Sophie West

Effect of CPAP on insulin resistance and HbA1c in men with obstructive sleep apnoea and type 2 diabetes

Background: The effects of continuous positive airway pressure (CPAP) for obstructive sleep apnoea (OSA) on insulin resistance are not clear. Trials have found conflicting results and no appropriate control groups have been used. Methods: Forty-two men with known type 2 diabetes and newly diagnosed OSA (>10 dips/h in oxygen saturation of >4%) were randomised to receive therapeutic (n = 20) or placebo CPAP (n = 22) for 3 months. Baseline tests were performed and repeated after 3 months. The study was double blind. Results: Results are expressed as mean (SD). CPAP improved the Epworth sleepiness score significantly more in the therapeutic group than in the placebo group (−6.6 (4.5) vs −2.6 (4.9), p = 0.01). The maintenance of wakefulness test improved significantly in the therapeutic group but not in the placebo group (+10.6 (13.9) vs −4.7 (11.8) min, p = 0.001). Glycaemic control and insulin resistance did not significantly change in either the therapeutic or placebo groups: HbA1c (−0.02 (1.5) vs +0.1 (0.7), p = 0.7, 95% CI −0.6% to +0.9%), euglycaemic clamp (M/I: +1.7 (14.1) vs −5.7 (14.8), p = 0.2, 95% CI −1.8 to +0.3 l/kg/min1000), HOMA-%S (−1.5 (2.3) vs −1.1 (1.8), p = 0.2, 95% CI −0.3% to +0.08%) and adiponectin (−1.1 (1.2) vs −1.1 (1.3), p = 0.2, 95% CI −0.7 to +0.6 &mgr;g/ml). Body mass index, bioimpedance and anthropometric measurements were unchanged. Hours of CPAP use per night were 3.6 (2.8) in the treatment group and 3.3 (3.0) in the placebo group (p = 0.8). There was no correlation between CPAP use and the measures of glycaemic control or insulin resistance. Conclusion: Therapeutic CPAP does not significantly improve measures of glycaemic control or insulin resistance in men with type 2 diabetes and OSA.

Prevalence of obstructive sleep apnoea in men with type 2 diabetes

Background: A study was undertaken to establish the prevalence of obstructive sleep apnoea (OSA) in men with type 2 diabetes. Methods: Men with type 2 diabetes from local hospital and selected primary care practitioner databases received questionnaires about snoring, apnoeas, and daytime sleepiness based on the Berlin questionnaire. Selected respondents had overnight oximetry to establish whether they had OSA. Comparisons of oximetry were made with those from a previous general population study. HbA1c results were collected. Results: 1682 men were sent questionnaires, 56% of whom replied. 57% scored as “high” and 39% as “low” risk for OSA; 4% were already known to have OSA. Oximetry was performed in 240 respondents from both risk groups: 31% of the “high” and 13% of the “low” risk group had significant OSA (more than 10 >4% Sao2 dips/hour or Sao2 tracing consistent with OSA). These results were verified by detailed sleep studies. Extrapolation of the oximetry data to the questionnaire respondent population suggests that 23% had OSA. Comparison of the oximetry results with men from a previous general population study (using only more than 10 >4% Sao2 dips/hour to define OSA) showed the prevalence of OSA is significantly higher in this diabetes population (17% v 6%, p<0.001). Multiple linear regression revealed BMI and diabetes as significant independent predictors of OSA. Following correction for BMI (which explained 13% of the variance in OSA), diabetes explained a further 8% of the variance (p<0.001). There was a low correlation between OSA severity and HbA1c in the subgroup recruited from the hospital database (r = 0.2, p = 0.006) which remained significant after allowing for obesity (p = 0.03). Conclusions: OSA is highly prevalent in men with type 2 diabetes; most are undiagnosed. Diabetes itself may be a significant independent contributor to the risk of OSA.

