Cardiometabolic Benefits of a Weight-Loss Mediterranean Diet/Lifestyle Intervention in Patients with Obstructive Sleep Apnea: The "MIMOSA" Randomized Clinical Trial.

Georgoulis M ，Yiannakouris N ，Kechribari I ，Lamprou K ，Perraki E ，Vagiakis E ，Kontogianni MD ... -  《Nutrients》

The effectiveness of a weight-loss Mediterranean diet/lifestyle intervention in the management of obstructive sleep apnea: Results of the "MIMOSA" randomized clinical trial.

Although continuous positive airway pressure (CPAP) is the first-line treatment for obstructive sleep apnea (OSA), lifestyle interventions have also emerged as complementary therapeutic choices. We aimed to explore whether the addition of a weight-loss Mediterranean diet/lifestyle intervention to OSA standard care, i.e. CPAP prescription and brief written healthy lifestyle advice, has an incremental effect on improving OSA severity, over the effect of standard care alone. We designed a parallel, randomized, controlled, superiority clinical trial. Eligible participants were adult, overweight men and women, diagnosed with moderate-to-severe OSA [apnea-hypopnea index (AHI)≥ 15 events/h] through an attended overnight polysomnography. Participants were blindly randomized to a standard care group (SCG, n = 65), a Mediterranean diet group (MDG, n = 62) or a Mediterranean lifestyle group (MLG, n = 60). All three study groups were prescribed with CPAP. The SCG additionally received written healthy lifestyle advice, while intervention arms were subjected to a 6-month behavioral intervention aiming at weight loss and increasing adherence to the Mediterranean diet. The MLG also received counselling on physical activity and sleep habits. Polysomnographic data and OSA symptoms were evaluated pre- and post-intervention. A total of 187 OSA patients were recruited. Seven patients were excluded post-randomization and 53/180 (29%) were lost to follow-up. No harms from the interventions applied were reported. According to intention-to-treat analysis (n = 180), mean (95% confidence interval) AHI change was -4.2 (-7.4, -1.0) for the SCG, -24.7 (-30.4, -19.1) for the MDG and -27.3 (-33.9, -20.6) for the MLG. Post-intervention age-, sex-, baseline- and CPAP use-adjusted AHI was significantly lower in the MDG and the MLG compared to the SCG (mean difference: -18.0, and -21.2, respectively, both P < 0.001), and the differences remained significant after further adjustment for body-weight change (P = 0.004 and 0.008, respectively). Other respiratory event indices, daytime sleepiness and insomnia were also significantly lower in both intervention arms compared to the SCG (all P < 0.05). The MLG only presented higher percent rapid-eye-movement sleep and lower daytime sleepiness compared to the MDG (both P < 0.05). Results were similar in the per-protocol analysis (n = 127). A dietary/lifestyle intervention on top of standard care leads to greater improvements in OSA severity and symptomatology compared to standard care alone. Benefits are evident regardless of CPAP use and weight loss. Clinicaltrials.gov NCT02515357, https://clinicaltrials.gov/ct2/show/NCT02515357.

Georgoulis M ，Yiannakouris N ，Kechribari I ，Lamprou K ，Perraki E ，Vagiakis E ，Kontogianni MD ... -  《-》

Sustained improvements in the cardiometabolic profile of patients with obstructive sleep apnea after a weight-loss Mediterranean diet/lifestyle intervention: 12-month follow-up (6 months post-intervention) of the "MIMOSA" randomized clinical trial.

Obstructive sleep apnea (OSA) and the metabolic syndrome (MS) frequently coexist and lead to increased cardiometabolic morbidity. We aimed to explore the long-term cardiometabolic benefits of a weight-loss Mediterranean diet/lifestyle intervention in OSA. As many as 180 adults with overweight/obesity and polysomnography-diagnosed moderate-to-severe OSA were randomized to a standard care (SCG, n = 62), a Mediterranean diet (MDG, n = 59) or a Mediterranean lifestyle group (MLG, n = 59). All groups were prescribed with continuous positive airway pressure (CPAP), while intervention arms (MDG/MLG) additionally participated in a 6-month weight-loss intervention based on the Mediterranean diet/lifestyle. Cardiometabolic parameters were evaluated at baseline and 12 months (6 months post-intervention). Data were analyzed using the intention-to-treat method, and 12-month between-group differences were explored while adjusting for age, sex, baseline status and CPAP use. Compared to the SCG, intervention arms exhibited lower insulin, triglycerides and high-sensitivity C-reactive protein, and higher high-density lipoprotein cholesterol; the MDG also exhibited lower diastolic blood pressure, while the MLG exhibited lower glucose and systolic blood pressure (all P < 0.050). The relative risk (95% confidence interval) of MS was 0.60 (0.36, 0.99) in the MDG versus the SCG, 0.33 (0.20, 0.55) in the MLG versus the SCG and 0.55 (0.32, 0.93) in the MLG versus the MDG. The risk of MS remained lower in the MLG versus the other study groups (both P < 0.050) after additional adjustment for body weight change. Cardiometabolic benefits of a 6-month healthy dietary/lifestyle intervention are sustainable 6 months post-intervention in OSA. ClinicalTrials.gov, NCT02515357, August 4, 2015.

