Type 2 diabetes mellitus is a chronic medical condition that imposes a substantial public health burden. It is estimated that nearly 25.8 million people in the United States have diabetes. Despite enormous advances in the management of diabetes, a significant number of those affected develop microvascular complications such as retinopathy, neuropathy, and nephropathy, as well as macrovascular complications including subclinical atherosclerosis, coronary artery disease, and cerebrovascular disease. While glycemic control is a central focus of diabetes management, targeting other factors that can either worsen glycemic control and/or increase the risk of macrovascular disease are concurrent therapeutic goals. A critical issue facing clinicians that manage diabetes is the need for additional strategies that can be added to the armamentarium for improving glycemic control. Research over the last decade has shown that obstructive sleep apnea (OSA) is a common condition in people with diabetes. Data from a number of different studies show that the prevalence of moderate to severe OSA in diabetics is more than 50%. Furthermore, observational and experimental evidence indicates that intermittent hypoxemia and recurrent arousals in OSA may alter glucose metabolism and worsen glycemic control. However, the impact of treating OSA with continuous positive airway pressure (CPAP) therapy on glycemic control is not well defined. Adequately powered randomized clinical trials have yet to be performed to demonstrate whether CPAP therapy for OSA in diabetics can improve glycemic control, decrease blood pressure, and reverse endothelial dysfunction. Our preliminary data suggest that treatment of OSA with CPAP for 6 months has favorable effects on glycemic control, postprandial hyperglycemia, diurnal blood pressure, and endothelial function. Based on these findings, the overarching goal of this proposal is to determine whether CPAP therapy for OSA in diabetics leads to improvements in (a) glycosylated hemoglobin (HbA1c);(b) glycemic variability as assessed by self-monitoring of blood glucose and continuous monitoring of glucose;(c) blood pressure;(d) sympathovagal balance;(e) endothelial function;(f) oxidative stress;and (g) dyslipidemia. We propose to conduct a randomized control trial in subjects with diabetes and moderate to severe OSA who will be randomly assigned for 6 months to CPAP with lifestyle counseling or lifestyle counseling alone. In the context of this clinical trial, we ill investigate the repertoire of aforementioned clinical outcomes.

Public Health Relevance

Emerging data suggests that obstructive sleep apnea can alter glucose metabolism and worsen glycemic control in patients with type 2 diabetes mellitus. While continuous positive airway pressure therapy (CPAP) is effective in treating obstructive sleep apnea, its effects on glycemic control, postprandial hyperglycemia, blood pressure, and endothelial function are unknown. We propose to conduct a single center, randomized controlled trial of CPAP vs. lifestyle counseling for 6 months in patients with type 2 diabetes to determine whether CPAP treatment for obstructive sleep apnea can improve glycemic, hemodynamic, and vascular outcomes.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
1R01HL117167-01A1
Application #
8694632
Study Section
Cardiovascular and Sleep Epidemiology Study Section (CASE)
Program Officer
Bonds, Denise
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Hall, Gentzon; Rowell, Janelle; Farinelli, Federica et al. (2014) Phosphodiesterase 5 inhibition ameliorates angiontensin II-induced podocyte dysmotility via the protein kinase G-mediated downregulation of TRPC6 activity. Am J Physiol Renal Physiol 306:F1442-50