Associations between Vitamin D Status and Polysomnographic Parameters in Adults with Obstructive Sleep Apnea.

Vitamin D deficiency (VDD) may be associated with obstructive sleep apnea (OSA) presence and is more pronounced with increasing OSA severity; however, the relationship between these two entities remains unclear. This was a cross-sectional study among 262 adults with in-hospital-attended polysomnography-diagnosed OSA and no additional major comorbidities, aiming to explore possible associations between serum 25-hydroxyvitamin D [25(OH)D] levels and polysomnographic parameters. Data on demographics, medical history, anthropometric indices, and lifestyle habits were collected at enrolment. Serum 25(OH)D was evaluated using chemiluminescence, with VDD defined as 25(OH)D < 20 ng/mL. VDD was observed in 63% of the participants. Serum 25(OH)D correlated negatively with apnea-hypopnea index and other polysomnographic indices (all p < 0.05). In logistic regression analysis, adjusting for age, sex, smoking, body mass index, physical activity, dietary vitamin D intake, and season of blood sampling, serum 25(OH)D was associated with lower odds of severe OSA [odds ratio (95% confidence interval): 0.94 (0.90-0.98)]. In the same multivariate model, VDD was associated with ~threefold higher odds of severe OSA [2.75 (1.38-5.48)]. In stratified analyses, VDD predicted OSA severity in the group of participants ≥50 y [3.54 (1.29-9.68)] and among those with body mass index ≥ 30 kg/m2 [3.38 (1.52-7.52)], but not in the younger and non-obese adults. This study provides further evidence of an inverse association between vitamin D levels and OSA severity and underscores the importance of considering vitamin D status as a potential modifiable factor in the comprehensive management of OSA.

Adherence to a "Western-type" dietary pattern is positively associated with the Apnea-Hypopnea Index in adults with obstructive sleep apnea.

Dietary habits have been associated with obstructive sleep apnea (OSA); however, the underlying mechanisms remain unclear. We hypothesized that adherence to dietary patterns may be associated with Apnea-Hypopnea Index (AHI) and OSA severity and that insulin resistance, oxidative stress, and inflammation may act as potential mediators of these associations. This was a cross-sectional study among 269 adult participants with polysomnography-diagnosed moderate-to-severe OSA. Dietary and physical activity habits were assessed through validated questionnaires, and biochemical, inflammatory, and oxidative stress markers were measured for all volunteers. Dietary patterns were identified using principal component analysis, and mediation analyses was also performed. A "Western-type" dietary pattern (characterized by high intakes of full-fat dairy, refined grains, potatoes, red meat, sweets, salty snacks, and soft drinks and low intakes of low-fat dairy and whole grains) was positively associated with AHI. Mediation analyses also revealed that insulin resistance partially explained this association. In multivariable models controlling for age, sex, smoking, socioeconomic status, obesity presence, energy intake, and physical activity level, participants in the highest quartile of adherence to the Western-type dietary pattern had ∼3.5 times higher likelihood of suffering from severe OSA, compared with participants in the lowest quartile of adherence (odds ratio [95% confidence interval]: 3.45 [1.21-9.94], P trend across quartiles: 0.024). After further adjustment for Homeostasis Model of Assessment-Insulin Resistance and high-sensitivity C-reactive protein, this association lost significance. Higher adherence to a less healthy, Western-type dietary pattern is positively associated with AHI and OSA severity, which may partially be mediated through insulin resistance.

Associations between serum vitamin D status and the cardiometabolic profile of patients with obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea (OSA) and the metabolic syndrome (MetS) frequently coexist. Low serum vitamin D has been positively associated with OSA presence and severity; however, data on its link to cardiometabolic features in patients with OSA remain scarce. We aimed to assess serum 25-hydroxyvitamin D [25(OH)D] and explore its association with cardiometabolic parameters in OSA. METHODS: This was a cross-sectional study among 262 patients (49 ± 9 years old, 73% men) with polysomnography-diagnosed OSA. Participants were evaluated in terms of anthropometric indices, lifestyle habits, blood pressure, biochemical, plasma inflammatory and urinary oxidative stress markers, and the presence of MetS. Serum 25(OH)D was assessed by chemiluminescence, and vitamin D deficiency (VDD) was defined as 25(OH)D < 20 ng/mL. RESULTS: Median (1st, 3rd quartile) serum 25(OH)D levels were 17.7 (13.4, 22.9) ng/mL and 63% of participants had VDD. Serum 25(OH)D correlated negatively with body mass index (BMI), homeostasis model of assessment of insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol, triglycerides, high-sensitivity C-reactive protein (hsCRP), and urinary oxidized guanine species (oxG), and positively with high-density lipoprotein cholesterol (all P < 0.050). In logistic regression analysis, serum 25(OH)D was associated with lower odds of MetS [odds ratio (95% confidence interval): 0.94 (0.90-0.98)], after adjustment for age, sex, season of blood sampling, Mediterranean diet score, physical activity, smoking, apnea-hypopnea index, HOMA-IR, hsCRP, and oxG. In the same multivariate model, VDD was associated with ~ twofold greater odds of MetS [2.39 (1.15, 4.97)]. CONCLUSION: VDD is highly prevalent and is associated with a detrimental cardiometabolic profile among patients with OSA.

