulin, etc) will be determined.
Eligibility Criteria
Criteria
Inclusion Criteria:
- Stable body weight (± 2 kg) for at least 3 months.
Exclusion Criteria:
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Evidence of acute or chronic inflammatory disease
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Infectious diseases
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Viral infection
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Cancer
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Alcohol consumption (i.e. more than 2 drinks/day, where 1 drink = 10 g alcohol).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Guelph, Human Nutraceutical Research Unit | Guelph | Ontario | Canada | N1G 2W1 |
Sponsors and Collaborators
- University of Guelph
- Public Health Agency of Canada (PHAC)
Investigators
- Principal Investigator: David M Mutch, PhD, University of Guelph
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 10AP033