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Zhang T, Pan Y, Sawa T, Akaike T, Matsunaga T. Supersulfide donors and their therapeutic targets in inflammatory diseases. Front Immunol 2025; 16:1581385. [PMID: 40308575 PMCID: PMC12040673 DOI: 10.3389/fimmu.2025.1581385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2025] [Accepted: 03/31/2025] [Indexed: 05/02/2025] Open
Abstract
Inflammation is one defense mechanism of the body that has multiple origins, ranging from physical agents to infectious agents including viruses and bacteria. The resolution of inflammation has emerged as a critical endogenous process that protects host tissues from prolonged or excessive inflammation, which can become chronic. Failure of the inflammation resolution is a key pathological mechanism that drives the progression of numerous inflammatory diseases. Owing to the various side effects of currently available drugs to control inflammation, novel therapeutic agents that can prevent or suppress inflammation are needed. Supersulfides are highly reactive and biologically potent molecules that function as antioxidants, redox regulators, and modulators of cell signaling. The catenation state of individual sulfur atoms endows supersulfides with unique biological activities. Great strides have recently been made in achieving a molecular understanding of these sulfur species, which participate in various physiological and pathological pathways. This review mainly focuses on the anti-inflammatory effects of supersulfides. The review starts with an overview of supersulfide biology and highlights the roles of supersulfides in both immune and inflammatory responses. The various donors used to generate supersulfides are assessed as research tools and potential therapeutic agents. Deeper understanding of the molecular and cellular bases of supersulfide-driven biology can help guide the development of innovative therapeutic strategies to prevent and treat diseases associated with various immune and inflammatory responses.
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Affiliation(s)
- Tianli Zhang
- Center for Integrated Control, Epidemiology and Molecular Pathophysiology of Infectious Diseases, Akita University, Akita, Japan
| | - Yuexuan Pan
- Department of Redox Molecular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Tomohiro Sawa
- Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Takaaki Akaike
- Department of Redox Molecular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
- Shimadzu × Tohoku University Supersulfides Life Science Co-creation Research Center, Sendai, Japan
| | - Tetsuro Matsunaga
- Center for Integrated Control, Epidemiology and Molecular Pathophysiology of Infectious Diseases, Akita University, Akita, Japan
- Shimadzu × Tohoku University Supersulfides Life Science Co-creation Research Center, Sendai, Japan
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Gong L, Su M, Xu JH, Peng ZF, Du L, Chen ZY, Liu YZ, Chan LC, Huang YL, Chen YT, Huang FY, Piao CL. Cross-sectional study of the association between triglyceride glucose-body mass index and obstructive sleep apnea risk. World J Diabetes 2025; 16:98519. [PMID: 40093293 PMCID: PMC11885970 DOI: 10.4239/wjd.v16.i3.98519] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 09/10/2024] [Accepted: 12/27/2024] [Indexed: 01/21/2025] Open
Abstract
BACKGROUND The triglyceride glucose-body mass index (TyG-BMI) is a novel indicator of insulin resistance (IR). Obstructive sleep apnea (OSA) is a prevalent disorder characterized by recurrent complete or partial collapse of the pharyngeal airway during sleep; however, the relationship between these two conditions remains unexplored. We hypothesized that a higher TyG-BMI is associated with the occurrence of OSA. AIM To assess the association between TyG-BMI and OSA in adults in the United States. METHODS A cross-sectional study was conducted utilizing data from the National Health and Nutrition Examination Surveys spanning from 2005-2008 to 2015-2018. TyG-BMI was calculated as Ln [triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2] × BMI. Restricted cubic splines were used to analyze the risk of TyG-BMI and OSA occurrence. To identify potential nonlinear relationships, we combined Cox proportional hazard regression with smooth curve fitting. We also conducted sensitivity and subgroup analyses to verify the robustness of our findings. RESULTS We included 16794 participants in the final analysis. Multivariate regression analysis showed that participants with a higher TyG-BMI had a higher OSA incidence. After adjusting for all covariates, TyG-BMI was positively correlated with the prevalence of OSA (odds ratio: 1.28; 95% confidence interval: 1.17, 1.40; P < 0.001); no significant nonlinear relationship was observed. Subgroup analysis showed no strong correlation between TyG-BMI and OSA in patients with diabetes. The correlation between TyG-BMI and OSA was influenced by age, sex, smoking status, marital status, hypertensive stratification, and obesity; these subgroups played a moderating role between TyG-BMI and OSA. Even after adjusting for all covariates, there was a positive association between TYG-BMI and OSA prevalence. CONCLUSION A higher TyG-BMI index is linked to higher chances of developing OSA. As TyG-BMI is an indicator of IR, managing IR may help reduce the risk of OSA.
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Affiliation(s)
- Li Gong
- Department of Diabetes, Shenzhen Bao'an Chinese Medicine Hospital Guangzhou University of Chinese Medicine, Shenzhen 518100, Guangdong Province, China
| | - Ming Su
- Department of Pneumology, Shenzhen Bao'an Chinese Medicine Hospital Guangzhou University of Chinese Medicine, Shenzhen 518100, Guangdong Province, China
| | - Jing-Han Xu
- Department of Endocrinology, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen 518100, Guangdong Province, China
| | - Zhen-Fei Peng
- Department of Diabetes, Shenzhen Bao'an Chinese Medicine Hospital Guangzhou University of Chinese Medicine, Shenzhen 518100, Guangdong Province, China
| | - Lin Du
- Department of Endocrinology, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen 518100, Guangdong Province, China
| | - Ze-Yao Chen
- Department of Endocrinology, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen 518100, Guangdong Province, China
| | - Yu-Zhou Liu
- Department of Diabetes, Shenzhen Bao'an Chinese Medicine Hospital Guangzhou University of Chinese Medicine, Shenzhen 518100, Guangdong Province, China
| | - Lu-Cia Chan
- Department of Endocrinology, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen 518100, Guangdong Province, China
| | - Yin-Luan Huang
- Department of Diabetes, Shenzhen Bao'an Chinese Medicine Hospital Guangzhou University of Chinese Medicine, Shenzhen 518100, Guangdong Province, China
| | - Yu-Tian Chen
- Department of Diabetes, Shenzhen Bao'an Chinese Medicine Hospital Guangzhou University of Chinese Medicine, Shenzhen 518100, Guangdong Province, China
| | - Feng-Yi Huang
- Department of Diabetes, Shenzhen Bao'an Chinese Medicine Hospital Guangzhou University of Chinese Medicine, Shenzhen 518100, Guangdong Province, China
| | - Chun-Li Piao
- Department of Endocrinology, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen 518100, Guangdong Province, China
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Chen Cardenas SM, Baker TA, Shimoda LA, Bernal-Mizrachi E, Punjabi NM. L-type calcium channel blockade worsens glucose tolerance and β-cell function in C57BL6/J mice exposed to intermittent hypoxia. Am J Physiol Endocrinol Metab 2025; 328:E161-E172. [PMID: 39763275 DOI: 10.1152/ajpendo.00423.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 11/08/2024] [Accepted: 12/02/2024] [Indexed: 01/24/2025]
Abstract
Intermittent hypoxemia (IH), a pathophysiologic consequence of obstructive sleep apnea (OSA), adversely affects insulin sensitivity, insulin secretion, and glucose tolerance. Nifedipine, an L-type calcium channel blocker frequently used for the treatment of hypertension, can also impair insulin sensitivity and secretion. However, the cumulative and interactive repercussions of IH and nifedipine on glucose homeostasis have not been previously investigated. Adult male C57BL6/J mice were exposed to either nifedipine or vehicle concurrently with IH or intermittent air (IA) over 5 days. IH exposure entailed cycling fractional-inspired oxygen levels between 0.21 and 0.055 at a rate of 60 events/h. Nifedipine (20 mg/kg/day) or vehicle was administered via subcutaneous osmotic pumps resulting in four groups of mice: IA-vehicle (control), IA-nifedipine, IH-vehicle, and IH-nifedipine. Compared with IA (control), IH increased fasting glucose (mean Δ: 33.0 mg/dL; P < 0.001) and insulin (mean Δ: 0.53 ng/mL; P < 0.001) with nifedipine having no independent effect. Furthermore, glucose tolerance was worse with nifedipine alone, and IH further exacerbated the impairment in glucose disposal (P = 0.013 for interaction). Nifedipine also decreased glucose-stimulated insulin secretion and the insulinogenic index, with addition of IH attenuating those measures further. There were no discernible alterations in insulin biosynthesis/processing, insulin content, or islet morphology. These findings underscore the detrimental impact of IH on insulin sensitivity and glucose tolerance while highlighting that nifedipine exacerbates these disturbances through impaired β-cell function. Consequently, cautious use of L-type calcium channel blockers is warranted in patients with OSA, particularly in those at risk for type 2 diabetes.NEW & NOTEWORTHY The results of this study demonstrate the interaction between intermittent hypoxemia (IH) and nifedipine in a murine model. IH raises fasting glucose and insulin levels, with nifedipine exacerbating these disturbances. Glucose tolerance worsens when nifedipine is administered alone, and IH magnifies the impairment in glucose disposal. These findings raise the possibility of potential deleterious effects of L-type calcium channel blockers in patients with obstructive sleep apnea (OSA).
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Affiliation(s)
- Stanley M Chen Cardenas
- Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
| | - Tess A Baker
- Division of Endocrinology, Diabetes, and Metabolism, Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, Florida, United States
| | - Larissa A Shimoda
- Division of Pulmonary, Critical Care, and Sleep Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
| | - Ernesto Bernal-Mizrachi
- Division of Endocrinology, Diabetes, and Metabolism, Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, Florida, United States
| | - Naresh M Punjabi
- Division of Pulmonary, Critical Care, and Sleep Medicine, Miller School of Medicine, University of Miami, Miami, Florida, United States
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Alami S, Schaller M, Blais S, Taupin H, Hernández González M, Gagnadoux F, Pinto P, Cano-Pumarega I, Bedert L, Braithwaite B, Servy H, Ouary S, Fabre C, Bazin F, Texereau J. Evaluating the Benefit of Home Support Provider Services for Positive Airway Pressure Therapy in Patients With Obstructive Sleep Apnea: Protocol for an Ambispective International Real-World Study. JMIR Res Protoc 2025; 14:e65840. [PMID: 39665447 PMCID: PMC11829180 DOI: 10.2196/65840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 11/29/2024] [Accepted: 12/02/2024] [Indexed: 12/13/2024] Open
Abstract
BACKGROUND Adherence and persistence to positive airway pressure (PAP) therapy are key factors for positive health outcomes. Home support providers participate in the home implementation and follow-up of PAP therapy for patients with obstructive sleep apnea (OSA). In Europe, home support provider service levels are country (or area) specific, resulting in differences in content and frequency of patient interactions. However, no robust evaluation of the impact of these differences on clinical and patient outcomes has been performed. OBJECTIVE The AWAIR study aims to evaluate and compare the impact of different home support provider service levels on PAP adherence and persistence in 4 European countries. METHODS This real-world, ambispective, cohort study-conducted in France, Belgium, Spain, and Portugal-will recruit adults with OSA who started PAP therapy between 2019 and 2023 and were followed by an Air Liquide Healthcare home support provider. Given the large number of eligible participants (around 150,000), the study will use a decentralized and digital approach. A patient video will present the study objectives and the participation process. A secure electronic solution will be used to manage patient information and consent, as well as to administer a web-based questionnaire. Retrospective data, collected during routine patient follow-up by home support providers, include the level of service and device data, notably PAP use. Prospective data collected using an electronic patient-reported outcome tool include health status, OSA-related factors, patient-reported outcomes including quality of life and symptoms, OSA and PAP literacy, patient-reported experience, and satisfaction with PAP therapy and service. Hierarchical models, adjusted for preidentified confounding factors, will be used to assess the net effect of home support provider services on PAP adherence and persistence while minimizing real-world study biases and considering the influence of country-level contextual factors. We hypothesize that higher levels of home support provider services will be positively associated with adherence and persistence to PAP therapy. RESULTS As of December 2024, the study has received approval in France, Portugal, and 2 regions of Spain. The study began enrollment in France in October 2024. Results are expected in the second quarter of 2025. CONCLUSIONS The AWAIR study has a unique design, leveraging an unprecedented number of eligible participants, decentralized technologies, and a real-world comparative methodology across multiple countries. This approach will highlight intercountry differences in terms of patient characteristics, PAP adherence, and persistence, as well as patient-reported outcomes, patient-reported experiences, and satisfaction with the home service provider. By assessing the added value of home support provider services, the results will support best practices for patient management and for decision-making by payers and authorities. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) PRR1-10.2196/65840.
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Affiliation(s)
- Sarah Alami
- Air Liquide Santé International, Bagneux, France
| | | | - Sylvie Blais
- Air Liquide Santé International, Bagneux, France
| | - Henry Taupin
- Air Liquide Santé International, Bagneux, France
| | | | - Frédéric Gagnadoux
- Department of Respiratory and Sleep Medicine, Angers University Hospital, Angers, France
| | - Paula Pinto
- Thorax Department, Unidade Local de Saúde Santa Maria, Lisbon, Portugal
- Faculty of Medicine of Lisbon, Instituto de Saúde Ambiental, Lisbon, Portugal
| | - Irene Cano-Pumarega
- Sleep Unit and Respiratory Department, Hospital Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, Spain
| | - Lieven Bedert
- Department of Respiratory Medicine, Ziekenhuisnetwerk Antwerpen Middelheim Hospital, Anvers, Belgium
| | | | | | | | | | | | - Joëlle Texereau
- Air Liquide Healthcare, Bagneux, France
- Cochin University Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France
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Zhou Y, Xue F. Exploring the Association Between Triglyceride-Glucose Indices and Their Derivatives With Obstructive Sleep Apnea: Insights From the National Health and Nutrition Examination Survey. Nat Sci Sleep 2025; 17:143-155. [PMID: 39872223 PMCID: PMC11771171 DOI: 10.2147/nss.s487596] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Accepted: 01/17/2025] [Indexed: 01/30/2025] Open
Abstract
Background Simple and affordable methods for evaluating Insulin Resistance (IR) have been suggested, such as the Triglyceride-Glucose (TyG) index and its variants, including the TyG-Body Mass Index (TyG-BMI), TyG-Waist Circumference (TyG-WC), and TyG-Waist-to-Height Ratio (TyG-WHtR). The aim of this study is to investigate the relationship between these TyG-related indices, which measure IR, and Obstructive Sleep Apnea (OSA). Methods This study analyzed NHANES data from 2007-2008, 2015-2016, and 2017-2020. TyG and its derivatives were evaluated as continuous and categorical variables in relation to OSA using multivariable logistic regression models. Subgroup analyses, dose-response relationships, and threshold effects were explored, and the diagnostic performance of TyG-related indices was assessed using AUC curves. Results The study included 8,374 participants. The fully adjusted Model 3 analysis (Note: Body Mass Index was not adjusted for TyG-BMI) of continuous variables showed a positive correlation between OSA and all four indices. All four TyG-related indicators showed statistically significant relationships with OSA when grouped into quartiles (TyG: AOR = 1.448, 95% CI: 1.260-1.663; TyG-BMI: AOR = 3.785, 95% CI: 3.319-4.317; TyG-WC: AOR = 2.089, 95% CI: 1.629-2.677; TyG-WHtR: AOR = 1.913, 95% CI: 1.548-2.363). Subgroup analysis revealed a stronger association of TyG-WHtR with OSA in the 41-59 age group (AOR = 1.459, 95% CI: 1.254-1.698) and the low-income group (AOR = 1.451, 95% CI: 1.241-1.698). TyG showed a linear relationship with OSA, while TyG-BMI, TyG-WC, and TyG-WHtR exhibited nonlinear relationships. The diagnostic capability was highest for TyG-WC, with an AUC of 0.647. Conclusion The study confirms strong associations between OSA and the TyG indices, particularly TyG-WC, which demonstrates significant predictive power for OSA risk. Future longitudinal studies are recommended to further investigate these associations and enhance OSA management in resource-constrained environments.
