Şahin ÖĞREDEN, Hale ARAL, Özgür YİĞİT, Güvenç GÜVENEN, Berrin BERÇİK İNAL, Mustafa ŞAHİN

Metabolic profi le and insulin resistance in patients with obstructive sleep apnea syndrome

Amaç: Bu çalışmada polisomnografi ile obstruktif uyku apne sendromu (OSAS) teşhisi konmuş hastaların aşağıda belirtilen metabolik parametreleri değerlendirildi: leptin, bozulmuş açlık glukozu, tiroid fonksiyonları, tiroid otoantikorları, lipid parametreleri, insülin seviyeleri, HOMA-IR indeks, obezite, ve metabolik sendrom sıklığı. Yöntem ve gereç: Apne-hipoapne indeksi (AHI) temel alınarak 3 hasta grubu (Grup I: n: 11 Erkek (E)/ 19 Kadın (K); Grup II: n: 19 E/10 K; Grup III: n: 21 E/10 K) ve vücut kitle indeksi (BMI) değeri ve yaş karşılaştırılmasını içeren iki kontrol grubu (obez (n = 18 E/12 K) ve normal (n = 12E/18K)) tanımlandı. Bulgular: Metabolik sendrom sıklığı hafi f OSAS’dan ciddi OSAS’ a doğru artmasına rağmen hasta grupları arasında anlamlı farklılık bulunamadı. İnsülin değerleri için farklılıklar gözlendi: normal kontrol obez kontrol karşısında (P < 0,0001): normal kontrol Grup I karşısında (P = 0,014); normal kontrol Grup II karşısında (P = 0,001); normal kontrol Grup III karşısında ( P < 0,0001); Grup I Grup III karşısında (P < 0,026).Sonuç: OSAS’lı hastalarda artan metabolik sendrom sıklığı ve artan insülin direnci bulundu. Metabolik sendromlu ve insülin direnci olan hastalarda diabetes mellitus ve kardiyovasküler hastalık riski artmıştır.

Obstruktif uyku apne sendromlu hastalarda metabolik profi l ve insülin direnci

Aim: Th e following metabolic parameters were assessed in patients with obstructive sleep apnea syndrome (OSAS) diagnosed by polysomnography (PSG): leptin, IFG (ımpaired fasting glucose), thyroid functions, thyroid autoantibodies, lipid parameters, insulin levels, HOMA-IR index, CRP, obesity, and metabolic syndrome frequency. Materials and methods: Th ree patient groups were defi ned based on apnea-hypoapnea index (AHI) levels (Group I: n: 11 male (M)/19 female (F); Group II: n: 19 M/10 F; Group III: n: 21 M/10 F) and 2 control groups (obese (n = 18 M/12 F) and normal (n = 12 M/18 F)) were included with comparable BMI value and age. Results: Th e frequencies of metabolic syndrome were compared between patient groups, and no signifi cant diff erence was found, despite an increased frequency of metabolic syndrome from mild OSAS to severe OSAS. Th e following signifi cant diff erences were observed for insulin values: normal controls versus obese controls (P < 0.0001), normal controls versus Group I (P = 0.014), normal controls versus Group II (P = 0.001), normal controls versus Group III (P < 0.0001), and Group I versus Group III (P = 0.026). Conclusion: An increased frequency of metabolic syndrome and insulin resistance was found in OSAS patients. OSAS patients with metabolic syndrome and insulin resistance are at an increased risk of diabetes mellitus and cardiovascular diseases.

