Diabetes Care Volume 37, September 2014
e202
RESPONSE TO COMMENT ON GUEST ET AL.
Clinical Outcomes and Cost-effectiveness of Continuous Positive Airway Pressure to Manage Obstructive Sleep Apnea in Patients With Type 2 Diabetes in the U.K. Diabetes Care 2014;37:1263–1271
Shahrad Taheri,1,2 Julian F. Guest,3,4 and John R. Stradling5
e-LETTERS – COMMENTS AND RESPONSES
Diabetes Care 2014;37:e202–e203 | DOI: 10.2337/dc14-1105 A potential association between obstructive sleep apnea (OSA) and diabetes is intriguing, as acknowledged in the commentary by Tahrani (1) on our article (2). OSA is prevalent among patients with diabetes and may contribute to several important aspects, including glycemic control, hypertension, cardiovascular disease, and microvascular complications (3,4). In our observational study in a clinical setting, patients with type 2 diabetes and untreated OSA developed higher HbA1c levels (and blood pressure) compared with best-matched patients treated with continuous positive airway pressure (CPAP), despite greater prescription of antidiabetes medications (2). Although data were unavailable, it is likely that the patients studied had significant symptomatic OSA given their BMI and the usual symptom-driven presentation to primary care. Tahrani (1) suggested that the degree and rapidity (occurring within a year) of the HbA1c difference between the groups was unusual. Several mechanisms for the potential impact of OSA on glycemic control have been proposed, including intermittent hypoxemia, hypercapnia, increased sympathetic drive, sleep disturbance, and short sleep duration (2). For example, even a few nights of partial sleep deprivation can have significant effects on glycemic control (5).
CPAP effects on the above mechanisms could explain the rapid and significant difference in glycemia between the patient groups. The degree of difference in HbA1c between the groups is also comparable to other studies. One study of diabetic patients observed that the adjusted mean HbA1c was 3.7% higher in severe OSA patients compared with those without OSA (6). There are, of course, many other potential factors that could also explain our findings, including poorer medication adherence that may accompany a group of patients who may not accept, or have been offered, CPAP treatment. Another possibility is potential cognitive decline with untreated OSA, which might have affected medication adherence. However, we believe these explanations are less likely as a nonadherent or cognitively impaired group would engage less with health care services and perhaps demonstrate early deterioration in other parameters such as blood pressure, but a difference in blood pressure between the groups was not observed until the fifth year after diagnosis. Given the observational nature of our study, we agree with Tahrani (1) that it is difficult to make confident statements regarding any causal relationship between OSA treatment, glycemic control, and hypertension, as discussed in
our article. Current evidence examining the relationship between diabetes and OSA suffers from several drawbacks, including mainly cross-sectional designs, selection bias, variation in diagnostic measures of OSA, lack of consideration for confounding factors, and short CPAP treatment duration (3). There are insufficient data from randomized controlled trials (RCTs) regarding the long-term impact of CPAP treatment on diabetes and its complications (3). While Tahrani proposes RCTs, it should be noted that longer-term placebo-controlled RCTs of OSA treatment in symptomatic patients are generally difficult to conduct and are hampered by CPAP treatment adherence problems. Even RCTs may show an experimental effect that is not due to direct effects of OSA relief but secondary effects such as improved cognition and exercise. In our study, as noted by Tahrani (1), we did not have sufficient data to examine optimal CPAP usage, as compliance data were very limited. It is currently unclear what optimal CPAP usage is, in particular for a potential impact on metabolism. Another issue is the timing of CPAP intervention in patients with diabetes; early intervention may be more effective. Given that current glycemic management approaches are insufficient, there is a need to carefully
1
Department of Medicine, Weill Cornell Medical College, New York, NY, and Doha, Qatar Department of Medicine, King’s College London, London, U.K. 3 Catalyst Health Economics Consultants, Northwood, Middlesex, U.K. 4 School of Biomedical Sciences, King’s College London, London, U.K. 5 Department of Respiratory Medicine, Oxford Biomedical Research Centre, University of Oxford, Oxford, U.K. 2
Corresponding author: Shahrad Taheri, [email protected]. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
care.diabetesjournals.org
examine whether OSA treatment can improve glycemic control in the long term in well-designed studies. Duality of Interest. No potential conflicts of interest relevant to this article were reported.
