human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background : The effects of continuous positive airway pressure ( CPAP ) for obstructive sleep apnoea ( OSA ) on insulin resistance are not clear . Trials have found conflicting results and no appropriate control groups have been used . Methods : Forty-two men with known type 2 diabetes and newly diagnosed OSA ( > 10 dips/h in oxygen saturation of > 4 % ) were r and omised to receive therapeutic ( n = 20 ) or placebo CPAP ( n = 22 ) for 3 months . Baseline tests were performed and repeated after 3 months . The study was double blind . Results : Results are expressed as mean ( SD ) . CPAP  improved the Epworth sleepiness score significantly more in the therapeutic group than in the placebo group ( −6.6 ( 4.5 ) vs −2.6 ( 4.9 ) , p = 0.01 ) . The maintenance of wakefulness test improved significantly in the therapeutic group but not in the placebo group ( + 10.6 ( 13.9 ) vs −4.7 ( 11.8 ) min , p = 0.001 ) . Glycaemic control and insulin resistance did not significantly change in either the therapeutic or placebo groups : HbA1c ( −0.02 ( 1.5 ) vs + 0.1 ( 0.7 ) , p = 0.7 , 95 % CI −0.6 % to + 0.9 % ) , euglycaemic clamp ( M/I : + 1.7 ( 14.1 ) vs −5.7 ( 14.8 ) , p = 0.2 , 95 % CI −1.8 to + 0.3 l/kg/min1000 ) , HOMA-%S ( −1.5 ( 2.3 ) vs −1.1 ( 1.8 ) , p = 0.2 , 95 % CI −0.3 % to + 0.08 % ) and adiponectin ( −1.1 ( 1.2 ) vs −1.1 ( 1.3 ) , p = 0.2 , 95 % CI −0.7 to + 0.6 & mgr;g/ml ) . Body mass index , bioimpedance and anthropometric measurements were unchanged . Hours of CPAP use per night were 3.6 ( 2.8 ) in the treatment group and 3.3 ( 3.0 ) in the placebo group ( p = 0.8 ) . There was no correlation between CPAP use and the measures of glycaemic control or insulin resistance . Conclusion : Therapeutic CPAP does not significantly improve measures of glycaemic control or insulin resistance in men with type 2 diabetes and OSA 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 prospect i ve 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 r and omly 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 Purpose Obstructive sleep apnea ( OSA ) is highly associated with type 2 diabetes mellitus ( DM ) , and treatment of OSA may have a positive impact on cardiometabolic profile . This study investigates the effects of continuous positive airway pressure ( CPAP ) treatment on glycemic control and cardiometabolic parameters in patients with diabetes . Methods Diabetic patients , who were newly diagnosed of OSA with an apnea hypopnea index ( AHI ) ≥15 and HbA1c ≥7 % , were r and omly assigned to either CPAP treatment or no treatment ( control ) for 3 months . Measurements included HbA1c , blood pressure , fasting glucose and lipids , urinary albumin , and peripheral arterial tonometry ( to assess endothelial function ) . Results Sixty-four patients ( 52 men ) were r and omized , with mean ( ±SD ) age of 55.0 ± 9.6 years , body mass index of 29.9 ± 5.3 kg/m2 , HbA1c of 8.1 ± 1.1 % , and AHI of 45.3 ± 23.2 events/h . In the intention-to-treat analysis , no significant change in HbA1c but reduction of systolic ( 10 mmHg ( −18 to −2 ) , p < 0.05 ) and diastolic ( 6 mmHg ( −11 to −1 ) , p < 0.05 ) blood pressures were found in the CPAP group compared to the control group . Excluding those with medication changes or initiated dietary program during the study period and those who dropped out , CPAP treatment decreased HbA1c ( intervention group , n = 27 ; control group , n = 26 ) by 0.4 % ( −0.7 to −0.1 ) , p = 0.027 . Conclusions In patients with type 2 DM and moderate to severe OSA , 3 months of CPAP therapy did not decrease HbA1c but lowered systolic and diastolic blood pressures . In view of a potentially limited effect size of CPAP treatment on glycemic control , sample size estimation for future r and omized controlled studies must make adequate allowance for influence from external factors of medications/diet and CPAP use Background — Obstructive sleep apnea syndrome ( OSAS ) , characterized by intermittent hypoxia/reoxygenation ( IHR ) , is an independent risk factor for cardiovascular disease . We investigated the