Blood Flow Responses to an Oral Glucose Tolerance Test in Type 2 Diabetes
Condition: Type 2 Diabetes; Insulin Resistance
MeSH terms: Diabetes Mellitus, Type 2; Insulin Resistance
Study type: Interventional

Summary: 
      The investigators wish to determine whether a short period of exercise training (5-10 days)
      improves the metabolic and cardiovascular response of people with or at risk of developing
      type 2 diabetes to eating a meal. In healthy people, blood flow to skeletal muscles increases
      after eating a meal, and this helps to regulate blood sugar levels by delivering blood sugar
      to muscles where it can be stored or metabolized. In people with or at risk of type 2
      diabetes, blood flow does not increase as much after eating a meal, and this may contribute
      to elevated blood sugar concentrations observed in these individuals. The investigators wish
      to determine whether exercise can improve this response.
    

Detailed description: 
      Insulin resistance is characterized by decreased sensitivity to the metabolic actions of
      insulin (glucose disposal) and is a hallmark of obesity and type 2 diabetes (T2D). Insulin
      resistance is also a prominent component of cardiovascular diseases (CVD), including
      hypertension, coronary artery disease, and atherosclerosis, which are characterized by
      endothelial dysfunction. Insulin stimulates two distinct signaling pathways in the
      endothelium. One produces the vasodilator nitric oxide (NO) through the insulin receptor
      substrate-1(IRS-1)/endothelial NO synthase (eNOS) pathway while the other stimulates
      production of endothelin-1 (ET-1), a vasoconstrictor, through the mitogen activated protein
      kinase (MAPK) pathway. Insulin-mediated glucose disposal is largely dependent upon the
      vasodilatory effects of insulin; however, in T2D, insulin-stimulated dilation is impaired as
      a result of an imbalance in NO and ET-1 production, leading to diminished microvascular
      perfusion and skeletal muscle glucose delivery in response to insulin. The effects of
      exercise on insulin signaling/action in the endothelium are not fully understood. The purpose
      of this study is determine the acute effects of aerobic exercise training on cardiometabolic
      responses to meal ingestion in individuals with insulin resistance or T2D. We will recruit 30
      previously sedentary (<60 minutes of planned exercise/week) men and women with insulin
      resistance (pre-diabetes) or T2D for participation in this study. Participants will undergo a
      screening procedure, including telephone screening and physical examination, as well as
      determination of body composition and fitness. Participants will be asked to complete 5-10
      days of supervised exercise training and will undergo testing to assess cardiovascular and
      metabolic responses to an oral glucose tolerance test, including muscle sympathetic nerve
      activity, blood flow, and circulating glucose and insulin concentrations at baseline and
      following training. In addition, participants will use continuous glucose monitoring systems
      for 3 days at baseline and during 3 days of exercise training to assess the effects of acute
      exercise on postprandial glucose responses to mixed meals in free-living individuals. The
      overall aim of the project is to determine whether or not acute exercise training influences
      postprandial metabolic, vascular or autonomic nervous system responses in individuals with
      insulin resistance or T2D.
    

Intervention name(s): Exercise
Intervention type(s): Behavioral
Intervention description(s): short period of exercise training (5-10 days)
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Type II Diabetes; Insulin Resistance; Exercise; Continuous Glucose Monitoring