Purpose of Review
Obstructive sleep apnea (OSA), obesity, and disturbed glucose homeostasis are usually considered distinct clinical condition, although they are tightly related to each other. The aim of our manuscript is to provide an overview of the current evidence on OSA, obesity, and disturbed glucose homeostasis providing epidemiologic evidence, biological insights, and therapeutic strategies.
The mechanisms hypothesized to be involved in this complex interplay are the following: (1) “direct weight-dependent” mechanisms, according to which fat excess compromises respiratory mechanics, and (2) “indirect weight-dependent” mechanisms such as hyperglycemia, insulin resistance and secondary hyperinsulinemia, leptin resistance and other hormonal dysregulations frequently found in subjects with obesity, type 2 diabetes, and/or sleep disorders. Moreover, the treatment of each of these clinical conditions, through weight loss induced by diet or bariatric surgery, the use of anti-obesity or antidiabetic drugs, and continuous positive airway pressure (CPAP), seems to positively influence the others.
These recent data suggest not only that there are multiple connections among these diseases but also that treating one of them may result in an improvement of the others.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Eckert DJ, White DP, Jordan AS, Malhotra A, Wellman A. Defining phenotypic causes of obstructive sleep apnea. Identification of novel therapeutic targets. Am J Respir Crit Care Med. 2013;188:996–1004.
American Academy of Sleep Medicine. International classification of sleep disorders: diagnostic and coding manual. 3rd ed. Darien: American Academy of Sleep Medicine; 2014.
Jordan AS, McSharry DG, Malhotra A. Adult obstructive sleep apnoea. Lancet. 2014;383:736–47. https://doi.org/10.1016/S0140-6736(13)60734-5.
Friedman M, Ibrahim H, Joseph NJ. Staging of obstructive sleep apnea/hypopnea syndrome: a guide to appropriate treatment. Laryngoscope. 2004;114:454–9. https://doi.org/10.1097/00005537-200403000-00013.
Kim AM, Keenan BT, Jackson N, Chan EL, Staley B, Poptani H, et al. Tongue fat and its relationship to obstructive sleep apnea. Sleep. 2014;37:1639–48. https://doi.org/10.5665/sleep.4072.
Punjabi NM. The epidemiology of adult obstructive sleep apnea. Proc Am Thorac Soc. 2008;5:136–43. https://doi.org/10.1513/pats.200709-155MG.
Pamidi S, Wroblewski K, Broussard J, Day A, Hanlon EC, Abraham V, et al. Obstructive sleep apnea in young lean men: impact on insulin sensitivity and secretion. Diabetes Care. 2012;35:2384–9. https://doi.org/10.2337/dc12-0841.
Kallianos A, Trakada G, Papaioannou T, Nikolopouloss I, Mitrakou A, Manios E, et al. Glucose and arterial blood pressure variability in obstructive sleep apnea syndrome. Eur Rev Med Pharmacol Sci. 2013;17:1932–7.
•• Nakata K, Miki T, Tanno M, Ohnishi H, Yano T, Muranaka A, et al. Distinct impacts of sleep-disordered breathing on glycemic variability in patients with and without diabetes mellitus. PLoS ONE. 2017;12:e0188689. https://doi.org/10.1371/journal.pone.0188689Severity of sleep Disorders Breathing was associated with higher Glicemic Variability.
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;328:1230–5.
Narkiewicz K, Somers VK. Sympathetic nerve activity in obstructive sleep apnoea. Acta Physiol Scand. 2003;177:385–90.
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;31:1071–8. https://doi.org/10.5665/sleep/31.8.1071.
Lopez PP, Stefan B, Schulman CI, Byers PM. Prevalence of sleep apnea in morbidly obese patients who presented for weight loss surgery evaluation: more evidence for routine screening for obstructive sleep apnea before weight loss surgery. Am Surg. 2008;74:834–8.
