Obstructive sleep apnoea and 12-month weight loss in adults with class 3 obesity attending a multidisciplinary weight management program

Obesity is a complex medical condition which is impacted by a variety of factors such as genetics, environment, culture and individual lifestyle [1]. Class 3 obesity refers to individuals with a body mass index (BMI) greater than 40 kg/m² and is linked to increased mortality as well as risk of a range of health concerns including hypertension, type 2 diabetes (T2DM), coronary artery disease, and obstructive sleep apnoea (OSA) [1, 2]. The relationship between class 3 obesity and these conditions is often reciprocal with evidence suggesting an interplay between obesity, T2DM and OSA, which results in an increase in incidence and severity of all three [3–5].

OSA is a condition characterized by recurrent loss of tone of the upper airway resulting in hypopnoea (partial obstruction) and apnoea (complete obstruction) causing hypoxia and subsequent waking from sleep [6]. It is a significant contributor to motor vehicle accidents when not treated [7], and has been shown to exacerbate long-term diabetes complications such as cardiovascular disease (CVD), neuropathy, retinopathy and nephropathy [8–11]. While polysomnography is the “gold standard” for OSA diagnosis, it is often not widely used due to its costs and reduced availability. In virtue of this, questionnaires are valuable for the screening of the disease. These include the Epworth Sleepiness Scale (ESS), the Berlin Questionnaire (BQ) as well as the STOP-Bang Questionnaire and the STOP Questionnaire [12, 13]. First line treatment for moderate to severe OSA is continuous positive airway pressure (CPAP) [14]. Unfortunately, compliance with CPAP at one year is estimated to be as low as 50 % due to discomfort experienced by patients, challenging treatment titration processes, cost of CPAP and other psychological factors [4, 15–17].

Obesity can affect the pathogenesis of OSA in multiple ways, including upper airway fat deposition and muscle impairment, pressure from abdominal fat, leptin resistance and increased inflammatory state [18]. Significant weight loss can also reduce symptoms of OSA [14, 19, 20], but long term weight loss which is sufficient enough to reduce the severity of OSA in individuals with class 3 obesity is difficult to achieve and maintain, particularly without bariatric surgery [21–23]. On the other hand, the role of OSA on weight gain and the development of obesity is more controversial. Several factors could affect the pathogenesis of obesity in people with OSA, including daytime sleepiness and associated reduced physical activity as well as sleep deprivation affecting hunger and satiety hormones, and altering brain activity in the reward centre [18, 24, 25]. This controversy is not helped by the fact that a meta-analysis of 25 randomised trials suggested an increase in weight over time for people with OSA using CPAP therapy [26]. One explanation for this is the reduction in sympathetic activation and leptin levels following CPAP treatment which could lead to weight gain [27, 28]. However, the trials included in the meta-analysis were not from weight management programs, nor in people with class 3 obesity. It is important to understand the impact of OSA and CPAP on weight outcomes within the context of a weight management program. Therefore, the aims of this study in people with class 3 obesity were:

This was a retrospective cohort study conducted in a publicly funded, hospital based, intensive, multidisciplinary weight management program in greater Sydney, which has been previously described [29, 30]. Patients included in the study had been enrolled in the program between March 2018 and March 2019, were over 18 years of age, had a BMI ≥40 kg/m², and had at least 12 months follow up in the program. Patients attended two education sessions prior to their first medical appointment with a physician. The multidisciplinary team is comprised of endocrinologists, gastroenterologist, diabetes specialist nurse (educator), dietitians, clinical psychologists, physiotherapists, and a psychiatrist, with patients being reviewed by a local sleep physician for OSA screening and CPAP therapy use/compliance. Patients are provided individualised care every 4-12 weeks depending on clinical need and availability. The study was approved by the South West Sydney Local Health District (SWSLHD) Human Research Ethics Committee as a Quality Assurance Project (Reference: CT22_2018).

A total of 178 patients joined the South Western Sydney Metabolic Rehabilitation and Bariatric Program between March 2018 and March 2019. Of those, 111 (62.4 %) attended follow-up at 12 months and had data available as shown in Fig. 1.

In this single centre cohort study, individuals with class 3 obesity attending a publicly funded weight management program had significant weight loss in both those with and without OSA. There was no significant difference in weight loss between the groups, and the use of CPAP in the OSA group did not affect the 12-month weight outcomes.