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.

BACKGROUND AND AIMS: 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. METHODS AND RESULTS: 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. CONCLUSION: Cardiometabolic benefits of a 6-month healthy dietary/lifestyle intervention are sustainable 6 months post-intervention in OSA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02515357, August 4, 2015.

Improvements in Plasma Tumor Necrosis Factor-Alpha Levels after a Weight-Loss Lifestyle Intervention in Patients with Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) and systemic inflammation typically coexist within a vicious cycle. This study aimed at exploring the effectiveness of a weight-loss lifestyle intervention in reducing plasma tumor necrosis factor-alpha (TNF-a), a well-established modulator of systematic inflammation in OSA. Eighty-four adult, overweight patients with a diagnosis of moderate-to-severe OSA were randomized to a standard care (SCG, n = 42) or a Mediterranean lifestyle group (MLG, n = 42). Both groups were prescribed continuous positive airway pressure (CPAP), while the MLG additionally participated in a 6-month behavioral intervention aiming at healthier weight and lifestyle habits according to the Mediterranean pattern. Plasma TNF-a was measured by an immunoenzymatic method both pre- and post-intervention. Drop-out rates were 33% (n = 14) for the SCG and 24% (n = 10) for the MLG. Intention-to-treat analysis (n = 84) revealed a significant decrease in median TNF-a only in the MLG (from 2.92 to 2.00 pg/mL, p = 0.001). Compared to the SCG, the MLG exhibited lower follow-up TNF-a levels (mean difference adjusted for age, sex, baseline TNF-a and CPAP use: -0.97 pg/mL, p = 0.014), and further controlling for weight loss did not attenuate this difference (p = 0.020). Per protocol analyses (n = 60) revealed similar results. In conclusion, a healthy lifestyle intervention can lower plasma TNF-a levels in patients with OSA.

Association of adherence to the Mediterranean diet and physical activity habits with the presence of insomnia in patients with obstructive sleep apnea.

PURPOSE: Insomnia and obstructive sleep apnea (OSA) are among the most prevalent sleep disorders and frequently co-occur, defining the sleep apnea-insomnia syndrome. However, data exploring associations between insomnia and lifestyle habits in patients with OSA are lacking. Therefore, the aim of the present study was to investigate potential associations between insomnia presence and individual lifestyle parameters in patients with mild/moderate-to-severe OSA evaluated by attended polysomnography. METHODS: These are secondary analyses, using data from a cross-sectional study among 269 Greek patients with OSA. Clinical, anthropometric, socioeconomic, and lifestyle data were collected for all participants. Insomnia presence was evaluated through the validated psychometric instrument "Athens Insomnia Scale" (AIS). Adherence to the Mediterranean diet was estimated with the MedDietScale index and physical activity habits were assessed through a validated questionnaire. Backward stepwise multiple logistic regression analysis was used to estimate the association between lifestyle habits (i.e., adherence to the Mediterranean diet and physical activity) and the likelihood of having insomnia, while adjusting for potential confounders. RESULTS: Of 269 patients newly diagnosed with OSA (aged 21-70 years; 73% men), 146 (54%) were categorized as having insomnia. In multivariable models, higher adherence to the Mediterranean diet and engagement in physical activity for ≥ 30 min/day were both associated with a lower likelihood of having insomnia (odds ratio (95% confidence intervals): 0.40 (0.18-0.91) and 0.49 (0.28-0.86), respectively). CONCLUSIONS: Results add to the limited data on the role of lifestyle in insomnia and should be further explored both in epidemiological and clinical studies.