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Affiliation(s)
- Yating Zhou
- Kunshan Hospital of Traditional Chinese Medicine, Kunshan City, Suzhou, Jiangsu Province, People’s Republic of China
| | - Fei Xue
- Kunshan Hospital of Traditional Chinese Medicine, Kunshan City, Suzhou, Jiangsu Province, People’s Republic of China
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Chen K, Ou B, Huang Q, Deng D, Xiang Y, Hu F. LncRNA NEAT1 aggravates human microvascular endothelial cell injury by inhibiting the Apelin/Nrf2/HO-1 signalling pathway in type 2 diabetes mellitus with obstructive sleep apnoea. Epigenetics 2024; 19:2293409. [PMID: 38232183 PMCID: PMC10795783 DOI: 10.1080/15592294.2023.2293409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 12/05/2023] [Indexed: 01/19/2024] Open
Abstract
Long noncoding RNAs (lncRNAs) regulate the progression of type 2 diabetes mellitus complicated with obstructive sleep apnoea (T2DM-OSA). However, the role of the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in T2DM-OSA remains unknown. This study aimed to reveal the function of NEAT1 in T2DM-OSA and the underlying mechanism. KKAy mice were exposed to intermittent hypoxia (IH) or intermittent normoxia to generate a T2DM-OSA mouse model. HMEC-1 cells were treated with high glucose (HG) and IH to construct a T2DM-OSA cell model. RNA expression was detected by qRT-PCR. The protein expression of Apelin, NF-E2-related factor 2 (Nrf2), haem oxygenase-1 (HO-1), and up-frameshift suppressor 1 (UPF1) was assessed using western blot. Cell injury was evaluated using flow cytometry, enzyme-linked immunosorbent assay, and oxidative stress kit assays. RIP, RNA pull-down, and actinomycin D assays were performed to determine the associations between NEAT1, UPF1, and Apelin. NEAT1 expression was upregulated in the aortic vascular tissues of mice with T2DM exposed to IH and HMEC-1 cells stimulated with HG and IH, whereas Apelin expression was downregulated. The absence of NEAT1 protected HMEC-1 cells from HG- and IH-induced damage. Furthermore, NEAT1 destabilized Apelin mRNA by recruiting UPF1. Apelin overexpression decreased HG- and IH-induced injury to HMEC-1 cells by activating the Nrf2/HO-1 pathway. Moreover, NEAT1 knockdown reduced HG- and IH-induced injury to HMEC-1 cells through Apelin. NEAT1 silencing reduced HMEC-1 cell injury through the Apelin/Nrf2/HO-1 signalling pathway in T2DM-OSA.Abbreviations: LncRNAs, long non-coding RNAs; T2DM, type 2 diabetes mellitus; OSA, obstructive sleep apnoea; NEAT1, nuclear paraspeckle assembly transcript 1; IH, intermittent hypoxia; HMEC-1, human microvascular endothelial cells; HG, high glucose; Nrf2, NF-E2-related factor 2; UPF1, up-frameshift suppressor 1; HO-1, haem oxygenase-1; qRT-PCR, quantitative real-time polymerase chain reaction; ELISA, enzyme-linked immunosorbent assay; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; TNF-α, tumour necrosis factor-α; CCK-8, Cell Counting Kit-8; IL-1β, interleukin-1β; ROS, reactive oxygen species; MDA, malondialdehyde; SOD, superoxide dismutase; RIP, RNA immunoprecipitation; SD, standard deviations; GSH, glutathione; AIS, acute ischaemic stroke; HMGB1, high mobility group box-1 protein; TLR4, toll-like receptor 4.
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Affiliation(s)
- Kai Chen
- Department of Cardiovascular Medicine Six Wards (Cardiovascular and Metabolic Diseases), Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, China
| | - Baiqing Ou
- Department of Cardiovascular Medicine Six Wards (Cardiovascular and Metabolic Diseases), Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, China
| | - Quan Huang
- Department of Cardiovascular Medicine Six Wards (Cardiovascular and Metabolic Diseases), Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, China
| | - Daqing Deng
- Department of Cardiovascular Medicine Six Wards (Cardiovascular and Metabolic Diseases), Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, China
| | - Yi Xiang
- Department of Cardiovascular Medicine Six Wards (Cardiovascular and Metabolic Diseases), Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, China
| | - Fang Hu
- Comprehensive internal medicine of Hunan Provincial People’s Hospital, Changsha, Hunan, China
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Ryskova L, Pospisilova K, Vavra J, Wolf T, Dvorak A, Vitek L, Polak J. Contribution of glucose and glutamine to hypoxia-induced lipid synthesis decreases, while contribution of acetate increases, during 3T3-L1 differentiation. Sci Rep 2024; 14:28193. [PMID: 39548264 PMCID: PMC11568125 DOI: 10.1038/s41598-024-79458-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Accepted: 11/08/2024] [Indexed: 11/17/2024] Open
Abstract
The molecular mechanisms linking obstructive sleep apnea syndrome (OSA) to obesity and the development of metabolic diseases are still poorly understood. The role of hypoxia (a characteristic feature of OSA) in excessive fat accumulation has been proposed. The present study investigated the possible effects of hypoxia (4% oxygen) on de novo lipogenesis by tracking the major carbon sources in differentiating 3T3-L1 adipocytes. Gas-permeable cultuware was employed to cultivate 3T3-L1 adipocytes in hypoxia (4%) for 7 or 14 days of differentiation. We investigated the contribution of glutamine, glucose or acetate using 13C or 14C labelled carbons to the newly synthesized lipid pool, changes in intracellular lipid content after inhibiting citrate- or acetate-dependent pathways and gene expression of involved key enzymes. The results demonstrate that, in differentiating adipocytes, hypoxia decreased the synthesis of lipids from glucose (44.1 ± 8.8 to 27.5 ± 3.0 pmol/mg of protein, p < 0.01) and partially decreased the contribution of glutamine metabolized through the reverse tricarboxylic acid cycle (4.6% ± 0.2-4.2% ± 0.1%, p < 0.01). Conversely, the contribution of acetate, a citrate- and mitochondria-independent source of carbons, increased upon hypoxia (356.5 ± 71.4 to 649.8 ± 117.5 pmol/mg of protein, p < 0.01). Further, inhibiting the citrate- or acetate-dependent pathways decreased the intracellular lipid content by 58% and 73%, respectively (p < 0.01) showing the importance of de novo lipogenesis in hypoxia-exposed adipocytes. Altogether, hypoxia modified the utilization of carbon sources, leading to alterations in de novo lipogenesis in differentiating adipocytes and increased intracellular lipid content.
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Affiliation(s)
- Lucie Ryskova
- Department of Pathophysiology, Third Faculty of Medicine, Charles University, Ruska 87, Prague, 100 00, Czech Republic
| | - Katerina Pospisilova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Jiri Vavra
- Department of Cell Biology, Faculty of Science, Charles University, Prague, Czech Republic
| | - Tomas Wolf
- Department of Pathophysiology, Third Faculty of Medicine, Charles University, Ruska 87, Prague, 100 00, Czech Republic
| | - Ales Dvorak
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Libor Vitek
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University, Prague, Czech Republic
- Department of Internal Medicine, Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital in Prague and First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Jan Polak
- Department of Pathophysiology, Third Faculty of Medicine, Charles University, Ruska 87, Prague, 100 00, Czech Republic.
- Department of Internal Medicine, Thomayer University Hospital, Videnska 800, Prague, 140 59, Czech Republic.
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Knowlden AP, Winchester LJ, MacDonald HV, Geyer JD, Higginbotham JC. Associations Among Cardiometabolic Risk Factors, Sleep Duration, and Obstructive Sleep Apnea in a Southeastern US Rural Community: Cross-Sectional Analysis From the SLUMBRx-PONS Study. JMIR Form Res 2024; 8:e54792. [PMID: 39514856 PMCID: PMC11584535 DOI: 10.2196/54792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 08/03/2024] [Accepted: 09/24/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Short sleep and obstructive sleep apnea are underrecognized strains on the public health infrastructure. In the United States, over 35% of adults report short sleep and more than 80% of individuals with obstructive sleep apnea remain undiagnosed. The associations between inadequate sleep and cardiometabolic disease risk factors have garnered increased attention. However, challenges persist in modeling sleep-associated cardiometabolic disease risk factors. OBJECTIVE This study aimed to report early findings from the Short Sleep Undermines Cardiometabolic Health-Public Health Observational study (SLUMBRx-PONS). METHODS Data for the SLUMBRx-PONS study were collected cross-sectionally and longitudinally from a nonclinical, rural community sample (n=47) in the southeast United States. Measures included 7 consecutive nights of wrist-based actigraphy (eg, mean of 7 consecutive nights of total sleep time [TST7N]), 1 night of sleep apnea home testing (eg, apnea-hypopnea index [AHI]), and a cross-sectional clinical sample of anthropometric (eg, BMI), cardiovascular (eg, blood pressure), and blood-based biomarkers (eg, triglycerides and glucose). Correlational analyses and regression models assessed the relationships between the cardiometabolic disease risk factors and the sleep indices (eg, TST7N and AHI). Linear regression models were constructed to examine associations between significant cardiometabolic indices of TST7N (model 1) and AHI (model 2). RESULTS Correlational assessment in model 1 identified significant associations between TST7N and AHI (r=-0.45, P=.004), BMI (r=-0.38, P=.02), systolic blood pressure (r=0.40, P=.01), and diastolic blood pressure (r=0.32, P=.049). Pertaining to model 1, composite measures of AHI, BMI, systolic blood pressure, and diastolic blood pressure accounted for 25.1% of the variance in TST7N (R2adjusted=0.25; F2,38=7.37; P=.002). Correlational analyses in model 2 revealed significant relationships between AHI and TST7N (r=-0.45, P<.001), BMI (r=0.71, P<.001), triglycerides (r=0.36, P=.03), and glucose (r=0.34, P=.04). Results from model 2 found that TST7N, triglycerides, and glucose accounted for 37.6% of the variance in the composite measure of AHI and BMI (R2adjusted=0.38; F3,38=8.63; P<.001). CONCLUSIONS Results from the SLUMBRx-PONS study highlight the complex interplay between sleep-associated risk factors for cardiometabolic disease. Early findings underscore the need for further investigations incorporating the collection of clinical, epidemiological, and ambulatory measures to inform public health, health promotion, and health education interventions addressing the cardiometabolic consequences of inadequate sleep. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) RR2-10.2196/27139.
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Affiliation(s)
- Adam P Knowlden
- Department of Health Science, The University of Alabama, Tuscaloosa, AL, United States
| | - Lee J Winchester
- Department of Kinesiology, The University of Alabama, Tuscaloosa, AL, United States
| | - Hayley V MacDonald
- Department of Kinesiology, The University of Alabama, Tuscaloosa, AL, United States
| | - James D Geyer
- Institute for Rural Health Research, College of Community Health Sciences, The University of Alabama, Tuscaloosa, AL, United States
| | - John C Higginbotham
- Research Institute of Pharmaceutical Sciences, The University of Mississippi, University, MS, United States
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Nag DS, Chatterjee A, Patel R, Sen B, Pal BD, Wadhwa G. Recent advances in managing obstructive sleep apnea. World J Clin Cases 2024; 12:5456-5461. [PMID: 39188611 PMCID: PMC11269999 DOI: 10.12998/wjcc.v12.i24.5456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Revised: 04/28/2024] [Accepted: 05/16/2024] [Indexed: 07/11/2024] Open
Abstract
Obstructive sleep apnea (OSA) is a rapidly increasing global concern. If it remains untreated, it can lead to cardiovascular, metabolic, and psychiatric complications and may result in premature death. The efficient and effective management of OSA can have a beneficial effect and help reduce the financial burden on the health sector. There has been constant development in OSA management, and numerous options are available. The mainstay of therapy is still the conventional measures and behavioral modifications. However, in cases of failure of these modalities, surgical therapy is the only option. Numerous studies have shown that proper management of OSA has beneficial effects with good long-term outcomes.
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Affiliation(s)
- Deb Sanjay Nag
- Department of Anaesthesiology, Tata Main Hospital, Jamshedpur 831001, Jharkhand, India
| | - Abhishek Chatterjee
- Department of Anaesthesiology, Tata Main Hospital, Jamshedpur 831001, Jharkhand, India
- Department of Anaesthesiology, Manipal Tata Medical College, Jamshedpur 831017, India
| | - Roushan Patel
- Department of Anaesthesiology, Tata Main Hospital, Jamshedpur 831001, Jharkhand, India
- Department of Anaesthesiology, Manipal Tata Medical College, Jamshedpur 831017, India
| | - Biswajit Sen
- Department of Anesthesiology, Tata Main Hospital, Jamshedpur 831001, India
| | - Bappa Ditya Pal
- Department of Anaesthesiology, Tata Main Hospital, Jamshedpur 831001, Jharkhand, India
| | - Gunjan Wadhwa
- Department of Anaesthesiology, Tata Main Hospital, Jamshedpur 831001, Jharkhand, India
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10
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Meng X, Wen H, Lian L. Association between triglyceride glucose-body mass index and obstructive sleep apnea: a study from NHANES 2015-2018. Front Nutr 2024; 11:1424881. [PMID: 39221158 PMCID: PMC11363548 DOI: 10.3389/fnut.2024.1424881] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Accepted: 08/06/2024] [Indexed: 09/04/2024] Open
Abstract
Background The association between TyG-BMI index and the risk of obstructive sleep apnea (OSA), a recently identified biomarker indicating insulin resistance, has yet to be elucidated. Therefore, this study aimed to investigate the association between TyG-BMI index and the risk of OSA using the NHANES database. Methods Analyses were performed on NHANES data conducted between 2015 and 2018. Logistic regression, stratified analyses, curve-fitting analyses, and threshold effects analyses were utilized to assess the association between TyG-BMI index and the risk of OSA. Results The study included 4,588 participants. Multifactorial logistic regression analyses found a significant association between TyG-BMI and increased risk of OSA [OR: 1.54 (CI:1.39-1.70)]. In stratified analyses, age interacted with the association, with TyG-BMI being associated with increased risk of OSA only in a subgroup of subjects younger than 60 years [1.31 (1.14-1.50)], but gender, smoking status, and alcohol use, did not influence the association. The presence of diabetes, hypertension, and cardiovascular diseases also modified the association, but the number of the included subjects with such conditions was significantly lower, therefore the significance of associations was not observed in those subgroups. Additionally, the risk was non-linearly associated, with the inflection point of TyG-BMI at 12.09, after which the lower slope in the risk was observed. Conclusion This study demonstrates that elevated levels of the TyG-BMI index are correlated with risk for OSA, underscoring the significance of these findings in facilitating early prevention or timely intervention for OSA.
