Erythropoietin response to intermittent hypoxia in health and type 2 diabetes

Patients with type 2 diabetes and aging individuals experience declines in maximal oxygen consumption. Hemoglobin mass, a component of oxygen transport, strongly correlates to maximal oxygen consumption. Interventions that increase hemoglobin mass may therefore increase maximal oxygen consumption in older adults and patients with type 2 diabetes. Intermittent hypoxia, characterized by alternating periods of breathing low levels of oxygen interspersed with periods breathing normoxic air, has the potential to elicit an acute increase in erythropoietin levels and hemoglobin mass. Despite several instances of repeated exposures to intermittent hypoxia increasing red blood cell count over the course of five days to three weeks, there exists a lack of consistent stimuli across the literature, with deviations in hypoxic duration, number of cycles, and hypoxic severity. Furthermore, studies that successfully increased oxygen transport following intermittent hypoxia did not measure erythropoietin levels, the hormone regulating red cell production, thereby eliminating the possibility for protocol comparison. Therefore, the following three studies aimed to identify the shortest intermittent hypoxia protocol to increase erythropoietin levels in healthy young individuals, and to apply this intermittent hypoxia protocol to older individuals and patients with type 2 diabetes, with the goal of potentially increasing hemoglobin mass. In the first study, we identified the shortest hypoxic protocol within the literature to increase EPO concentrations among young healthy adults. The EPO response to the 32 total hypoxic minutes was no different than a 2-hour continuous hypoxia protocol. In the second study, we demonstrated that EPO concentrations increased following the same intermittent hypoxia in middle-aged adults but found no increase to hemoglobin mass. In the third study, we demonstrated a lack of EPO response to intermittent hypoxia in patients with type 2 diabetes. Furthermore, this study was the first to report hemoglobin mass levels in patients with type 2 diabetes. Collectively, the overall findings highlight the acute effects of intermittent hypoxia on erythropoietin in health and type 2 diabetes.