Higher refined cereal grain intake is positively associated with apnoea-hypopnoea index in patients with obstructive sleep apnoea.

BACKGROUND: Given that obesity is a well-known risk factor for obstructive sleep apnoea (OSA) development, dietary habits may be involved in its pathogenesis. However, little is known about the associations between dietary habits and OSA severity. The present study aimed to investigate possible associations between cereal grain intake and apnoea/hypopnoea indices in OSA patients. METHODS: This was a cross-sectional study of 269 patients (21-70 years; 73.2% males) diagnosed with OSA via an attended in-hospital polysomnography. Information on demographics, medical history, anthropometric indices and lifestyle habits were collected at enrolment. Biochemical measurements were performed in all study participants using standard procedures. Cereal grain consumption was evaluated using a validated food frequency questionnaire. Severe OSA was defined as having an apnoea-hypopnoea index ≥30 events h-1 . RESULTS: In adjusted analyses, higher intake of refined cereal grains was positively associated with apnoea-hypopnoea index (ptrend = 0.022), after adjusting for age, sex, socio-economic parameters, smoking habits, waist circumference, physical activity level, adequacy of night-time sleep, diet's quality as assessed by a relevant score, insulin resistance and C-reactive protein levels). Multiple logistic regression analysis also showed that energy-adjusted refined grain intake was associated with increased likelihood of severe OSA (odds ratio = 1.56, 95% confidence interval = 1.06-2.30). Νo association between apnoea/hypopnoea indices and non-refined grain intake was observed in this study. CONCLUSIONS: The findings show that obstructive sleep apnoea (OSA) is associated with cereal grain intake and suggest that a higher intake of refined cereal grains may be a risk factor for OSA severity.

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.

STUDY OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Mediterranean Diet/Lifestyle Intervention in Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/NCT02515357; Identifier: NCT02515357. CITATION: 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.

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.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: A weight-loss Mediterranean diet/lifestyle intervention on top of CPAP has anti-inflammatory and antioxidant benefits in OSA. REGISTRATION: The trial was prospectively registered at ClinicalTrials.gov (NCT02515357) on August 4, 2015.

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

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. TRIAL REGISTRATION: Clinicaltrials.gov NCT02515357, https://clinicaltrials.gov/ct2/show/NCT02515357.

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

Although continuous positive airway pressure (CPAP) is the first-line treatment for obstructive sleep apnea (OSA), its cardiometabolic benefits are questionable. Our aim was to explore whether the combination of a weight-loss Mediterranean diet/lifestyle intervention with OSA standard care leads to greater cardiometabolic improvements compared with standard care alone. We randomly assigned 187 adult, overweight, polysomnography-diagnosed moderate-to-severe OSA patients 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 groups were prescribed with CPAP. Additionally, the SCG only received brief written healthy lifestyle advice, while intervention arms were subjected to a six-month weight-loss behavioral intervention based on the Mediterranean diet. The MLG also received guidance for improving physical activity and sleep habits. Glucose metabolism indices, blood lipids, liver enzymes and blood pressure improved only in intervention arms, and were significantly lower compared to the SCG post-intervention (all p < 0.05). The age-, sex-, baseline- and CPAP use-adjusted relative risk (95% confidence interval) of metabolic syndrome was 0.58 (0.34-0.99) for the MDG and 0.30 (0.17-0.52) for the MLG compared to the SCG. The MLG additionally presented a lower relative risk of metabolic syndrome compared to the MDG (0.52 (0.30-0.89)). After further adjustment for body-weight change, a lower relative risk of metabolic syndrome was still evident for the MLG compared to the SCG. In conclusion, although standard care alone does not improve OSA patients' cardiometabolic profile, its combination with a weight-loss Mediterranean diet/lifestyle intervention leads to significant cardiometabolic benefits.

Associations between Red Meat Intake and Sleep Parameters in Patients with Obstructive Sleep Apnea.