Comparison of three ways to determine and deliver pressure during nasal CPAP therapy for obstructive sleep apnoea

Background: The simplest method of initiating and maintaining therapeutic continuous positive airways pressure (CPAP) therapy for obstructive sleep apnoea (OSA) has not been established. Methods: Ninety eight subjects with OSA requiring CPAP treatment (more than 10 dips in oxygen desaturation of >4% per hour of sleep study and Epworth Sleepiness Score (ESS) >9) were randomised prospectively to three different methods of CPAP delivery for 6 months: (1) autotitration pressure throughout; (2) autotitration pressure for 1 week followed by fixed pressure (95th centile) thereafter; and (3) fixed pressure determined by algorithm (based on neck size and dip rate). Patients and investigators were blind to group allocation. One week after initiation the patients were routinely reviewed by sleep nurses. Study assessments took place before starting CPAP treatment and 1 and 6 months after to assess ESS, maintenance of wakefulness test, 24 hour blood pressure, general health (SF-36), and sleep apnoea related quality of life. CPAP internal monitoring data were also collected. Results: There were no significant differences in any of the outcome measures or CPAP monitoring data between the three groups. The 95th centile CPAP pressures delivered in the 6 month and 1 week autotitration groups were higher than in the algorithm group, but the median pressures were lowest in the 6 month autotitration group. Conclusions: The method of determining CPAP pressure for treatment of moderate to severe OSA makes no significant difference to clinical outcome measures. The autotitration CPAP machine used has no advantage in this setting over simpler methods of pressure determination.

The prevalence of retinopathy in men with Type 2 diabetes and obstructive sleep apnoea

Diabet. Med. 27, 423–430 (2010)

The effect of continuous positive airway pressure treatment on physical activity in patients with obstructive sleep apnoea: A randomised controlled trial.

BACKGROUND Continuous positive airway pressure (CPAP) improves daytime sleepiness in patients with obstructive sleep apnoea (OSA). The effect of CPAP on physical activity is unclear. We hypothesized that activity would increase after CPAP treatment. METHODS A double blind, parallel, randomised, controlled trial using therapeutic and placebo CPAP was performed in men with newly diagnosed OSA (more than 10>4% SaO(2) dips/hour and Epworth Sleepiness Score [ESS] 9). Activity was measured by wrist actigraphy before and after three months of CPAP therapy. RESULTS Thirty-six men completed 1 week of continuous actigraphy before and after therapeutic CPAP (n=16) or placebo CPAP (n=20). The two groups were well-matched at baseline, with no significant differences in mean age, body mass index, ESS and SaO(2) dips/hour. Mean (SD) ESS and modified maintenance of wakefulness test (OSLER) improved significantly after CPAP. ESS change in the therapeutic group was -6.1 (4.4), compared to placebo, -2.8 (5.0); difference between groups p=0.04; OSLER (minutes), therapeutic +10.4 (14.4), placebo -5.0 (12.0), p=0.003. There was no significant difference between groups in mean hourly activity levels for the seven days at baseline; activity levels did not significantly change in either group after CPAP [daytime activity (arbitrary units): therapeutic -13.9 (93.1) vs. placebo +8.3 (62.9), p=0.4]. There was no correlation between change in activity and CPAP use. CONCLUSION Activity does not increase after CPAP in men with OSA, despite improvements in daytime sleepiness. The reasons for this are not clear, but may be due to longstanding, habitual patterns of activity.

High prevalence of sleep disordered breathing in patients with diabetic macular edema.

Background: Diabetic retinopathy is more common and severe in patients with sleep disordered breathing (SDB). This study aimed to establish whether this is also true for patients with diabetic clinically significant macular edema (CSME). It is hypothesized that SDB, through intermittent hypoxia and blood pressure oscillations, might provoke worsening of CSME. Methods: Patients with CSME had a home sleep study (ApneaLink; ResMed) to identify SDB. These results were compared with relevant control populations. Macular thickness was measured using optical coherence tomography, and retinal photographs were graded to assess the severity of retinopathy. Results: Eighty of 195 patients (40 men) consented, with average age of 64.7 (11.7) years, neck circumference of 40.4 (5.4) cm, body mass index of 30.2 (6.2) kg/m2, glycosylated hemoglobin (HbA1c) 7.8% (1.4%) [62 (8.0) mmol/mol], and Epworth sleepiness scale of 7.4 (4.8). Overall, 54% had an oxygen desaturation index ≥10, and 31% had an apnea-hypopnea index ≥15. This SDB prevalence is probably higher than would be expected from the available matched control data. Those with SDB were not sleepier, but they were older and more obese. No significant relationship was identified between the degree of macular thickness and the severity of SDB. Conclusion: Individuals with CSME have a high prevalence of SDB. Sleep disordered breathing may contribute to the pathophysiology of CSME, but the mechanism remains unclear. Given the high prevalence, retinal specialists should perhaps consider a diagnosis of SDB in patients with CSME.