underlying molecular mechanisms of this association in a translational study . Methods and Results — In a novel in vitro model of IHR , we used HeLa cells transfected with reporter constructs and DNA binding assays for the master transcriptional regulators of the inflammatory and adaptive pathways ( NF&kgr;B and HIF-1 , respectively ) to investigate underlying transcriptional events initiated by repeated cell exposure to IHR . Furthermore , we prospect ively studied 19 male OSAS patients ( median apnea-hypopnea frequency , 48.5 episodes per hour ; interquartile range [ IQR ] , 28.5 to 72.9 ) and 17 matched normal control subjects . Circulating levels of the proinflammatory cytokine tumor necrosis factor-&agr ; and the adaptive factor erythropoietin were assayed in all subjects at baseline and again after 6 weeks of continuous positive airway pressure therapy in patients . Full blood count was measured as part of a detailed baseline evaluation . HeLa cells exposed to IHR demonstrated selective activation of the proinflammatory transcription factor NF&kgr;B ( P<0.001 by ANOVA ) , whereas the adaptive regulator HIF-1 was not activated , as demonstrated by luciferase reporter assays and DNA binding studies . Circulating tumor necrosis factor-&agr ; levels were higher in OSAS patients ( 2.56 pg/mL ; IQR , 2.01 to 3.42 pg/mL ) than in control subjects ( 1.25 pg/mL ; IQR , 0.94 to 1.87 ; P<0.001 ) but normalized with continuous positive airway pressure therapy ( 1.24 pg/mL ; IQR , 0.78 to 2.35 pg/mL ; P=0.002 ) . In contrast , erythropoietin levels were similar throughout . Furthermore , circulating neutrophil levels were higher in OSAS patients than in control subjects , whereas the hematocrit was unaltered . Conclusions — These data demonstrate selective activation of inflammatory over adaptive pathways in IHR and OSAS , which may be an important molecular mechanism of cardiovascular disease Background — Indirect evidence implicates endothelial dysfunction in the pathogenesis of vascular diseases associated with obstructive sleep apnea ( OSA ) . We investigated directly whether dysfunction and inflammation occur in vivo in the vascular endothelium of patients with OSA . The effects of continuous positive airway pressure ( CPAP ) therapy on endothelial function and repair capacity were assessed . Methods and Results — Thirty-two patients with newly diagnosed OSA and 15 control subjects were studied . Proteins that regulate basal endothelial nitric oxide ( NO ) production ( endothelial NO synthase [ eNOS ] and phosphorylated eNOS ) and inflammation ( cyclooxygenase-2 and inducible NOS ) and markers of oxidative stress ( nitrotyrosine ) were quantified by immunofluorescence in freshly harvested venous endothelial cells before and after 4 weeks of CPAP therapy . Vascular reactivity was measured by flow-mediated dilation . Circulating endothelial progenitor cell levels were quantified to assess endothelial repair capacity . Baseline endothelial expression of eNOS and phosphorylated eNOS was reduced by 59 % and 94 % , respectively , in patients with OSA compared with control subjects . Expression of both nitrotyrosine and cyclooxygenase-2 was 5-fold greater in patients with OSA than in control subjects , whereas inducible NOS expression was 56 % greater . Expression of eNOS and phosphorylated eNOS significantly increased , whereas expression of nitrotyrosine , cyclooxygenase-2 , and inducible NOS significantly decreased in patients who adhered to CPAP ≥4 hours daily . Baseline flow-mediated dilation and endothelial progenitor cell levels were lower in patients than in control subjects , and both significantly increased in patients who adhered to CPAP ≥4 hours daily . Conclusions — OSA directly affects the vascular endothelium by promoting inflammation and oxidative stress while decreasing NO availability and repair capacity . Effective CPAP therapy is associated with the reversal of these alterations BACKGROUND Type 2 diabetes and obstructive sleep apnea ( OSA ) are frequently comorbid conditions . OSA is associated with increased insulin resistance , but studies of continuous positive