BACKGROUND: Although lifestyle changes have been investigated as a therapeutic choice in regard to obstructive sleep apnea (OSA) severity, data exploring associations between apnea and hypopnea indices and dietary habits are scarce. OBJECTIVE: The aim was to investigate possible relationships between apnea and hypopnea indices and red meat intake in a cohort of Greek patients with mild or moderate to severe OSA evaluated by polysomnography. DESIGN: This is a cross-sectional study. Data were collected from November 2014 through July 2018. PARTICIPANTS/SETTING: The sample consisted of 243 patients (21 to 70 years old) who were recently diagnosed with OSA, by overnight attended polysomnography in the Sleep Disorders Center of "Evangelismos" Hospital, Athens Medical School (Greece). The patients included were free of other chronic diseases and had not changed their dietary habits for at least 6 months before evaluation. MAIN OUTCOME MEASURES: Information on participants' dietary intake, food group consumption, physical activity, smoking, sleep habits, and anthropometric measures were collected. Dietary intake was evaluated by food frequency questionnaire and 24-hour dietary recalls. Adherence to the Mediterranean diet was also evaluated using the Mediterranean Diet Score. STATISTICAL ANALYSES PERFORMED: General linear models were used to examine the relation between red meat intake and sleep parameters, while adjusting for potential confounders. Multiple logistic regression was also applied to estimate the association between red meat intake and the likelihood of severe OSA. RESULTS: Higher intakes of total red meat and unprocessed red meat were associated with higher values of apnea and hypopnea indices, after controlling for age, sex, waist circumference, socioeconomic parameters, smoking, physical activity, adequacy of nighttime sleep, and intake of foods or food components in the Mediterranean diet other than red meat (P trend for increasing quartiles of intake ≤0.02). Compared with patients in the lowest quartile of energy-adjusted total red meat intake (≤0.59 servings/day per 1,000 kcal), patients in the highest quartile (≥1.18 servings/day) had three times higher likelihood of having severe OSA (odds ratio: 3.09, 95% CI: 1.17 to 8.14). CONCLUSIONS: The results provide evidence of a positive association between total red meat and unprocessed red meat intake with apnea or hypopnea indices and suggest that red meat consumption is associated with OSA severity.

Incidence of Hyponatremia During a Continuous 246-km Ultramarathon Running Race.

Purpose: The purpose of this observational study was to examine the incidence of exercise-associated hyponatremia (EAH) in a 246-km continuous ultra-marathon. Methods: Over 2 years, 63 male finishers of the annual Spartathlon ultra-marathon foot race from Athens to Sparta, Greece were included in the data analysis. A blood sample was drawn from an antecubital vein the day before the race as well as within 15 min post-race and analyzed for sodium concentration. During the second year of data collection, blood was also drawn at the 93-km checkpoint (n = 29). Height and weight were measured pre and post-race. Results: Mean race time of all subjects was 33 ± 3 h with a range of 23.5 and 36.0 h. Of the 63 finishers recruited, nine began the race with values indicative of mild hyponatremia. Seven runners were classified as hyponatremic at the 93-km checkpoint, three of whom had sodium levels of severe hyponatremia. After the race, 41 total finishers (65%) developed either mild (n = 27, 43%) or severe hyponatremia (n = 14, 22%). Mean change in bodyweight percentage and serum sodium from pre-race to post-race was -3.6 ± 2.7% (-2.5 ± 1.9 kg) and -6.6 ± 5.6 mmol·L-1, respectively. Pre-race serum sodium level was not a significant predictor of post-race serum sodium levels (ß = 0.08, R 2 = 0.07, P = 0.698), however, there was a significant negative association between change in bodyweight percentage and post-race serum sodium concentration (ß = -0.79, R 2 = 0.29, P = 0.011). Conclusion: The incidence of EAH of 52 and 65%, when excluding or including these individuals with pre-race hyponatremia, was the highest reported in current literature.

Adherence to the Mediterranean diet and IVF success rate among non-obese women attempting fertility.