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Affiliation(s)
- Xingru Meng
- Department of Respiratory Medicine, Dongguan Hospital of Traditional Chinese Medicine, Dongguan, Guangdong, China
| | - Haihua Wen
- The Ninth Clinical Medical College, Guangzhou University of Chinese Medicine, Dongguan, Guangdong, China
| | - Leshen Lian
- Department of Respiratory Medicine, Dongguan Hospital of Traditional Chinese Medicine, Dongguan, Guangdong, China
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11
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Tenda ED, Henrina J, Cha JH, Triono MR, Putri EA, Aristy DJ, Tahapary DL. Obstructive sleep apnea: Overlooked comorbidity in patients with diabetes. World J Diabetes 2024; 15:1448-1460. [PMID: 39099813 PMCID: PMC11292334 DOI: 10.4239/wjd.v15.i7.1448] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 05/08/2024] [Accepted: 06/06/2024] [Indexed: 07/08/2024] Open
Abstract
In this review article, we explore the interplay between obstructive sleep apnea (OSA) and type 2 diabetes mellitus (T2DM), highlighting a significant yet often overlooked comorbidity. We delve into the pathophysiological links between OSA and diabetes, specifically how OSA exacerbates insulin resistance and disrupts glucose metabolism. The research examines the prevalence of OSA in diabetic patients and its role in worsening diabetes-related complications. Emphasizing the importance of comprehensive management, including weight control and positive airway pressure therapy, the study advocates integrated approaches to improve outcomes for patients with T2DM and OSA. This review underscores the necessity of recognizing and addressing OSA in diabetes care to ensure more effective treatment and better patient outcomes.
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Affiliation(s)
- Eric D Tenda
- Division of Respirology and Critical Care, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo Hospital, DKI Jakarta, Jakarta Pusat 10430, Indonesia
- Head of Research Group Artificial Intelligence and Digital Health, Indonesian Medical Education and Research Institute, Faculty of Medicine University of Indonesia, DKI Jakarta, Jakarta Pusat 10430, Indonesia
| | - Joshua Henrina
- Division of Respirology and Critical Care, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo Hospital, DKI Jakarta, Jakarta Pusat 10430, Indonesia
| | - Jin H Cha
- Division of Respirology and Critical Care, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo Hospital, DKI Jakarta, Jakarta Pusat 10430, Indonesia
| | - Muhammad R Triono
- Division of Respirology and Critical Care, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo Hospital, DKI Jakarta, Jakarta Pusat 10430, Indonesia
| | - Ersananda A Putri
- Division of Respirology and Critical Care, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo Hospital, DKI Jakarta, Jakarta Pusat 10430, Indonesia
| | - Dahliana J Aristy
- Division of Respirology and Critical Care, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo Hospital, DKI Jakarta, Jakarta Pusat 10430, Indonesia
| | - Dicky L Tahapary
- Division of Endocrinology, Metabolism and Diabetes, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo Hospital, DKI Jakarta, Jakarta Pusat 10430, Indonesia
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12
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Lin R, Yan W, He M, Liu B, Su X, Yi M, Zhang Y. The benefits of hypoglycemic therapy for patients with obstructive sleep apnea. Sleep Breath 2024; 28:1355-1363. [PMID: 38489146 DOI: 10.1007/s11325-024-03015-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 02/26/2024] [Accepted: 02/28/2024] [Indexed: 03/17/2024]
Abstract
PURPOSE Obstructive sleep apnea (OSA) is often associated with glycemic abnormalities. This study is conducted to investigate the effects of hypoglycemic therapy on OSA-related indicators. METHOD We systematically searched Web of Science, PubMed, Embase, and the Cochrane Library for articles on OSA patients receiving any hypoglycemic drugs, published until December 25, 2022. Seven original studies were finally included. The proposal was registered with PROSPERO (CRD42022351206). RESULTS In summary, in addition to reduced glycosylated hemoglobin A1c (HbA1c), we found that hypoglycemic treatment can lower the apnea-hypopnea index (AHI) by 7.07/h (p = 0.0001). Although long-term treatment (> 12 weeks) achieved a more significant reduction in HbA1c (- 1.57% vs. - 0.30%) compared to short-term treatment (≤ 12 weeks), there was no significant difference between the two in terms of AHI (intergroup p-value = 0.27). We also found that patients using sodium glucose cotransporter 2 inhibitors (SGLT2i) experienced a greater reduction in AHI (- 11.00/h, p < 0.00001). Additionally, hypoglycemic treatment also showed certain improvements in related indicators like Epworth Sleepiness Scale, body mass index, and blood pressure. CONCLUSIONS Our results affirm the benefits of hypoglycemic treatment for OSA patients and highlight the notable effect of SGLT2i. Further researches are needed to help doctors gain a comprehensive understanding of the interaction between OSA and glycemic abnormalities.
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Affiliation(s)
- Ruihan Lin
- Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Xiangya Medical School, Central South University, Changsha, China
- Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Wenjie Yan
- Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Xiangya Medical School, Central South University, Changsha, China
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Meng He
- Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China
| | - Bin Liu
- Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China
| | - Xiaoli Su
- Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
| | - Minhan Yi
- School of Life Sciences, Central South University, Changsha, China.
| | - Yuan Zhang
- Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
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Behnoush AH, Khalaji A, Ghondaghsaz E, Masrour M, Shokri Varniab Z, Khalaji S, Cannavo A. Triglyceride-glucose index and obstructive sleep apnea: a systematic review and meta-analysis. Lipids Health Dis 2024; 23:4. [PMID: 38185682 PMCID: PMC10773018 DOI: 10.1186/s12944-024-02005-3] [Citation(s) in RCA: 48] [Impact Index Per Article: 48.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Accepted: 01/01/2024] [Indexed: 01/09/2024] Open
Abstract
BACKGROUND Obstructive sleep apnea (OSA) has a bidirectional association with metabolic syndrome, and insulin resistance (IR). The triglyceride-glucose (TyG) index could be a simply calculated marker of IR in OSA. However, its clinical application appears still limited. Hence, this systematic review and meta-analysis aimed to respond to this question by analyzing all the existing studies showing an association between OSA and the TyG index. METHODS Four online databases, including PubMed, Scopus, the Web of Science, and Embase were searched for studies evaluating the TyG index in OSA. After screening and data extraction, a random-effect meta-analysis was performed to compare the TyG index in OSA patients vs. healthy controls by calculating standardized mean difference (SMD) and 95% confidence interval (CI) and pooling the area under the curves (AUCs) for diagnosis of OSA based on this index. RESULTS Ten studies involving 16,726 individuals were included in the current systematic review. Meta-analysis indicated that there was a significantly higher TyG index in patients with OSA, compared with the healthy controls (SMD 0.856, 95% CI 0.579 to 1.132, P < 0.001). Also, TyG had a diagnostic ability for OSA representing a pooled AUC of 0.681 (95% CI 0.627 to 0.735). However, based on the two studies' findings, no difference between different severities of OSA was observed. Finally, our data showed that the TyG index is a good potential predictor of adverse outcomes in these patients. CONCLUSION Our study revealed that the TyG index is an easy-to-measure marker of IR for assessing OSA, both in diagnosis and prognosis. Our study supports its implementation in routine practice to help clinicians in decision-making and patient stratification.
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Affiliation(s)
- Amir Hossein Behnoush
- School of Medicine, Tehran University of Medical Sciences, Poursina St., Keshavarz Blvd, Tehran, 1417613151, Iran
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Amirmohammad Khalaji
- School of Medicine, Tehran University of Medical Sciences, Poursina St., Keshavarz Blvd, Tehran, 1417613151, Iran.
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
| | - Elina Ghondaghsaz
- Undergraduate Program in Neuroscience, University of British Columbia, Vancouver, BC, Canada
| | - Mahdi Masrour
- School of Medicine, Tehran University of Medical Sciences, Poursina St., Keshavarz Blvd, Tehran, 1417613151, Iran
| | - Zahra Shokri Varniab
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Soheil Khalaji
- School of Medicine, Tehran University of Medical Sciences, Poursina St., Keshavarz Blvd, Tehran, 1417613151, Iran
| | - Alessandro Cannavo
- Department of Translational Medicine Sciences, Federico II University of Naples, Naples, Italy
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14
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Correia S, Gonzalez M, Deger M, Pitts P. The Value of Implementing a Digital Approach in the Obstructive Sleep Apnoea Patient Pathway: A Spanish Example. OPEN RESPIRATORY ARCHIVES 2024; 6:100289. [PMID: 38225949 PMCID: PMC10788272 DOI: 10.1016/j.opresp.2023.100289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Accepted: 11/02/2023] [Indexed: 01/17/2024] Open
Abstract
Introduction Continuous positive airway pressure (CPAP) is the gold standard therapy for obstructive sleep apnoea (OSA). However, non-adherence is common and costly. The COVID-19 pandemic required the use of novel solutions to ensure service provision and quality of care. This retrospective analysis determined the impact and value of a digital versus standard pathway for the management of OSA in Spain. Methods A time-driven activity-based costing approach was applied to OSA management over 1 year using a standard or digital pathway. The standard pathway included face-to-face appointments at the time of diagnosis, then after 1-3 months and every 6 months thereafter. The digital pathway had fewer face-to-face appointments and utilised telemonitoring. A cost analysis was performed to determine the per-patient cost per healthcare professional (HCP) for a digital pathway for therapy implementation and follow-up compared with the standard pathway. Results Compared with the standard pathway, the digital pathway decreased the waiting list time from 18 to 2 months, the overall pathway time from 12 to 6 months, HCP cost per patient from €95 to €85, and number of hospital appointments per patient from 6 to 3.1. Furthermore, CPAP device usage improved from 5.7 to 6.3 h/night and the proportion of individuals defined as adherent increased from 79% to 91%. Conclusions Implementation of digital processes using available technology reduced HCP time and costs, and improved adherence to CPAP in people with OSA. Greater utilisation of a digital pathway could improve access to therapy, allow personalised patient management, and facilitate better clinical outcomes.
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Affiliation(s)
| | - Monica Gonzalez
- Sleep and Ventilation Unit, Pneumology Department, Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Marqués de Valdecilla, University of Cantabria, Santander, Spain
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15
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Boye KS, Ford JH, Thieu VT, Lage MJ, Terrell KA. The Association Between Obesity and the 5-Year Prevalence of Morbidity and Mortality Among Adults with Type 2 Diabetes. Diabetes Ther 2023; 14:709-721. [PMID: 36820959 PMCID: PMC9948793 DOI: 10.1007/s13300-023-01384-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 02/10/2023] [Indexed: 02/24/2023] Open
Abstract
INTRODUCTION This retrospective claims database study examined the prevalence of mortality and morbidity among adults with type 2 diabetes (T2D) and obesity. METHODS The study used deidentified data from 2007 to 2021 from the Optum® Market Clarity Dataset. A cohort of adults with T2D and obesity were identified, and age- and sex-adjusted prevalence rates were calculated for mortality, a composite cardiovascular outcome (CCO), a composite microvascular outcome (CMO), and other complications. Results were examined overall and by obesity class (class 1, class 2, and class 3). RESULTS For the 15,970 adults included in the study, the prevalence of CCO and CMO after 5 years was 15.3% and 60.7%, respectively. The 5-year prevalence of mortality was 10.9%. There were statistically significant differences in prevalence rates by obesity class, with obesity class 3 associated with higher rates of morbidity and mortality compared to obesity classes 1 or 2. Specifically, after 5 years, the prevalence of mortality was 9.4%, 10.3% and 13.6% for obese classes 1, 2 and 3, respectively (P < 0.05 between class 3 and class 2 or 1). Similarly, For obesity classes 1, 2 and 3, the 5-year prevalence of CCO was 13.0%, 14.5% and 18.4% and the rates for CMO were 58.0%, 57.9% and 64.8%, respectively (both P < 0.05 between class 3 and class 2 or 1). Regarding other complications, differences in the prevalence of atherosclerotic cardiovascular disease (ASCVD) and obstructive sleep apnea (OSA) were statistically significantly higher with increasing obesity class. CONCLUSIONS The results indicate that for a cohort of adults with T2D and obesity, obesity class 3 is associated with significantly higher mortality and morbidity, including CCO, CMO, ASCVD and OSA. These findings suggest that treatment which reduces obesity among individuals with T2D may have significant health benefits, although additional studies are needed to confirm the results.
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Affiliation(s)
- Kristina S Boye
- Value, Evidence, and Outcomes Department, Eli Lilly and Company, Lilly Corporate Center, 893 Delaware Street, Indianapolis, IN, 46225, USA
| | - Janet H Ford
- Value, Evidence, and Outcomes Department, Eli Lilly and Company, Lilly Corporate Center, 893 Delaware Street, Indianapolis, IN, 46225, USA
| | - Vivian T Thieu
- Medical Affairs, Diabetes, Eli Lilly and Company, Lilly Corporate Center, 893 Delaware Street, Indianapolis, IN, 46225, USA
| | - Maureen J Lage
- HealthMetrics Outcomes Research, 17 Benton's Knoll, Guilford, CT, 06437, USA.
| | - Kendra A Terrell
- Value, Evidence, and Outcomes Department, Eli Lilly and Company, Lilly Corporate Center, 893 Delaware Street, Indianapolis, IN, 46225, USA
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16
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Koh HCE, van Vliet S, Cao C, Patterson BW, Reeds DN, Laforest R, Gropler RJ, Ju YES, Mittendorfer B. Effect of obstructive sleep apnea on glucose metabolism. Eur J Endocrinol 2022; 186:457-467. [PMID: 35118996 PMCID: PMC9172969 DOI: 10.1530/eje-21-1025] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 02/04/2022] [Indexed: 11/08/2022]
Abstract
BACKGROUND Obstructive sleep apnea (OSA) is prevalent in people with obesity and is a major risk factor for type 2 diabetes (T2D). The effect of OSA on metabolic function and the precise mechanisms (insulin resistance, β-cell dysfunction, or both) responsible for the increased T2D risk in people with OSA are unknown. DESIGN AND METHODS We used a two-stage hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopically labeled glucose and palmitate tracer infusions and 18F-fluorodeoxyglucose injection and positron emission tomography to quantify multi-organ insulin action and oral and intravenous tolerance tests to evaluate glucose-stimulated insulin secretion in fifteen people with obesity and OSA and thirteen people with obesity without OSA. RESULTS OSA was associated with marked insulin resistance of adipose tissue triglyceride lipolysis and glucose uptake into both skeletal muscles and adipose tissue, whereas there was no significant difference between the OSA and control groups in insulin action on endogenous glucose production, basal insulin secretion, and glucose-stimulated insulin secretion during both intravenous and oral glucose tolerance tests. CONCLUSIONS These data demonstrate that OSA is a key determinant of insulin sensitivity in people with obesity and underscore the importance of taking OSA status into account when evaluating metabolic function in people with obesity. These findings may also have important clinical implications because disease progression and the risk of diabetes-related complications vary by T2D subtype (i.e. severe insulin resistance vs insulin deficiency). People with OSA may benefit most from the targeted treatment of peripheral insulin resistance and early screening for complications associated with peripheral insulin resistance.
