睡眠呼吸暂停与糖尿病之间的联系
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Quick answer: obstructive sleep apnea and type 2 diabetes are bidirectionally linked. Studies in the American Journal of Respiratory and Critical Care Medicine and Diabetes Care show OSA prevalence of 60-80 percent in patients with type 2 diabetes, and conversely a meta-analysis in Sleep Medicine Reviews found patients with severe untreated OSA have roughly twice the risk of developing type 2 diabetes compared to non-OSA controls after adjusting for weight and age. The mechanism involves intermittent nocturnal hypoxia, sympathetic activation, and disrupted sleep architecture, all of which are associated with increased insulin resistance and impaired glucose metabolism. Treating OSA with CPAP may modestly improve insulin sensitivity and HbA1c in some patients, though weight loss has a larger effect (American Diabetes Association Standards of Care). The American Academy of Sleep Medicine recommends OSA screening in patients with type 2 diabetes plus BMI over 30.
The American Diabetes Association estimates that nearly 30 million Americans live with diabetes.
Even more concerning, diabetes is the 7th leading cause of death in the U.S. The condition can be caused by an autoimmune problem, where the body attacks the cells in the pancreas that produce insulin to keep blood sugar levels in check. This is known as type 1 diabetes. Or, the condition can be type 2 diabetes which arises from insulin resistance--where the body doesn’t respond to insulin and blood sugar remains at abnormal levels. Type 2 diabetes is more common and is not an autoimmune disease but rather a “lifestyle disease” once known as adult-onset or noninsulin-dependent diabetes. There is no cure for type 2 diabetes, but it can be managed and prevented.
2 型糖尿病通常与肥胖、高血压和心脏病有关，但最近的研究发现，睡眠呼吸暂停也与此有关。.
Sleep apnea is more than just an issue with sleep quality. Sleep apnea is the interruption of breathing, typically caused when tissue in the back of the throat collapses into the airway, blocking the breath, and is associated with a host of health issues. Experts have grown certain that the disorder increases cardiovascular (heart) risk, for example. There's also mounting evidence that sleep apnea may contribute to problems like insulin resistance, glucose intolerance and type 2 diabetes.
“If you have hypertension (high blood pressure), you’re more likely to have obstructive sleep apnea; and if you have sleep apnea, you are more likely to have hypertension,"says Said Mostafavi, M.D., the Chief Medical Officer for Advanced Sleep Medicine Services, Inc. and a sleep specialist. "In the same way, if you have diabetes, you’re more likely to have sleep apnea; and if you have sleep apnea you’re more likely to have diabetes. So even though we don’t understand all the mechanisms, we know there is a connection between diabetes and sleep apnea. Incidence of OSA in patients with diabetes is higher than the general population regardless of BMI. Prevalence of OSA is 71% in patients with type 2 diabetes. This is significantly greater than the general population at 4-10%."
睡眠呼吸暂停和糖尿病相关
研究表明，约71%的糖尿病患者可能患有睡眠呼吸暂停。睡眠呼吸暂停与糖尿病之间存在关联或许会让公众感到惊讶，但医生和科学家已经注意到一些相关的模式。.
“过去五到十年间发表的多项研究表明，睡眠呼吸暂停与糖尿病，尤其是2型糖尿病之间存在密切联系，”昂热大学医学教授、睡眠呼吸障碍专科医生弗雷德里克·加尼亚杜克斯（Frédéric Gagnadoux）说道。 2012年的一项综述对这两种疾病之间的关联证据进行了分析，根据五项研究（共涉及1200名患者）的平均结果估计，约71%的2型糖尿病患者可能患有睡眠呼吸暂停¹。
这种联系也存在于反向。2014 年的一项研究调查了参与欧洲睡眠呼吸暂停队列研究的 6616 名受试者，并分析了同时患有睡眠呼吸暂停和 2 型糖尿病的人数。结果显示，即使研究人员考虑了肥胖等其他风险因素，重度睡眠呼吸暂停患者中仍有 28.9% 患有糖尿病。换句话说，近三分之一的重度睡眠呼吸暂停患者同时患有 2 型糖尿病。.
研究人员还发现，睡眠呼吸暂停症状更严重的人更容易患上2型糖尿病：糖尿病的患病率随睡眠呼吸暂停的严重程度而变化。该研究的结论是：“阻塞性睡眠呼吸暂停（OSA）严重程度的增加与同时患有2型糖尿病（T2DM）的可能性增加以及2型糖尿病患者血糖控制不佳相关。”.
根据阻塞性睡眠呼吸暂停（OSA）严重程度分层的糖尿病患者调整后的平均HbA1c水平
This evidence has pushed the American Academy of Sleep Medicine to advise that anyone with type 2 diabetes should get a test for sleep apnea.
睡眠呼吸暂停会导致低氧血症和睡眠断断续续，这可能导致糖尿病。
尽管有证据表明糖尿病和睡眠呼吸暂停之间存在密切联系，但研究人员仍然不知道睡眠呼吸暂停究竟是如何导致糖尿病的，也不知道是否存在其他潜在疾病会导致这两种疾病。.
