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      Effect of Glucose Improvement on Nocturnal Sleep Breathing Parameters in Patients with Type 2 Diabetes: The Candy Dreams Study

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          Abstract

          Type 2 diabetes exerts a negative impact on sleep breathing. It is unknown whether a long-term improvement in glycemic control ameliorates this effect. We conducted an interventional study with 35 patients with type 2 diabetes and obstructive sleep apnea (OSA) to explore this. At home, sleep breathing parameters were assessed at baseline and after a 4-month period in which antidiabetic therapy was intensified. Patients who decreased their body mass index ≥2kg/m 2 were excluded. Those with an HbA1c reduction ≥0.5% were considered good responders ( n = 24). After the follow-up, good responders exhibited an improvement in the apnea–hypopnea index (AHI: 26-1 (95% IC: 8.6–95.0) vs. 20.0 (4.0–62.4) events/hour, p = 0.002) and in time with oxygen saturation below 90% (CT90: 13.3 (0.4–69.0) vs. 8.1 (0.4–71.2) %, p = 0.002). No changes were observed in the group of non–responders ( p = 0.722 and p = 0.138, respectively). The percentage of moderate and severe OSA decreased among good responders ( p = 0.040). In the wider population, the change in HbA1c correlated positively to decreases in AHI (r = 0.358, p = 0.035) and negatively to increases in the minimum arterial oxygen saturation (r = −0.386, p = 0.039). Stepwise multivariate regression analysis showed that baseline AHI and the absolute change in HbA1c independently predicted decreased AHI (R 2 = 0.496). The improvement of glycemic control exerts beneficial effects on sleep breathing parameters in type 2 diabetes, which cannot be attributed merely to weight loss.

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          Obstructive sleep apnea: a cardiometabolic risk in obesity and the metabolic syndrome.

          Obstructive sleep apnea (OSA) is an underdiagnosed condition characterized by recurrent episodes of obstruction of the upper airway leading to sleep fragmentation and intermittent hypoxia during sleep. Obesity predisposes to OSA, and the prevalence of OSA is increasing worldwide because of the ongoing epidemic of obesity. Recent evidence has shown that surrogate markers of cardiovascular risk, including sympathetic activation, systemic inflammation, and endothelial dysfunction, are significantly increased in obese patients with OSA versus those without OSA, suggesting that OSA is not simply an epiphenomenon of obesity. Moreover, findings from animal models and patients with OSA show that intermittent hypoxia exacerbates the metabolic dysfunction of obesity, augmenting insulin resistance and nonalcoholic fatty liver disease. In patients with the metabolic syndrome, the prevalence of moderate to severe OSA is very high (∼60%). In this population, OSA is independently associated with increased glucose and triglyceride levels as well as markers of inflammation, arterial stiffness, and atherosclerosis. A recent randomized, controlled, crossover study showed that effective treatment of OSA with continuous positive airway pressure for 3 months significantly reduced several components of the metabolic syndrome, including blood pressure, triglyceride levels, and visceral fat. Finally, several cohort studies have consistently shown that OSA is associated with increased cardiovascular mortality, independent of obesity. Taken together, these results support the concept that OSA exacerbates the cardiometabolic risk attributed to obesity and the metabolic syndrome. Recognition and treatment of OSA may decrease the cardiovascular risk in obese patients. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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            Effect of liraglutide 3.0 mg in individuals with obesity and moderate or severe obstructive sleep apnea: the SCALE Sleep Apnea randomized clinical trial

            Background: Obesity is strongly associated with prevalence of obstructive sleep apnea (OSA), and weight loss has been shown to reduce disease severity. Objective: To investigate whether liraglutide 3.0 mg reduces OSA severity compared with placebo using the primary end point of change in apnea–hypopnea index (AHI) after 32 weeks. Liraglutide's weight loss efficacy was also examined. Subjects/Methods: In this randomized, double-blind trial, non-diabetic participants with obesity who had moderate (AHI 15–29.9 events h−1) or severe (AHI ⩾30 events h−1) OSA and were unwilling/unable to use continuous positive airway pressure therapy were randomized for 32 weeks to liraglutide 3.0 mg (n=180) or placebo (n=179), both as adjunct to diet (500 kcal day−1 deficit) and exercise. Baseline characteristics were similar between groups (mean age 48.5 years, males 71.9%, AHI 49.2 events h−1, severe OSA 67.1%, body weight 117.6 kg, body mass index 39.1 kg m−2, prediabetes 63.2%, HbA1c 5.7%). Results: After 32 weeks, the mean reduction in AHI was greater with liraglutide than with placebo (−12.2 vs −6.1 events h−1, estimated treatment difference: −6.1 events h−1 (95% confidence interval (CI), −11.0 to −1.2), P=0.0150). Liraglutide produced greater mean percentage weight loss compared with placebo (−5.7% vs −1.6%, estimated treatment difference: −4.2% (95% CI, −5.2 to −3.1%), P<0.0001). A statistically significant association between the degree of weight loss and improvement in OSA end points (P<0.01, all) was demonstrated post hoc. Greater reductions in glycated hemoglobin (HbA1c) and systolic blood pressure (SBP) were seen with liraglutide versus placebo (both P<0.001). The safety profile of liraglutide 3.0 mg was similar to that seen with doses ⩽1.8 mg. Conclusions: As an adjunct to diet and exercise, liraglutide 3.0 mg was generally well tolerated and produced significantly greater reductions than placebo in AHI, body weight, SBP and HbA1c in participants with obesity and moderate/severe OSA. The results confirm that weight loss improves OSA-related parameters.
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              Microarousals during sleep are associated with increased levels of lipids, cortisol, and blood pressure.