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Affiliation(s)
| | | | - Chao Cao
- Center for Human Nutrition, St. Louis, MO 63110, USA
| | | | | | | | | | - Yo-El S. Ju
- Department of Neurology, St. Louis, MO 63110, USA
- Hope Center for Neurological Disorders at Washington University School of Medicine, St. Louis, MO 63110, USA
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Schipper SBJ, Van Veen MM, Elders PJM, van Straten A, Van Der Werf YD, Knutson KL, Rutters F. Sleep disorders in people with type 2 diabetes and associated health outcomes: a review of the literature. Diabetologia 2021; 64:2367-2377. [PMID: 34401953 PMCID: PMC8494668 DOI: 10.1007/s00125-021-05541-0] [Citation(s) in RCA: 88] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 05/25/2021] [Indexed: 12/14/2022]
Abstract
Sleep disorders are linked to development of type 2 diabetes and increase the risk of developing diabetes complications. Treating sleep disorders might therefore play an important role in the prevention of diabetes progression. However, the detection and treatment of sleep disorders are not part of standardised care for people with type 2 diabetes. To highlight the importance of sleep disorders in people with type 2 diabetes, we provide a review of the literature on the prevalence of sleep disorders in type 2 diabetes and the association between sleep disorders and health outcomes, such as glycaemic control, microvascular and macrovascular complications, depression, mortality and quality of life. Additionally, we examine the extent to which treating sleep disorders in people with type 2 diabetes improves these health outcomes. We performed a literature search in PubMed from inception until January 2021, using search terms for sleep disorders, type 2 diabetes, prevalence, treatment and health outcomes. Both observational and experimental studies were included in the review. We found that insomnia (39% [95% CI 34, 44]), obstructive sleep apnoea (55-86%) and restless legs syndrome (8-45%) were more prevalent in people with type 2 diabetes, compared with the general population. No studies reported prevalence rates for circadian rhythm sleep-wake disorders, central disorders of hypersomnolence or parasomnias. Additionally, several cross-sectional and prospective studies showed that sleep disorders negatively affect health outcomes in at least one diabetes domain, especially glycaemic control. For example, insomnia is associated with increased HbA1c levels (2.51 mmol/mol [95% CI 1.1, 4.4]; 0.23% [95% CI 0.1, 0.4]). Finally, randomised controlled trials that investigate the effect of treating sleep disorders in people with type 2 diabetes are scarce, based on a small number of participants and sometimes inconclusive. Conventional therapies such as weight loss, sleep education and cognitive behavioural therapy seem to be effective in improving sleep and health outcomes in people with type 2 diabetes. We conclude that sleep disorders are highly prevalent in people with type 2 diabetes, negatively affecting health outcomes. Since treatment of the sleep disorder could prevent diabetes progression, efforts should be made to diagnose and treat sleep disorders in type 2 diabetes in order to ultimately improve health and therefore quality of life.
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Affiliation(s)
- Samantha B J Schipper
- Department of Epidemiology and Data Science, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands
- Amsterdam Public Health Research Institute, Amsterdam, the Netherlands
| | - Maaike M Van Veen
- Centre of Expertise on Sleep and Psychiatry, GGZ Drenthe Mental Health Institute, Assen, the Netherlands
- Centre of Expertise on Sleep and Psychiatry, GGZ Drenthe Mental Health Institute, Assen, the Netherlands
| | - Petra J M Elders
- Amsterdam Public Health Research Institute, Amsterdam, the Netherlands
- Department of General Practice, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands
| | - Annemieke van Straten
- Amsterdam Public Health Research Institute, Amsterdam, the Netherlands
- Faculty of Behavioural and Movement Sciences, Vrije Universiteit, Amsterdam, the Netherlands
| | - Ysbrand D Van Der Werf
- Department of Anatomy & Neurosciences, Amsterdam UMC, Amsterdam, the Netherlands
- Amsterdam Neuroscience, Amsterdam, the Netherlands
| | | | - Femke Rutters
- Department of Epidemiology and Data Science, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands.
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18
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Hu XM, Wei WT, Huang DY, Lin CD, Lu F, Li XM, Liao HS, Yu ZH, Weng XP, Wang SB, Hou CL, Jia FJ. The Assessment of Sleep Quality in Patients Following Valve Repair and Valve Replacement for Infective Endocarditis: A Retrospective Study at a Single Center. Med Sci Monit 2021; 27:e930596. [PMID: 34433799 PMCID: PMC8406810 DOI: 10.12659/msm.930596] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Background The aim of this study was to measure sleep quality among patients who underwent infective endocarditis (IE) surgery and identify the risk factors involved in sleep disorders. Material/Methods In this study, we used actigraphy, the Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleep Scale (ESS) to determine the clinical characteristics of sleep disorders in 116 patients with IE who were in rehabilitation after surgery. Results Our results showed that 46 (39.7%) patients had sleep efficiency over 85%, while 70 (60.3%) patients had sleep efficiency below 85%. The correlation analysis showed that sleep efficiency was related to the duration of the disease, with a longer duration leading to lower sleep efficiency (P=0.031). The sleep efficiency of patients with IE following surgery was also affected by alcohol consumption; however, surprisingly, patients with “heavy” alcohol consumption had higher sleep efficiency (P=0.030). We found a significant correlation between sleep efficiency and postoperative interleukin-6 (IL) levels, C-reactive protein (CRP) levels, and preoperative erythrocyte sedimentation rate (P<0.05). No significant correlation was found between brain natriuretic peptide levels and sleep efficiency, PSQI score, or ESS score. Postoperative hemoglobin (Hb) level was associated with sleep efficiency (R=0.194, P=0.036), but there was no statistically significant correlation between the PSQI and ESS scores. Postoperative alanine transaminase (ALT) showed a significant negative correlation with sleep efficiency (R=−0.27, P=0.003). Conclusions We found a high prevalence of sleep disorders in patients with IE along with an increase in inflammatory factors, including postoperative IL-6, CRP, ALT, and Hb levels.
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Affiliation(s)
- Xiang-Ming Hu
- Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China (mainland).,Department of Comprehensive Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China (mainland)
| | - Wen-Ting Wei
- Department of Comprehensive Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China (mainland)
| | - De-Yi Huang
- Department of Comprehensive Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China (mainland)
| | - Cai-Di Lin
- Department of Comprehensive Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China (mainland)
| | - Fen Lu
- Department of Comprehensive Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China (mainland)
| | - Xiao-Ming Li
- Department of Comprehensive Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China (mainland)
| | - Huo-Sheng Liao
- Department of Comprehensive Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China (mainland)
| | - Zhi-Hong Yu
- Department of Comprehensive Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China (mainland)
| | - Xiao-Ping Weng
- Department of Comprehensive Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China (mainland)
| | - Shi-Bin Wang
- Guangdong Mental Health Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China (mainland)
| | - Cai-Lan Hou
- Guangdong Mental Health Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China (mainland)
| | - Fu-Jun Jia
- Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China (mainland).,Guangdong Mental Health Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China (mainland)
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19
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Ngoo QZ, A NF, A B, Wh WH. Evaluation of Retinal Nerve Fiber Layer Thickness and Optic Nerve Head Parameters in Obstructive Sleep Apnoea Patients. KOREAN JOURNAL OF OPHTHALMOLOGY 2021; 35:223-230. [PMID: 34120421 PMCID: PMC8200590 DOI: 10.3341/kjo.2020.0019] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Accepted: 04/21/2021] [Indexed: 11/23/2022] Open
Abstract
PURPOSE To study the retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) parameters in obstructive sleep apnoea (OSA) patients and their relationship with severity of the disease. METHODS A cross-sectional, hospital-based study. Fifty-four OSA subjects and 54 controls were recruited. Candidate that fulfil the criteria with normal ocular examinations then proceed with spectrum domain Cirrus optical coherence tomography examinations. ONH parameters and RNFL thickness were evaluated. Apnoea-hypopnoea index (AHI) of the OSA group were obtained from the medical record. RESULTS In OSA, mean of average RNFL thickness was 93.87 µm, standard deviation (SD) = 9.17, p = 0.008 (p < 0.05) while superior RNFL thickness was 113.59 µm, SD = 16.29, p ≤ 0.001 (p < 0.05). RNFL thickness fairly correlate with severity of the disease (AHI), superior RNFL with R = 0.293, R2 = 0.087, p = 0.030 (p < 0.05), and nasal RNFL R = 0.292, R2 = 0.085, p = 0.032. No significant difference and correlation observed on ONH parameters. In control group, mean of average RNFL thickness was 98.96 µm, SD = 10.50, p = 0.008 (p < 0.05) while superior RNFL thickness was 125.76 µm, SD = 14.93, p ≤ 0.001 (p < 0.05). CONCLUSIONS The mean of the average and superior RNFL thickness were significantly lower in the OSA group compare to control. Regression analysis showed RNFL thickness having significantly linear relationship with the AHI, specifically involving the superior and nasal quadrant.
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Affiliation(s)
- Qi Zhe Ngoo
- Department of Ophthalmology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Malaysia
| | - Nazihatul Fikriah A
- Department of Ophthalmology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Malaysia
| | - Baharudin A
- Department of Otorhinolaryngology-Head and Neck Surgery, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia
| | - Wan Hazabbah Wh
- Department of Ophthalmology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Malaysia
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20
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Balat K, Pazarlı AC, İnönü Köseoğlu H, Yaşayancan N, Demir O. Importance of Anthropometric Measurements to Determine Cardiometabolic Diseases in Obstructive Sleep Apnea Syndrome. Turk Thorac J 2021; 22:11-17. [PMID: 33646098 DOI: 10.5152/turkthoracj.2020.19105] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Accepted: 01/09/2020] [Indexed: 11/22/2022]
Abstract
OBJECTIVE Obesity is considered a major risk factor for obstructive sleep apnea syndrome (OSAS). This study aimed to examine the correlation between anthropometric measurements, which have been recently defined and are indicative of abdominal obesity and cardiometabolic diseases, OSAS severity, and polysomnography (PSG) parameters in patients with OSAS. MATERIAL AND METHODS This retrospective cohort study included patients who underwent all-night polysomnography with a prediagnosis of OSAS. These patients were categorized as having mild (5-15), moderate (15-30), and severe (>30) OSAS according to the apnea-hypopnea index (AHI). The anthropometric measurements used in the study consisted of waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), (waist/hip)-to-height ratio (WHHR), a body shape index (ABSI), body adiposity index (BAI), abdominal volume index (AVI), and conicity index (CI). RESULTS A total of 410 individuals were enrolled in the study (31 control subjects and 129 with mild, 101 with moderate, and 149 with severe OSAS). A significant difference was observed between groups in terms of all anthropometric measurements (p<0.05). The difference between the groups was significant in terms of diabetes mellitus, hypertension, and cardiovascular disease (p<0.05). There was a significant correlation between each of the anthropometric measurements and the PSG parameters. In the receiver operating characteristic analysis, cutoff values that predicted severe OSAS were ABSI>0.08, BAI>28.29, AVI>25.54, and CI>1.37. Multiple regression analyses demonstrated that age, sex, and AVI were independent predictors that determine OSAS presence. CONCLUSION Anthropometric parameters that are indicators of abdominal obesity were found to be robustly correlated with cardiometabolic diseases and the severity of OSAS.
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Affiliation(s)
- Kenan Balat
- Department of Pulmonary Diseases, Gaziosmanpaşa University School of Medicine, Tokat, Turkey
| | - Ahmet Cemal Pazarlı
- Department of Pulmonary Diseases, Gaziosmanpaşa University School of Medicine, Tokat, Turkey
| | - Handan İnönü Köseoğlu
- Department of Pulmonary Diseases, Gaziosmanpaşa University School of Medicine, Tokat, Turkey
| | - Nurşen Yaşayancan
- Department of Pulmonary Diseases, Gaziosmanpaşa University School of Medicine, Tokat, Turkey
| | - Osman Demir
- Department of Biostatistics and Medical Informatics, Gaziosmanpaşa University School of Medicine, Tokat, Turkey
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21
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Abstract
Women with polycystic ovary syndrome (PCOS) have a substantially increased risk for diabetes and cardiovascular disease. Obstructive sleep apnea (OSA) is the most common sleep disorder in PCOS. Recent population-based studies indicate a high incidence of OSA among adult women with PCOS. Obesity and increasing age are the main factors for this association. There is strong evidence indicating that OSA is an important modulator of metabolic risk in the general population. There is also some evidence to suggest that OSA may contribute to insulin resistance and glucose intolerance among women PCOS, and thus increase their metabolic risk. The potential mechanisms for adverse metabolic consequences of OSA are likely to be multiple. Whether treatment of OSA in PCOS improves metabolic outcomes requires further rigorous research.
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Affiliation(s)
- Susan Sam
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Chicago, 5841 S. Maryland Avenue, 60637, Chicago, IL, USA
| | - Esra Tasali
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Chicago, 5841 S. Maryland Avenue, 60637, Chicago, IL, USA.,Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, 5841 S. Maryland Avenue, 60637, Chicago, IL, USA
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22
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Michalek-Zrabkowska M, Macek P, Martynowicz H, Gac P, Mazur G, Grzeda M, Poreba R. Obstructive Sleep Apnea as a Risk Factor of Insulin Resistance in Nondiabetic Adults. Life (Basel) 2021; 11:life11010050. [PMID: 33451031 PMCID: PMC7828530 DOI: 10.3390/life11010050] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 01/05/2021] [Accepted: 01/11/2021] [Indexed: 01/01/2023] Open
Abstract
OBJECTIVE The aim of this research was to assess the relationship between prevalence and severity of obstructive sleep apnea (OSA) and insulin resistance among patients with increased risk of OSA without diabetes mellitus. METHOD AND MATERIALS our study group involved 102 individuals with suspected OSA, mean age 53.02 ± 12.37 years. Data on medical history, medication usage, sleep habits, sleep quality and daytime sleepiness, were obtained using questionnaires. All patients underwent standardized full night polysomnography. Serum fasting insulin and glucose concentration were analyzed, the homeostatic model assessment-insulin resistance (HOMA-IR) index was calculated. RESULTS polysomnographic study indicated that in the group with OSA mean values of apnea-hypopnea index (AHI), oxygen desaturation index (ODI), duration of SpO2 < 90% and average desaturation drop were significantly higher compared to the group without OSA, while the minimum SpO2 was significantly lower. The carbohydrate metabolism parameters did not differ within those groups. Significantly higher fasting insulin concentration and HOMA-IR index were found in the group with AHI ≥ 15 compared to the group with AHI < 15 and in the group with AHI ≥ 30 compared to the group with AHI < 30. Higher AHI and ODI were independent risk factors for higher fasting insulin concentration and higher HOMA-IR index. Increased duration of SpO2 < 90% was an independent risk factor for higher fasting glucose concentration. CONCLUSIONS Individuals with moderate to severe OSA without diabetes mellitus had a higher prevalence of insulin resistance.