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1. Guilleminault C, Tilkian A, Dement WC. Th e sleep apnea syndromes. Ann Rev Med 1976; 27: 465-484.
2. Guilleminault C, van den Hoed J, Mitler MM. Clinical overview of the sleep apnea syndromes. New York: Alan R Liss 1978; 1-12.
3. Kales A, Caldwell A, Cadieux R, Vela-Bueno A, Ruch L, Mayers S. Severe obstructive sleep apnea-II: Associated psychopathology and psychosocial consequences. J Chron Dis 1985; 38: 427-434.
4. Köktürk O. Uykunun izlenmesi. Normal uyku. Tüberküloz ve Toraks 1999; 47: 372-380.
5. Lin CC, Tsan KW, Chen PJ. Th e relationship between sleep apnea syndrome and hypothyroidism. Chest 1992; 102: 1663-7.
6. Popovici I, Khawaja I. Effi cacy of thyroid function tests in patients suspected of having obstructive sleep apnea. Chest 1997; 112: 149S.
7. Winkelman JW, Goldman H, Piscatelli N, Lukas S, Dorsey CM, Cunningham S. Are thyroid function tests necessary in patients with suspected sleep apnea? Sleep 1996; 19: 790-3.
8. Skjodt NM, Atkar R, Easton PA. Screening for hypothyroidism in sleep apnea. Am J Respir Crit Care Med 1999; 160: 732.5
9. Wolk R, Shamsuzzaman ASM, Somers VK. Obesity, Sleep Apnea and Hypertension. Hypertension 2003; 42; 1067-1074
10. Koskenvuo M, Kaprio J, Partinen M, Langinvainio H, Sarna S, Heikkila K. Snoring as a risk factor for hypertension and angina pectoris. Lancet 1985; 1: 893-6.
11. Baguet JP, Narkiewicz K, Mallion JM. Update on Hypertension Management: obstructive sleep apnea and hypertension. J Hypertens 2006; 24: 205-8.
12. Wolk R, Shamsuzzaman ASM, Somers VK. Obesity, Sleep Apnea and Hypertension. Hypertension 2003; 42; 1067-1074.
13. Ridker PM, Rifai N, Stampfer MJ, Hennekens CH, Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 2000;101: 1767-72.
14. Yokoe T, Minoguchi K, Matsuo H, Oda N, Minoguchi H, Yoshino G et al. Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreased by nasal continuous positive airway pressure. Circulation 2003; 107: 1129-34.
15. Guilleminault C, Kirisoglu C, Ohayon MM. C-reactive protein and sleep-disordered breathing. Sleep 2004; 27: 1507-11.
16. Shamsuzzaman AS, Winnicki M, Lanfranchi P, Wolk R, Kara T, Accurso V et al. Elevated C-reactive protein in patients with obstructive sleep apnea. Circulation 2002; 105: 2462-2464.
17. Reichmuth KJ, Austin D, Skatrud JB, Young T. Association of sleep apnea and type II diabetes: a population-based study. Am J Respir Crit Care Med 2005; 172: 1590-5.
18. 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.
19. Coughlin SR, Mawdsley L, Mugarza JA, Calverley PM, Wilding JP. Obstructive sleep apnoea is independently associated with an increased prevalence of metabolic syndrome. Eur Heart J 2004; 25: 735-741.
20. Parish JM, Adam T, Facchiano L. Relationship of metabolic syndrome and obstructive sleep apnea. J Clin Sleep Med 2007;3: 467-472.
21. Tkacova R, Dorkova Z, Molcanyiova A, Radikova Z, Klimes I, Tkac I: Cardiovascular risk and insulin resistance in patients with obstructive sleep apnea. Med Sci 2008; 14: 438-444.
22. Ip MS, Lam B, Ng MMT, Lam WK, Tsang KWT, Lam KSL. Obstructive sleep apnea is independently associated with insulin resistance. Am J Respir Crit Care Med 2002; 165: 670-676.
23. Vgontzas AN, Papanicolaou DA, Bixler EO, Hopper K, Lotsikas A, Lin HM et al. Sleep apnea and daytime sleepiness and fatigue: relation to visceral obesity, insulin resistance, and hypercytokinemia. J Clin Endocrinol Metab 2000; 85: 1151-8.
24. Brooks B, Cistulli PA, Borkman M, Ross G, McGhee S, Grunstein RR et al. Obstructive sleep apnea in obese noninsulin-dependent diabetic patients: eff ect of continuous positive airway pressure treatment on insulin responsiveness. J Clin Endocrinol Metab 1994; 79: 1681-1685.
25. Smurra M, Phillip P, Taillard J, Guilleminault C, Bioulac B, Gin H. CPAP treatment does not aff ect glucose-insulin metabolism in sleep apneic patients. Sleep Med 2001; 2: 207-213.
26. Dursun N. Leptinin kardiyovasküler etkileri. Erciyes Tıp Dergisi (Erciyes Medical Journal) 2005; 27: 167-176.
27. Hekimoğlu A. Leptin ve Fizyopatolojik Olaylardaki Rolü. Dicle Tıp Dergisi 2006; 33: 259-267.
28. Harsch IA, Hahn EG, Konturek PC. Insulin resistance and other metabolic aspects of the obstructive sleep apnea syndrome. Med Sci Monit 2005; 11: 70-75.
29. Popko K, Gorska E, Wasik M, Stoklosa A, Plywaczewski R, Winiarska M et al. Frequency of Distribution of leptin receptor gene polymorphism in obstructive sleep apnea patients Jour. of Physiology and Pharmacology 2007; 58: 551-561.
30. Sanner BM, Kollhosser P, Buechner N, Zidek W, Tepel M. Infl uence of treatment on leptin levels in patients with obstructive sleep apnea. Eur Respir J 2004; 23: 601-604.
31. 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.
32. Chin K, Shimizu K, Nakamura T, Narai N, Masuzaki H, Ogawa Y et al. Changes in intra-abdominal visceral fat and serum leptin levels in patients with obstructive sleep apnea syndrome following nasal continuous positive airway pressure therapy. Circulation 1999; 100: 706-712.