Pleurodesis for malignant pleural effusions: current controversies and variations in practices.

Purpose of review Malignant pleural effusions are common, and pleurodesis remains the best method to control re-accumulation of the pleural fluid. There are few randomized controlled trials studying the optimal management of malignant pleural effusions. A recent international survey of pleurodesis practice has highlighted variations in how pleurodesis is performed worldwide. Future research should target these areas of variation to determine the best practice protocols. Recent findings The selection of pleurodesing agents remains controversial. Talc is more effective, but is associated with more adverse effects. Talc pleurodesis is followed by systemic and pulmonary inflammation. This is probably related to systemic embolization of talc following its intrapleural administration, though there are other potential causes that may also play a role. Summary The practice of pleurodesis varies considerably among individual pulmonologists and among different countries, in most technical aspects. This review serves to highlight some of these variations in practice, as well as reviewing the current literature on pleurodesis practice.

Serum urate levels are unchanged with continuous positive airway pressure therapy for obstructive sleep apnea: a randomized controlled trial

OBJECTIVE Hyperuricemia is associated with the presence and severity of obstructive sleep apnea (OSA). Previous work has shown that treatment of OSA with continuous positive airway pressure (CPAP) therapy reduces urinary uric acid excretion and serum urate, but there has been no previous randomized controlled investigation on the effects of CPAP therapy on serum urate; we aimed to assess this association. METHODS Serum urate was measured in samples from participants of a previously published randomized controlled trial. Samples were taken at baseline and after 3months from men with known type 2 diabetes mellitus (T2DM) and newly diagnosed OSA, randomized to receive either therapeutic (n=19) or placebo (n=19) CPAP for 3months. RESULTS Both groups were well matched at baseline, with no significant difference in age, body mass index (BMI), glycosylated hemoglobin (HbA1c), or oxygen desaturation index (ODI). There was no significant difference in therapeutic or placebo CPAP usage. There was no significant difference in urate levels between groups at baseline (362μmol/L [standard deviation {SD}, 96] vs 413μmol/L [SD, 91] [reference range, 110-428μmol/L]) or at 3months. Baseline urate did not correlate with ODI, BMI, or HbA1c. The mean change in urate at 3months did not significantly differ between treatment groups (-7.6μmol/L [SD, 35.9] vs -6.2μmol/L [SD, 46.2]) (P=.9; [95% confidence interval, -28.7 to +25.9]). CONCLUSION Our randomized controlled trial has shown no significant reduction in serum urate following 3months treatment with therapeutic or placebo CPAP.

Obstructive sleep apnoea in adults

#### Case scenario A 50 year old long distance lorry driver attends for a review of his heavy goods vehicle licence. His body mass index is 30, and he says his wife complains that he snores loudly. The history of loud snoring in this overweight man should raise concern about possible obstructive sleep apnoea. As he is a lorry driver this diagnosis is particularly important. Obstructive sleep apnoea is characterised by snoring, recurrent episodes of upper airway obstruction during sleep (apnoeas and hypopnoeas), and arousals. The resulting sleep disturbance can cause excessive and disabling daytime sleepiness. The term obstructive sleep apnoea syndrome is used for people who have features of obstructive sleep apnoea on a sleep study and also have resulting daytime sleepiness. #### How common is it?

Platelet function (measured by Platelet Function Analyser - 100) and obstructive sleep apnoea

It is known that platelet activation occurs in patients withacute coronary syndromes and antiplatelet drugs providesignificant therapeutic benefit in these people (Boersma et al.,2002; Ott et al., 1996; Wodlinger and Pieper, 2003; Yusufet al., 2003). The platelet function analyser (PFA-100) is aunique device, which simulates high shear-dependent plateletfunction in vitro (Francis, 2004; Jilma, 2001; Kundu et al.,1995). This is a relatively new test, determining platelet-relatedprimary haemostasis, by measuring the time needed for aplatelet plug to form after activation of platelets by patho-physiologically relevant stimuli. Citrated whole blood isaspirated under high shear (5000–6000 s