Sushmita Pamidi

Obstructive sleep apnea and type 2 diabetes: is there a link?

Type 2 diabetes is a chronic illness that is increasing in epidemic proportions worldwide. Major factors contributing to the development of type 2 diabetes include obesity and poor lifestyle habits (e.g., excess dietary intake and limited physical activity). Despite the proven efficacy of lifestyle interventions and the use of multiple pharmacological agents, the economic and public health burden of type 2 diabetes remains substantial. Obstructive sleep apnea (OSA) is a treatable sleep disorder that is pervasive among overweight and obese adults, who represent about two thirds of the U.S. population today. An ever-growing number of studies have shown that OSA is associated with insulin resistance, glucose intolerance and type 2 diabetes, independent of obesity. Evidence from animal and human models that mimic OSA provides potential mechanisms for how OSA may alter glucose metabolism. Up to 83% of patients with type 2 diabetes suffer from unrecognized OSA and increasing severity of OSA is associated with worsening glucose control. However, it is still unclear whether OSA may lead to the development of diabetes over time. More data from large-scale longitudinal studies with rigorous assessments of diabetes and OSA are needed. In addition, there is still controversy whether continuous positive airway pressure (CPAP) treatment of OSA improves glucose metabolism. Large-scale randomized-controlled trials of CPAP treatment of OSA with well-validated assessments of insulin sensitivity and glucose tolerance are needed. These studies may reveal that OSA represents a novel, modifiable risk factor for the development of prediabetes and type 2 diabetes.

Obstructive Sleep Apnea in Young Lean Men: Impact on insulin sensitivity and secretion

OBJECTIVE To assess whether the presence of obstructive sleep apnea (OSA) affects glucose metabolism in young, lean individuals who are healthy and free of cardiometabolic disease. RESEARCH DESIGN AND METHODS In a prospective design, 52 healthy men (age 18–30 years; BMI 18–25 kg/m2) underwent laboratory polysomnogram followed by a morning oral glucose tolerance test (OGTT). We stratified all subjects according to the presence or absence of ethnicity-based diabetes risk and family history of diabetes. We then used a frequency-matching approach and randomly selected individuals without OSA, yielding a total of 20 control men without OSA and 12 men with OSA. Indices of glucose tolerance, insulin sensitivity, and insulin secretion (early phase and total) were compared between men with OSA and control subjects. The incremental areas under the glucose (incAUCglu) and insulin (incAUCins) curves were calculated using the trapezoidal method from 0 to 120 min during the OGTT. RESULTS Men with OSA and control subjects were similar in terms of age, BMI, ethnicity-based diabetes risk, family history of diabetes, and level of exercise. Both groups had normal systolic and diastolic blood pressure and fasting lipid levels. After ingestion of a glucose load, men with OSA had 27% lower insulin sensitivity (estimated by Matsuda index) and 37% higher total insulin secretion (incAUCins) than the control subjects, despite comparable glucose levels (incAUCglu). CONCLUSIONS In young, lean, and healthy men who are free of cardiometabolic disease, the presence of OSA is associated with insulin resistance and a compensatory rise in insulin secretion to maintain normal glucose tolerance. Thus, OSA may increase the risk of type 2 diabetes independently of traditional cardiometabolic risk factors.

Eight Hours of Nightly Continuous Positive Airway Pressure Treatment of Obstructive Sleep Apnea Improves Glucose Metabolism in Patients with Prediabetes. A Randomized Controlled Trial

RATIONALE Although obstructive sleep apnea (OSA) is associated with impaired glucose tolerance and diabetes, it remains unclear whether OSA treatment with continuous positive airway pressure (CPAP) has metabolic benefits. OBJECTIVES To determine the effect of 8-hour nightly CPAP treatment on glucose metabolism in individuals with prediabetes and OSA. METHODS In a randomized controlled parallel group study, 39 participants were randomly assigned to receive either 8-hour nightly CPAP (n = 26) or oral placebo (n = 13). Sleep was polysomnographically recorded in the laboratory on each night. CPAP adherence was ensured by continuous supervision. Participants continued their daily routine activities outside the laboratory. Glucose metabolism was assessed at baseline and after 2 weeks of assigned treatment using both the oral and intravenous glucose tolerance tests. The primary outcome was the overall glucose response as quantified by the area under the curve for glucose during 2-hour oral glucose tolerance testing. Secondary outcomes included fasting and 2-hour glucose and insulin, the area under the curves for insulin and insulin secretion, norepinephrine, insulin sensitivity, acute insulin response to glucose, and 24-hour blood pressure. MEASUREMENTS AND MAIN RESULTS The overall glucose response was reduced (treatment difference: -1,276.9 [mg/dl] · min [95% confidence interval, -2,392.4 to -161.5]; P = 0.03) and insulin sensitivity was improved (treatment difference: 0.77 [mU/L](-1) · min(-1) [95% confidence interval, 0.03-1.52]; P = 0.04) with CPAP as compared with placebo. Additionally, norepinephrine levels and 24-hour blood pressure were reduced with CPAP as compared with placebo. CONCLUSIONS In patients with prediabetes, 8-hour nightly CPAP treatment for 2 weeks improves glucose metabolism compared with placebo. Thus, CPAP treatment may be beneficial for metabolic risk reduction. Clinical trial registered with www.clinicaltrials.gov (NCT 01156116).

