Exploring the Molecular Basis to Healthy Obesity: The Diabetes Risk Assessment Study

Not Applicable

Completed

• Conditions: Type-2 Diabetes; Obesity; Metabolic Syndrome; Dyslipidemia
• Interventions: Other: High fat/high calorie meal

• Registration Number: NCT01884714
• Lead Sponsor: University of Guelph

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.

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:

1. Recruit a sample of lean, lean/diabetic, obese, and obese/diabetic research participants from the Guelph community.

2. 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.

3. Define the metabotype of these 4 groups by profiling plasma metabolites with mass spectrometry. The current study will examine only blood metabolites.

4. Define subcutaneous adipose tissue gene expression profiles of these 4 groups using microarray technology.

Study Timeline

• Study Start: 2011-07
• Study First Submitted: 2013-06-18
• Study First Submitted QC: 2013-06-20
• Study First Posted: 2013-06-24
• Primary Completion: 2013-12
• Study Completion: 2013-12
• Status Verified: 2016-07
• Last Update Submitted: 2016-07-06
• Last Update Posted: 2016-07-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• Stable body weight (± 2 kg) for at least 3 months.

Exclusion Criteria

• Evidence of acute or chronic inflammatory disease
• Infectious diseases
• Viral infection
• Cancer
• Alcohol consumption (i.e. more than 2 drinks/day, where 1 drink = 10 g alcohol).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
High fat/high calorie meal	High fat/high calorie meal	All subjects are provided a high calorie (\~1300kcal) and high fat (\~60g fat) breakfast meal.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Examine global serum metabolite profiles associated with obesity and diabetes.	baseline	Serum metabolites will be measured using gas chromatography coupled with mass spectrometry.
Analyze adipose tissue gene expression in obese and diabetic subjects	baseline	Gene expression analyzed using microarrays
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.
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.

Trial Locations

Locations (1)

University of Guelph, Human Nutraceutical Research Unit; 🇨🇦 Guelph, Ontario, Canada