In recent years, there has been increasingly more research performed on the clinical implications of sleep disordered breathing on insulin resistance and glucose intolerance. Carly Hingson, Doctor of Pharmacy Candidate, Mercer University College of Pharmacy puts it all together in her special report: Sleep-Related Breathing Disorders and Diabetes
Sleep-Related Breathing Disorders and Diabetes
Carly Hingson, Doctor of Pharmacy Candidate
Mercer University College of Pharmacy
In recent years, there has been increasingly more research performed on the clinical implications of sleep disordered breathing on insulin resistance and glucose intolerance. The International Diabetes Federation released a report on this subject at the June 2008 Annual Scientific Sessions of the American Diabetes Association. There is now a goal to improve clinical practice and increase research in order to determine the relationship between sleep disorders, such as obstructive sleep apnea, and type 2 diabetes.
Obstructive sleep apnea is characterized by episodes of decreased or no airflow into the lungs. It is caused by collapse of the upper airway during periods of rest such as sleep. Obesity has been found to be the most important determinant of sleep apnea, although anatomical structure of the respiratory tract can play a role. The constant disruption in sleep results in subsequent daytime drowsiness the following day.
Metabolic syndrome is characterized by risk factors for cardiovascular disease and type 2 diabetes mellitus. These include arterial hypertension, increased triglycerides, abdominal obesity, decreased HDL, and increased blood glucose. Insulin resistance is the strongest predictor for developing the condition. Both apnea and metabolic syndrome are associated with similar cardiovascular problems. Patients with obstructive sleep apnea experience a decline in cardiac function associated with the respiratory variances they go through. The changes that occur in arterial blood pressure and heart rate may lead to an increased risk for developing coronary artery and cerebrovascular disease.
Many researchers postulate that insulin resistance is the underlying factor of metabolic syndrome. It has been identified that most people with this condition do have insulin resistance, therefore an increased risk for type 2 diabetes. Abdominal obesity in particular, is highly correlated with resistance to insulin. The International Diabetes Federation advises that increased waist circumference should be included in the diagnosis of metabolic syndrome.
In 1988, Dr. Gerald Reaven clustered several cardiovascular risk factors together, including dyslipidemia, hypertension, and hyperglycemia. He called this “Syndrome X” and recognized it as a major risk factor for developing cardiovascular disease. It is now being suggested by many that the syndrome should also comprise obstructive sleep apnea and be renamed to “Syndrome Z”. The prevalence of metabolic syndrome is almost 40% greater in patients with obstructive sleep apnea. Longitudinal studies have demonstrated patients with apnea are at an increased risk of type 2 diabetes from mechanisms independent of obesity. While it is unclear as to what the correlation is, research shows that the two conditions are related. Laboratory studies have demonstrated marked alterations in glucose metabolism including decreased glucose tolerance and insulin sensitivity in sleep-restricted patients. It is possible that mechanisms of obstructive sleep apnea induce the appearance of metabolic syndrome or it could be that the apnea is actually part of the syndrome. In an attempt to make this determination, scientists are studying whether the alteration in glucose metabolism is due to the hypoxia experienced, or the lack of restful sleep. One study demonstrated that states of hypoxia caused worsening of glucose tolerance and increased circulating levels of epinephrine. It has been found that periods of intermittent hypoxia, as with sleep apnea, have a more potent effect systemically, than in sustained hypoxic conditions. The repetitive cycles of hypoxia-reoxygenation increase oxidative stress and affect the modulation of glucose transport and utilization. There have been studies on sleep restriction that show patients exhibit a worsening of glucose tolerance, increased levels of evening cortisol, and increased sympathetic activity. Neuroendocrine abnormalities with the hormones leptin and ghrelin were seen, which correlate with increased hunger and appetite and may lead to weight gain. Also, an inflammatory response was seen that may alter glucose and insulin homeostasis. Collectively, these studies have shown that hypoxia and sleep loss may be independent causes of the metabolic changes observed in patients with sleep apnea.
Based on emerging data, The International Diabetes Federation Taskforce on Epidemiology and Prevention has issued recommendations for all patients that have type 2 diabetes or metabolic syndrome to be screened for obstructive sleep apnea. Excessive daytime sleepiness is a key symptom of the condition. The primary characteristic during sleep is loud snoring with repeated absence or cessation of breathing. This can be identified by questionnaires such as the Berlin Questionnaire or the Epworth Sleepiness Scale and can be confirmed by referral for a sleep study.
Conversely, patients diagnosed with obstructive sleep apnea should be screened for metabolic disorders, including type 2 diabetes. Waist circumference, blood pressure, fasting lipid profile, and fasting blood glucose should all be considered.
If obstructive sleep apnea is diagnosed, weight loss for patients who are overweight is the primary treatment. Continuous positive airway pressure (CPAP) is the best treatment for patients classified as moderate to severe. The benefits of this therapy for sleep apnea are well recognized. The benefits on glucose metabolism have not been definitively established. Various studies have demonstrated improvement in blood pressure and insulin sensitivity with use. In 2004, Harsch et al. concluded that CPAP treatment increased insulin sensitivity in non-diabetic patients with obstructive sleep apnea syndrome significantly after two nights of treatment and was still found to be beneficial after 3 months of therapy. This was the largest study to demonstrate a beneficial effect on glucose metabolism with the use of CPAP. This year a follow up study was performed and confirmed the benefit for an average of 2.9 years. Other studies have confirmed improvement in hemoglobin A1C with the use of CPAP. Until there are controlled clinical trials on the metabolic effects of CPAP, it will be difficult to determine if there is a causal association or just a correlation with the improvement of glucose metabolism. Based on the information documented at this time, it is proposed that CPAP treatment may prevent or delay progression to type 2 diabetes in patients with obstructive sleep apnea.
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