Untreated OSA ups metabolic and CV stress
Obstructive sleep apnoea (OSA), if left untreated for just a few days, can increase the levels of blood glucose, plasma free fatty acids (FFA), stress hormones, and blood pressure during sleep, a study has shown, lending support to regular use of continuous positive airway pressure (CPAP).
“Clinicians should be aware of the vulnerability of OSA patients to metabolic dysfunction during sleep and the cardiovascular effects of even short-term OSA exposure,” said the researchers led by Dr Jonathan Jun of Johns Hopkins University in Baltimore, Maryland, US. “Diabetic patients are particularly susceptible to nocturnal glucose elevation.”
The crossover trial involved 31 patients (mean age 50.8 years, 67.7 percent males) with moderate-to-severe OSA who had been accustomed to treatment with CPAP. The patients were randomized to either CPAP therapy or CPAP withdrawal for 2 days while sleeping in a sleep lab with polysomnography. The patients underwent 1–4 weeks of washout period before crossing over to the other group. Blood samples were drawn every 20 minutes during the study. [J Clin Endocrinol Metab 2017;102:3172-3181]
OSA was suppressed during CPAP exposure while it recurred with CPAP withdrawal (mean AHI*, 60.7). During the CPAP withdrawal phase, patients experienced more hypoxaemia and disrupted sleep, with a longer time spent with SpO2** <90 percent, increased frequency of ≥3 percent oxygen desaturation, and more sleep arousals compared with the CPAP exposure phase (p<0.0001 for all). Increase in heart rate also occurred.
In terms of metabolic measures, dynamic increases in nocturnal glucose by ~6 mg/dL (p=0.028), FFA (p=0.007), and cortisol (p=0.037) were observed with CPAP withdrawal, in proportion to increases in respiratory events, sleep disruption, and heart rate; although the researchers noted that “many metabolic parameters normalized shortly after awakening in the morning.”
“OSA recurrence during CPAP withdrawal increases FFA and glucose during sleep … Recurring exposure to these metabolic changes may foster diabetes and cardiovascular disease,” they said.
According to the researchers, the rise in nocturnal glucose levels with OSA was driven primarily by patients with diabetes (~17 mg/dL increase), indicating that diabetes predisposed to glucose elevation seen with OSA during CPAP withdrawal. They also noted that the rise was not due to increased glucose production, but rather, reduced glucose clearance.
“The marked OSA-induced hyperglycaemia we observed in diabetics highlights the importance of diagnosing and treating OSA in such patients,” said Jun and co-authors.
“The heart rate antecedent to blood draws was highly predictive of metabolic disturbances. A 1-beat per minute increase of heart rate was associated with an increase in FFA by 0.003 mmol/L (p=0.030), glucose by 1.01 mg/dL (p=0.008), insulin by 0.22 μU/mL (p=0.007), and of lactate by 0.016 mmol/L (p=0.001),” they added.
With regards to cardiometabolic outcomes, CPAP withdrawal was associated with increased arterial stiffness (p=0.008) and systolic blood pressure (p=0.017), although glucose production, oral glucose tolerance, insulin, triglycerides, cholesterol, or the inflammation biomarker hsCRP*** were not affected.
“Our findings challenge exclusive reliance on AHI for OSA risk stratification. We found that nocturnal heart rate, hypoxaemia, sleep fragmentation, and diabetes status were more informative for predicting real time metabolic outcomes,” Jun and co-authors.
“Going forward, metrics we examined (particularly, heart rate) should be validated in other cohorts as a predictor of morbidity and mortality.”