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Affiliation(s)
- Monika Michalek-Zrabkowska
- Department of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, 213 Borowska St., 50-556 Wroclaw, Poland; (M.M.-Z.); (P.M.); (H.M.); (G.M.); (R.P.)
| | - Piotr Macek
- Department of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, 213 Borowska St., 50-556 Wroclaw, Poland; (M.M.-Z.); (P.M.); (H.M.); (G.M.); (R.P.)
| | - Helena Martynowicz
- Department of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, 213 Borowska St., 50-556 Wroclaw, Poland; (M.M.-Z.); (P.M.); (H.M.); (G.M.); (R.P.)
| | - Pawel Gac
- Department of Hygiene, Wroclaw Medical University, 7 Mikulicza-Radeckiego St., 50-345 Wroclaw, Poland;
| | - Grzegorz Mazur
- Department of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, 213 Borowska St., 50-556 Wroclaw, Poland; (M.M.-Z.); (P.M.); (H.M.); (G.M.); (R.P.)
| | - Magda Grzeda
- Department of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, 213 Borowska St., 50-556 Wroclaw, Poland; (M.M.-Z.); (P.M.); (H.M.); (G.M.); (R.P.)
- Correspondence: ; Tel.: +48-530-173-222
| | - Rafal Poreba
- Department of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, 213 Borowska St., 50-556 Wroclaw, Poland; (M.M.-Z.); (P.M.); (H.M.); (G.M.); (R.P.)
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23
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Transcriptomic Changes of Murine Visceral Fat Exposed to Intermittent Hypoxia at Single Cell Resolution. Int J Mol Sci 2020; 22:ijms22010261. [PMID: 33383883 PMCID: PMC7795619 DOI: 10.3390/ijms22010261] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 11/22/2020] [Accepted: 12/24/2020] [Indexed: 12/12/2022] Open
Abstract
Intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea (OSA) and induces metabolic dysfunction manifesting as inflammation, increased lipolysis and insulin resistance in visceral white adipose tissues (vWAT). However, the cell types and their corresponding transcriptional pathways underlying these functional perturbations are unknown. Here, we applied single nucleus RNA sequencing (snRNA-seq) coupled with aggregate RNA-seq methods to evaluate the cellular heterogeneity in vWAT following IH exposures mimicking OSA. C57BL/6 male mice were exposed to IH and room air (RA) for 6 weeks, and nuclei from vWAT were isolated and processed for snRNA-seq followed by differential expressed gene (DEGs) analyses by cell type, along with gene ontology and canonical pathways enrichment tests of significance. IH induced significant transcriptional changes compared to RA across 14 different cell types identified in vWAT. We identified cell-specific signature markers, transcriptional networks, metabolic signaling pathways, and cellular subpopulation enrichment in vWAT. Globally, we also identify 298 common regulated genes across multiple cellular types that are associated with metabolic pathways. Deconvolution of cell types in vWAT using global RNA-seq revealed that distinct adipocytes appear to be differentially implicated in key aspects of metabolic dysfunction. Thus, the heterogeneity of vWAT and its response to IH at the cellular level provides important insights into the metabolic morbidity of OSA and may possibly translate into therapeutic targets.
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24
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O'Mahony AM, Garvey JF, McNicholas WT. Technologic advances in the assessment and management of obstructive sleep apnoea beyond the apnoea-hypopnoea index: a narrative review. J Thorac Dis 2020; 12:5020-5038. [PMID: 33145074 PMCID: PMC7578472 DOI: 10.21037/jtd-sleep-2020-003] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Obstructive sleep apnoea (OSA) is a growing and serious worldwide health problem with significant health and socioeconomic consequences. Current diagnostic testing strategies are limited by cost, access to resources and over reliance on one measure, namely the apnoea-hypopnoea frequency per hour (AHI). Recent evidence supports moving away from the AHI as the principle measure of OSA severity towards a more personalised approach to OSA diagnosis and treatment that includes phenotypic and biological traits. Novel advances in technology include the use of signals such as heart rate variability (HRV), oximetry and peripheral arterial tonometry (PAT) as alternative or additional measures. Ubiquitous use of smartphones and developments in wearable technology have also led to increased availability of applications and devices to facilitate home screening of at-risk populations, although current evidence indicates relatively poor accuracy in comparison with the traditional gold standard polysomnography (PSG). In this review, we evaluate the current strategies for diagnosing OSA in the context of their limitations, potential physiological targets as alternatives to AHI and the role of novel technology in OSA. We also evaluate the current evidence for using newer technologies in OSA diagnosis, the physiological targets such as smartphone applications and wearable technology. Future developments in OSA diagnosis and assessment will likely focus increasingly on systemic effects of sleep disordered breathing (SDB) such as changes in nocturnal oxygen and blood pressure (BP); and may also include other factors such as circulating biomarkers. These developments will likely require a re-evaluation of the diagnostic and grading criteria for clinically significant OSA.
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Affiliation(s)
- Anne M O'Mahony
- School of Medicine, University College Dublin, Dublin, Ireland
| | - John F Garvey
- School of Medicine, University College Dublin, Dublin, Ireland
| | - Walter T McNicholas
- School of Medicine, University College Dublin, Dublin, Ireland.,First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
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25
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孙 海, 秦 彦, 魏 永. [Progress in obstructive sleep apnea and atherosclerosis]. LIN CHUANG ER BI YAN HOU TOU JING WAI KE ZA ZHI = JOURNAL OF CLINICAL OTORHINOLARYNGOLOGY, HEAD, AND NECK SURGERY 2020; 34:958-960. [PMID: 33254309 PMCID: PMC10128521 DOI: 10.13201/j.issn.2096-7993.2020.10.023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Indexed: 11/12/2022]
Abstract
Obstructive sleep apnea（OSA） is a common sleep-disordered disease which is characterized by repetitive narrowing or occlusion of the pharynx causing intermittent hypoxia, repetitive arousals, sleep deprivation, and excessive daytime sleepiness. OSA can contribute to atherosclerosis through direct and indirect mechanisms. Animal and clinical studies have shown a close relationship between OSA and atherosclerosis and its risk factors. However, current studies showed inconsistent results. In the future, further research both basic and clinical studies need to be fulfilled. Future studies are needed to investigate underlying mechanisms between OSA and atherosclerosis.
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Affiliation(s)
- 海丽 孙
- 首都医科大学附属北京安贞医院耳鼻咽喉科(北京，100029)
- 北京市心肺血管研究所上气道功能障碍相关心血管病重点实验室
| | - 彦文 秦
- 北京市心肺血管研究所上气道功能障碍相关心血管病重点实验室
| | - 永祥 魏
- 首都医科大学附属北京安贞医院耳鼻咽喉科(北京，100029)
- 北京市心肺血管研究所上气道功能障碍相关心血管病重点实验室
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26
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Mikołajczyk-Solińska M, Śliwińska A, Kosmalski M, Drzewoski J. The Phenotype of Elderly Patients with Type 2 Diabetes Mellitus and Poor Sleep Quality. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:E5992. [PMID: 32824748 PMCID: PMC7459960 DOI: 10.3390/ijerph17165992] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 08/12/2020] [Accepted: 08/16/2020] [Indexed: 12/02/2022]
Abstract
BACKGROUND Sleep disturbances are a common problem among patients with Type 2 diabetes mellitus (T2DM). The aim of the study was to identify the phenotype of T2DM patients with poor sleep quality. METHODS An observational, cross-sectional study was conducted between May 2013 and August 2015. One hundred and sixty consecutive patients with T2DM: 74 women and 86 men, with a median age of 69.50 years (59.00; 79.50 years) were enrolled in the study. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. RESULTS Poor sleep quality was noted in 85 (53%) patients. Sleep disorders were associated with older age, as well as female gender, longer duration of diabetes, lower level of fasting plasma glucose, glycated hemoglobin A1c, estimated glomerular filtration rate, triglycerides, waist-to-hip ratio, and the presence of nephropathy. A multivariate logistic regression revealed that sleep disorders were associated with older age (Odd Ratio (OR) = 1.11, 95% Confidence Interval (CI) 1.07-1.15). Fifty-one patients (31.87%) were treated with sleeping pills. We found that older age, female gender, longer duration of diabetes, lower level of fasting plasma glucose, glycated hemoglobin A1c, estimated glomerular filtration rate, triglycerides, and the presence of nephropathy were linked with more frequent usage of hypnotics. A multivariate logistic regression demonstrated that older age (OR = 1.09, 95% CI 1.05-1.14) and nephropathy (OR = 2.79, 95% CI 1.24-6.28) were associated with a more frequent receiving the hypnotics, whereas male gender (OR = 0.30, 95% CI 0.13-0.71) has less frequent hypnotics usage. CONCLUSION Although, we assessed a wide range of patients' characteristics, age had the most negative impact on the quality of sleep in patients with T2DM. We detected more frequent use of hypnotics in older females, with coexisting nephropathy.
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Affiliation(s)
- Melania Mikołajczyk-Solińska
- Department of Internal Medicine, Diabetology and Clinical Pharmacology, Medical University of Lodz, 92-213 Lodz, Poland
| | - Agnieszka Śliwińska
- Department of Nucleic Acids Biochemistry, Medical University of Lodz, 92-213 Lodz, Poland;
| | - Marcin Kosmalski
- Department of Clinical Pharmacology, Medical University of Lodz, 90-153 Lodz, Poland;
| | - Józef Drzewoski
- Central Teaching Hospital of Medical University of Lodz, 92-213 Lodz, Poland;
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27
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Stefanovski D, Boston RC, Punjabi NM. Sleep-Disordered Breathing and Free Fatty Acid Metabolism. Chest 2020; 158:2155-2164. [PMID: 32565268 DOI: 10.1016/j.chest.2020.05.600] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Revised: 05/15/2020] [Accepted: 05/24/2020] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Sleep-disordered breathing (SDB) is independently associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. However, data on whether SDB alters the metabolism of free fatty acids (FFAs) are lacking. RESEARCH QUESTION The primary objective of the current study was to characterize alterations in FFA metabolism across the spectrum of SDB severity. STUDY DESIGN AND METHODS The study sample included 118 participants with and without SDB who underwent full-montage polysomnography, the frequently sampled IV glucose tolerance test (FSIGTT), and body composition measurements including determination of percent body fat. Parameters of lipolysis suppression, time to FFA nadir, and FFA rebound after an IV glucose challenge were derived using a mathematical model. Multivariable regression analyses were used to characterize the independent associations between SDB severity and parameters of FFA metabolism. RESULTS SDB severity, as assessed by the apnea-hypopnea index, was associated with adipocyte insulin resistance, a decrease in the glucose- and insulin-mediated suppression of lipolysis, a longer duration to reach a nadir in FFA levels during the FSIGTT, and a sluggish rebound in FFA levels after suppression. Severity of SDB-related hypoxemia was independently associated with adipocyte insulin resistance and the time to reach the FFA nadir during the FSIGTT. Finally, a higher percentage of stage N3 sleep was positively associated with greater suppression of lipolysis and a faster rebound in the FFA levels during the FSIGTT. INTERPRETATION Independent of adiposity, SDB is associated with impairments in FFA metabolism, which may contribute to the development of glucose intolerance and type 2 diabetes in SDB.
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Affiliation(s)
- Darko Stefanovski
- Department of Clinical Studies, New Bolton Center, University of Pennsylvania, New Bolton, Philadelphia, PA
| | - Ray C Boston
- Department of Clinical Studies, New Bolton Center, University of Pennsylvania, New Bolton, Philadelphia, PA
| | - Naresh M Punjabi
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
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28
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Ramsey AK, Reed L, Gillespie MB. Sleep-Disordered Breathing in Geriatric Populations. CURRENT OTORHINOLARYNGOLOGY REPORTS 2020. [DOI: 10.1007/s40136-020-00264-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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Feher M, Hinton W, Munro N, de Lusignan S. Obstructive sleep apnoea in Type 2 diabetes mellitus: increased risk for overweight as well as obese people included in a national primary care database analysis. Diabet Med 2019; 36:1304-1311. [PMID: 31001841 PMCID: PMC6767542 DOI: 10.1111/dme.13968] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/15/2019] [Indexed: 12/13/2022]
Abstract
AIMS To determine obstructive sleep apnoea prevalence in people with Type 2 or Type 1 diabetes in a national primary care setting, stratified by BMI category, and to explore the relationship between patient characteristics and obstructive sleep apnoea. METHODS Using the Royal College of General Practitioners Research and Surveillance Centre database, a cross-sectional analysis was conducted. Diabetes type was identified using a seven-step algorithm and was grouped by Type 2 diabetes, Type 1 diabetes and no diabetes. The clinical characteristics of these groups were analysed, BMI-stratified obstructive sleep apnoea prevalence rates were calculated, and a multilevel logistic regression analysis was completed on the Type 2 diabetes group. RESULTS Analysis of 1 275 461 adult records in the Royal College of General Practitioners Research and Surveillance Centre network showed that obstructive sleep apnoea was prevalent in 0.7%. In people with Type 2 diabetes, obstructive sleep apnoea prevalence increased with each increasing BMI category, from 0.5% in those of normal weight to 9.6% in those in the highest obesity class. By comparison, obstructive sleep apnoea prevalence rates for these BMI categories in Type 1 diabetes were 0.3% and 4.3%, and in those without diabetes 1.2% and 3.9%, respectively. Obstructive sleep apnoea was more prevalent in men than women in both diabetes types. When known risk factors were adjusted for, there were increased odds ratios for obstructive sleep apnoea in people with Type 2 diabetes in the overweight and higher BMI categories. CONCLUSIONS Obstructive sleep apnoea was reported in people with both types of diabetes across the range of overweight categories and not simply in the highest obesity class.
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Affiliation(s)
- M. Feher
- Department of Clinical and Experimental MedicineUniversity of SurreyGuildfordUK
| | - W. Hinton
- Department of Clinical and Experimental MedicineUniversity of SurreyGuildfordUK
| | - N. Munro
- Department of Clinical and Experimental MedicineUniversity of SurreyGuildfordUK
| | - S. de Lusignan
- Department of Clinical and Experimental MedicineUniversity of SurreyGuildfordUK
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RELATIONSHIP BETWEEN OBSTRUCTIVE SLEEP APNEA AND THE PRESENCE AND SEVERITY OF DIABETIC RETINOPATHY. Retina 2019; 38:2197-2206. [PMID: 28937527 DOI: 10.1097/iae.0000000000001848] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE To evaluate the relationship between obstructive sleep apnea (OSA) and the presence and severity of diabetic retinopathy (DR). METHODS Three hundred seventeen patients with International Classification of Diseases diagnoses of both DR and OSA were evaluated retrospectively. Diabetic retinopathy severity and diabetic macular edema status were determined by diagnostic coding and medical records. Obstructive sleep apnea severity and additional sleep measures were obtained from overnight polysomnography. Analysis was performed using multivariable logistic regression. RESULTS After adjustment, an association was seen between DR and severe OSA (odds ratio [OR]: 2.18, 95% confidence interval [CI]: 1.14-4.18, P = 0.019). Proliferative DR was associated with severe OSA versus no DR (OR: 2.40, 95% CI: 1.12-5.14, P = 0.024) and mild nonproliferative DR (OR: 2.87, 95% CI: 1.26-6.55, P = 0.012). Comparing all nonproliferative DR with proliferative DR, proliferative DR and severe OSA were associated (OR: 2.20, 95% CI: 1.03-4.70, P = 0.043), as well as diabetic macular edema and severe OSA (OR: 2.89, 95% CI: 1.58-5.27, P = 0.001). No association was seen between DR/diabetic macular edema and secondary sleep measures. CONCLUSION The findings suggest an increased risk of DR, proliferative DR, and diabetic macular edema in patients with severe OSA. Ophthalmologists following these patients should be aware of this association to better manage ocular sequelae of diabetes.