References 1. Tahrani AA. Comment on Guest et al. Clinical outcomes and cost-effectiveness of continuous positive airway pressure to manage obstructive
Taheri, Guest, and Stradling
sleep apnea in patients with type 2 diabetes in the U.K. Diabetes Care 2014;37:1263–1271 (Letter). Diabetes Care 2014;37:e200–e201. DOI: 10.2337/dc14-1000 2. Guest JF, Panca M, Sladkevicius E, Taheri S, Stradling J. Clinical outcomes and costeffectiveness of continuous positive airway pressure to manage obstructive sleep apnea in patients with type 2 diabetes in the U.K. Diabetes Care 2014;37:1263–1271 3. Pallayova M, Banerjee D, Taheri S. Novel insights into metabolic sequelae of obstructive sleep apnoea: A link between hypoxic stress
and chronic diabetes complications. Diabetes Res Clin Pract 2014;104:197–205 4. Banerjee D, Leong WB, Arora T, et al. The potential association between obstructive sleep apnea and diabetic retinopathy in severe obesitythe role of hypoxemia. PLoS One 2013;8:e79521 5. Spiegel K, Leproult R, Van Cauter E. Impact of sleep debt on metabolic and endocrine function. Lancet 1999;354:1435–1439 6. Aronsohn RS, Whitmore H, Van Cauter E, Tasali E. Impact of untreated obstructive sleep apnea on glucose control in type 2 diabetes. Am J Respir Crit Care Med 2010;181:507–513
e203
Copyright of Diabetes Care is the property of American Diabetes Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
e202
RESPONSE TO COMMENT ON GUEST ET AL.
Clinical Outcomes and Cost-effectiveness of Continuous Positive Airway Pressure to Manage Obstructive Sleep Apnea in Patients With Type 2 Diabetes in the U.K. Diabetes Care 2014;37:1263–1271
Shahrad Taheri,1,2 Julian F. Guest,3,4 and John R. Stradling5
e-LETTERS – COMMENTS AND RESPONSES
Diabetes Care 2014;37:e202–e203 | DOI: 10.2337/dc14-1105 A potential association between obstructive sleep apnea (OSA) and diabetes is intriguing, as acknowledged in the commentary by Tahrani (1) on our article (2). OSA is prevalent among patients with diabetes and may contribute to several important aspects, including glycemic control, hypertension, cardiovascular disease, and microvascular complications (3,4). In our observational study in a clinical setting, patients with type 2 diabetes and untreated OSA developed higher HbA1c levels (and blood pressure) compared with best-matched patients treated with continuous positive airway pressure (CPAP), despite greater prescription of antidiabetes medications (2). Although data were unavailable, it is likely that the patients studied had significant symptomatic OSA given their BMI and the usual symptom-driven presentation to primary care. Tahrani (1) suggested that the degree and rapidity (occurring within a year) of the HbA1c difference between the groups was unusual. Several mechanisms for the potential impact of OSA on glycemic control have been proposed, including intermittent hypoxemia, hypercapnia, increased sympathetic drive, sleep disturbance, and short sleep duration (2). For example, even a few nights of partial sleep deprivation can have significant effects on glycemic control (5).
