Acute hypoxia and exercise improve insulin sensitivity (Si2*) in individuals with type 2 diabetes - Mackenzie et al. (2011)

Key Points

  • Hypoxic rest and exercise in hypoxia both increase insulin sensitivity in type 2 diabetic patients

  • We must consider how hypoxia stimulates the sympathetic nervous system when using it as a therapeutic tool for glycemic control

The Breathing Diabetic Summary

Similar to LeCoultre et al. (2013), this study was partially motivated by the fact that some studies show that hypoxia improves insulin sensitivity, whereas others show that hypoxia causes insulin resistance.  We also know from Navarrete-Opazo and Mitchell (2014) that the beneficial effects of hypoxia are dose dependent, which helps explain some of these disparities.  However, in addition to looking at the effects of hypoxia on insulin resistance, this study also looked at the combined effects of hypoxia and exercise on insulin sensitivity. We know from Azevedo et al. (1995) that hypoxia stimulates glucose transport independent of insulin, similar to the effects of exercise.  The current authors wanted to see if these mechanisms (hypoxia & exercise) had additive effects.

Their study protocol involved 4 groups: One group rested in hypoxia for 60 min, one group rested in normoxia for 60 min, one group exercised in normoxia for 60 min, and one group exercised in hypoxia for 60 min.  Oxygen levels for the hypoxic group were maintained at ~14.6%, which is within the therapeutic range.  They also monitored the participants’ blood oxygen saturations to ensure they never fell below 70% (but results showed that they never fell below 88%, again, definitely in the therapeutic range).  All participants had type 2 diabetes.

The author’s found that just resting in hypoxia for 60 min decreased blood sugar levels compared to normoxic rest.  However, insulin levels were unchanged, indicating that hypoxic rest increased insulin sensitivity.  On the other hand, hypoxia plus exercise significantly decreased circulating insulin levels 4 h after exercise, but had less effect on blood sugar levels.  Perhaps unsurprisingly, exercise alone (in normoxia) improved insulin sensitivity when compared to normoxic rest.  Finally, hypoxic exercise also improved insulin sensitivity when compared to normoxic exercise, showing an additive effect of hypoxia and exercise.

A possible explanation for these results is that, because mitochondria require oxygen for energy production, hypoxia increases glucose uptake to compensate for lack of O2.  Specifically, hypoxia might stimulate the sympathetic nervous system to release adrenaline and increases the body’s dependency on glucose.  These hormones also increase the body’s endogenous production of glucose, so it makes sense that the body would be “primed” to dispose of glucose during these scenarios.  However, it’s a somewhat grey area.  Hypoxia increases glucose disposal, i.e., lowers blood sugar.  But, through activating the sympathetic nervous system, it also increases the body’s endogenous production of glucose.  Thus, glucose transport caused by hypoxia might be offset (or even overpowered) by the stress hormones that are released.  (Note: this is why Principle 3 emphasizes “easy” breath holds where you can recover between 3-5 breaths.  Principle 3 aims to minimize the sympathetic response, but maximize the glucose disposal and insulin sensitivity benefits of hypoxia.)

Overall, this paper shows improved insulin sensitivity following moderate hypoxia. There are clearly some things that need to be taken into consideration, most importantly the role of hormones and the sympathetic response that occurs during hypoxia.However, it appears that hypoxia can potentially be used to improve glycemic control in diabetics.

Abstract from Paper

Background Hypoxia has been shown to increase glucose uptake in skeletal muscle using the contraction-stimulated pathway, independent of the actions of insulin. Yet, the same stress has also been linked with causing insulin resistance and hyperglycaemia. The aim of this study was to examine the effects of acute hypoxia with and without exercise on insulin sensitivity (SI 2*) in individuals with type 2 diabetes.

Methods Eight type 2 diabetic patients completed 60 min of the following: (1) normoxic rest; (2) hypoxic rest [O2 = 14.6 (0.4)%]; (3) normoxic exercise and (4) hypoxic exercise [O2 = 14.6 (0.4)%]. Exercise trials were set at 90% of lactate threshold. Each condition was followed by a labeled intravenous glucose tolerance test to provide estimations of insulin sensitivity (SI 2*) and beta-cell function.

Results Two-compartmental analysis showed that insulin sensitivity (SI 2*) was higher following hypoxic rest compared with normoxic rest (p = 0.047). Insulin sensitivity (SI 2*) was also higher following hypoxic exercise [4.37 (0.48) × 10−4/min (μU/mL)] compared with normoxic exercise [3.24 (0.51) × 10−4/min (μU/mL)] (p = 0.048). Acute insulin response to glucose was reduced following hypoxic rest versus normoxic rest (p = 0.014).

Conclusions This study demonstrated that (1) hypoxic-induced improvements in glucose tolerance in the 4 h following exposure can be attributed to improvements in peripheral insulin sensitivity (SI 2*) and (2) exercise and hypoxia have an additive effect on insulin sensitivity (SI 2*) in type 2 diabetic patients. Acute hypoxia may therefore improve short-term glycaemic control in individuals with type 2 diabetes. The application of these findings in the clinic will require further investigation.

Journal Reference:
Richard Mackenzie, Neil Maxwell, Paul Castle, Gary Brickley, and Peter Watt, (2011) Acute hypoxia and exercise improve insulin sensitivity (Si2*) in individuals with type 2 diabetes, Diabetes Metab Res Rev, 27, 94–101, DOI:10.1002/dmrr.1156.