Georgoulis M ，Yiannakouris N ，Kechribari I ，Lamprou K ，Perraki E ，Vagiakis E ，Kontogianni MD ... -  《-》

A weight-loss Mediterranean diet/lifestyle intervention ameliorates inflammation and oxidative stress in patients with obstructive sleep apnea: results of the "MIMOSA" randomized clinical trial.

Inflammation and oxidative stress are implicated in obstructive sleep apnea (OSA) pathophysiology. We aimed at exploring whether the combination of a weight-loss Mediterranean diet/lifestyle intervention with OSA standard care, i.e., continuous positive airway pressure (CPAP) prescription, can lead to greater improvements in inflammation and oxidative stress, compared to standard care alone. This was a randomized controlled clinical trial in 187 adult, overweight patients with moderate-to-severe OSA. Participants were randomized to a standard care (SCG, n = 65), a Mediterranean diet (MDG, n = 62) or a Mediterranean lifestyle group (MLG, n = 60). All groups received OSA standard care. Intervention arms participated in a 6-month behavioral weight-loss intervention based on the Mediterranean diet, while the MLG also received counselling on physical activity and sleep habits. Seven patients were excluded and 53/180 were lost to follow-up. In intention to treat analysis (n = 180), the SCG did not exhibit changes in any of the markers assessed. Post-intervention age-, sex-, baseline- and CPAP use-adjusted plasma high sensitivity C-reactive protein levels (mg/L) were lower in the MDG and the MLG compared to the SCG (mean difference - 1.33, P = 0.039 and - 1.68, P = 0.007, respectively). The MLG also exhibited lower urinary 8-iso prostaglandin F2a levels (ng/mg creatinine) compared to the SCG and the MDG (mean difference - 1.10, P < 0.0001 and - 0.80, P = 0.001, respectively). Adiponectin and oxidized guanine levels were not altered in any of the study groups. Results were similar in per protocol analysis (n = 127). A weight-loss Mediterranean diet/lifestyle intervention on top of CPAP has anti-inflammatory and antioxidant benefits in OSA. The trial was prospectively registered at ClinicalTrials.gov (NCT02515357) on August 4, 2015.

Georgoulis M ，Yiannakouris N ，Tenta R ，Fragopoulou E ，Kechribari I ，Lamprou K ，Perraki E ，Vagiakis E ，Kontogianni MD ... -  《-》

Dose-response relationship between weight loss and improvements in obstructive sleep apnea severity after a diet/lifestyle interventions: secondary analyses of the "MIMOSA" randomized clinical trial.

Lifestyle-induced weight loss is a complementary therapeutic approach for obstructive sleep apnea (OSA). We aimed at identifying the dose-response relationship between weight loss and OSA severity improvement. This is a secondary analysis of a 6-month clinical trial in 180 adult, overweight/obese moderate-to-severe OSA patients. Participants were randomized to a standard care, a Mediterranean diet, or a Mediterranean lifestyle arm. All patients were prescribed with continuous positive airway pressure (CPAP), while intervention arms additionally participated in a weight-loss dietary/lifestyle intervention. Based on percent change in weight at 6 months, participants were categorized into a weight-stable/gain (WS/GG) group or 3 weight-loss groups (WLG): < 5%WLG, 5%-10%WLG, and ≥ 10%WLG. Polysomnographic data and OSA symptoms were evaluated preintervention and postintervention. Respiratory events and oximetry indices improved only in patients who lost weight and improvements were proportional to the degree of weight loss. Median percent change in apnea-hypopnea index (AHI) was -11.7%, - 37.9%, and - 49.3% in the < 5%WLG, 5%-10%WLG, and ≥ 10%WLG, respectively (P < .001). Compared to the WS/GG, the age-, sex-, baseline-, and CPAP use-adjusted relative risk (95% confidence interval) of severe OSA (AHI ≥ 30 events/h) was 0.45 (0.23-0.87) in the 5%-10%WLG and 0.32 (0.17-0.64) in the ≥ 10%WLG; the risk was also lower in the ≥ 10%WLG vs the < 5%WLG (0.42 [0.22-0.82]). Insomnia and daytime sleepiness also improved more in participants exhibiting ≥ 5% weight loss. Even a < 5% weight loss can reduce respiratory events, but a ≥ 5% and ideally ≥ 10% weight loss is necessary for reducing the prevalence of severe OSA. Registry: ClinicalTrials.gov; Name: Mediterranean Diet/Lifestyle Intervention in Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/NCT02515357; Identifier: NCT02515357. Georgoulis M, Yiannakouris N, Kechribari I, et al. Dose-response relationship between weight loss and improvements in obstructive sleep apnea severity after a diet/lifestyle intervention: secondary analyses of the "MIMOSA" randomized clinical trial. J Clin Sleep Med. 2022;18(5):1251-1261.

Georgoulis M ，Yiannakouris N ，Kechribari I ，Lamprou K ，Perraki E ，Vagiakis E ，Kontogianni MD ... -  《-》