Although significant, the percentage weight loss over the 12-month period in this high-risk population was modest (6-7 %), which is akin to previous studies [29–31]. The impact of OSA on obesity is not completely understood. While multiple mechanisms would logically link the sleep deprivation experienced by patients with OSA to weight gain such as reduction in physical activity and eating behaviours favouring high calorie containing foods [32, 33], as well as an activation of the hypothalamic-pituitary-adrenal axis and increased cortisol, the long term evidence of the impact of OSA on weight is sparse [34]. While the increased tiredness and sleepiness often associated with OSA would not favour successful weight loss interventions, patients who use CPAP generally report dramatic improvements in alertness, mood and quality of life, each of which may be essential in attempting to lose weight [35]. However, a systematic review of over 3000 patients from 25 randomised controlled trials suggested an increase in weight over time for people with OSA using CPAP therapy [26], that was greater with increasing baseline weight. Thus, it is perhaps not surprising that in this study, those with OSA treated with CPAP did not appear to have improved weight loss compared to those with untreated OSA. Therefore, weight loss in OSA patients seems to be multifactorial, and cannot at this stage be solely achieved with CPAP therapy. Indeed, multiple factors have been hypothesised for this finding, including the reduction in sympathetic activity leading to reduced lipolysis and energy expenditure, leading to weight gain [26]. Of note, the systematic review did not evaluate the effect of CPAP on weight loss among patients following a weight management program. Furthermore, these studies did not evaluate the weight loss in people with class 3 obesity.

While there may be the preconceived notion that being diagnosed with OSA impacts on the ability for patients to lose weight, our study suggests that weight loss outcomes are similar, regardless of the presence of OSA diagnosis at baseline or the use of CPAP. This has implications for both patients and clinicians alike, in alleviating the concerns of how OSA diagnosis or use of CPAP may impact weight loss. Instead, emphasis can be placed on implementing lifestyle changes that may induce a modest amount of weight loss that can be beneficial to the metabolic risk profile of individuals with class 3 obesity [3, 36].

There are, however, undeniable benefits of CPAP therapy in improving OSA severity and thereby sleep quality on overall health. Several studies have shown a high prevalence of T2DM in patients with OSA and vice versa[37, 38], OSA being an independent risk factor for the development of T2DM [39]. We have recently demonstrated that patients with class 3 obesity had a reduction in their HbA1c by 0.47 % over 6 months in this weight management program [30]. In this study, we report no difference at baseline in the proportion of patients who have T2DM, nor in the daily dose of insulin in all three groups. However, the reduction in HbA1c was consistent with our previous study and was similar regardless of CPAP use. This supports the notion that OSA diagnosis or CPAP use may not affect glycaemic control, in the parameters of a medical weight management program in people with class 3 obesity. There are inconsistent findings in the effects of CPAP use for 1-6 months on improvement of glycaemic control [40–43]. Well-controlled experiments with compliant CPAP use for 8 h a night have shown to improve glucose metabolism in one to two weeks [44, 45]. However, the largest study to date which included close to 900 participants followed over 4.3 years showed no significant difference between the CPAP and usual care groups in their serum glucose or HbA1c [46]. Larger studies of longer duration are needed to assess the impact of CPAP on the prevention of T2DM.

People with OSA on CPAP had a significant drop in the total and LDL cholesterol levels at 12 months compared to baseline, whereas there was no significant change in those with OSA not on CPAP, nor in those without OSA. This is interesting, given that there were no differences in use of cholesterol lowering medications overall or in any of the groups from baseline to 12 months. While clear evidence of the benefits of CPAP use on reducing cholesterol levels is lacking, it has been postulated that CPAP may improve patients’ lipid profile by reducing the intermittent hypoxia, as well as through increased physical activity [47]. These findings should be confirmed in larger trials, and possible mechanisms warrant further investigation.

