Type 2 diabetes and pre-diabetes are associated with obstructive sleep apnea in extremely obese subjects: a cross-sectional study

Jan Magnus Fredheim, Jan Rollheim, Torbjørn Omland, Dag Hofsø, Jo Røislien, Kristian Vegsgaard, Jøran Hjelmesæth, Jan Magnus Fredheim, Jan Rollheim, Torbjørn Omland, Dag Hofsø, Jo Røislien, Kristian Vegsgaard, Jøran Hjelmesæth

Abstract

Background: Obstructive sleep apnea (OSA) is a common yet underdiagnosed condition. The aim of our study is to test whether prediabetes and type 2 diabetes are associated with obstructive sleep apnea (OSA) in extremely obese (BMI ≥ 40 kg/m²) subjects.

Methods: One hundred and thirty seven consecutive extremely obese patients (99 females) from a controlled clinical trial [MOBIL-study (Morbid Obesity treatment, Bariatric surgery versus Intensive Lifestyle intervention Study) (ClinicalTrials.gov number NCT00273104)] underwent somnography with Embletta® and a 2-hour oral glucose tolerance test (OGTT). OSA was defined by an apnea-hypopnea index (AHI) ≥ 5 events/hour. Patients were categorized into three groups according to criteria from the American Diabetes Association: normal glucose tolerance, pre-diabetes and type 2 diabetes. Multiple logistic regression analysis was used to identify possible determinants of OSA.

Results: The patients had a mean (SD) age of 43 (11) years and a body mass index (BMI) of 46.9 (5.7) kg/m². Males had significantly higher AHI than females, 29 (25) vs 12 (17) events/hour, p < 0.001. OSA was observed in 81% of men and in 55% of women, p = 0.008. Twenty-nine percent of subjects had normal glucose tolerance, 42% had pre-diabetes and 29% had type 2 diabetes. Among the patients with normal glucose tolerance 33% had OSA, while 67% of the pre-diabetic patients and 78% of the type 2 diabetic patients had OSA, p < 0.001. After adjusting for age, gender, BMI, high sensitive CRP and HOMA-IR, both pre-diabetes and type 2 diabetes were still associated with OSA, odds ratios 3.18 (95% CI 1.00, 10.07), p = 0.049 and 4.17 (1.09, 15.88), p = 0.036, respectively. Mean serum leptin was significantly lower in the OSA than in the non-OSA group, while other measures of inflammation did not differ significantly between groups.

Conclusions: Type 2 diabetes and pre-diabetes are associated with OSA in extremely obese subjects.

Trial registration: MOBIL-study (Morbid Obesity treatment, Bariatric surgery versus Intensive Lifestyle intervention Study) (ClinicalTrials.gov number NCT00273104).

Figures

Figure 1
Figure 1
Flow chart of 181 patients screened for participation in the MOBIL-study. Initially three patients were excluded due to a BMI < 35 kg/m² and nine due to failed sleep registrations. Twenty nine of these patients had a BMI < 40 kg/m² and three had a missing OGTT, thereby leaving 137 extremely obese patients for inclusion in the present analysis.
Figure 2
Figure 2
Categories of morbidly obese subjects according to various levels of the apnea-hypopnea index (AHI). Dotted bars represent patients without OSA (AHI < 5 events/hour). Mild OSA is defined as AHI 5 - 15 events/hour, moderate OSA as 15 - 30 events/hour and severe OSA as > 30 events/hour.
Figure 3
Figure 3
Prevalence of OSA in 137 extremely obese subjects (101 females) according to various categories of glucose tolerance.
Figure 4
Figure 4
Prevalence of OSA in 137 extremely obese subjects (101 females) according to various categories of glucose tolerance. Females are subgrouped according to menopausal status. The mean (SD) ages of men, premenopausal- and postmenopausal women were 44 (11), 38 (8) and 57 (7) years, respectively.