STUDY QUESTION: Is adherence to the Mediterranean diet (MedDiet) associated with better IVF performance in women attempting fertility? SUMMARY ANSWER: Greater adherence to the MedDiet, defined using the validated Mediterranean diet score (MedDietScore), was associated with a higher likelihood of achieving clinical pregnancy and live birth among non-obese women <35 years of age. WHAT IS KNOWN ALREADY: Diet impacts fertility and certain nutrients and food groups appear to have a greater effect on reproductive health, but there are relatively few published data on the role of dietary patterns, and the MedDiet in particular, on assisted reproductive performance. STUDY DESIGN, SIZE, DURATION: This prospective cohort study included 244 non-obese women (22-41 years of age; BMI < 30 kg/m2) who underwent a first IVF treatment in an Assisted Conception Unit in Athens, Greece, between November 2013 and September 2016. The study was designed to evaluate the influence of habitual dietary intake and lifestyle on fertility outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Diet was assessed before the IVF treatment via a validated food-frequency questionnaire. Adherence to the MedDiet was assessed through the MedDietScore (range: 0-55), with higher scores indicating greater adherence. Intermediate outcomes (oocyte yield, fertilization rate and embryo quality measures) and clinical endpoints (implantation, clinical pregnancy and live birth) were abstracted from electronic medical records. Associations between MedDietScore and IVF outcomes were analysed using generalized linear models adjusting for age, ovarian stimulation protocol, BMI, physical activity, anxiety levels, infertility diagnosis, caloric intake and supplements use. MAIN RESULTS AND THE ROLE OF CHANCE: No association of MedDietScore with any of the intermediate outcomes or with implantation was found. However, compared with women in the highest tertile of the MedDietScore (≥36, n = 86), women in the lowest tertile (≤30, n = 79) had significantly lower rates of clinical pregnancy (29.1 vs 50.0%, P = 0.01) and live birth (26.6 vs 48.8%, P = 0.01). The multivariable-adjusted relative risk (95% CI) for clinical pregnancy comparing women in the lowest with women in the highest tertile of the MedDietScore was 0.35 (0.16-0.78; P-trend=0.01), and for live birth it was 0.32 (0.14-0.71; P-trend = 0.01). These associations were significantly modified by women's age (P-interaction <0.01 for both outcomes). MedDietScore was positively related to clinical pregnancy and live birth among women <35 years old (P ≤ 0.01) but not among women ≥35 years. Among women <35 years, a beneficial 5-point increase in the MedDietScore was associated with ~2.7 times higher likelihood of achieving clinical pregnancy and live birth. LIMITATIONS, REASONS FOR CAUTION: Our finding cannot be generalized to the whole reproductive population nor to obese women nor to women attending infertility clinics around the world. In addition, due to the observational study design, causal inference is limited. WIDER IMPLICATIONS OF THE FINDINGS: The results suggest that diet modifications and greater compliance to the Mediterranean diet may help increase the chances of a successful pregnancy and delivering a live baby for women undergoing IVF treatment. STUDY FUNDING/COMPETING INTEREST(S): This work was partially supported by a grand from Harokopio University (KE321). All authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: NCT03050944.

Association between adherence to the Mediterranean diet and semen quality parameters in male partners of couples attempting fertility.

STUDY QUESTION: Is adherence to the Mediterranean diet (MedDiet) associated with better semen quality in men of subfertile couples attempting fertility? SUMMARY ANSWER: Greater adherence to the MedDiet, as assessed through the validated Mediterranean diet score (MedDietScore), was significantly associated with higher sperm concentration, total sperm count and sperm motility. WHAT IS KNOWN ALREADY: A-posteriori dietary pattern approaches have revealed that dietary patterns characterized by high intakes of fruits, vegetables, whole grains, fish and low intake of meat are associated with better semen quality. Yet, whether adherence to the MedDiet is associated with better semen profile remains largely unexplored. STUDY DESIGN, SIZE, AND DURATION: This was a cross-sectional study of 225 men from couples attending a fertility clinic in Athens, Greece, recruited between November 2013 and May 2016. The study was designed to evaluate the influence of habitual dietary intake and lifestyle on fertility outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Men aged 26-55 years, 51.1% overweight or obese, 20.9% smokers, with complete dietary data were analyzed. Diet was assessed via a food-frequency questionnaire and adherence to the MedDiet was assessed through the MedDietScore (range: 0-55; higher scores indicating greater adherence to MedDiet). Semen quality was evaluated according to World Health Organization 2010 guidelines. Multiple logistic regression analysis was used to evaluate associations between tertiles of the MedDietScore and the likelihood of having abnormal semen parameters, after adjusting for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to men in the highest tertile of the MedDietScore (≥37, N = 66), a higher percentage of men in the lowest tertile of the score (≤30, N = 76) exhibited below the WHO reference values for sperm concentration (47.4% vs 16.7%, P < 0.001), total sperm count (55.3% vs 22.7%, P < 0.001), total motility (65.8% vs 31.8%, P < 0.001), progressive motility (84.2 vs 62.1%, P = 0.011) and sperm morphology (50.0 vs 28.8%, P = 0.023). In the multivariable adjusted models, men in the lowest tertile of the MedDietScore had ~2.6 times higher likelihood of having abnormal sperm concentration, total sperm count and motility, compared to men in the highest tertile of the score. LIMITATIONS, REASONS FOR CAUTION: The main limitation of the study stems from its cross-sectional nature, limiting our ability to determine causality. WIDER IMPLICATIONS OF THE FINDINGS: The results suggest that greater compliance to the MedDiet may help improve semen quality. Whether this translates into differences in male fertility remains to be elucidated. Our findings are consistent with previous studies showing that dietary patterns with some of the characteristics of the MedDiet, i.e. rich in fruit, vegetables, legumes and whole grains, are associated with better measures of semen quality. STUDY FUNDING/COMPETING INTERESTS: No funding was obtained. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: n/a.