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31
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Magnitude and Determinants of Patients at Risk of Developing Obstructive Sleep Apnea in a Non-Communicable Disease Clinic. ACTA ACUST UNITED AC 2019; 55:medicina55070391. [PMID: 31330779 PMCID: PMC6681367 DOI: 10.3390/medicina55070391] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2019] [Revised: 07/13/2019] [Accepted: 07/16/2019] [Indexed: 12/15/2022]
Abstract
Background and Objective: Obstructive sleep apnea (OSA) is a common chronic disorder worldwide, which can adversely affect the cardiovascular system among non-communicable disease (NCD) patients. It is underdiagnosed—or rather not diagnosed—in primary care settings due to the costly diagnostic techniques involved. This study aimed to assess the number of study participants at risk of developing OSA and to assess and quantify the risk factors associated with this disorder. Materials and Methods: A cross-sectional study was performed in an NCD clinic of a rural health training center, Karikalampakkam, Puducherry of South India from August 2018 to October 2018. A Modified Berlin Questionnaire (MBQ) was used to screen the study participants at risk for OSA. Four-hundred-and-seventy-three people aged 18 years and above were included in the study, using systematic random sampling. Respondents’ socio-demographic and morbidity characteristics, as well as clinical and anthropometric parameters including body weight, height, blood pressure, neck, hip and waist circumference were collected. Data was captured using Epicollect5 and analyzed using SPSS version 20.0. Results: One-fourth (25.8%) of the respondents were at high risk of developing OSA. In terms of gender, 27.9% of the men and 23.8% of the women were at high risk for OSA. In univariate analyses, the risk of developing OSA was significantly associated with a history of diabetes mellitus, hypertension, dyslipidemia and gastro-esophageal reflux disease, weight, body mass index, neck, waist and hip circumference, waist–hip ratio, and systolic and diastolic blood pressure. Multivariate logistic regression analysis showed that a history of dyslipidemia (aOR, 95% CI = 2.34, 1.22–4.48), body mass index (aOR, 95% CI = 1.15, 1.06–1.22) and waist circumference (aOR, 95% CI = 1.10, 1.07–1.14) emerged as significant predictors of risk for OSA. Conclusions: A considerable proportion of NCD patients with easily detectable attributes are at risk of developing OSA, but still remain undiagnosed at a primary health care setting. The results obtained using MBQ in this study were comparable to studies performed using polysomnography. Dyslipidemia, body mass index and waist circumference were independent risk factors for predicting a risk of developing OSA. Prospective studies are needed to confirm whether a reduction in these risk factors could reduce the risk for OSA.
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Togo J, Hu S, Li M, Niu C, Speakman JR. Impact of dietary sucrose on adiposity and glucose homeostasis in C57BL/6J mice depends on mode of ingestion: liquid or solid. Mol Metab 2019; 27:22-32. [PMID: 31255519 PMCID: PMC6717800 DOI: 10.1016/j.molmet.2019.05.010] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Revised: 05/27/2019] [Accepted: 05/29/2019] [Indexed: 12/12/2022] Open
Abstract
Objective Although it is widely accepted that obesity results from an imbalance of energy intake and expenditure, the mechanisms underlying this process and effective strategies for prevention and treatment are unclear. Growing evidence suggests excess consumption of sugar may play an important role, yet we showed previously in mice that consuming up to 30% of calories as sucrose in the diet had no impact on weight regulation. Since in humans consumption of sugar-sweetened beverages has been widely implicated, we investigated whether the mode of ingestion (solid or liquid) had different impacts on body weight regulation and glucose homeostasis. Methods Dietary sucrose was delivered in solid (as part of a standard pelleted rodent chow) and liquid (in drinking water) to C57BL/6 mice for 8 weeks. Body weight, body composition, energy intake and expenditure were monitored, as well as glucose and insulin tolerance tests. Expression of sweet taste receptors on the tongue, and glycogen and fat contents of the liver were also measured. Results Consumption of sucrose-sweetened water, but not equivalent levels of solid sucrose, led to body fat gain in C57BL/6 mice. Glucose intolerance was positively correlated to body fatness, rather than sucrose intake. Conclusions Our data support the suggestion that consumption of liquid sucrose may be an important contributor to dysregulation of body weight and related metabolic syndromes.
Liquid sucrose intake was associated with increased energy consumption and greater body fat gain. The same level of sucrose in a solid diet did not lead to higher energy intake or elevated body weight and fatness. Elevated adiposity was correlated with impairment of glucose homeostasis and insulin resistance. Glucose homeostasis and insulin resistance were related to adiposity and the mode but not the level of sucrose intake.
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Affiliation(s)
- Jacques Togo
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, PR China; University of Chinese Academy of Sciences, Shijingshan District, Beijing, 100049, PR China
| | - Sumei Hu
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, PR China
| | - Min Li
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, PR China; University of Chinese Academy of Sciences, Shijingshan District, Beijing, 100049, PR China
| | - Chaoqun Niu
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, PR China
| | - John R Speakman
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, PR China; Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, AB24 2TZ, UK; CAS Center of Excellence for Animal Evolution and genetics, Kunming, PR China.
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Zhou J, Huang X, Jiang X. Effects of Obstructive Sleep Apnea-Hypopnea Syndrome on Serum Carcinoembryonic Antigen Levels in Patients with Type 2 Diabetes Mellitus. Med Sci Monit 2019; 25:3558-3565. [PMID: 31086125 PMCID: PMC6530438 DOI: 10.12659/msm.913713] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background Type 2 diabetes mellitus (T2DM) is related to the serum carcinoembryonic antigen (CEA) level, which is used as a marker of colorectal cancer. Obstructive sleep apnea-hypopnea syndrome (OSAS) has been recently reported to have cancer-promoting effects. The aim of our study was to observe the effect of OSAS on serum levels of CEA in patients with T2DM. Material/Methods We enrolled 401 T2DM patients in this study. There were 244 patients with OSAS and 157 patients without OSAS. Results The CEA level in T2DM patients with OSAS was higher than that in those without OSAS (p<0.05). The participants with AHI scores ≥30 had higher CEA levels than those with 5≤ AHI scores <30 (p<0.05). The AHI score and ODI score were independently associated with increased risk of high CEA level in T2DM patients (odds ratio [OR]=1.052, 95% confidence interval [CI]: 1.011~1.095) and (OR=1.214, 95% CI: 1.070~1.377). Moreover, among male T2DM patients, the AHI score and ODI score had a linear correlation with the CEA level; this association was also observed in T2DM patients who smoked, had an HbA1c level ≥7%, or had a BMI ≥28 kg/m2 (all p<0.05). Conclusions The AHI score and ODI score were positively associated with the CEA level in T2DM patients. The relationship was stronger in male T2DM patients and in those who smoked, were obese, or had poor glycemic control. The mechanism may be related to metabolic disorders, and the potential increased risk of colorectal cancer should be investigated in a prospective study.
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Affiliation(s)
- Jiayan Zhou
- Department of Endocrinology, First People's Hospital of Changzhou, Changzhou, Jiangsu, China (mainland)
| | - Xiaolin Huang
- Department of Endocrinology, First People's Hospital of Changzhou, Changzhou, Jiangsu, China (mainland)
| | - Xiaohong Jiang
- Department of Endocrinology, First People's Hospital of Changzhou, Changzhou, Jiangsu, China (mainland)
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Baril AA, Osorio RS, Carrier J, Kaminska M, Gosselin N. Reply to Kawada: Obstructive Sleep Apnea and Cognitive Decline in Older Adults. Am J Respir Crit Care Med 2019; 199:1169-1170. [PMID: 30648882 PMCID: PMC6515864 DOI: 10.1164/rccm.201812-2280le] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Affiliation(s)
- Andrée-Ann Baril
- 1 Boston University School of Medicine Boston, Massachusetts and.,2 Hôpital du Sacré-Coeur de Montréal Montréal, Québec, Canada
| | - Ricardo S Osorio
- 3 NYU Langone Medical Center Manhattan, New York and.,4 Nathan S. Kline Institute for Psychiatric Research Orangeburg, New York
| | - Julie Carrier
- 2 Hôpital du Sacré-Coeur de Montréal Montréal, Québec, Canada.,5 Université de Montréal Montréal, Québec, Canada
| | - Marta Kaminska
- 6 McGill University Health Center Montréal, Québec, Canada
| | - Nadia Gosselin
- 2 Hôpital du Sacré-Coeur de Montréal Montréal, Québec, Canada.,5 Université de Montréal Montréal, Québec, Canada
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Chattu VK, Chattu SK, Burman D, Spence DW, Pandi-Perumal SR. The Interlinked Rising Epidemic of Insufficient Sleep and Diabetes Mellitus. Healthcare (Basel) 2019; 7:E37. [PMID: 30841553 PMCID: PMC6473416 DOI: 10.3390/healthcare7010037] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Revised: 02/26/2019] [Accepted: 02/28/2019] [Indexed: 12/15/2022] Open
Abstract
For healthy existence, humans need to spend one-third of their time sleeping. Any qualitative or quantitative disturbances in sleep would result in an increased prevalence of obesity, metabolic disorders, diabetes, cardiovascular diseases, and hypertension. The paper aims to highlight the growing global problem of insufficient sleep and its significant impact on the rising incidence of diabetes mellitus. An extensive literature search was done in all major databases for "insufficient sleep" and "Diabetes Mellitus" for this review. Shorter (<6 h) and longer (>9 h) durations of sleep have been adversely related to insulin resistance. Though the relation between insufficient sleep and diabetes mellitus is more or less understood, little is known about how oversleeping or hypersomnia (10⁻12 h) increases the risk of diabetes. The relationship between sleep disturbances and diabetes is dual-sided, as chronic sleep disturbances would elevate the risk of developing insulin resistance, while diabetes would worsen the quality of sleep. Both the qualitative and quantitative disturbances in sleep significantly increase the risk of developing diabetes, which is supported by numerous community-based and hospital-based epidemiological studies discussed in this review. Obstructive sleep apnea is one of the most common sleep disorders and is characterized by chronic intermittent hypoxia and increased sympathetic activity, thus leading to a higher prevalence of diabetes. Sleep therapy may serve as a low-cost method for fighting against the rising epidemic of diabetes.
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Affiliation(s)
- Vijay Kumar Chattu
- Faculty of Medical Sciences, The University of the West Indies, St. Augustine, Trinidad and Tobago.
- Global Institute of Public Health, Thiruvananthapuram, Kerala 695024, India.
| | - Soosanna Kumary Chattu
- Faculty of Medical Sciences, The University of the West Indies, St. Augustine, Trinidad and Tobago.
| | - Deepa Burman
- School of Medicine, University of Pittsburgh, 4200 Fifth Ave, Pittsburgh, PA 15260, USA.
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Zhang Y, Xing Y, Yuan H, Gang X, Guo W, Li Z, Wang G. Impaired Glucose Metabolisms of Patients with Obstructive Sleep Apnea and Type 2 Diabetes. J Diabetes Res 2018; 2018:6714392. [PMID: 30671481 PMCID: PMC6323486 DOI: 10.1155/2018/6714392] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 11/04/2018] [Indexed: 01/17/2023] Open
Abstract
AIMS Obstructive sleep apnea (OSA) is a very common disorder which is associated with metabolic comorbidities. The aims of this study were to analyze clinical data of patients with OSA and evaluate influence of sleep-disordered breathing on glycometabolism and its underlying mechanisms. METHODS We designed a cross-sectional study involving 53 OSA patients in The First Hospital of Jilin University from March 2015 to March 2016. They underwent a full-night polysomnography, measurement of fasting blood glucose and blood lipid profiles. Besides, we chose 20 individuals with type 2 diabetes mellitus (T2DM) as a subgroup for an in-depth study. This group additionally underwent a steamed bread meal test and measurement of HbA1c, C-reactive protein, tumor necrosis factor-α, interleukin 6, morning plasma cortisol, and growth hormone. RESULTS The two groups which with or without T2DM showed no significant differences in baseline characteristics. As for OSA patients with T2DM, the severe OSA group had higher homeostasis model assessment of insulin resistance (HOMA-IR) (P = 0.013) than the mild-to-moderate OSA group, whereas had lower morning plasma cortisol levels (P = 0.005) than the mild-to-moderate OSA group. AHI was positive correlated with HOMA-IR (r = 0.523, P = 0.018), yet negative correlated with morning plasma cortisol (r = -0.694, P = 0.001). However, nadir SpO2 was positive correlated with morning plasma cortisol (r s = 0.646, P = 0.002), while negative correlated with HOMA-IR (r s = -0.489, P = 0.029). CONCLUSIONS Our study showed that sleep-disordered breathing exerted negative influence on glucose metabolisms. The impairment of hypothalamic-pituitary-adrenal axis activity may be one of the underlying mechanisms of the glycometabolic dysfunctions in OSA with T2DM patients.
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Affiliation(s)
- Ye Zhang
- Department of Endocrinology & Metabolism, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Yanpeng Xing
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Haibo Yuan
- Department of Respiratory, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Xiaokun Gang
- Department of Endocrinology & Metabolism, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Weiying Guo
- Department of Endocrinology & Metabolism, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Zhuo Li
- Department of Endocrinology & Metabolism, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Guixia Wang
- Department of Endocrinology & Metabolism, The First Hospital of Jilin University, Changchun, Jilin, China
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Abstract
Obstructive sleep apnoea (OSA) is a highly prevalent disorder, which causes significant nocturnal and daytime symptoms, reduced quality of life, and impaired functional capacity. Importantly, however, OSA also appears to predispose to the development of a number of cardiovascular and metabolic diseases, including diabetes, hypertension, and stroke. In this review we explore its relationship with coronary artery disease (CAD), discussing mechanisms whereby it may promote the development of atherosclerosis, evidence of its effect on CAD incidence and outcomes, and coronary imaging studies in subjects with OSA. Finally, we shall evaluate the current evidence regarding the impact of continuous positive airway pressure therapy on CAD outcomes in OSA patients.