Elmasry A, Lindberg E, Berne C, Janson C, Gislason T, Awad Tageldin M, et al. Sleep-disordered breathing and glucose metabolism in hypertensive men: a population-based study. J Intern Med. 2001;249(2):153–61.
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;32:1017–9.
• Manin G, Pons A, Baltzinger P, Moreau F, Iamandi C, Wilhelm JM, et al. Obstructive sleep apnoea in people with type 1 diabetes: prevalence and association with micro- and macrovascular complications. Diabet Med. 2015;32:90–6 The prevalence of moderate to severe OSA was 46.3% in long-standing T1DM.
Borel AL, Benhamou PY, Baguet JP, Halimi S, Levy P, Mallion JM, et al. High prevalence of obstructive sleep apnoea syndrome in a type 1 diabetic adult population: a pilot study. Diabet Med. 2010;27:1328–9.
Vgontzas AN, Kales A. Sleep and its disorders. Ann Rev Med. 1999;50:387–400.
Davies RJ, Ali NJ, Stradling JR. Neck circumference and other clinical features in the diagnosis of the obstructive sleep apnoea syndrome. Thorax. 1992;47:101–5.
Altan O, Gulay H, Husniye Y, Gunay C, Erkan A, Zekeriya K, et al. Neck circumference as a measure of central obesity: associations with metabolic syndrome and obstructive sleep apnea syndrome beyond waist circumference. Clin Nutr. 2009;28:46–51.
Cizza G, de Jonge L, Piaggi P, Mattingly M, Zhao X, Lucassen E, et al. Neck circumference is a predictor of metabolic syndrome and obstructive sleep apnea in short-sleeping obese men and women. Metab Syndr Relat Disord. 2014 May;12(4):231–41.
Ford MD. MPH risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome. Diabetes Care. 2005;28(7):1769–78.
Shelton KE, Woodson H, Gay S, Suratt PM. Pharyngeal fat in obstructive sleep apnea. Am Rev Respir Dis. 1993;148:462–6. https://doi.org/10.1164/ajrccm/148.2.462.
Salome CM, King GG, Berend N. Physiology of obesity and effects on lung function. J Appl Physiol (1985). 2010;108:206–11. https://doi.org/10.1152/japplphysiol.00694.2009.
Mortimore IL, Marshall I, Wraith PK, Sellar RJ, Douglas NJ. Neck and total body fat deposition in nonobese and obese patients with sleep apnea compared with that in control subjects. Am J Respir Crit Care Med. 1998;157:280–3.
• Appleton SL, Vakulin A, Wittert GA, Martin SA, Grant JF, Taylor AW. The association of obstructive sleep apnea (OSA) and nocturnal hypoxemia with the development of abnormal HbA1c in a population cohort of men without diabetes. Diabetes Res Clin Pract. 2016;114:151–9. https://doi.org/10.1016/j.diabres.2015.12.007Development of abnormal glycaemic metabolism was associated with nocturnal hypoxemia. Improved management of OSA and glycaemic control may occur if patients presenting with one abnormality are assessed for the other.
• Appleton SL, Vakulin A, McEvoy RD, Wittert GA, Martin SA, Grant JF, et al. Nocturnal hypoxemia and severe obstructive sleep apnea are associated with incident type 2 diabetes in a population cohort of men. J Clin Sleep Med. 2015;11:609–14. https://doi.org/10.5664/jcsm.4768Severe undiagnosed OSA and nocturnal hypoxemia were independently associated with the development of diabetes.
• Torrella M, Castells I, Gimenez-Perez G, Recasens A, Miquel M, Simo O, et al. Intermittent hypoxia is an independent marker of poorer glycaemic control in patients with uncontrolled type 2 diabetes. Diabetes Metab. 2015;41:312–8. https://doi.org/10.1016/j.diabet.2015.01.002Intermittent hypoxia, a consequence of sleep apnoea, is frequent and has a strong independent association with poorer glycaemic control in patients with uncontrolled T2D.
