Intermittent hypoxia training in prediabetes patients: Beneficial effects on glucose homeostasis, hypoxia tolerance and gene expression

Abstract

The present study investigated the beneficial effects of intermittent hypoxia training (IHT) in humans under prediabetic conditions. We found that three-week moderate IHT induced higher HIF-1a mRNA expressions as well as its target genes, which were positively correlated with higher tolerance to acute hypoxia and better glucose homeostasis in both middle-aged healthy and prediabetic subjects. This small clinical trial has provided new data suggesting a potential utility of IHT for management of prediabetes patients. AbstractThe present study aimed at examining beneficial effects of intermittent hypoxia training (IHT) under prediabetic conditions. We investigate the effects of three-week IHT on blood glucose level, tolerance to acute hypoxia, and leukocyte mRNA expression of hypoxia inducible factor 1a (HIF-1a) and its target genes, i.e. insulin receptor, facilitated glucose transporter-solute carrier family-2, and potassium voltage-gated channel subfamily J. Seven healthy and 11 prediabetic men and women (44-70 years of age) were examined before, next day and one month after three-week IHT (3 sessions per week, each session consisting 4 cycles of 5-min 12% O 2 and 5-min room air breathing). We found that IHT afforded beneficial effects on glucose homeostasis in patients with prediabetes reducing fasting glucose and during standard oral glucose tolerance test. The most pronounced positive effects were observed at one month after IHT termination. IHT also significantly increased the tolerance to acute hypoxia (i.e. SaO 2 level at 20th min of breathing with 12% O 2 ) and improved functional parameters of respiratory and cardiovascular systems. IHT stimulated HIF-1a mRNA expression in blood leukocytes in healthy and prediabetic subjects, but in prediabetes patients the maximum increase was lagged. The greatest changes in mRNA expression of HIF-1a target genes occurred a month after IHT and coincided with the largest decrease in blood glucose levels. The higher expression of HIF-1a was positively associated with higher tolerance to hypoxia and better glucose homeostasis. In conclusion, our results suggest that IHT may be useful for preventing the development of type 2 diabetes.

Physiological and Biological Responses to Short-Term Intermittent Hypobaric Hypoxia Exposure: From Sports and Mountain Medicine to New Biomedical Applications

“…Intermittent exposure to both normobaric and hypobaric hypoxia has been related to some protective effects (Cai et al, 2003 ; Costa et al, 2013 ) and beneficial outcomes in several pathological conditions, especially in those related to metabolic syndrome (Marquez et al, 2013 ; Leone and Lalande, 2017 ; Serebrovska et al, 2017 ). The possible role of intermittent hypoxia on body weight control has also attracted considerable attention.…”

Effects of Living High-Training Low and High on Body Composition and Metabolic Risk Markers in Overweight and Obese Females

“…From the theoretical point of view, exercise combined with hypoxic exposure could be much helpful to reduce more blood lipids. For prediabetes patients, it has also been repeated breath intermittent hypoxia (12% O 2 ) could decrease serum glucose, cholesterol, and LDL [52,53]. Applying hypoxic training to improve blood lipids in individuals with obesity is one of the main expectations.…”

Effects of four weeks intermittent hypoxia intervention on glucose homeostasis, insulin sensitivity, GLUT4 translocation, insulin receptor phosphorylation, and Akt activity in skeletal muscle of obese mice with type 2 diabetes

“…It has also been demonstrated that a few weeks of exercise in moderate hypoxia resulted in more significant weight loss in individuals with obesity, as compared to exercising with the same or higher intensities under normoxia [ 10 – 12 ]. However, there have been only a small number of reports on the effects of repeated exposure to IHI for several weeks, without a combination of other types of intervention, on fasting blood glucose (FBG) and insulin (FBI) [ 7 , 13 ], with inconsistent outcomes. For example, Serebrovska et al [ 7 ] reported that in older adults with pre-diabetes, nine sessions of IHI in three weeks with the fraction of oxygen in the inspired air (FiO 2 ) of 0.12, did not result in a significant decrease in FBG at the end of the intervention period, but a significant decrease was found one month post the intervention.…”

“…However, there have been only a small number of reports on the effects of repeated exposure to IHI for several weeks, without a combination of other types of intervention, on fasting blood glucose (FBG) and insulin (FBI) [ 7 , 13 ], with inconsistent outcomes. For example, Serebrovska et al [ 7 ] reported that in older adults with pre-diabetes, nine sessions of IHI in three weeks with the fraction of oxygen in the inspired air (FiO 2 ) of 0.12, did not result in a significant decrease in FBG at the end of the intervention period, but a significant decrease was found one month post the intervention. Schreuder et al [ 13 ] reported that an eight-week exercise-program significantly improved physical fitness of type 2 diabetes patients, but the addition of hypoxia (0.165 FiO 2 ) did not potentiate the effects of the exercise on fitness, vascular function and glucose homeostasis.…”