Variation at ABO histo-blood group and FUT loci and diffuse and intestinal gastric cancer risk in a European population.

ABO blood serotype A is known to be associated with risk of gastric cancer (GC), but little is known how ABO alleles and the fucosyltransferase (FUT) enzymes and genes which are involved in Lewis antigen formation [and in Helicobacter pylori (H. pylori) binding and pathogenicity] may be related to GC risk in a European population. The authors conducted an investigation of 32 variants at ABO and FUT1-7 loci and GC risk in a case-control study of 365 cases and 1,284 controls nested within the EPIC cohort (the EPIC-Eurgast study). Four variants (including rs505922) in ABO, and allelic blood group A (AO+AA, odds ratio=1.84, 95%CI=1.20-2.80) were associated with diffuse-type GC; however, conditional models with other ABO variants indicated that the associations were largely due to allelic blood group A. One variant in FUT5 was also associated with diffuse-type GC, and four variants (and haplotypes) in FUT2 (Se), FUT3 (Le) and FUT6 with intestinal-type GC. Further, one variant in ABO, two in FUT3 and two in FUT6 were associated with H. pylori infection status in controls, and two of these (in FUT3 and FUT6) were weakly associated with intestinal-type GC risk. None of the individual variants surpassed a Bonferroni corrected p-value cutoff of 0.0016; however, after a gene-based permutation test, two loci [FUT3(Le)/FUT5/FUT6 and FUT2(Se)] were significantly associated with diffuse- and intestinal-type GC, respectively. Replication and functional studies are therefore recommended to clarify the role of ABO and FUT alleles in H. pylori infection and subtype-specific gastric carcinogenesis.

Leukocyte telomere length in relation to pancreatic cancer risk: a prospective study.

BACKGROUND: Several studies have examined leukocyte telomere length (LTL) as a possible predictor for cancer at various organ sites. The hypothesis originally motivating many of these studies was that shorter telomeres would be associated with an increase in cancer risk; the results of epidemiologic studies have been inconsistent, however, and suggested positive, negative, or null associations. Two studies have addressed the association of LTL in relation to pancreatic cancer risk and the results are contrasting. METHODS: We measured LTL in a prospective study of 331 pancreatic cancer cases and 331 controls in the context of the European Prospective Investigation into Cancer and Nutrition (EPIC). RESULTS: We observed that the mean LTL was higher in cases (0.59 ± 0.20) than in controls (0.57 ± 0.17), although this difference was not statistically significant (P = 0.07), and a basic logistic regression model showed no association of LTL with pancreas cancer risk. When adjusting for levels of HbA1c and C-peptide, however, there was a weakly positive association between longer LTL and pancreatic cancer risk [OR, 1.13; 95% confidence interval (CI), 1.01-1.27]. Additional analyses by cubic spline regression suggested a possible nonlinear relationship between LTL and pancreatic cancer risk (P = 0.022), with a statistically nonsignificant increase in risk at very low LTL, as well as a significant increase at high LTL. CONCLUSION: Taken together, the results from our study do not support LTL as a uniform and strong predictor of pancreatic cancer. IMPACT: The results of this article can provide insights into telomere dynamics and highlight the complex relationship between LTL and pancreatic cancer risk.

Mediterranean diet and diabetes: prevention and treatment.

The aim of the present review is to examine current scientific knowledge on the association between the Mediterranean diet and diabetes mellitus (mostly type 2 diabetes). A definition of the Mediterranean diet and the tools widely used to evaluate adherence to this traditional diet (Mediterranean diet indices) are briefly presented. The review focuses on epidemiological data linking adherence to the Mediterranean diet with the risk of diabetes development, as well as evidence from interventional studies assessing the effect of the Mediterranean diet on diabetes control and the management of diabetes-related complications. The above mentioned data are explored on the basis of evaluating the Mediterranean diet as a whole dietary pattern, rather than focusing on the effect of its individual components. Possible protective mechanisms of the Mediterranean diet against diabetes are also briefly discussed.

