Blood Flow Responses to an Oral Glucose Tolerance Test in Type 2 Diabetes

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.

Inclusion criteria

• Insulin resistant: diagnosed with pre-diabetes or fasting blood glucose >/= 100 mg/dL
• T2D: diagnosed by primary care physician
• BMI: less than 43 kg/m2
• Age: 30-65

Exclusion criteria

• Smoking
• Insulin use (other than once daily)
• Underlying conditions that limit ability to exercise safely
• Recent weight gain or loss (> 5% of body weight in 3 months)
• Physically active (> 30 min aerobic exercise, 2 d/wk)
• Recent (< 3 mo) changes in medication use or dose
• Uncontrolled T2D (HbA1c > 10%)
• Advanced retinopathy or neuropathy
• Pregnancy