              Previous work has demonstrated a link between restricted sleep and risk indicators for cardiovascular and metabolic disease, such as levels of cortisol, lipids, and glucose. The present study sought to identify relations between polysomnographic measures of disturbed sleep (frequency of arousals from sleep, total sleep time, and sleep efficiency) and a number of such indicators. A second purpose was to relate the number of arousals to mood, stress, work characteristics, and other possible predictors in daily life. Twenty-four people (10 men, 14 women; mean age 30 years), high vs. low on burnout, were recruited from a Swedish IT company. Polysomnographically recorded sleep was measured at home before a workday. Blood pressure, heart rate, morning blood sample, and saliva samples of cortisol were measured the subsequent working day. They were also recorded for diary ratings of sleep and stress, and a questionnaire with ratings of sleep, stress, work conditions, and mood was completed. A stepwise regression analysis using sleep parameters as predictors brought out number of arousals as the best predictor of morning cortisol (serum and saliva), heart rate, systolic and diastolic blood pressure, total cholesterol, high-density lipoprotein (HDL)-, low-density lipoprotein (LDL)-cholesterol, and LDL/HDL-ratio. Work stress/unclear boundaries between work and leisure time was the best predictor of arousals among the stress variables. Consistent with sleep restriction experiments, sleep fragmentation was associated with elevated levels of metabolic and cardiovascular risk indicators of stress-related disorders. Number of arousals also seems to be related to workload/stress.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                04 April 2020
                April 2020
                : 9
                : 4
                : 1022
                Affiliations
                [1 ]Endocrinology and Nutrition Department, University Hospital Arnau de Vilanova, Obesity, Diabetes and Metabolism (ODIM) research group, IRBLleida, University of Lleida, 25198 Lleida, Spain; liligutierrezc@ 123456gmail.com (L.G.-C.); karolopezc@ 123456gmail.com (C.L.-C.); esanchez@ 123456irblleida.cat (E.S.); martahernandezg@ 123456gmail.com (M.H.); angelacamposjimenez@ 123456gmail.com (A.C.)
                [2 ]Respiratory Department, University Hospital Arnau de Vilanova-Santa María, Translational Research in Respiratory Medicine, IRBLleida, University of Lleida, 25198 Lleida, Spain; febarbe.lleida.ics@ 123456gencat.cat (F.B.); mdalmases.lleida.ics@ 123456gencat.cat (M.D.); annamichelagaeta@ 123456hotmail.it (A.M.G.); pcarmona@ 123456irblleida.cat (P.C.)
                [3 ]Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
                [4 ]Endocrinology and Nutrition Department, University Hospital Vall d’Hebron, Diabetes and Metabolism Research Unit, Vall d’Hebron Institut de Recerca (VHIR), Autonomous University of Barcelona, 08035 Barcelona, Spain; cristina.hernandez@ 123456vhir.org
                [5 ]Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
                Author notes
                Author information
                https://orcid.org/0000-0001-7345-1601
                https://orcid.org/0000-0002-3109-1721
                https://orcid.org/0000-0003-0475-3096
                https://orcid.org/0000-0001-9684-0183
                Article
                jcm-09-01022
                10.3390/jcm9041022
                7230160
                32260419
                21a68f1e-316a-48bc-8165-069ffb3af8d5
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 18 February 2020
                : 01 April 2020
                Categories
                Article

                diabetes,apnea,hypoxia,glycated hemoglobin
                diabetes, apnea, hypoxia, glycated hemoglobin

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