For the past 100 years, cardiovascular disease has been the leading cause of death in the United States. An aging population, increasing levels of obesity and the predominance of a sedentary lifestyle contribute to the growing incidence of type 2 diabetes, one of the major modifiable risk factors for cardiovascular disease. It is now predicted that 1 in 3 adults will develop diabetes by 2050, implying that a large percentage of the population will become at high risk for cardiovascular disease, the most common cause of death in patients with type 2 diabetes. While exercise reduces insulin resistance and the elevated glucose levels associated with type 2 diabetes, only 28% of the adult population with diabetes meet physical activity recommendations. Thus, our overall objective is to identify an alternative, non-pharmacological intervention that prevents the development of type 2 diabetes in individuals with prediabetes, and treats the insulin resistance and hyperglycemia in patients already diagnosed with type 2 diabetes.

The Nobel Prize in Physiology was recently awarded to scientists who established the basis for our understanding of how varying oxygen levels affect cellular metabolism, which paved the way for promising new strategies to fight diseases. Breathing low levels of oxygen, or hypoxia, stimulates glucose uptake in skeletal muscle via 5' adenosine monophosphate-activated protein kinase (AMPK), the same signaling pathway as muscle contraction, which acts independently from the actions of insulin. Thus, patients with type 2 diabetes were exposed to either normoxia or 60 min of continuous hypoxia (fraction of inspired oxygen of \~0.15, arterial oxygen saturation of 92%) immediately before performing a 4-hour intravenous glucose tolerance test. Hypoxia lowered blood glucose levels and did not affect insulin concentrations, therefore, it was suggested that the improved glycemic control was caused by the activation of the AMPK pathway in combination with an improved insulin sensitivity. Similarly, a single exposure to intermittent hypoxia, consisting of 6 min at a fraction of inspired oxygen of 0.13 alternated with 6 min of normoxia for 1 hour, improved glycemic control in patients with type 2 diabetes. Specifically, there was a greater decrease in glucose levels measured immediately after intermittent hypoxia, and the increase in glucose levels following a meal was attenuated following intermittent hypoxia when compared to a placebo condition. A decrease in glucose levels was also observed following a single session of intermittent hypoxia, consisting of brief desaturation and resaturation cycles to maintain an arterial oxygen saturation of 80% for approximately 70 min, in overweight and obese individuals with normal baseline glucose levels.

The specific aim of this research project is to identify whether exposure to intermittent hypoxia during an oral glucose tolerance test attenuates the increase in glucose levels in healthy individuals, individuals with prediabetes and patients with type 2 diabetes. It is hypothesized that exposure to intermittent hypoxia will attenuate the increase in glucose levels in response to an oral glucose tolerance test in healthy individuals, individuals with prediabetes and patients with type 2 diabetes.