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Affiliation(s)
- Swapna Mandal
- Department of Respiratory and Sleep Medicine, Royal Free Hospital, London, UK.,University College London, UK
| | - Brian D Kent
- Sleep Disorders Centre, Guy's & St. Thomas' Hospitals, London, UK.,King's College London, London, UK
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Abstract
Obstructive sleep apnoea (OSA) is recognized as a major public health burden conveying a significant risk of cardiovascular diseases (CVD) and mortality. Continuous positive airway pressure (CPAP) is the treatment of choice for the majority of patients with OSA but the benefit of CPAP on CVD is uncertain. Thus, a greater understanding of the mechanisms by which OSA leads to CVD might identify novel therapeutic approaches. Intermittent hypoxia (IH), a hallmark feature of OSA, plays a key role in the pathogenesis and experimental studies using animal and cell culture studies suggest that IH mediates CVD through activation of multiple mechanistic pathways such as sympathetic excitation, inflammation, oxidative stress or metabolic dysregulation. Recurrent arousals, intrathoracic pressure swings and concomitant obesity likely play important additive roles in this process. In this review, the available evidence of the pathophysiological mechanisms of CVD in OSA is explored with a specific emphasis on IH, recurrent arousals and intrathoracic pressure swings as the main pathophysiological triggers.
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Affiliation(s)
- Silke Ryan
- Pulmonary and Sleep Disorders Unit, St. Vincent's University Hospital, Dublin, Ireland.,School of Medicine, University College Dublin, Dublin, Ireland
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Catestatin serum levels are increased in male patients with obstructive sleep apnea. Sleep Breath 2018; 23:473-481. [PMID: 30088239 DOI: 10.1007/s11325-018-1703-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Revised: 07/03/2018] [Accepted: 07/30/2018] [Indexed: 12/24/2022]
Abstract
PURPOSE Obstructive sleep apnea (OSA) is a complex sleep disorder associated with autonomic and sympathetic dysregulation. To the contrary, catestatin, an endogenous pleiotropic peptide cleaved from chromogranin A, is known for its inhibitory effects on catecholamine release and sympathetic activity. The aims of the study were to determine catestatin serum levels among male OSA patients compared to healthy control subjects and to explore associations of catestatin with anthropometric, polysomnographic, and lipid profile parameters. METHODS Seventy-eight male OSA patients aged 50.3 ± 8.8 years and 51 age/sex/BMI-matched control subjects aged 50.4 ± 7.8 years were enrolled in the study. Catestatin serum levels were determined by an enzyme-linked immunosorbent assay (ELISA). RESULTS Catestatin serum levels were significantly higher among OSA patients compared to control subjects (2.9 ± 1.2 vs. 1.5 ± 1.1 ng/mL, p < 0.001). Serum catestatin levels significantly correlated with apnea-hypopnea index (AHI) among non-obese OSA subjects (r = 0.466, p = 0.016; β = 0.448, p = 0.026), while in whole OSA population, catestatin levels significantly correlated with neck circumference (r = 0.318, p < 0.001; β = 0.384, p < 0.001) and high-density lipoprotein (HDL) cholesterol (r = - 0.320, p < 0.001; β = - 0.344, p < 0.001). In multivariate-adjusted regression model, serum catestatin was significant and independent predictor of OSA status (OR 4.98, 95% CI 2.17-11.47, p < 0.001). CONCLUSIONS Catestatin serum levels are significantly increased in male OSA population and positively correlate with disease severity in non-obese patients. OSA status is independently predicted by catestatin levels; however, this finding is restricted to patients with moderate-to-severe disease. Further studies are necessary to elucidate the mechanistic role of catestatin in the complex pathophysiology of OSA.
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Gu X, Yang W, Luo X, Wang X, Tang J, Cai Z. Bioinformatics analysis to reveal the key genes related to obstructive sleep apnea. Sleep Breath 2018; 23:259-267. [PMID: 29992456 DOI: 10.1007/s11325-018-1694-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Revised: 05/31/2018] [Accepted: 06/26/2018] [Indexed: 12/17/2022]
Abstract
PURPOSE Obstructive sleep apnea (OSA) is induced by obstruction of the upper airway, which can raise multiple health risks. This study is designed to reveal the key genes involved in OSA. METHODS GSE38792 was extracted from Gene Expression Omnibus database, including ten visceral adipose tissues from OSA patients and eight visceral adipose tissues from normal controls. Differential expression analysis was conducted using limma package, and then the functions of the differentially expressed genes (DEGs) were analyzed using DAVID database, followed by protein-protein interaction (PPI) network, and integrated regulatory network analysis was performed using Cytoscape software. RESULTS A total of 368 DEGs (176 upregulated and 192 downregulated) were identified in OSA samples. Epstein-Barr virus infection (involving IL10RB, MAPK9, and MAPK10) and olfactory transduction were the main pathways separately enriched for the upregulated genes and the downregulated genes. After the PPI network was built, the top ten network nodes (such as TXN) were selected according to node degrees. Two significant PPI network modules were identified. Moreover, the integrated regulatory network was constructed. CONCLUSION IL10RB, MAPK9, MAPK10, and TXN might function in the pathogenesis of OSA.
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Affiliation(s)
- Xiandong Gu
- Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, No.164, LanXi Road, Shanghai, 200063, China
| | - Wei Yang
- Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, No.164, LanXi Road, Shanghai, 200063, China
| | - Xuming Luo
- Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, No.164, LanXi Road, Shanghai, 200063, China
| | - Xiongbiao Wang
- Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, No.164, LanXi Road, Shanghai, 200063, China
| | - Jihong Tang
- Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, No.164, LanXi Road, Shanghai, 200063, China
| | - Zhuying Cai
- Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, No.164, LanXi Road, Shanghai, 200063, China.
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Liguori C, Placidi F, Palmieri MG, Izzi F, Ludovisi R, Mercuri NB, Pierantozzi M. Continuous Positive Airway Pressure Treatment May Improve Optic Nerve Function in Obstructive Sleep Apnea: An Electrophysiological Study. J Clin Sleep Med 2018; 14:953-958. [PMID: 29852910 DOI: 10.5664/jcsm.7158] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Accepted: 02/20/2018] [Indexed: 01/21/2023]
Abstract
STUDY OBJECTIVES Obstructive sleep apnea (OSA) is a sleep disorder frequently associated with optic nerve diseases. Moreover, untreated patients with severe OSA may show optic nerve dysfunction as documented by electrophysiological studies using visual evoked potentials (VEP). Because continuous positive airway pressure (CPAP) treatment has proved to restore the physiologic nocturnal breathing, thus preventing nocturnal hypoxemia and reducing inflammation, in this study we tested whether 1-year CPAP treatment may modify VEP responses in patients with severe OSA. METHODS VEP were recorded at baseline and after 1 year of CPAP treatment in 20 patients with severe OSA, divided in two groups on the basis of CPAP adherence, and compared to a healthy control group. RESULTS Patients with good adherence to CPAP therapy (CPAP+; n = 10) showed VEP P100 amplitude significantly higher than patients with poor adherence to CPAP therapy (CPAP-; n = 10). Moreover, the CPAP+ group showed VEP responses similar to those in the control group (n = 26). Considering the mean difference of VEP responses between baseline and follow-up, the CPAP+ group showed a significant increase in VEP P100 amplitude and a significant decrease in VEP P100 latency compared to the CPAP- group. CONCLUSIONS This study documented that CPAP therapy significantly improves VEP in patients with OSA who are adherent to the treatment. We hypothesize that CPAP treatment, minimizing the metabolic, inflammatory and ischemic consequences of OSA, may normalize the altered VEP responses in patients with OSA by restoring and preserving optic nerve function.
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Affiliation(s)
- Claudio Liguori
- Sleep Medicine Centre, Neurophysiopathology Unit, Department of Systems Medicine, University of Rome "Tor Vergata," Rome, Italy
| | - Fabio Placidi
- Sleep Medicine Centre, Neurophysiopathology Unit, Department of Systems Medicine, University of Rome "Tor Vergata," Rome, Italy
| | - Maria Giuseppina Palmieri
- Sleep Medicine Centre, Neurophysiopathology Unit, Department of Systems Medicine, University of Rome "Tor Vergata," Rome, Italy
| | - Francesca Izzi
- Sleep Medicine Centre, Neurophysiopathology Unit, Department of Systems Medicine, University of Rome "Tor Vergata," Rome, Italy
| | - Raffaella Ludovisi
- Sleep Medicine Centre, Neurophysiopathology Unit, Department of Systems Medicine, University of Rome "Tor Vergata," Rome, Italy
| | - Nicola Biagio Mercuri
- Sleep Medicine Centre, Neurophysiopathology Unit, Department of Systems Medicine, University of Rome "Tor Vergata," Rome, Italy.,Neurology Unit, Department of Systems Medicine, University of Rome "Tor Vergata," Rome, Italy.,Fondazione Santa Lucia IRCCS, Rome, Italy
| | - Mariangela Pierantozzi
- Neurology Unit, Department of Systems Medicine, University of Rome "Tor Vergata," Rome, Italy
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Sleep-disordered breathing, circulating exosomes, and insulin sensitivity in adipocytes. Int J Obes (Lond) 2018; 42:1127-1139. [PMID: 29892042 PMCID: PMC6195831 DOI: 10.1038/s41366-018-0099-9] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2017] [Revised: 02/20/2018] [Accepted: 03/12/2018] [Indexed: 12/21/2022]
Abstract
BACKGROUND Sleep-disordered-breathing (SDB), which is characterized by chronic intermittent hypoxia (IH) and sleep fragmentation (SF), is a prevalent condition that promotes metabolic dysfunction, particularly among patients suffering from obstructive hypoventilation syndrome (OHS). Exosomes are generated ubiquitously, are readily present in the circulation, and their cargo may exert substantial functional cellular alterations in both physiological and pathological conditions. However, the effects of plasma exosomes on adipocyte metabolism in patients with OHS or in mice subjected to IH or SF mimicking SDB are unclear. METHODS Exosomes from fasting morning plasma samples from obese adults with polysomnographically-confirmed OSA before and after 3 months of adherent CPAP therapy were assayed. In addition, C57BL/6 mice were randomly assigned to (1) sleep control (SC), (2) sleep fragmentation (SF), and (3) intermittent hypoxia (HI) for 6 weeks, and plasma exosomes were isolated. Equivalent exosome amounts were added to differentiated adipocytes in culture, after which insulin sensitivity was assessed using 0 nM and 5 nM insulin-induced pAKT/AKT expression changes by western blotting. RESULTS When plasma exosomes were co-cultured and internalized by human naive adipocytes, significant reductions emerged in Akt phosphorylation responses to insulin when compared to exosomes obtained after 24 months of adherent CPAP treatment (n = 24; p < 0.001), while no such changes occur in untreated patients (n = 8). In addition, OHS exosomes induced significant increases in adipocyte lipolysis that were attenuated after CPAP, but did not alter pre-adipocyte differentiation. Similarly, exosomes from SF- and IH-exposed mice induced attenuated p-AKT/total AKT responses to exogenous insulin and increased glycerol content in naive murine adipocytes, without altering pre-adipocyte differentiation. CONCLUSIONS Using in vitro adipocyte-based functional reporter assays, alterations in plasma exosomal cargo occur in SDB, and appear to contribute to adipocyte metabolic dysfunction. Further exploration of exosomal miRNA signatures in either human subjects or animal models and their putative organ and cell targets appears warranted.
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Mok Y, Tan CW, Wong HS, How CH, Tan KLA, Hsu PP. Obstructive sleep apnoea and Type 2 diabetes mellitus: are they connected? Singapore Med J 2018; 58:179-183. [PMID: 28429032 DOI: 10.11622/smedj.2017027] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Obstructive sleep apnoea (OSA), a sleep-related breathing condition, is diagnosed based on a patient's apnoea-hypopnea index from a sleep study, and the presence or absence of symptoms. Diabetes mellitus (DM) and OSA share a significant common risk factor, obesity, with all three conditions contributing to the risk of developing cardiovascular diseases. The pathophysiological links between OSA and DM are still unclear, but intermittent hypoxia may be an important mechanism. More awareness of the possible link between OSA and DM is needed, given their increasing prevalence locally and worldwide. Continuous positive airway pressure is the standard treatment for OSA, while weight loss through dietary and lifestyle modifications is important to holistically manage patients with either condition. There is currently insufficient evidence to support the benefits of screening every diabetic patient for OSA. However, diabetic patients with symptoms suggestive of OSA should be referred to a sleep specialist for further evaluation.
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Affiliation(s)
- Yingjuan Mok
- Department of Respiratory and Critical Care Medicine, Changi General Hospital, Singapore
| | - Chee Wei Tan
- Family Medicine, Changi General Hospital, Singapore
| | - Hang Siang Wong
- Department of Respiratory and Critical Care Medicine, Changi General Hospital, Singapore
| | - Choon How How
- Care and Health Integration, Changi General Hospital, Singapore
| | - Kah Leong Alvin Tan
- Department of Otorhinolaryngology - Head and Neck Surgery, Changi General Hospital, Singapore
| | - Pon Poh Hsu
- Department of Otorhinolaryngology - Head and Neck Surgery, Changi General Hospital, Singapore
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Garcia KA, Wohlgemuth WK, Ferrannini E, Mari A, Gonzalez A, Mendez AJ, Bizzotto R, Skyler JS, Schneiderman N, Hurwitz BE. Sleeping oxygen saturation, rapid eye movement sleep, and the adaptation of postprandial metabolic function in insulin sensitive and resistant individuals without diabetes. Physiol Behav 2018; 191:123-130. [PMID: 29655763 DOI: 10.1016/j.physbeh.2018.04.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Revised: 02/27/2018] [Accepted: 04/07/2018] [Indexed: 12/25/2022]
Abstract
AIMS Sleeping oxygen saturation (SaO2) and sleep stage duration have been linked with prediabetic alterations but the pathogenic pathways are not well understood. This study of insulin sensitive and resistant adults examined the effect on postprandial metabolic regulation of repeated mixed-meal challenges of different carbohydrate loading. The aim was to examine whether the relationship between lower sleeping oxygen saturation (SaO2) and poorer fasting and postprandial metabolic function may be linked with reduced slow wave sleep (SWS) and rapid eye movement (REM) duration, independent of age, sex and total adiposity. METHODS The 24 men and women, aged 25-54 years, had no diabetes or other diagnosed conditions, were evaluated with polysomnography to derive indices of SaO2 and sleep architecture. In addition, an OGTT and two 14-h serial mixed-meal tests were administered over 3 successive in-patient days. The carbohydrate content of the mixed-meals was manipulated to compare a standard-load day with a double-load day (300 vs. 600 kcal/meal). Quantitative modeling was applied to derive β-cell glucose sensitivity (β-GS), early insulin secretion rate sensitivity (ESRS), and total postprandial insulinemia (AUCINS). RESULTS Analyses showed that, for the 14-h tests, the SaO2 relationship with metabolic outcomes was associated significantly with percent time spent in REM but not SWS, independent of age, sex and total adiposity. Specifically, indirect pathways indicated that lower SaO2 was related to shorter REM duration, and shorter REM was respectively associated with higher β-GS, ESRS, and AUCINS for the 300- and 600-load days (300 kcal/meal: β = -8.68, p < .03, β = -8.54, p < .002, and β = -10.06, p < .008; 600 kcal/meal: β = -11.45, p < .003, β = -11.44, p < .001, and β = -11.00, p < .03). CONCLUSION Sleeping oxygen desaturation and diminished REM duration are associated with a metabolic pattern that reflects a compensatory adaptation of postprandial insulin metabolism accompanying preclinical diabetic risk.