References

    1. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993;328:1230–1235. doi: 10.1056/NEJM199304293281704.
    1. Young T, Finn L, Peppard PE, Szklo-Coxe M, Austin D, Nieto FJ. et al.Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort. Sleep. 2008;31:1071–1078.
    1. Punjabi NM. The epidemiology of adult obstructive sleep apnea. Proc Am Thorac Soc. 2008;5:136–143. doi: 10.1513/pats.200709-155MG.
    1. Shah N, Roux F. The relationship of obesity and obstructive sleep apnea. Clin Chest Med. 2009;30:455–65. doi: 10.1016/j.ccm.2009.05.012. vii.
    1. Caples SM, Gami AS, Somers VK. Obstructive sleep apnea. Ann Intern Med. 2005;142:187–197.
    1. Ursavas A, Ilcol YO, Nalci N, Karadag M, Ege E. Ghrelin, leptin, adiponectin, and resistin levels in sleep apnea syndrome: Role of obesity. Ann Thorac Med. 2010;5:161–165. doi: 10.4103/1817-1737.65050.
    1. Shaw JE, Punjabi NM, Wilding JP, Alberti KG, Zimmet PZ. Sleep-disordered breathing and type 2 diabetes: a report from the International Diabetes Federation Taskforce on Epidemiology and Prevention. Diabetes Res Clin Pract. 2008;81:2–12. doi: 10.1016/j.diabres.2008.04.025.
    1. Chasens ER, Weaver TE, Umlauf MG. Insulin resistance and obstructive sleep apnea: is increased sympathetic stimulation the link? Biol Res Nurs. 2003;5:87–96. doi: 10.1177/1099800403257088.
    1. Pallayova M, Steele KE, Magnuson TH, Schweitzer MA, Hill NR, Bevans-Fonti S. et al.Sleep apnea predicts distinct alterations in glucose homeostasis and biomarkers in obese adults with normal and impaired glucose metabolism. Cardiovasc Diabetol. 2010;9:83. doi: 10.1186/1475-2840-9-83.
    1. Rasche K, Keller T, Tautz B, Hader C, Hergenc G, Antosiewicz J. et al.Obstructive sleep apnea and type 2 diabetes. Eur J Med Res. 2010;15(Suppl 2):152–156.
    1. Wysocka E, Cofta S, Dziegielewska S, Gozdzik J, Torlinski L, Batura-Gabryel H. Adipocytokines in sleep apnea syndrome. Eur J Med Res. 2009;14(Suppl 4):255–258.
    1. Guest CB, Park MJ, Johnson DR, Freund GG. The implication of proinflammatory cytokines in type 2 diabetes. Front Biosci. 2008;13:5187–5194.
    1. Ahima RS, Osei SY. Adipokines in obesity. Front Horm Res. 2008;36:182–197.
    1. Tantucci C, Scionti L, Bottini P, Dottorini ML, Puxeddu E, Casucci G. et al.Influence of autonomic neuropathy of different severities on the hypercapnic drive to breathing in diabetic patients. Chest. 1997;112:145–153. doi: 10.1378/chest.112.1.145.
    1. Bottini P, Redolfi S, Dottorini ML, Tantucci C. Autonomic neuropathy increases the risk of obstructive sleep apnea in obese diabetics. Respiration. 2008;75:265–271. doi: 10.1159/000100556.
    1. Soriano-Co M, Vanhecke TE, Franklin BA, Sangal RB, Hakmeh B, McCullough PA. Increased Central Adiposity in Morbidly Obese Patients with Obstructive Sleep Apnea. Intern Med J. 2010.
    1. Balkau B, Vol S, Loko S, Andriamboavonjy T, Lantieri O, Gusto G. et al.High baseline insulin levels associated with 6-year incident observed sleep apnea. Diabetes Care. 2010;33:1044–1049. doi: 10.2337/dc09-1901.
    1. Seicean S, Kirchner HL, Gottlieb DJ, Punjabi NM, Resnick H, Sanders M. et al.Sleep-disordered breathing and impaired glucose metabolism in normal-weight and overweight/obese individuals: the Sleep Heart Health Study. Diabetes Care. 2008;31:1001–1006. doi: 10.2337/dc07-2003.
    1. Keckeis M, Lattova Z, Maurovich-Horvat E, Beitinger PA, Birkmann S, Lauer CJ. et al.Impaired glucose tolerance in sleep disorders. PLoS One. 2010;5:e9444. doi: 10.1371/journal.pone.0009444.
    1. Meslier N, Gagnadoux F, Giraud P, Person C, Ouksel H, Urban T. et al.Impaired glucose-insulin metabolism in males with obstructive sleep apnoea syndrome. Eur Respir J. 2003;22:156–160. doi: 10.1183/09031936.03.00089902.
    1. Hofso D, Nordstrand N, Johnson LK, Karlsen TI, Hager H, Jenssen T, Obesity related cardiovascular risk factors after weight loss: a clinical trial comparing gastric bypass and intensive lifestyle intervention. Eur J Endocrinol. 2010.
    1. Hofso D, Ueland T, Hager H, Jenssen T, Bollerslev J, Godang K. et al.Inflammatory mediators in morbidly obese subjects: associations with glucose abnormalities and changes after oral glucose. Eur J Endocrinol. 2009;161:451–458. doi: 10.1530/EJE-09-0421.
