Exploring the Molecular Basis to Healthy Obesity: The Diabetes Risk Assessment Study
Condition: Obesity; Type-2 Diabetes; Metabolic Syndrome; Dyslipidemia
MeSH terms: Diabetes Mellitus; Obesity; Diabetes Mellitus, Type 2; Metabolic Syndrome; Dyslipidemias
Study type: Interventional

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.
    

Intervention name(s): High fat/high calorie meal
Intervention type(s): Other
Intervention description(s): All subjects are provided a high calorie (~1300kcal) and high fat (~60g fat) breakfast meal.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: diabetes; obesity; metabolism; clinical study