CPAP effects on the above mechanisms could explain the rapid and significant difference in glycemia between the patient groups. The degree of difference in HbA1c between the groups is also comparable to other studies. One study of diabetic patients observed that the adjusted mean HbA1c was 3.7% higher in severe OSA patients compared with those without OSA (6). There are, of course, many other potential factors that could also explain our findings, including poorer medication adherence that may accompany a group of patients who may not accept, or have been offered, CPAP treatment. Another possibility is potential cognitive decline with untreated OSA, which might have affected medication adherence. However, we believe these explanations are less likely as a nonadherent or cognitively impaired group would engage less with health care services and perhaps demonstrate early deterioration in other parameters such as blood pressure, but a difference in blood pressure between the groups was not observed until the fifth year after diagnosis. Given the observational nature of our study, we agree with Tahrani (1) that it is difficult to make confident statements regarding any causal relationship between OSA treatment, glycemic control, and hypertension, as discussed in
our article. Current evidence examining the relationship between diabetes and OSA suffers from several drawbacks, including mainly cross-sectional designs, selection bias, variation in diagnostic measures of OSA, lack of consideration for confounding factors, and short CPAP treatment duration (3). There are insufficient data from randomized controlled trials (RCTs) regarding the long-term impact of CPAP treatment on diabetes and its complications (3). While Tahrani proposes RCTs, it should be noted that longer-term placebo-controlled RCTs of OSA treatment in symptomatic patients are generally difficult to conduct and are hampered by CPAP treatment adherence problems. Even RCTs may show an experimental effect that is not due to direct effects of OSA relief but secondary effects such as improved cognition and exercise. In our study, as noted by Tahrani (1), we did not have sufficient data to examine optimal CPAP usage, as compliance data were very limited. It is currently unclear what optimal CPAP usage is, in particular for a potential impact on metabolism. Another issue is the timing of CPAP intervention in patients with diabetes; early intervention may be more effective. Given that current glycemic management approaches are insufficient, there is a need to carefully
1
Department of Medicine, Weill Cornell Medical College, New York, NY, and Doha, Qatar Department of Medicine, King’s College London, London, U.K. 3 Catalyst Health Economics Consultants, Northwood, Middlesex, U.K. 4 School of Biomedical Sciences, King’s College London, London, U.K. 5 Department of Respiratory Medicine, Oxford Biomedical Research Centre, University of Oxford, Oxford, U.K. 2
Corresponding author: Shahrad Taheri, [email protected]. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
care.diabetesjournals.org
examine whether OSA treatment can improve glycemic control in the long term in well-designed studies. Duality of Interest. No potential conflicts of interest relevant to this article were reported.
References 1. Tahrani AA. Comment on Guest et al. Clinical outcomes and cost-effectiveness of continuous positive airway pressure to manage obstructive
Taheri, Guest, and Stradling
sleep apnea in patients with type 2 diabetes in the U.K. Diabetes Care 2014;37:1263–1271 (Letter). Diabetes Care 2014;37:e200–e201. DOI: 10.2337/dc14-1000 2. Guest JF, Panca M, Sladkevicius E, Taheri S, Stradling J. Clinical outcomes and costeffectiveness of continuous positive airway pressure to manage obstructive sleep apnea in patients with type 2 diabetes in the U.K. Diabetes Care 2014;37:1263–1271 3. Pallayova M, Banerjee D, Taheri S. Novel insights into metabolic sequelae of obstructive sleep apnoea: A link between hypoxic stress
and chronic diabetes complications. Diabetes Res Clin Pract 2014;104:197–205 4. Banerjee D, Leong WB, Arora T, et al. The potential association between obstructive sleep apnea and diabetic retinopathy in severe obesitythe role of hypoxemia. PLoS One 2013;8:e79521 5. Spiegel K, Leproult R, Van Cauter E. Impact of sleep debt on metabolic and endocrine function. Lancet 1999;354:1435–1439 6. Aronsohn RS, Whitmore H, Van Cauter E, Tasali E. Impact of untreated obstructive sleep apnea on glucose control in type 2 diabetes. Am J Respir Crit Care Med 2010;181:507–513
e203
Copyright of Diabetes Care is the property of American Diabetes Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
