0
Correspondence |

ResponseResponse FREE TO VIEW

Jean-Louis Pépin, MD, PhD; Caroline Minville, MD; Marie-Noëlle Hilleret, MD; Renaud Tamisier, MD, PhD; Judith Aron-Wisnewsky, MD; Karine Clément, MD, PhD; Candice Trocme, PhD; Jean-Christian Borel, PhD; Patrick Lévy, MD, PhD; Jean-Pierre Zarski, MD, PhD
Author and Funding Information

From the Université Joseph Fourier (Drs Pépin, Minville, Tamisier, Borel, and Lévy), INSERM U 1042, Laboratoire HP2, Hypoxie Physiopathologies, Pôle Thorax et Vaisseaux, CHU de Grenoble; Institut universitaire de cardiologie et de pneumologie de Québec (Dr Minville); Département d’Hépato Gastroentérologie (Drs Hilleret and Zarski), Pôle Digidune, CHU de Grenoble; Assistance Publique-Hôpitaux de Paris (Drs Aron-Wisnewsky and Clément), Département Cœur et métabolisme, Centre de Nutrition Humaine (CRNH) Hôpital Pitié-Salpétrière; INSERM UMRS 872 Team 7 (Drs Aron-Wisnewsky and Clement), Nutriomique, Université Pierre et Marie Curie-Paris 6, Centre de Recherche des Cordeliers; and Laboratoire de Biochimie des Enzymes et des Protéines (Dr Trocme), CGD (Institut de Biologie et de Pathologie), CHU de Grenoble.

CORRESPONDENCE TO: Jean-Louis Pépin, MD, PhD, Université Joseph Fourier, Laboratoire HP2, INSERM U1042, Grenoble Cedex 09, France; e-mail: JPepin@chu-grenoble.fr


Drs Pépin and Zarski contributed equally to this work.

FINANCIAL/NONFINANCIAL DISCLOSURES: The authors have reported to CHEST the following conflicts of interest: Dr Tamisier has received consulting fees from Respicardia, Inc; unrestricted research funds from ResMed Foundation, Agiradom, Orkyn, Fondation de la recherche medicale, and Direction de la recherche Clinique du CHU de Grenoble; and lecture fees from HealthID, Inc; Périmètre, SA; American Thoracic Society; and European Respiratory Society. Drs Pépin, Minville, Hilleret, Aron-Wisnewsky, Clement, Trocme, Borel, Lévy, and Zarski have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(2):e67-e68. doi:10.1378/chest.14-0981
Text Size: A A A
Published online
To the Editor:

We thank Drs Mirrakhimov and Mirrakhimov for their interest in our recent article in CHEST.1 They mainly raise the question of a potential role for nonalcoholic fatty pancreatic disease (NAFPD) as an underlying mechanism for the association between OSA and type 2 diabetes.

Rapidly accumulating data from both epidemiologic and clinical studies have suggested that OSA is independently associated with alterations in glucose metabolism as well as with an increased risk of developing type 2 diabetes. Multiple mechanistic pathways contribute to the deteriorated plasma glucose/insulin homeostasis in OSA, the primary one being sympathetic overactivity, due to sleep fragmentation and intermittent hypoxia. Independent of autonomic nervous system activation, intermittent hypoxia in rodent models contributes to decreased glucose use in oxidative muscle fibers. Intermittent hypoxia also seems to be responsible for increased β-cell proliferation and cell death, the latter being due to oxidative stress.

OSA is also commonly associated with obesity and independently participates in the development of visceral obesity. Adipocytes exposed to hypoxia exhibit a dysregulated production of adipocytokines, which may contribute to insulin resistance and metabolic syndrome in patients with OSA. We have demonstrated in morbid obesity that chronic intermittent hypoxia is strongly associated with nonalcoholic fatty liver disease (NAFLD) and more severe fibrotic or inflammatory liver injuries.2 There are different aspects of lipid storage that are not systematically detrimental. For example, lipid droplets can act as a defense mechanism to compensate for dysregulated lipolysis in liver. Whether this phenomenon exists in the pancreas is unknown.