Mondini S, Guilleminault C. Abnormal breathing patterns during sleep in diabetes. Ann Neurol. 1985;17:391–5.
Gao L, Ortega-Saenz P, Garcia-Fernandez M, Gonzalez-Rodriguez P, Caballero-Eraso C, Lopez-Barneo J. Glucose sensing by carotid body glomus cells: potential implications in disease. Front Physiol. 2014;5:398. https://doi.org/10.3389/fphys.2014.00398.
Alvarez-Buylla R, de Alvarez-Buylla ER. Carotid sinus receptors participate in glucose homeostasis. Respir Physiol. 1988;72:347–59.
Kline DD, Peng YJ, Manalo DJ, Semenza GL, Prabhakar NR. Defective carotid body function and impaired ventilatory responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1 alpha. Proc Natl Acad Sci U S A. 2002;99:821–6.
Kadoglou NP, Avgerinos ED, Liapis CD. An update on markers of carotid atherosclerosis in patients with type 2 diabetes. Biomark Med. 2010;4:601–9.
Bottini P, Redolfi S, Dottorini ML, Tantucci C. Autonomic neuropathy increases the risk of obstructive sleep apnea in obese diabetics. Respiration. 2008;75:265–71.
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):152–6.
Bottini P, Dottorini ML, Cristina Cordoni M, Casucci G, Tantucci C. Sleep-disordered breathing in nonobese diabetic subjects with autonomic neuropathy. Eur Respir J. 2003;22:654–60.
Ficker JH, Dertinger SH, Siegfried W, Konig HJ, Pentz M, Sailer D, et al. Obstructive sleep apnoea and diabetes mellitus: the role of cardiovascular autonomic neuropathy. Eur Respir J. 1998;11:14–9.
•• Ryan S. Adipose tissue inflammation by intermittent hypoxia: mechanistic link between obstructive sleep apnoea and metabolic dysfunction. J Physiol. 2017;595:2423–30 IH leads to pancreatic β-cell dysfunction and insulin resistance in insulin target organs, skeletal muscle, and adipose tissue.
Polak J, Shimoda LA, Drager LF, Undem C, McHugh H, Polotsky VY, et al. Intermittent hypoxia impairs glucose homeostasis in C57BL6/J mice: partial improvement with cessation of the exposure. Sleep. 2013;36:1483–90; 1490A−1490B. https://doi.org/10.5665/sleep.3040.
Narkiewicz K, van de Borne PJ, Montano N, Dyken ME, Phillips BG, Somers VK. Contribution of tonic chemoreflex activation to sympathetic activity and blood pressure in patients with obstructive sleep apnea. Circulation. 1998;97:943–5.
Andrews RC, Walker BR. Glucocorticoids and insulin resistance: old hormones, new targets. Clin Sci (Lond). 1999;96:513–23.
Coste O, Beers PV, Bogdan A, Charbuy H, Touitou Y. Hypoxic alterations of cortisol circadian rhythm in man after simulation of a long duration weight. Steroids. 2005;70:803–10.
•• Lee EJ, Heo W, Kim JY, Kim H, Kang MJ, Kim BR, et al. Alteration of infiammatory mediators in the upper and lower airways under chronic intermittent hypoxia: preliminary animal study. Mediators Inflamm. 2017;2017:4327237 Chronic intermittent hypoxia for 4 weeks altered the levels of inflammatory mediators in both the nose and lungs of mouse model.
Wieser V, Moschen AR, Tilg H. Inflammation, cytokines and insulin resistance: a clinical perspective. Arch Immunol er Exp (Warsz). 2013;61:119–25.
• Brusik M, Strbova Z, Petrasova D, Pobeha P, Kuklisova Z, Tkacova R, et al. Increased resting energy expenditure and insulin resistance in male patients with moderate-to severe obstructive sleep apnoea. Physiol Res. 2016;65:969–77 Male patients with moderate-to severe OSA have increased REE paralleled by impaired insulin sensitivity.