    1. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010;33(Suppl 1):S62–S69.
    1. Levy JC, Matthews DR, Hermans MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. 1998;21:2191–2192. doi: 10.2337/diacare.21.12.2191.
    1. Iber C, Ancoli-Israel S, Chesson A, Quan SF. The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications. 2007. for the American Academy of Sleep Medicine. Westchester, III: American Academy of Sleep Medicine; 2007. Ref Type: Report.
    1. Douglas NJ. Home diagnosis of the obstructive sleep apnoea/hypopnoea syndrome. Sleep Med Rev. 2003;7:53–59. doi: 10.1053/smrv.2001.0205.
    1. Ng SS, Chan TO, To KW, Ngai J, Tung A, Ko FW. et al.Validation of Embletta portable diagnostic system for identifying patients with suspected obstructive sleep apnoea syndrome (OSAS) Respirology. 2010;15:336–342. doi: 10.1111/j.1440-1843.2009.01697.x.
    1. Dingli K, Coleman EL, Vennelle M, Finch SP, Wraith PK, Mackay TW. et al.Evaluation of a portable device for diagnosing the sleep apnoea/hypopnoea syndrome. European Respiratory Journal. 2003;21:253–259. doi: 10.1183/09031936.03.00298103.
    1. Stepnowsky CJ Jr, Orr WC, Davidson TM. Nightly variability of sleep-disordered breathing measured over 3 nights. Otolaryngol Head Neck Surg. 2004;131:837–843. doi: 10.1016/j.otohns.2004.07.011.
    1. Ferri R, Bruni O, Miano S, Smerieri A, Spruyt K, Terzano MG. Inter-rater reliability of sleep cyclic alternating pattern (CAP) scoring and validation of a new computer-assisted CAP scoring method. Clin Neurophysiol. 2005;116:696–707. doi: 10.1016/j.clinph.2004.09.021.
    1. Norman RG, Pal I, Stewart C, Walsleben JA, Rapoport DM. Interobserver agreement among sleep scorers from different centers in a large dataset. Sleep. 2000;23:901–908.
    1. Epstein LJ, Kristo D, Strollo PJ Jr, Friedman N, Malhotra A, Patil SP. et al.Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. J Clin Sleep Med. 2009;5:263–276.
    1. American Diabetes Association. Standards of medical care in diabetes--2010. Diabetes Care. 2010;33(Suppl 1):S11–S61.
    1. Foster GD, Sanders MH, Millman R, Zammit G, Borradaile KE, Newman AB. et al.Obstructive sleep apnea among obese patients with type 2 diabetes. Diabetes Care. 2009;32:1017–1019. doi: 10.2337/dc08-1776.
    1. Elmasry A, Lindberg E, Berne C, Janson C, Gislason T, Awad TM. et al.Sleep-disordered breathing and glucose metabolism in hypertensive men: a population-based study. J Intern Med. 2001;249:153–161. doi: 10.1046/j.1365-2796.2001.00787.x.
    1. Resta O, Caratozzolo G, Pannacciulli N, Stefano A, Giliberti T, Carpagnano GE. et al.Gender, age and menopause effects on the prevalence and the characteristics of obstructive sleep apnea in obesity. Eur J Clin Invest. 2003;33:1084–1089. doi: 10.1111/j.1365-2362.2003.01278.x.
    1. Tiihonen M, Partinen M, Narvanen S. The severity of obstructive sleep apnoea is associated with insulin resistance. J Sleep Res. 1993;2:56–61. doi: 10.1111/j.1365-2869.1993.tb00062.x.
    1. Pillar G, Shehadeh N. Abdominal fat and sleep apnea: the chicken or the egg? Diabetes Care. 2008;31(Suppl 2):S303–S309.
    1. Vgontzas AN, Bixler EO, Chrousos GP. Metabolic disturbances in obesity versus sleep apnoea: the importance of visceral obesity and insulin resistance. J Intern Med. 2003;254:32–44. doi: 10.1046/j.1365-2796.2003.01177.x.
    1. Levy P, Bonsignore MR, Eckel J. Sleep, sleep-disordered breathing and metabolic consequences. Eur Respir J. 2009;34:243–260. doi: 10.1183/09031936.00166808.
    1. Sinha MK, Caro JF. Clinical aspects of leptin. Vitam Horm. 1998;54:1–30.
    1. Zirlik S, Hauck T, Fuchs FS, Neurath MF, Konturek PC, Harsch IA. Leptin, Obestatin and Apelin levels in patients with obstructive sleep apnoea syndrome. Med Sci Monit. 2011;17:CR159–CR164.
    1. Kapsimalis F, Varouchakis G, Manousaki A, Daskas S, Nikita D, Kryger M. et al.Association of sleep apnea severity and obesity with insulin resistance, C-reactive protein, and leptin levels in male patients with obstructive sleep apnea. Lung. 2008;186:209–217. doi: 10.1007/s00408-008-9082-x.
    1. Arner P. Not all fat is alike. Lancet. 1998;351:1301–1302. doi: 10.1016/S0140-6736(05)79052-8.

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