Obstructive Sleep Apnea: Role in the Risk and Severity of Diabetes

Obstructive sleep apnea (OSA) is a treatable sleep disorder that is pervasive among overweight and obese individuals. Current evidence supports a robust association between OSA and insulin resistance, glucose intolerance and the risk of type 2 diabetes, independent of obesity. Up to 83% of patients with type 2 diabetes suffer from unrecognized OSA and increasing severity of OSA is independently associated with poorer glucose control. Evidence from animal and human models that mimic OSA supports a potential causal role for OSA in altered glucose metabolism. Robust prospective and randomized clinical trials are still needed to test the hypothesis that effective treatment of OSA may prevent the development of type 2 diabetes and its complications, or reduce its severity. Type 2 diabetes is occurring at alarming rates worldwide and despite available treatment options, the economic and public health burden of this epidemic remains enormous. OSA might represent a novel, modifiable risk factor for the development of prediabetes and type 2 diabetes.

Prevalence, clinical features, and CPAP adherence in REM-related sleep-disordered breathing: a cross-sectional analysis of a large clinical population

PurposeDue to inconsistent definitions used in the literature, the prevalence of rapid eye movement (REM)-related sleep-disordered breathing (SDB) has been quite variable and its clinical significance remains unclear. This study aimed to compare the prevalence of and clinical characteristics between various criteria for defining REM-related SDB. We also investigated how frequently CPAP therapy was recommended in patients with REM-related SDB and if they had lower CPAP adherence compared to non-stage-specific SDB.MethodsIn this cross-sectional study, we evaluated 1,019 consecutive adults referred for a polysomnogram for suspicion of SDB. The prevalence of REM-related SDB was calculated based on “traditional criteria” commonly reported in the literature and a “strict criteria” that minimized the contribution of SDB during non-REM sleep.ResultsThe prevalence of REM-related SDB ranged from 13.5% to 36.7%. There were no clinically significant differences between the strict definition and the traditional definition of REM-related SDB. REM-related SDB was more prevalent in women, younger individuals and African Americans. Compared to non-stage-specific obstructive sleep apnea (OSA), patients with REM-related SDB were equally symptomatic and hypersomnolent. CPAP titration was recommended in 88% of patients with REM-related SDB vs. 94% of patients with non-stage-specific OSA (p < 0.001). There was no significant difference in CPAP adherence between the two groups.ConclusionsRegardless of how REM-related SDB is defined, it was highly prevalent in our large clinical cohort. Compared to non-stage-specific OSA, these patients were equally hypersomnolent and adherent to CPAP therapy despite having overall significantly milder OSA. Further research is needed to better establish whether these patients will derive any benefit from long-term CPAP therapy.

The Impact of Sleep Consultation Prior to a Diagnostic Polysomnogram on Continuous Positive Airway Pressure Adherence

BACKGROUND Polysomnograms (PSGs) are routinely ordered by nonsleep specialists. However, it is unknown whether a sleep specialist consultation prior to a diagnostic PSG influences adherence to continuous positive airway pressure (CPAP) therapy. METHODS This study was done at the University of Chicago Sleep Disorders Center and included 403 patients with obstructive sleep apnea who had CPAP adherence data available. CPAP was set up at home, and objective adherence was remotely monitored during the first 30 days of therapy. Physicians who ordered PSGs were divided into two groups: sleep specialists and nonsleep specialists. RESULTS Patients were aged 52.5 ± 14 years, 47% were men, and 54% were African American. Mean daily CPAP use was greater in patients who were referred by sleep specialists (n = 105, 279 ± 179 min/d) than in patients referred by nonsleep specialists (n = 298, 219 ± 152 min/d, P = .005). In the linear regression model adjusting for several covariates, only two predictors were significantly associated with CPAP adherence. A sleep specialist consultation prior to the diagnostic PSG was associated with 58.2 min more per day (P = .002), and African American race was associated with 56.0 min less per day (P = .002) of CPAP use. CONCLUSIONS In this cohort study, CPAP adherence was significantly higher with a sleep specialist consultation prior to the diagnostic PSG. In addition, African American race was associated with worse adherence to therapy. A better understanding of predictors of CPAP adherence may be useful in identifying patients who may benefit from a sleep specialist consultation prior to ordering a diagnostic PSG.