The link, or part of it, may be due to the fact that sleep apnea and diabetes share some risk factors. Obesity and cardiovascular disease are related to both conditions. Sleep apnea doesn’t just increase the likelihood of developing cardiovascular disease-- heart problems can also lead to sleep apnea. Also, people who have diabetes are at least twice as likely to develop heart disease,according to the National Institute of Diabetes and Digestive and Kidney Diseases.
肥胖是心脏病的另一个已知风险因素，此外，一项针对 306 名患有糖尿病的肥胖患者的研究发现，其中高达 86% 的人还患有未确诊的睡眠呼吸暂停^3。这些疾病似乎都与此有关。.
根据睡眠呼吸暂停对身体的影响，专家们确实对这种联系背后的生物学机制有一些线索。.
“睡眠呼吸暂停在夜间会造成两大后果，”加尼亚杜克斯说。他指出，一是低氧血症，即血液中氧气浓度降至正常水平以下；二是睡眠片段化。“我们从动物研究中得知，这两者都是导致胰岛素抵抗的风险因素，”他补充道。.
Hypoxemia can set off a chain reaction in the body that leads to impaired glucose tolerance and increased oxidative stress, which means the body has an excess amount of molecules called reactive oxygen species. These molecules can disrupt the body’s ability to repair itself. The whole process can also contribute to insulin resistance.
任何形式的睡眠碎片化都会使人体处于应激状态，并导致皮质醇（一种能强烈影响新陈代谢的激素）的释放。反复觉醒还会导致胰岛素抵抗、食欲增加以及对碳水化合物的渴望。所有这些变化都可能诱发糖尿病。睡眠变异性增加甚至与血糖控制问题有关⁴。“睡眠呼吸暂停越严重，患者的血糖控制就越受影响，”Mostafavi说道。.
持续气道正压通气疗法可缓解睡眠呼吸暂停，并可能有助于控制糖尿病。
由于睡眠呼吸暂停和糖尿病似乎存在关联，研究人员试图确定治疗这种睡眠障碍是否有助于改善患者的糖尿病病情。然而，研究睡眠呼吸暂停治疗金标准——持续气道正压通气（CPAP）疗法——效果的研究结果却不尽相同。
一方面，一些研究表明，持续气道正压通气（CPAP）疗法可能改善糖尿病。2012 年的一项研究调查了 50 名中重度睡眠呼吸暂停患者，以了解 CPAP 是否真的能够帮助他们控制糖尿病。研究人员将参与者分为两组，一组接受 CPAP 治疗，另一组接受安慰剂 CPAP 治疗，疗程为八周。研究团队发现，CPAP 疗法虽然不能使血糖水平完全恢复正常，但确实改善了重度睡眠呼吸暂停患者的胰岛素敏感性⁵。.
在另一项为期六个月的试验中，50 名患有睡眠呼吸暂停和糖尿病的患者被分为两组：一组接受 CPAP 治疗，另一组未接受治疗。治疗组的胰岛素抵抗和敏感性以及葡萄糖耐量指标均有所改善，夜间血氧水平也相应提高^6。.
另一方面，澳大利亚一项针对 298 名受试者的研究，分别给予他们真正的 CPAP 或安慰剂，结果发现血糖控制并未得到改善^7。为了解释他们的研究结果，澳大利亚研究团队写道：“阻塞性睡眠呼吸暂停的影响可能主要与糖尿病的发生发展有关，但与已确诊糖尿病的控制无关。”
Gagnadoux 的研究试图厘清持续气道正压通气（CPAP）对同时患有糖尿病和睡眠呼吸暂停的患者是否有效的原因。他和同事研究了 762 名在首次多导睡眠图检查后被诊断为睡眠呼吸暂停的患者。参与者中包括 497 名已确诊糖尿病的患者。其余 265 名患者在研究开始前未被诊断出患有糖尿病，但由于血糖水平升高而被选中。.
研究团队的发现或许可以解释为什么专家们一直难以理解 CPAP 是否能够帮助缓解糖尿病症状。.
总体而言，他们发现睡眠呼吸暂停病情越严重的患者，血糖控制越差，这意味着他们的血糖更容易升高<sup>8</sup>。然而，在他们治疗的既往确诊糖尿病患者群体中，这种模式并不明显。“这可能意味着，治疗阻塞性睡眠呼吸暂停对新确诊患者的血糖控制效果更佳，”Gagnadoux解释道。已经控制好糖尿病的患者在开始使用CPAP治疗后可能不会看到改善。但这并不意味着CPAP治疗没有价值。.
“当治疗同时患有睡眠呼吸暂停和糖尿病的患者时，你不仅要治疗睡眠呼吸暂停，还要尽力治疗糖尿病，”加尼亚杜克斯说。迄今为止，研究表明，单独治疗睡眠呼吸暂停并不能帮助控制糖尿病。.