• Araujo Lda S, Fernandes JF, Klein MR, Sanjuliani AF. Obstructive sleep apnea is independently associated with inflammation and insulin resistance, but not with blood pressure, plasma catecholamines, and endothelial function in obese subjects. Nutrition. 2015;31:1351–7. https://doi.org/10.1016/j.nut.2015.05.017In obese individuals OSA is independently associated with inflammation and insulin resistance.
Lam JC, Lam B, Yao TJ, Lai AY, Ooi CG, Tam S, et al. A randomized controlled trial of nasal continuous positive airway pressure on insulin sensitivity in obstructive sleep apnoea. Eur Respir J. 2010;35:138–45.
West SD, Nicoll DJ, Wallace TM, Matthews DR, Stradling JR. Effect of CPAP on insulin resistance and HbA1c in men with obstructive sleep apnoea and type 2 diabetes. Orax. 2007;62:969–74.
Kohler M, Stoewhas AC, Ayers L, Senn O, Bloch KE, Russi EW, et al. Effects of continuous positive airway pressure therapy withdrawal in patients with obstructive sleep apnea: a randomized controlled trial. Am J Respir Crit Care Med. 2011;184:1192–9.
Hoyos CM, Killick R, Yee BJ, Phillips CL, Grunstein RR, Liu PY. Cardiometabolic changes after continuous positive airway pressure for obstructive sleep apnoea: a randomised sham-controlled study. Orax. 2012;67:1081–9.
Hein MS, Schlenker EH, Patel KP. Altered control of ventilation in streptozotocin-induced diabetic rats. Proc Soc Exp Biol Med. 1994;207:213–9. https://doi.org/10.3181/00379727-207-43809.
Ramadan W, Petitjean M, Loos N, Geloen A, Vardon G, Delanaud S. Effect of high-fat diet and metformin treatment on ventilation and sleep apnea in non-obese rats. Respir Physiol Neurobiol. 2006;150:52–65. https://doi.org/10.1016/j.resp.2005.02.011.
Chalacheva P, Thum J, Yokoe T, O’Donnell CP, Khoo MC. Development of autonomic dysfunction with intermittent hypoxia in a lean murine model. Respir Physiol Neurobiol. 2013;188:143–51. https://doi.org/10.1016/j.resp.2013.06.002.
Jun JC, Shin MK, Devera R, Yao Q, Mesarwi O, Bevans-Fonti S, et al. Intermittent hypoxia-induced glucose intolerance is abolished by alphaadrenergic blockade or adrenal medullectomy. Am J Physiol Endocrinol Metab. 2014;307:E1073–83. https://doi.org/10.1152/ajpendo.00373.2014.
Somers VK, Dyken ME, Clary MP, Abboud FM. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest. 1995;96:1897–904. https://doi.org/10.1172/JCI118235.
Delarue J, Magnan C. Free fatty acids and insulin resistance. Curr Opin Clin Nutr Metab Care. 2007;10:142–8. https://doi.org/10.1097/MCO.0b013e328042ba90.
• Weiszenstein M, Shimoda LA, Koc M, Seda O, Polak J. Inhibition of lipolysis ameliorates diabetic phenotype in a mouse model of obstructive sleep apnea. Am J Respir Cell Mol Biol. 2016;55:299–307. https://doi.org/10.1165/rcmb.2015-0315OCAugmented lipolysis contributes to insulin resistance and glucose intolerance observed in mice exposed to IH. Acipimox treatment ameliorated the metabolic consequences of IH and might represent a novel treatment option for patients with obstructive sleep apnea.
Sherwani SI, Aldana C, Usmani S, Adin C, Kotha S, Khan M, et al. Intermittent hypoxia exacerbates pancreatic beta-cell dysfunction in a mouse model of diabetes mellitus. Sleep. 2013;36:1849–58. https://doi.org/10.5665/sleep.3214.