airway pressure ( CPAP ) have shown inconsistent effects on glycemic control . However , endpoints such as hemoglobin A1c and insulin sensitivity might not reflect short-term changes in glycemic control during sleep . METHODS We used a continuous glucose-monitoring system to measure interstitial glucose every 5 minutes during polysomnography in 20 patients with type 2 diabetes and newly diagnosed OSA . The measurements were repeated after an average of 41 days of CPAP ( range 26 - 96 days ) . All patients were on a stable diet and medications . Each 30-second epoch of the polysomnogram was matched with a continuous glucose-monitoring system reading , and the sleeping glucose level was calculated as the average for all epochs scored as sleeping . RESULTS The mean sleeping glucose decreased from untreated ( 122.0 + /- 61.7 mg/dL ) to treated ( 102.9 + /- 39.4 mg/dL ; p = 0.03 by Wilcoxon paired rank test ) . The sleeping glucose was more stable after treatment , with the median SD decreasing from 20.0 to 13.0 mg/dL ( p = 0.005 ) and the mean difference between maximum and minimum values decreasing from 88 to 57 mg/dL ( p= 0.003 ) . The change in the mean hemoglobin A1c from 7.1 % to 7.2 % was not significant . CONCLUSIONS Our study is limited by the lack of a control group , but the results suggest that sleeping glucose levels decrease and are more stable after patients with type 2 diabetes and OSA are treated with CPAP CONTEXT Few prospect i ve intervention studies have examined the effect of continuous positive airway pressure ( CPAP ) therapy on cardiovascular disease ( CVD ) risk factors in diabetes . OBJECTIVE Our objective was to determine whether CPAP improves CVD risk factors in patients with type 2 diabetes and obstructive sleep apnea ( OSA ) . DESIGN AND SETTING This was a r and omized parallel group intervention trial in an urban Australian community . PATIENTS Fifty-nine participants of the Fremantle Diabetes Study Phase II at high risk for OSA consented to confirmatory polysomnography followed by r and omization to a  
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background : The effects of continuous positive airway pressure ( CPAP ) for obstructive sleep apnoea ( OSA ) on insulin resistance are not clear . Trials have found conflicting results and no appropriate control groups have been used . Methods : Forty-two men with known type 2 diabetes and newly diagnosed OSA ( > 10 dips/h in oxygen saturation of > 4 % ) were r and omised to receive therapeutic ( n = 20 ) or placebo CPAP ( n = 22 ) for 3 months . Baseline tests were performed and repeated after 3 months . The study was double blind . Results : Results are expressed as mean ( SD ) . CPAP  improved the Epworth sleepiness score significantly more in the therapeutic group than in the placebo group ( −6.6 ( 4.5 ) vs −2.6 ( 4.9 ) , p = 0.01 ) . The maintenance of wakefulness test improved significantly in the therapeutic group but not in the placebo group ( + 10.6 ( 13.9 ) vs −4.7 ( 11.8 ) min , p = 0.001 ) . Glycaemic control and insulin resistance did not significantly change in either the therapeutic or placebo groups : HbA1c ( −0.02 ( 1.5 ) vs + 0.1 ( 0.7 ) , p = 0.7 , 95 % CI −0.6 % to + 0.9 % ) , euglycaemic clamp ( M/I : + 1.7 ( 14.1 ) vs −5.7 ( 14.8 ) , p = 0.2 , 95 % CI −1.8 to + 0.3 l/kg/min1000 ) , HOMA-%S ( −1.5 ( 2.3 ) vs −1.1 ( 1.8 ) , p = 0.2 , 95 % CI −0.3 % to + 0.08 % ) and adiponectin ( −1.1 ( 1.2 ) vs −1.1 ( 1.3 ) , p = 0.2 , 95 % CI −0.7 to + 0.6 & mgr;g/ml ) . Body mass index , bioimpedance and anthropometric measurements were unchanged . Hours of CPAP use per night were 3.6 ( 2.8 ) in the treatment group and 3.3 ( 3.0 ) in the placebo group ( p = 0.8 ) . There was no correlation between CPAP use and the measures of glycaemic control or insulin resistance . Conclusion : Therapeutic CPAP does not significantly improve measures of glycaemic control or insulin resistance in men with type 2 diabetes and OSA 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 prospect i ve 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 r and omly 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 