尽管如此，莫斯塔法维医生仍然建议医生考虑对睡眠呼吸暂停患者使用持续气道正压通气（CPAP）疗法，尤其是那些同时患有睡眠呼吸暂停和糖尿病的患者。“关于CPAP治疗和血糖控制的数据并不一致，我不能断言使用CPAP就能治愈糖尿病，”他说道。“有些人确实感觉有所改善，有些人则没有。但睡眠呼吸暂停本身就是一种需要治疗的严重疾病。”
随着研究的深入，越来越明显的是，医生应该与糖尿病患者讨论睡眠问题。
即使专家们尚不完全了解糖尿病和睡眠呼吸暂停之间关系的确切机制，但他们确信这种关系确实存在。此外，这种关联性非常强，而且任何一种疾病若不及时治疗都可能造成严重后果，因此医生应该认真考虑询问糖尿病患者的睡眠质量。.
莫斯塔法维建议其他医生在接诊病人时要详细了解病史。“如果你的病人超重，就问问他们是否打鼾，或者他们的伴侣是否抱怨过他们睡觉时发出噪音。还要问问他们是否嗜睡——这是睡眠呼吸暂停的典型症状：白天嗜睡，”他说。但一定要询问他们的伴侣。“最可靠、最准确的病史总是来自他们的伴侣，而最不可靠的病史则来自病人本人。睡眠者自己听不到自己的鼾声，但如果他们的伴侣抱怨，你就可以相信他们了。”
无论后续研究是否支持CPAP疗法有助于控制糖尿病的观点，在两种疾病同时发生时进行治疗都至关重要。忽视其中任何一种都无济于事。.
“单独治疗睡眠呼吸暂停症的好处就足够大了，而对于同时患有糖尿病的患者来说，治疗睡眠呼吸暂停症的弊端几乎为零，”莫斯塔法维说。.
如果这些研究中的一些发现经进一步证实，那么持续气道正压通气（CPAP）疗法可能不仅仅能改善睡眠，还有助于糖尿病管理。如果您有患者，请询问他们是否打鼾，并与他们的伴侣沟通。如果您需要评估患者嗜睡程度的工具，请下载 爱普沃斯嗜睡量表：
引用的研究：
1. Pamidi, S. & E. Tasali, (2012). Obstructive Sleep Apnea and Type 2 Diabetes: Is There a Link?. Front Neurol, 3(126), eCollection.PubMed 2. Kent, B.D., et al., (2014). Diabetes mellitus prevalence and control in sleep-disordered breathing: the European Sleep Apnea Cohort (ESADA) study. Chest, 146(4), 982-990.PubMed 3. Foster, G.D. et al., (2009). Obstructive Sleep Apnea Among Obese Patients with Type 2 Diabetes. Diabetes Care, 32(6), 1017-1019. PubMed 4. Tachikawa R. et al., (2016). Higher Sleep Variability is Associated with Poorer Glycaemic Control in Patients with Type 1 Diabetes. Am J Respir Crit Care Med, . PubMed 5. Weinstock T.G. et al., (2012). A Controlled Trial of CPAP Therapy on Metabolic Control in Individuals with Impaired Glucose Tolerance and Sleep Apnea. Sleep, 35(5), 617-625B.PubMed 6. Martínez-Cerón E. et al., (2016). Effect of CPAP on Glycemic Control in Patients with Obstructive Sleep Apnea and Type 2 Diabetes. A Randomized Clinical Trial. Am J Respir Crit Care Med. . 7. Shaw J.E. et al., (2016). The Effect of Treatment of Obstructive Sleep Apnea on Glycemic Control in Type 2 Diabetes. Am J Respir Crit Care Med, .PubMed 8. Priou T. et al, (2015). Association Between Obstructive Sleep Apnea Severity and Glucose Control in Patients with Untreated Versus Treated Diabetes. J Sleep Res, 24(4), 425-431.PubMed
Frequently asked questions
Untreated sleep apnea is associated with -- not proven to cause -- increased risk of developing type 2 diabetes. Meta-analyses suggest patients with severe untreated OSA have about twice the risk of developing type 2 diabetes after adjusting for weight (Sleep Medicine Reviews, multiple cohorts). The relationship is bidirectional: each condition increases the prevalence of the other.
Studies estimate 60-80 percent of patients with type 2 diabetes have some degree of obstructive sleep apnea, versus roughly 25 percent of the general adult population (American Journal of Respiratory and Critical Care Medicine). Prevalence is highest in patients with poorly controlled blood sugar and BMI above 30.
Evidence suggests CPAP may modestly improve insulin sensitivity and HbA1c in some patients with moderate-to-severe OSA, but the effect is generally smaller than what is achieved with weight loss or medication adjustment (American Diabetes Association Standards of Care). CPAP is not a substitute for diabetes care -- it is one component of overall metabolic management.
The American Academy of Sleep Medicine and American Diabetes Association recommend OSA screening in patients with type 2 diabetes who have BMI above 30, daytime sleepiness, hypertension, or other OSA symptoms. A home sleep test is typically the most efficient initial screening tool.
A 10 percent body-weight reduction may reduce AHI by an average of about 26 percent based on cohort data. Larger losses sometimes resolve mild OSA. For moderate-to-severe disease, weight loss typically reduces severity but does not fully eliminate the diagnosis. Repeat sleep study after substantial weight loss is the only way to confirm.