Manzella D, Parillo M, Razzino T, Gnasso P, Buonanno S, Gargiulo A, et al. Soluble leptin receptor and insulin resistance as determinant of sleep apnea. Int J Obes Relat Metab Disord. 2002;26:370–5. https://doi.org/10.1038/sj.ijo.0801939.
Ip MS, Lam KS, Ho C, Tsang KW, Lam W. Serum leptin and vascular risk factors in obstructive sleep apnea. Chest. 2000;118:580–6. https://doi.org/10.1378/chest.118.3.580.
Polotsky M, Elsayed-Ahmed AS, Pichard L, Harris CC, Smith PL, Schneider H, et al. Effects of leptin and obesity on the upper airway function. J Appl Physiol. 2012;112:1637–43. https://doi.org/10.1152/japplphysiol.01222.2011.
O’Donnell CP, Schaub CD, Haines AS, Berkowitz DE, Tankersley CG, Schwartz AR, et al. Leptin prevents respiratory depression in obesity. Am J Respir Crit Care Med. 1999;159:1477–84. https://doi.org/10.1164/ajrccm.159.5.9809025.
Lo Re V III, Schutte-Rodin S, Kostman JR. Obstructive sleep apnoea among HIV patients. Int J STD AIDS. 2006;17:614–20. https://doi.org/10.1258/095646206778113078.
Correia ML, Rahmouni K. Role of leptin in the cardiovascular and endocrine complications of metabolic syndrome. Diabetes Obes Metab. 2006;8:603–10. https://doi.org/10.1111/j.1463-1326.2005.00562.
• Pierce AM, Brown LK. Obesity hypoventilation syndrome: current theories of pathogenesis. Curr Opin Pulm Med. 2015;21:557–62. https://doi.org/10.1097/MCP.0000000000000210Leptin resistance in obesity and OHS likely contributes to blunting of ventilatory drive and inadequate chemoreceptor response to hypercarbia and hypoxemia.
Huang W, Ramsey KM, Marcheva B, Bass J. Circadian rhythms, sleep, and metabolism. J Clin Invest. 2011;121:2133–41.
•• Reutrakul S, Siwasaranond N, Nimitphong H, Saetung S, Chirakalwasan N, Chailurkit LO, et al. Associations between nocturnal urinary 6-sulfatoxymelatonin, obstructive sleep apnea severity and glycemic control in type 2 diabetes. Chronobiol Int. 2017;34:382–92 The presence and severity of obstructive sleep apnea as well as the presence of diabetic retinopathy were associated with lower nocturnal melatonin secretion, with an indirect adverse effect on glycemic control.
Peschke E, Muhlbauer E. New evidence for a role of melatonin in glucose regulation. Best Pract Res Clin Endocrinol Metab. 2010;24:829–41.
McMullan CJ, Schernhammer ES, Rimm EB, Hu FB, Forman JP. Melatonin secretion and the incidence of type 2 diabetes. JAMA. 2013;309:1388–96.
Peschke E, Frese T, Chankiewitz E, Peschke D, Preiss U, Schneyer U, et al. Diabetic Goto Kakizaki rats as well as type 2 diabetic patients show a decreased diurnal serum melatonin level and an increased pancreatic melatonin-receptor status. J Pineal Res. 2006;40:135–43.
Anandam A, Akinnusi M, Kufel T, Porhomayon J, El-Solh AA. Effects of dietary weight loss on obstructive sleep apnea: a meta-analysis. Sleep Breath. 2013;17:227–34. https://doi.org/10.1007/s11325-012-0677-3.
Foster GD, Borradaile KE, Sanders MH, Millman R, Zammit G, Newman AB, et al. A randomized study on the effect of weight loss on obstructive sleep apnea amongobese patients with type 2 diabetes: the Sleep AHEAD study. Arch Intern Med. 2009;169:1619–26. https://doi.org/10.1001/archinternmed.2009.266.