Genetic association of gastric cancer with miRNA clusters including the cancer-related genes MIR29, MIR25, MIR93 and MIR106: results from the EPIC-EURGAST study.

MicroRNAs (miRNAs) are post-transcriptional gene regulators involved in a wide range of biological processes including tumorigenesis. Deregulation of miRNA pathways has been associated with cancer but the contribution of their genetic variability to this disorder is poorly known. We analyzed the genetic association of gastric cancer (GC) and its anatomical and histological subtypes, with 133 single-nucleotide polymorphisms (SNPs) tagging 15 isolated miRNAs and 24 miRNA clusters potentially involved in cancer, in 365 GC cases and 1,284 matched controls within the European Prospective Investigation into Cancer and Nutrition cohort. Various SNPs were associated with GC under the log-additive model. Furthermore, several of these miRNAs passed the gene-based permutation test when analyzed according to GC subtypes: three tagSNPs of the miR-29a/miR-29b-1 cluster were associated with diffuse subtype (minimum p-value = 1.7 × 10(-4) ; odds ratio, OR = 1.72; 95% confidence interval, CI = 1.30-2.28), two tagSNPs of the miR-25/miR-93/miR-106b cluster were associated with cardia GC (minimum p-value = 5.38 × 10(-3) ; OR = 0.56, 95% CI = 0.37-0.86) and one tagSNP of the miR-363/miR-92a-2/miR-19b-2/miR-20b/miR-18b/miR-106a cluster was associated with noncardia GC (minimum p-value = 5.40 × 10(-3) ; OR = 1.41, 95% CI = 1.12-1.78). Some functionally validated target genes of these miRNAs are implicated in cancer-related processes such as methylation (DNMT3A, DNMT3B), cell cycle (E2F1, CDKN1A, CDKN1C), apoptosis (BCL2L11, MCL1), angiogenesis (VEGFA) and progression (PIK3R1, MYCN). Furthermore, we identified genetic interactions between variants tagging these miRNAs and variants in their validated target genes. Deregulation of the expression of these miRNAs in GC also supports our findings, altogether suggesting for the fist time that genetic variation in MIR29, MIR25, MIR93 and MIR106b may have a critical role in genetic susceptibility to GC and could contribute to the molecular mechanisms of gastric carcinogenesis.

Additive influence of genetic predisposition and conventional risk factors in the incidence of coronary heart disease: a population-based study in Greece.

OBJECTIVES: An additive genetic risk score (GRS) for coronary heart disease (CHD) has previously been associated with incident CHD in the population-based Greek European Prospective Investigation into Cancer and nutrition (EPIC) cohort. In this study, we explore GRS-'environment' joint actions on CHD for several conventional cardiovascular risk factors (ConvRFs), including smoking, hypertension, type-2 diabetes mellitus (T2DM), body mass index (BMI), physical activity and adherence to the Mediterranean diet. DESIGN: A case-control study. SETTING: The general Greek population of the EPIC study. PARTICIPANTS AND OUTCOME MEASURES: 477 patients with medically confirmed incident CHD and 1271 controls participated in this study. We estimated the ORs for CHD by dividing participants at higher or lower GRS and, alternatively, at higher or lower ConvRF, and calculated the relative excess risk due to interaction (RERI) as a measure of deviation from additivity. RESULTS: The joint presence of higher GRS and higher risk ConvRF was in all instances associated with an increased risk of CHD, compared with the joint presence of lower GRS and lower risk ConvRF. The OR (95% CI) was 1.7 (1.2 to 2.4) for smoking, 2.7 (1.9 to 3.8) for hypertension, 4.1 (2.8 to 6.1) for T2DM, 1.9 (1.4 to 2.5) for lower physical activity, 2.0 (1.3 to 3.2) for high BMI and 1.5 (1.1 to 2.1) for poor adherence to the Mediterranean diet. In all instances, RERI values were fairly small and not statistically significant, suggesting that the GRS and the ConvRFs do not have effects beyond additivity. CONCLUSIONS: Genetic predisposition to CHD, operationalised through a multilocus GRS, and ConvRFs have essentially additive effects on CHD risk.