Depressive symptoms and obesity as predictors of sleepiness and quality of life in patients with REM-related obstructive sleep apnea: Cross-sectional analysis of a large clinical population

BACKGROUND The clinical significance of rapid eye-movement (REM)-related obstructive sleep apnea (OSA) is unknown. Moreover, it is unclear what the determinants of sleepiness and quality of life (QoL) are among these patients. Our aim was to identify whether the apnea-hypopnea index during REM sleep (AHI(REM)), AHI during NREM sleep (AHI(NREM)), depressive symptoms, or obesity are independent predictors of excessive daytime sleepiness and reduced QoL in patients with REM-related OSA. We also assessed if these characteristics were predictors of sleepiness and QoL in all patients with OSA (AHI ≥ 5) as well as in non-stage specific OSA. METHODS This was a cross-sectional analysis of a clinic-based population with OSA. In order to minimize the contribution of AHI(NREM), we defined REM-related OSA using the following criteria: an overall AHI ≥ 5, AHI(REM)/AHI(NREM) ≥ 2, AHI(NREM) the lowest quartile of the entire cohort. We examined the predictors of subjective sleepiness using the Epworth Sleepiness Scale (ESS) and QoL using the short-form quality of life questionnaire-12 (SF-12). RESULTS Of 1019 consecutive adults that were referred for their first in-laboratory polysomnogram for suspicion of OSA over a 10 month period, 931 had OSA. REM-related OSA was present in 126 patients. In adjusted linear regression models, AHI(NREM) was a significant predictor of sleepiness in the entire cohort of patients with OSA as well as non-stage specific OSA, but not in the REM-related OSA group. AHI(REM) was not a significant predictor of ESS or QoL in any of the three groups. However, greater depressive symptoms and body mass index were significant independent predictors of ESS and reduced QoL in the REM-related OSA group. CONCLUSION Higher depression scores and obesity, rather than the severity of OSA (as measured by AHI(NREM) and AHI(REM)), were predictive of sleepiness and QoL scores in patients with REM-related OSA.

Six-Minute Walk Test in Scleroderma-Associated Pulmonary Arterial Hypertension: Are We Counting What Counts?

> Everything that can be counted does not necessarily count; > > Everything that counts cannot necessarily be counted > > —Albert Einstein Systemic scleroderma (SSc) is a multisystem disease with protean manifestations, but pulmonary involvement is the leading cause of mortality. Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are 2 serious pulmonary complications of SSc that commonly cause clinical symptoms of dyspnea and exercise intolerance, can be associated with severe functional limitation, and often have a poor prognosis for longterm survival. SSc-associated PAH (SSc-PAH) is a serious disease of progressive pulmonary vascular obliteration characterized by persistent elevation of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR). Untreated SSc-PAH usually results in right-sided heart failure and high risk of death. The average survival in SSc patients diagnosed with PAH is 1–2 years1–3. Patients with SSc-PAH have a worse prognosis than most other PAH patients, including primary or idiopathic PAH (IPAH)4,5. Many new PAH-specific therapies have been studied and are available for the treatment of patients with SSc-PAH. These include prostacyclin derivatives (intravenous epoprostenol, subcutaneous or intravenous treprostinil), a novel family of oral endothelin receptor antagonists (bosentan, sitaxsentan, and ambrisentan), as well as an oral phosphodiesterase type 5 inhibitor (sildenafil)6. Treatment of PAH patients, including SSc-PAH, with these PAH-specific medications is associated with subjective and objective clinical benefit. Given that PAH is a disease of disturbed pulmonary hemodynamics, reductions in mean PAP and PVR, as well as improved right ventricular (RV) function, as evidenced by increased cardiac output, have been expectations of PAH therapy. However, repeated assessment of pulmonary hemodynamics by invasive rightheart catheterization is not feasible, and not necessarily indicated. Doppler echocardiographic assessment of RV systolic pressure (RVSP) is commonly used as a surrogate for systolic PAP. Moreover, other echo parameters, such … See Limitations to the 6-minute walk test in interstitial lung disease and pulmonary hypertension in scleroderma, page 330 Address reprint requests to Dr. S. Mehta, Division of Respirology, London Health Sciences Center-Victoria Hospital, Room E2.623, Professional Building, 800 Commissioner’s Road East, London, Ontario N6A 5W9, Canada. E-mail: sanjay.mehta{at}lhsc.on.ca

W-I-075 THE IMPACT OF SLEEP CONSULTATION PRIOR TO A DIAGNOSTIC POLYSOMNOGRAMON CPAP ADHERENCE

differences. In comparison of PSG parameters between 2 groups, older women showed the percentage of S3 and REM decreased but the percentage of S2 sleep increased. The older group also showed mean arterial oxygen in each stage was significant low and AHI, Non-REM AHI, Supine AHI were well correlated with ODI and DI. Conclusion: Even in pre-menopausal women, night symptoms and PSG parameters continue to be aggravated with age. But pre-menopause women are less likely to be aware of the progression of SDB because of lack of the change in daytime symptoms with age.