Purpose Obstructive sleep apnea ( OSA ) is highly associated with type 2 diabetes mellitus ( DM ) , and treatment of OSA may have a positive impact on cardiometabolic profile . This study investigates the effects of continuous positive airway pressure ( CPAP ) treatment on glycemic control and cardiometabolic parameters in patients with diabetes . Methods Diabetic patients , who were newly diagnosed of OSA with an apnea hypopnea index ( AHI ) ≥15 and HbA1c ≥7 % , were r and omly assigned to either CPAP treatment or no treatment ( control ) for 3 months . Measurements included HbA1c , blood pressure , fasting glucose and lipids , urinary albumin , and peripheral arterial tonometry ( to assess endothelial function ) . Results Sixty-four patients ( 52 men ) were r and omized , with mean ( ±SD ) age of 55.0 ± 9.6 years , body mass index of 29.9 ± 5.3 kg/m2 , HbA1c of 8.1 ± 1.1 % , and AHI of 45.3 ± 23.2 events/h . In the intention-to-treat analysis , no significant change in HbA1c but reduction of systolic ( 10 mmHg ( −18 to −2 ) , p < 0.05 ) and diastolic ( 6 mmHg ( −11 to −1 ) , p < 0.05 ) blood pressures were found in the CPAP group compared to the control group . Excluding those with medication changes or initiated dietary program during the study period and those who dropped out , CPAP treatment decreased HbA1c ( intervention group , n = 27 ; control group , n = 26 ) by 0.4 % ( −0.7 to −0.1 ) , p = 0.027 . Conclusions In patients with type 2 DM and moderate to severe OSA , 3 months of CPAP therapy did not decrease HbA1c but lowered systolic and diastolic blood pressures . In view of a potentially limited effect size of CPAP treatment on glycemic control , sample size estimation for future r and omized controlled studies must make adequate allowance for influence from external factors of medications/diet and CPAP use Background — Obstructive sleep apnea syndrome ( OSAS ) , characterized by intermittent hypoxia/reoxygenation ( IHR ) , is an independent risk factor for cardiovascular disease . We investigated the underlying molecular mechanisms of this association in a translational study . Methods and Results — In a novel in vitro model of IHR , we used HeLa cells transfected with reporter constructs and DNA binding assays for the master transcriptional regulators of the inflammatory and adaptive pathways ( NF&kgr;B and HIF-1 , respectively ) to investigate underlying transcriptional events initiated by repeated cell exposure to IHR . Furthermore , we prospect ively studied 19 male OSAS patients ( median apnea-hypopnea frequency , 48.5 episodes per hour ; interquartile range [ IQR ] , 28.5 to 72.9 ) and 17 matched normal control subjects . Circulating levels of the proinflammatory cytokine tumor necrosis factor-&agr ; and the adaptive factor erythropoietin were assayed in all subjects at baseline and again after 6 weeks of continuous positive airway pressure therapy in patients . Full blood count was measured as part of a detailed baseline evaluation . HeLa cells exposed to IHR demonstrated selective activation of the proinflammatory transcription factor NF&kgr;B ( P<0.001 by ANOVA ) , whereas the adaptive regulator HIF-1 was not activated , as demonstrated by luciferase reporter assays and DNA binding studies . Circulating tumor necrosis factor-&agr ; levels were higher in OSAS patients ( 2.56 pg/mL ; IQR , 2.01 to 3.42 pg/mL ) than in control subjects ( 1.25 pg/mL ; IQR , 0.94 to 1.87 ; P<0.001 ) but normalized with continuous positive airway pressure therapy ( 1.24 pg/mL ; IQR , 0.78 to 2.35 pg/mL ; P=0.002 ) . In contrast , erythropoietin levels were similar throughout . Furthermore , circulating neutrophil levels were higher in OSAS patients than in control subjects , whereas the hematocrit was unaltered . Conclusions — These data demonstrate selective activation of inflammatory over adaptive pathways in IHR and OSAS , which may be an important molecular mechanism of cardiovascular disease Background — Indirect evidence implicates endothelial dysfunction in the pathogenesis of vascular diseases associated with obstructive sleep apnea ( OSA ) . We investigated