Kuna ST, Reboussin DM, Borradaile KE, Sanders MH, Millman RP, Zammit G, et al. Long-term effect of weight loss on obstructive sleep apnea severity in obese patients with type 2 diabetes. Sleep. 2013;36(5):641–649A. https://doi.org/10.5665/sleep.2618.
Beglinger C, Degen L. Gastrointestinal satiety signals in humans—physiologic roles for GLP-1 and PYY ? Physiol Behav. 2007;89(4):460–4.
• Blackman A, Foster GD, Zammit G, Rosenberg R, Aronne L, Wadden T, et al. Effect of liraglutide 3.0 mg in individuals with obesity and moderate or severe obstructive sleep apnea: the SCALE Sleep Apnea randomized clinical trial. Int J Obes (Lond). 2016;40(8):1310–9. https://doi.org/10.1038/ijo.2016.52As an adjunct to diet and exercise, liraglutide 3.0 mg was generally well tolerated and produced significantly greater reductions than placebo in AHI, body weight, SBP and HbA1c in participants with obesity and moderate/severe OSA.
Varela JE, Hinojosa MW, Nguyen NT. Resolution of obstructive sleep apnea after laparoscopic gastric bypass. Obes Surg. 2007;17:1279–82. https://doi.org/10.1007/s11695-007-9228-6.
• Arble DM, Sandoval DA, Seeley RJ. Mechanisms underlying weight loss and metabolic improvements in rodent models of bariatric surgery. Diabetologia. 2015;58:211–20. https://doi.org/10.1007/s00125-014-3433-3Bariatric surgery is the most successful treatment for significant weight loss, resolution of type 2 diabetes and the prevention of future weight gain.
Sarkhosh K, Switzer NJ, El-Hadi M, Birch DW, Shi X, Karmali S. The impact of bariatric surgery on obstructive sleep apnea: a systematic review. Obes Surg. 2013;23(3):414–23. https://doi.org/10.1007/s11695-012-0862-2.
Sandoval D. Bariatric surgeries: beyond restriction and malabsorption. Int J Obes (Lond). 2011;35:S45–9. https://doi.org/10.1038/ijo.2011.148.
Hutter MM, Schirmer BD, Jones DB, Ko CY, Cohen ME, Merkow RP, et al. First report from the American College of Surgeons Bariatric Surgery Center Network: laparoscopic sleeve gastrectomy has morbidity and effectiveness positioned between the band and the bypass. Ann Surg. 2011;254:410–20; discussion 420–2. https://doi.org/10.1097/SLA.0b013e31822c9dac.
Carlin AM, Zeni TM, English WJ, Hawasli AA, Genaw JA, Krause KR, et al. The comparative effectiveness of sleeve gastrectomy, gastric bypass, and adjustable gastric banding procedures for the treatment of morbid obesity. Ann Surg. 2013;257:791–7. https://doi.org/10.1097/SLA.0b013e3182879ded.
Dixon JB, Schachter LM, O’Brien PE, Jones K, Grima M, Lambert G, et al. Surgical vs conventional therapy for weight loss treatment of obstructive sleep apnea: a randomized controlled trial. JAMA. 2012;308:1142–9. https://doi.org/10.1001/2012.jama.11580.
Pallayova M, Steele KE, Magnuson TH, Schweitzer MA, Smith PL, Patil SP, et al. Sleep apnea determines soluble TNF-α receptor 2 response to massive weight loss. Obes Surg. 2011;21(9):1413–23. https://doi.org/10.1007/s11695-011-0359-4.
• Shaw JE, Punjabi NM, Naughton MT, Willes L, Bergenstal RM, Cistulli PA, et al. The effect of treatment of obstructive sleep apnea on glycemic control in type 2 diabetes. Am J Respir Crit Care Med. 2016;194:486–92 This trial showed no effect of positive airway pressure therapy on glycemic control in patients with relatively well-controlled type 2 diabetes and obstructive sleep apnea.
