HONG KONG – Treating obstructive sleep apnoea with nasal continuous positive airway pressure improves insulin sensitivity, finds a recent study published in the European Respiratory Journal.

Researchers of the Department of Medicine, Queen Mary Hospital, Hong Kong, China, compared insulin sensitivity of 31 patients with moderate obstructive sleep apnoea who had received nCPAP to a similar control group of 30 patients who only received sham nCPAP.

Patients in the first group improved their insulin sensitivity as measured by the short insulin tolerance test. Other evaluations included blood pressure, metabolic profile, urinary catecholamines and intra-abdominal fat. Patients who received therapeutic nCPAP were also evaluated at 12 weeks.

Therapeutic nCPAP treatment of OSA improved insulin sensitivity after one week in nondiabetic males, and the improvement was maintained after 12 weeks of treatment in those with moderate obesity.

“These findings suggest that OSA is an independent risk factor for adverse glucose metabolism, but the detrimental effects may be less prominent in nonobese subjects compared with moderately obese subjects. The pathogenetic pathway of impaired insulin sensitivity may involve sympathetic activation and other adiposity-related mechanisms.”

Sleep disorder causes metabolic havoc

As to the question of how obstructive sleep apnoea adversely affects glucose metabolism or contributes to its complications, many different mechanisms have been described. Firstly, sleep abnormalities influence endocrine function. The result is a rise in cortisol levels via an increased activity in the hypothalamic-pituitary-adrenal axis, directly contributing to hyperglycaemia. Secondly, inflammatory cytokines are released in response to the intermittent hypoxia and re-oxygenation that accompany the condition, not only decreasing insulin sensitivity, but also inducing a chronic state of inflammation. Finally, the induction of oxidative stress caused by alternating phases of lack of oxygen and re-oxygenation releases end products of glycation implicated in vascular complications of diabetes.

“The effect of co-existent obesity on glucose metabolism in OSA has been a contentious issue. Obesity, especially visceral obesity, is an important determinant of insulin sensitivity, and an inevitable confounder in studies of adverse metabolic effects of OSA.

In this study, patients who were morbidly obese had been excluded, with the speculation that severe obesity may have an overwhelming effect on insulin resistance masking any contribution by OSA.

After 12 weeks of CPAP treatment there was no effect on obesity itself: there were no changes in BMI, waist circumference or in the amount of visceral fat. Moderately obese subjects exhibited a better metabolic response compared with the nonobese. “Although the physical mass of patients remained static, the composites of adiposity might have changed at the molecular levels after treatment.”

As to why obese patients suffering from obstructive sleep apnoea may benefit more from nCPAP than those who are not overweight, the authors conclude:
“A number of inflammatory and neurohumoral mediators are produced from the adipose tissues, especially from the visceral adipose tissues which have been demonstrated to be involved in the pathogenesis of insulin resistance. With the application of nCPAP treatment in the obese apnoeic group, the changes of these mediators and, hence, insulin sensitivity might have been more pronounced than the nonobese apnoeic group.”

“Our findings strongly support the notion that OSA has a causal role on insulin resistance, and the improvement with CPAP treatment carries clinical relevance”.

“Treatment of OSA improves insulin sensitivity in the short term, suggesting a causal relationship between OSA and insulin resistance. Early effective nCPAP treatment of OSA may favourably impact on the natural course of glucose metabolism in otherwise healthy subjects.”

Reference:
Lam JC et al.  Eur Respir J. 2010 Jan;35(1):138-45