directly whether dysfunction and inflammation occur in vivo in the vascular endothelium of patients with OSA . The effects of continuous positive airway pressure ( CPAP ) therapy on endothelial function and repair capacity were assessed . Methods and Results — Thirty-two patients with newly diagnosed OSA and 15 control subjects were studied . Proteins that regulate basal endothelial nitric oxide ( NO ) production ( endothelial NO synthase [ eNOS ] and phosphorylated eNOS ) and inflammation ( cyclooxygenase-2 and inducible NOS ) and markers of oxidative stress ( nitrotyrosine ) were quantified by immunofluorescence in freshly harvested venous endothelial cells before and after 4 weeks of CPAP therapy . Vascular reactivity was measured by flow-mediated dilation . Circulating endothelial progenitor cell levels were quantified to assess endothelial repair capacity . Baseline endothelial expression of eNOS and phosphorylated eNOS was reduced by 59 % and 94 % , respectively , in patients with OSA compared with control subjects . Expression of both nitrotyrosine and cyclooxygenase-2 was 5-fold greater in patients with OSA than in control subjects , whereas inducible NOS expression was 56 % greater . Expression of eNOS and phosphorylated eNOS significantly increased , whereas expression of nitrotyrosine , cyclooxygenase-2 , and inducible NOS significantly decreased in patients who adhered to CPAP ≥4 hours daily . Baseline flow-mediated dilation and endothelial progenitor cell levels were lower in patients than in control subjects , and both significantly increased in patients who adhered to CPAP ≥4 hours daily . Conclusions — OSA directly affects the vascular endothelium by promoting inflammation and oxidative stress while decreasing NO availability and repair capacity . Effective CPAP therapy is associated with the reversal of these alterations BACKGROUND Type 2 diabetes and obstructive sleep apnea ( OSA ) are frequently comorbid conditions . OSA is associated with increased insulin resistance , but studies of continuous positive airway pressure ( CPAP ) have shown inconsistent effects on glycemic control . However , endpoints such as hemoglobin A1c and insulin sensitivity might not reflect short-term changes in glycemic control during sleep . METHODS We used a continuous glucose-monitoring system to measure interstitial glucose every 5 minutes during polysomnography in 20 patients with type 2 diabetes and newly diagnosed OSA . The measurements were repeated after an average of 41 days of CPAP ( range 26 - 96 days ) . All patients were on a stable diet and medications . Each 30-second epoch of the polysomnogram was matched with a continuous glucose-monitoring system reading , and the sleeping glucose level was calculated as the average for all epochs scored as sleeping . RESULTS The mean sleeping glucose decreased from untreated ( 122.0 + /- 61.7 mg/dL ) to treated ( 102.9 + /- 39.4 mg/dL ; p = 0.03 by Wilcoxon paired rank test ) . The sleeping glucose was more stable after treatment , with the median SD decreasing from 20.0 to 13.0 mg/dL ( p = 0.005 ) and the mean difference between maximum and minimum values decreasing from 88 to 57 mg/dL ( p= 0.003 ) . The change in the mean hemoglobin A1c from 7.1 % to 7.2 % was not significant . CONCLUSIONS Our study is limited by the lack of a control group , but the results suggest that sleeping glucose levels decrease and are more stable after patients with type 2 diabetes and OSA are treated with CPAP CONTEXT Few prospect i ve intervention studies have examined the effect of continuous positive airway pressure ( CPAP ) therapy on cardiovascular disease ( CVD ) risk factors in diabetes . OBJECTIVE Our objective was to determine whether CPAP improves CVD risk factors in patients with type 2 diabetes and obstructive sleep apnea ( OSA ) . DESIGN AND SETTING This was a r and omized parallel group intervention trial in an urban Australian community . PATIENTS Fifty-nine participants of the Fremantle Diabetes Study Phase II at high risk for OSA consented to confirmatory polysomnography followed by r and omization to a  
    Output:
    