Sivam S, Phillips CL, Trenell MI, Yee BJ, Liu PY, Wong KK, et al. Effects of 8 weeks of continuous positive airway pressure on abdominal adiposity in obstructive sleep apnoea. Eur Respir J. 2012;40:913–8.
Hecht L, Mohler R, Meyer G. Effects of CPAP-respiration on markers of glucose metabolism in patients with obstructive sleep apnoea syndrome: a systematic review and meta-analysis. Ger Med Sci. 2011;9:Doc20.
•• Chen L, Kuang J, Pei JH, Chen HM, Chen Z, Li ZW, et al. Continuous positive airway pressure and diabetes risk in sleep apnea patients: a systemic review and meta-analysis. Eur J Intern Med. 2017;39:39–50. https://doi.org/10.1016/j.ejim.2016.11.010These findings support the use of CPAP in non-diabetic and pre-diabetic patients with OSA to reduce change of HOMA-IR and possibly reduce the risk of developing type 2 diabetes in this patient population.
Ramadan W, Dewasmes G, Petitjean M, Wiernsperger N, Delanaud S, Geloen A, et al. Sleep apnea is induced by a high-fat diet and reversed and prevented by metformin in non-obese rats. Obesity (Silver Spring). 2007;15:1409–18. https://doi.org/10.1038/oby.2007.169.
El-Sharkawy AA, Abdelmotaleb GS, Aly MK, Kabel AM. Effect of metformin on sleep disorders in adolescent girls with polycystic ovarian syndrome. J Pediatr Adolesc Gynecol. 2014;27(6):347–52. https://doi.org/10.1016/j.jpag.2014.01.004.
•• Furukawa S, Miyake T, Senba H, Sakai T, Furukawa E, Yamamoto S, et al. The effectiveness of dapagliflozin for sleep-disordered breathing among Japanese patients with obesity and type 2 diabetes mellitus. Endocr J. 2018;65(9):953–61. https://doi.org/10.1507/endocrj.EJ17-0545Dapagliflozin might improve moderate to severe SDB but not mild SDB in Japanese patients with obesity and type 2 diabetes mellitus.
•• Sawada K, Karashima S, Kometani M, Oka R, Takeda Y, Sawamura T, et al. Effect of sodium glucose cotransporter 2 inhibitors on obstructive sleep apnea in patients with type 2 diabetes. Endocr J. 2018;65(4):461–7 SGLT2i reduced not only HbA1c, BW and BMI but also AHI significantly and therefore has potential as an effective treatment of OSAS.
Bertuglia S, Reiter RJ. Melatonin reduces microvascular damage and insulin resistance in hamsters due to chronic intermittent hypoxia. J Pineal Res. 2009;46:307–13.
Hernandez C, Abreu J, Abreu P, Castro A, Jimenez A. Nocturnal melatonin plasma levels in patients with OSAS: the effect of CPAP. Eur Respir J. 2007;30:496–500.
• Tuomi T, Nagorny CLF, Singh P, Bennet H, Yu Q, Alenkvist I, et al. Increased melatonin signaling is a risk factor for type 2 diabetes. Cell Metab. 2016;23:1067–77 An enhanced melatonin signaling in islets reduces insulin secretion, leading to hyperglycemia and greater future risk of T2D. The findings also imply that melatonin physiologically serves to inhibit nocturnal insulin release.
Conflict of Interest
The authors declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the Topical Collection on Metabolism
About this article
Cite this article
Pugliese, G., Barrea, L., Laudisio, D. et al. Sleep Apnea, Obesity, and Disturbed Glucose Homeostasis: Epidemiologic Evidence, Biologic Insights, and Therapeutic Strategies. Curr Obes Rep (2020). https://doi.org/10.1007/s13679-020-00369-y
- Obstructive sleep apnea
- Type 2 diabetes mellitus
- Metabolic syndrome