Drs Mirrakhimov and Mirrakhimov correctly underline the lack of data regarding NAFPD in patients with OSA. A high-fat diet in rodents induces fat accumulation, inflammatory cell infiltration, and fibrosis in the pancreas with secondary insulin resistance and features of both NAFLD and NAFPD. Recently, both diabetes and NAFLD have been demonstrated as associated factors of fatty pancreas, independent of age, sex, adiposity, and other cardiometabolic risk factors.3 Further studies in rodent models exposed to intermittent hypoxia and in OSA cohorts need to address this issue.

Effective treatment of OSA has been proposed as an important target for improving cardiometabolic risk and reducing ectopic fat. Recent literature shows that it is not realistic to expect a clinically relevant decrease in abdominal and liver fat with CPAP therapy. The range of response, if any, is not equivalent to lipid-lowering drugs or weight-loss programs. However, men with OSA at baseline had a smaller reduction in body weight and fewer metabolic improvements associated with lifestyle intervention than men without OSA.4 Also, after bariatric surgery, epicardial fat volume loss, another feature of ectopic fat, was limited in patients with OSA.5 Intermittent hypoxia may induce a high level of fibrosis in different ectopic adipose tissues, which can initiate resistance to weight loss or CPAP intervention efficacy.

In conclusion, all the features of ectopic fat deposits (ie, abdominal, hepatic, pancreatic, and epicardial) need to be better documented in OSA cohorts. The mechanisms by which OSA induces a resistance to classic intervention addressing ectopic fat syndrome are promising research avenues.

References

Minville C, Hilleret M-N, Tamisier R, et al. Nonalcoholic fatty liver disease, nocturnal hypoxia, and endothelial function in patients with sleep apnea. Chest. 2014;145(3):525-533. [CrossRef] [PubMed]
 
Aron-Wisnewsky J, Minville C, Tordjman J, et al. Chronic intermittent hypoxia is a major trigger for non-alcoholic fatty liver disease in morbid obese. J Hepatol. 2012;56(1):225-233. [CrossRef] [PubMed]
 
Wang CY, Ou HY, Chen MF, Chang TC, Chang CJ. Enigmatic ectopic fat: prevalence of nonalcoholic fatty pancreas disease and its associated factors in a Chinese population. J Am Heart Assoc. 2014;3(1):e000297. [CrossRef] [PubMed]
 
Borel A-L, Leblanc X, Alméras N, et al. Sleep apnoea attenuates the effects of a lifestyle intervention programme in men with visceral obesity. Thorax. 2012;67(8):735-741. [CrossRef] [PubMed]
 
Gaborit B, Jacquier A, Kober F, et al. Effects of bariatric surgery on cardiac ectopic fat: lesser decrease in epicardial fat compared to visceral fat loss and no change in myocardial triglyceride content. J Am Coll Cardiol. 2012;60(15):1381-1389. [CrossRef] [PubMed]
 

Figures

Tables

References

Minville C, Hilleret M-N, Tamisier R, et al. Nonalcoholic fatty liver disease, nocturnal hypoxia, and endothelial function in patients with sleep apnea. Chest. 2014;145(3):525-533. [CrossRef] [PubMed]
 
Aron-Wisnewsky J, Minville C, Tordjman J, et al. Chronic intermittent hypoxia is a major trigger for non-alcoholic fatty liver disease in morbid obese. J Hepatol. 2012;56(1):225-233. [CrossRef] [PubMed]
 
Wang CY, Ou HY, Chen MF, Chang TC, Chang CJ. Enigmatic ectopic fat: prevalence of nonalcoholic fatty pancreas disease and its associated factors in a Chinese population. J Am Heart Assoc. 2014;3(1):e000297. [CrossRef] [PubMed]
 
Borel A-L, Leblanc X, Alméras N, et al. Sleep apnoea attenuates the effects of a lifestyle intervention programme in men with visceral obesity. Thorax. 2012;67(8):735-741. [CrossRef] [PubMed]
 
Gaborit B, Jacquier A, Kober F, et al. Effects of bariatric surgery on cardiac ectopic fat: lesser decrease in epicardial fat compared to visceral fat loss and no change in myocardial triglyceride content. J Am Coll Cardiol. 2012;60(15):1381-1389. [CrossRef] [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543