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

Abstract

The 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 1α (HIF-1α) 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% O₂ 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. SaO₂ level at 20th min of breathing with 12% O₂) and improved functional parameters of respiratory and cardiovascular systems. IHT stimulated HIF-1α 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-1α target genes occurred a month after IHT and coincided with the largest decrease in blood glucose levels. The higher expression of HIF-1α 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. Impact statement 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-1α 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.

Keywords: Intermittent hypoxia; adaptation; diabetes; hyperglycemia; hypoxia inducible factor-1; hypoxia inducible factor-1-regulated genes.

Figure 1

Effect of IHT on mRNA expression of hypoxia inducible factor 1α (HIF-1α) (a), facilitated glucose transporter–solute carrier family-2 (SLC2) (b), insulin receptor (INSR) (c), and potassium voltage-gated channel subfamily J (KCNJ8) (d) in healthy subjects and prediabetic patients. Data are presented as mean ± SD. *P < 0.05 vs. pre-IHT baseline; ^P < 0.05 vs. 1 wk IHT; ⁺P < 0.05 vs. 3 wk IHT; and ^#P < 0.05 vs. healthy group. IHT: intermittent hypoxia training

Figure 2

Relationships between baseline SaO₂ at 20th minute of acute hypoxic test (AHT, breathing with 12% of oxygen) and baseline fasting glucose (a), baseline 2 h post-OGTT glucose (b), baseline mRNA expression of HIF-1α (c), and % changes in mRNA expression of HIF-1α between the pre-IHT baseline and post-IHT values (d). HIF: hypoxia inducible factor; OGTT: oral glucose tolerance test. Symbols of correlation coefficient (*P < 0.05 or **P < 0.01) indicate a significant degree of linear relationship between the variables