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Affiliation(s)
- Karin A Garcia
- Behavioral Medicine Research Center, University of Miami, Miami, FL, USA; Department of Psychology, University of Miami, Coral Gables, FL, USA
| | | | - Ele Ferrannini
- National Research Council Institute of Clinical Physiology, Pisa, Italy
| | - Andrea Mari
- National Research Council Institute of Neurosciences, Padua, Italy
| | - Alex Gonzalez
- Behavioral Medicine Research Center, University of Miami, Miami, FL, USA
| | - Armando J Mendez
- Behavioral Medicine Research Center, University of Miami, Miami, FL, USA; Division of Endocrinology, Diabetes and Metabolism, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Roberto Bizzotto
- National Research Council Institute of Neurosciences, Padua, Italy
| | - Jay S Skyler
- Division of Endocrinology, Diabetes and Metabolism, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Neil Schneiderman
- Behavioral Medicine Research Center, University of Miami, Miami, FL, USA; Department of Psychology, University of Miami, Coral Gables, FL, USA; Division of Endocrinology, Diabetes and Metabolism, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Barry E Hurwitz
- Behavioral Medicine Research Center, University of Miami, Miami, FL, USA; Department of Psychology, University of Miami, Coral Gables, FL, USA; Division of Endocrinology, Diabetes and Metabolism, Miller School of Medicine, University of Miami, Miami, FL, USA.
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Obesity, obstructive sleep apnea and type 2 diabetes mellitus: Epidemiology and pathophysiologic insights. SLEEP MEDICINE AND DISORDERS : INTERNATIONAL JOURNAL 2018; 2:52-58. [PMID: 30167574 PMCID: PMC6112821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/03/2022]
Abstract
Obesity is a major global health issue, and its prevalence is increasing. Obesity is associated with much comorbidity such as obstructive sleep apnea (OSA), type 2 diabetes mellitus (T2DM), and cardiovascular diseases (CVD). Obesity is also one of the major causative factors of OSA, and OSA itself can promote the onset of after T2DM because hypoxic episodes decrease insulin sensitivity, and activation of the sympathetic pathway leads to the release of inflammatory markers associated with insulin resistance. Continuous Positive Airway Pressure (CPAP) can be used to ameliorate both conditions, as CPAP decreased hypoxia episodes and increases insulin sensitivity and improves glucose metabolism. Weight-loss strategies play an important role in improving OSA, T2DM, and other associated comorbidities. Lifestyle modification of diet and exercise, medications or bariatric surgery should be considered weight loss. The purpose of this review is to describe the relationship between obesity, OSA, and T2DM.
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Archontogeorgis K, Papanas N, Nena E, Tzouvelekis A, Tsigalou C, Voulgaris A, Xanthoudaki M, Mouemin T, Froudarakis M, Steiropoulos P. Insulin Sensitivity and Insulin Resistance in Non-Diabetic Middle-Aged Patients with Obstructive Sleep Apnoea Syndrome. Open Cardiovasc Med J 2017; 11:159-168. [PMID: 29399212 PMCID: PMC5761020 DOI: 10.2174/1874192401711010159] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Revised: 12/18/2017] [Accepted: 12/26/2017] [Indexed: 01/03/2023] Open
Abstract
Background: Obstructive sleep apnoea syndrome (OSAS) has been linked with abnormal glucose metabolism, insulin resistance (IR) and development of diabetes mellitus. Methods: Non-diabetic patients (n=69) with OSAS, diagnosed by polysomnography, were prospectively recruited. To evaluate IR among OSAS patients, the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and Insulin sensitivity by Quantitative Insulin sensitivity Check Index (QUICKI) were used. Results: HOMA-IR was positively associated with body-mass index (BMI) (ρ=0.364, p=0.002), time with oxyhaemoglobin saturation <90% (ρ=0.291, p=0.015), arousal index (ρ=0.268, p=0.027), Epworth sleepiness scale (ESS) score (ρ=0.293, p=0.019) and negatively with average oxyhaemoglobin saturation (ρ=-0.398, p=0.001) and minimum oxyhaemoglobin saturation (ρ=-0.327, p=0.006). QUICKI was positively associated with forced vital capacity (r=0.301, p=0.014), average oxyhaemoglobin saturation (r=0.443, p<0.001), minimum oxyhaemoglobin saturation (ρ=0.318, p=0.008), and negatively associated with sleep stage transitions (r=-0.266, p=0.032), oxygen desaturation index (r=-0.404, p=0.005), time with oxyhaemoglobin saturation <90% (r=-0.311, p=0.019), arousal index (r=-0.344, p=0.004) and ESS score (r=-0.299, p=0.016). After adjustment for age and BMI, HOMA-IR was associated with sleep stage transitions, time with oxyhaemoglobin saturation <90%, average oxyhaemoglobin saturation, minimum oxyhaemoglobin saturation and arousal index. QUICKI was associated with oxygen desaturation index, sleep stage transitions, ESS score, minimum oxyhaemoglobin saturation and arousal index. Conclusions: An independent association between OSAS and IR in patients without pre-existing diabetes mellitus was observed. Recurrent hypoxia and sleep fragmentation in OSAS are associated with IR in these patients.
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Affiliation(s)
- K Archontogeorgis
- MSc Program in Sleep Medicine, Medical School, Democritus University of Thrace, Alexandroupolis, Greece
| | - N Papanas
- Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece
| | - E Nena
- Laboratory of Hygiene and Environmental Protection, Medical School, Democritus University of Thrace, Alexandroupolis, Greece
| | - A Tzouvelekis
- Division of Immunology, Biomedical Sciences Research Center "Alexander Fleming", Athens, Greece
| | - C Tsigalou
- Laboratory of Biopathology, University General Hospital of Evros, Alexandroupolis, Greece
| | - A Voulgaris
- Department of Pneumonology, Medical School, Democritus University of Thrace, Alexandroupolis , Greece
| | - M Xanthoudaki
- Department of Pneumonology, Medical School, Democritus University of Thrace, Alexandroupolis , Greece
| | - T Mouemin
- Department of Pneumonology, Medical School, Democritus University of Thrace, Alexandroupolis , Greece
| | - M Froudarakis
- Department of Pneumonology, Medical School, Democritus University of Thrace, Alexandroupolis , Greece
| | - P Steiropoulos
- MSc Program in Sleep Medicine, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.,Department of Pneumonology, Medical School, Democritus University of Thrace, Alexandroupolis , Greece
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Pomatto LCD, Davies KJA. The role of declining adaptive homeostasis in ageing. J Physiol 2017; 595:7275-7309. [PMID: 29028112 PMCID: PMC5730851 DOI: 10.1113/jp275072] [Citation(s) in RCA: 134] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2017] [Accepted: 09/01/2017] [Indexed: 12/12/2022] Open
Abstract
Adaptive homeostasis is "the transient expansion or contraction of the homeostatic range for any given physiological parameter in response to exposure to sub-toxic, non-damaging, signalling molecules or events, or the removal or cessation of such molecules or events" (Davies, 2016). Adaptive homeostasis enables biological systems to make continuous short-term adjustments for optimal functioning despite ever-changing internal and external environments. Initiation of adaptation in response to an appropriate signal allows organisms to successfully cope with much greater, normally toxic, stresses. These short-term responses are initiated following effective signals, including hypoxia, cold shock, heat shock, oxidative stress, exercise-induced adaptation, caloric restriction, osmotic stress, mechanical stress, immune response, and even emotional stress. There is now substantial literature detailing a decline in adaptive homeostasis that, unfortunately, appears to manifest with ageing, especially in the last third of the lifespan. In this review, we present the hypothesis that one hallmark of the ageing process is a significant decline in adaptive homeostasis capacity. We discuss the mechanistic importance of diminished capacity for short-term (reversible) adaptive responses (both biochemical and signal transduction/gene expression-based) to changing internal and external conditions, for short-term survival and for lifespan and healthspan. Studies of cultured mammalian cells, worms, flies, rodents, simians, apes, and even humans, all indicate declining adaptive homeostasis as a potential contributor to age-dependent senescence, increased risk of disease, and even mortality. Emerging work points to Nrf2-Keap1 signal transduction pathway inhibitors, including Bach1 and c-Myc, both of whose tissue concentrations increase with age, as possible major causes for age-dependent loss of adaptive homeostasis.
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Affiliation(s)
- Laura C. D. Pomatto
- Leonard Davis School of Gerontology of the Ethel Percy Andrus Gerontology CenterUniversity of Southern CaliforniaLos AngelesCA 90089USA
| | - Kelvin J. A. Davies
- Leonard Davis School of Gerontology of the Ethel Percy Andrus Gerontology CenterUniversity of Southern CaliforniaLos AngelesCA 90089USA
- Molecular and Computational Biology Program, Department of Biological Sciences of the Dornsife College of LettersArts & Sciences: the University of Southern CaliforniaLos AngelesCA 90089‐0191USA
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Pazarlı AC, Köseoğlu Hİ, Kutlutürk F, Gökçe E. Association of Acromegaly and Central Sleep Apnea Syndrome. Turk Thorac J 2017; 20:157-159. [PMID: 30407161 DOI: 10.5152/turkthoracj.2017.17003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2017] [Accepted: 07/21/2017] [Indexed: 01/05/2023]
Abstract
Acromegaly is usually characterized by the excessive secretion of growth hormone (GH) after the closure of epiphyseal plaques, resulting from functional pituitary adenomas. The most common manifestations of acromegaly are acral and soft tissue overgrowth, diabetes mellitus, hypertension, and heart and respiratory failure. In patients, obstruction of the upper airway may develop due to enlargement of the tongue and thickening of the tissues of the larynx; consequently, obstructive sleep apnea syndrome (OSAS) occurs commonly in acromegaly. Previous studies have shown an association between acromegaly and central sleep apnea syndrome (CSAS). Some of these described patients described showed that an elevation in the GH level may cause a defect in the respiratory drive. Most systemic diseases seen in acromegaly require effective treatment. We believe that it is necessary to perform effective treatments by examining respiratory disorders in sleep.
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Affiliation(s)
- Ahmet Cemal Pazarlı
- Department of Pulmonary Diseases, Gaziopsmanpaşa University School of Medicine, Tokat, Turkey
| | - Handan İnönü Köseoğlu
- Department of Pulmonary Diseases, Gaziopsmanpaşa University School of Medicine, Tokat, Turkey
| | - Faruk Kutlutürk
- Department of Internal Medicine, Gaziosmanpaşa University School of Medicine, Tokat, Turkey
| | - Erkan Gökçe
- Department of Radiology, Gaziosmanpaşa University School of Medicine, Tokat, Turkey
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Smith KE, Kelly AC, Min CG, Weber CS, McCarthy FM, Steyn LV, Badarinarayana V, Stanton JB, Kitzmann JP, Strop P, Gruessner AC, Lynch RM, Limesand SW, Papas KK. Acute Ischemia Induced by High-Density Culture Increases Cytokine Expression and Diminishes the Function and Viability of Highly Purified Human Islets of Langerhans. Transplantation 2017; 101:2705-2712. [PMID: 28263224 PMCID: PMC6319561 DOI: 10.1097/tp.0000000000001714] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Revised: 01/24/2017] [Accepted: 02/16/2017] [Indexed: 11/25/2022]
Abstract
BACKGROUND Encapsulation devices have the potential to enable cell-based insulin replacement therapies (such as human islet or stem cell-derived β cell transplantation) without immunosuppression. However, reasonably sized encapsulation devices promote ischemia due to high β cell densities creating prohibitively large diffusional distances for nutrients. It is hypothesized that even acute ischemic exposure will compromise the therapeutic potential of cell-based insulin replacement. In this study, the acute effects of high-density ischemia were investigated in human islets to develop a detailed profile of early ischemia induced changes and targets for intervention. METHODS Human islets were exposed in a pairwise model simulating high-density encapsulation to normoxic or ischemic culture for 12 hours, after which viability and function were measured. RNA sequencing was conducted to assess transcriptome-wide changes in gene expression. RESULTS Islet viability after acute ischemic exposure was reduced compared to normoxic culture conditions (P < 0.01). Insulin secretion was also diminished, with ischemic β cells losing their insulin secretory response to stimulatory glucose levels (P < 0.01). RNA sequencing revealed 657 differentially expressed genes following ischemia, with many that are associated with increased inflammatory and hypoxia-response signaling and decreased nutrient transport and metabolism. CONCLUSIONS In order for cell-based insulin replacement to be applied as a treatment for type 1 diabetes, oxygen and nutrient delivery to β cells will need to be maintained. We demonstrate that even brief ischemic exposure such as would be experienced in encapsulation devices damages islet viability and β cell function and leads to increased inflammatory signaling.
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Affiliation(s)
- Kate E. Smith
- Department of Surgery, University of Arizona, Tucson, AZ
- Department of Physiological Sciences GIDP, University of Arizona, Tucson, AZ
| | - Amy C. Kelly
- School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ
| | - Catherine G. Min
- Department of Surgery, University of Arizona, Tucson, AZ
- Department of Physiological Sciences GIDP, University of Arizona, Tucson, AZ
| | - Craig S. Weber
- Department of Physiology, University of Arizona, Tucson, AZ
| | - Fiona M. McCarthy
- School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ
| | - Leah V. Steyn
- Department of Surgery, University of Arizona, Tucson, AZ
| | | | | | | | - Peter Strop
- Sanofi-Aventis Group, Tucson, AZ
- Icagen, Inc., Tucson, AZ
| | | | | | - Sean W. Limesand
- School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ
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Antiobesity and Anti-Inflammatory Effects of Orally Administered Bonito Extracts on Mice Fed a High-Fat Diet. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2017; 2017:9187167. [PMID: 29292401 PMCID: PMC5674501 DOI: 10.1155/2017/9187167] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/16/2017] [Accepted: 07/05/2017] [Indexed: 01/03/2023]
Abstract
Background The condensed fermentative extract of bonito (BoE), skipjack tuna (Katsuwonus pelamis), has claimed its health conditioning effects against lifestyle-related diseases such as hypertension and type 2 diabetes. Methods We evaluated the antiobesity and anti-inflammatory effects of BoE on mice fed a high-fat diet (HFD). Mice (9 weeks of age) were maintained for 11 weeks on HFD with or without BoE (50 mg or 500 mg/kg). Results Compared with untreated mice, BoE50 or BoE500 mice achieved maximum weight reductions of 7.4% (males) and 11.4% (females), and visceral fat in male BoE500 mice was more decreased among all mice (P = 0.00459). Furthermore, an antiobesity gene uncoupling protein-1 was significantly induced in the visceral fat tissues of male BoE500 (P = 0.0110) and female BoE50 and BoE500 mice (P = 0.0110 and P = 0.0110, resp.). Finally, we detected reduced amount of granulocyte-colony stimulating factor (P = 0.0250) in the sera of female BoE50 and interleukin- (IL-) 5 (P = 0.0120), IL-6 (P = 0.0118), and IL-13 (P = 0.0243) in female BoE500 mice. Conclusion The antiobesity and anti-inflammatory effects of BoE were demonstrated with our examination system and any toxic adverse effects were not observed in mice during the 3-month investigation.
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