Hypertension is another well-known risk factor for cardiovascular disease and overall mortality. Blood pressure decreases during sleep, which is likely related to decreases in sympathetic output. A lack of this “nocturnal dipping”, which is inevitably the case in patients with OSA, has been associated with a greater risk of cardiovascular mortality [48]. Even a 10mm Hg increase in mean night-time systolic blood pressure has been shown to be associated with a 21 % increase in cardiovascular mortality [49]. Multiple large studies have shown that people who sleep less than five hours per night have a greater risk of hypertension than those sleeping more than 7 h per night [50, 51]. Therefore, it seems logical that improving sleep would reduce the incidence of hypertension in patients with OSA. A retrospective study in patients with T2DM and newly diagnosed OSA, showed that the use of CPAP for 9-12 months lead to a significant reduction in blood pressure [52]. Thus, improving OSA severity and thereby increasing sleep quality has the potential to substantially improve cardiovascular morbidity and mortality. Hence, it is encouraging to see a significant reduction in the Epworth Sleepiness Scale score over a 12-month period in all three groups in our study. In addition to the benefits of reduced sleepiness on driving and day to day functioning, it may be that the benefits of the reduction in sleepiness on weight outcomes are seen later than at the 12-month period.

As many patients in this study, and people with class 3 obesity in general, would often meet the criteria for bariatric surgery, it is of utmost importance to optimise pre-operative health, including OSA severity, to minimise peri-operative complications. Indeed, there is a positive association between OSA severity and post-operative risk, including increased risk of shock and cardiac arrest [53]. Therefore, improving OSA status prior to bariatric surgery may prevent peri-operative complications. In virtue of this, clinicians and allied health professionals should focus on emphasising improvements in OSA status, and herewith CPAP compliance, in addition to weight loss per se, in patients with class 3 obesity.

The main strength of this study is that it is based in a real-world weight management program, that included all patients from a publicly funded metabolic program within a hospital service. These findings can therefore inform other multidisciplinary medical weight management programs. Limitations are that this is a single centre with a relatively small cohort of patients, and only 12 months follow up. Multicentre studies which include large sample sizes and longer follow up would help corroborate the findings from this study. Furthermore, a larger sample size would have allowed us to assess the severity of OSA, and its impact on weight loss. Finally, reasons for why patients did or did not commence CPAP were not explored in this study. Such analysis may help identify barriers not only to CPAP use, but also to weight loss.

This single centre retrospective cohort study demonstrated that the presence of OSA at baseline or the use of CPAP does not affect weight or glycaemic outcomes at 12 months in people with class 3 obesity in the context of a medical weight management program. Findings from this study suggest that the focus should remain on implementing lifestyle changes and medical weight management in people with class 3 obesity, regardless of OSA status.

The authors would like to thank all the patients and staff in the South Western Sydney Metabolic Rehabilitation and Bariatric Program (SWS MRBP) at Camden Hospital. The help from Kyaw Phone Myint, Kathryn Skelsey, Kathy Grudzinskas and Hayley O’Donnell is particularly appreciated.

SK made a substantial contribution to the concept and design, data collection and analysis and interpretation of data, and drafting of the article. FT and DG made a substantial contribution to data collection, analysis and interpretation of data and drafting of the article. RC made a substantial contribution to data analysis and drafting of the article. SO and JJ made a substantial contribution to data collection and revised the article critically for important intellectual content. LL and NK helped in the study design and revised the article critically for important intellectual content. AT revised the article critically for important intellectual content. MKP made a substantial contribution to the concept and design, data analysis and drafting the article, and revised the article critically for important intellectual content. All authors read and approved the final manuscript.

The study was funded from internal departmental funds from Western Sydney University.

The datasets used and analysed during the current study are available from the corresponding author on reasonable request.

Sophie Kobuch, Email: sophie.kobuch@ths.tas.gov.au.

Fiona Tsang, Email: fiona.tsang@health.nsw.gov.au.

Ritesh Chimoriya, Email: r.chimoriya@westernsydney.edu.au.

Daniel Gossayn, Email: dgossayn@gmail.com.

Sarah O’Brien, Email: sarahMargaret.obrien@health.nsw.gov.au.

Javeria Jamal, Email: 18067343@student.westernsydney.edu.au.

Leon Laks, Email: Leon.Laks@asdiagnostics.com.au.

Abd Tahrani, Email: abd.tahrani@nhs.net.

Nic Kormas, Email: nkormas@mediadome.net.au.

Milan K Piya, Email: m.piya@westernsydney.edu.au.