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: We investigated the effect of pioglitazone in comparison with and in combination with simvastatin on insulin resistance , plasma adiponectin , postpr and ial plasma glucose , insulin , and intact proinsulin levels in a nondiabetic population at cardiovascular risk . One hundred twenty-five nondiabetic patients at cardiovascular risk were r and omized to pioglitazone ( PIO ) , pioglitazone and simvastatin ( PIO/SIM ) , or simvastatin ( SIM ) treatments . Blood sample s were taken for the measurement of adiponectin and lipid levels . In addition , an oral glucose load with the measurements of glucose , insulin , and intact proinsulin levels was performed . Adiponectin levels increased from 14.0+/-8.2 to 27.6+/-14.5 microg/mL ( P<.0001 ) during PIO treatment and from 11.7+/-10.0 to 26.7+/-15.7 microg/mL ( P<.0001 ) during PIO/SIM treatment . A decrease in adiponectin levels from 15.5+/-12.7 to 11.6+/-7.0 microg/mL ( P<.05 ) was observed during SIM treatment . Although fasting intact proinsulin levels remained unchanged , the increase in postpr and ial intact proinsulin levels could be reduced from 29.5+/-21.4 to 22.1+/-17.5 pmol/L ( P<.01 ) during PIO treatment and from 24.3+/-27.4 to 21.1+/-16.5 mmol/L ( P<.05 ) during PIO/SIM treatment . Lipid parameters improved during SIM treatment but not during PIO treatment . Combined treatment with PIO/SIM was superior in improving overall cardiovascular risk profile than every single drug Background —Biological mechanisms underlying statin and angiotensin II type 1 receptor blocker therapies differ . Therefore , we compared vascular and metabolic responses to these therapies either alone or in combination in hypercholesterolemic , hypertensive patients . Methods and Results —This was a r and omized , double-blind , placebo-controlled crossover trial with 3 treatment arms ( each 2 months ) and 2 washout periods ( each 2 months ) . Forty-seven hypertensive , hypercholesterolemic patients were given simvastatin 20 mg and placebo , simvastatin 20 mg and losartan 100 mg , or losartan 100 mg and placebo daily during each 2-month treatment period . Losartan alone or combined therapy significantly reduced blood pressure compared with simvastatin alone . Compared with losartan alone , simvastatin alone or combined therapy significantly changed lipoproteins . All 3 treatment arms significantly improved flow-mediated dilator response to hyperemia and decreased plasma malondialdehyde and monocyte chemoattractant protein-1 levels relative to baseline measurements . However , these parameters were changed to a greater extent with combined therapy compared with simvastatin or losartan alone ( both P<0.001 and P=0.030 for monocyte chemoattractant protein-1 by ANOVA ) . Combined therapy or losartan alone significantly increased plasma adiponectin levels and insulin sensitivity ( determined by QUICKI ) relative to baseline measurements . These changes were significantly greater than in the group treated with simvastatin alone ( P<0.001 for adiponectin , P=0.029 for QUICKI by ANOVA ) . Conclusions —Simvastatin combined with losartan improves endothelial function and reduces inflammatory markers to a greater extent than monotherapy with either drug in hypercholesterolemic , hypertensive patients OBJECTIVES Statins and fibrates alter lipids , apolipoproteins and inflammatory markers in persons without HIV . The objective of this study was to evaluate changes in lipoproteins , apolipoproteins and other markers of inflammation with the use of pravastatin and fenofibrate . DESIGN Evaluation of participants in ACTG A5087 , a r and omized trial of pravastatin 40 mg/day or fenofibrate 200 mg/day for the treatment of dyslipidemia . Participants that failed single-agent therapy at week 12 were given the combination . METHODS Participants with available specimens were tested for apolipoproteins A1 and B , adiponectin , plasminogen-activator inhibitor type 1 ( PAI-1 ) , P-selectin , and high-sensitivity C-reactive protein ( hs-CRP ) . RESULTS 74 participants ( 37 per r and omized arm ) received either pravastatin or fenofibrate for 12 weeks with 60 receiving combination treatment from weeks 12 - 48 . There were no significant changes in hs-CRP , PAI-1 , and P-selectin . From baseline to week 12 , the median Apo B levels (-8 mg/dL , P=0.01 for fenofibrate and -27 mg/dL , P<0.01 for pravastatin ) and ApoB/A1 ratios ( -0.16 , P<0.01 for both arms ) significantly decreased . From baseline to week 48 , median adiponectin ( -1 ng/dL , P<0.01 ) , Apo B ( -22 mg/dL , P<0.01 ) and Apo B/A1 ratios ( -0.2 , P<0.01 ) all decreased in those who went on combination therapy , whereas Apo A1 ( 9.5 mg/dL , P=0.01 ) levels increased . CONCLUSION Treatment with pravastatin or fenofibrate improves the atherogenic lipid profile within the first 12 weeks and is sustained through 48 weeks with combination therapy . Adiponectin levels decrease with lipid-lowering therapy . However , markers of inflammation and platelet activation were not appreciably changed suggesting that the biologic properties of these agents differ in persons with HIV infection OBJECTIVES We investigated whether atorvastatin might decrease insulin sensitivity and increase ambient glycemia in hypercholesterolemic patients . BACKGROUND Clinical trials suggest that some statin treatments might increase the incidence of diabetes despite reductions in low-density lipoprotein ( LDL ) cholesterol and improvement in endothelial dysfunction . METHODS A r and omized , single-blind , placebo-controlled parallel study was conducted in 44 patients taking placebo and in 42 , 44 , 43 , and 40 patients given daily atorvastatin 10 , 20 , 40 , and 80 mg , respectively , during a 2-month treatment period . RESULTS Atorvastatin 10 , 20 , 40 , and 80 mg significantly reduced LDL cholesterol ( 39 % , 47 % , 52 % , and 56 % , respectively ) and apolipoprotein B levels ( 33 % , 37 % , 42 % , and 46 % , respectively ) after 2 months of therapy when compared with either baseline ( all p < 0.001 by paired t test ) or placebo ( p < 0.001 by analysis of variance [ ANOVA ] ) . Atorvastatin 10 , 20 , 40 , and 80 mg significantly increased fasting plasma insulin ( mean changes : 25 % , 42 % , 31 % , and 45 % , respectively ) and glycated hemoglobin levels ( 2 % , 5 % , 5 % , and 5 % , respectively ) when compared with either baseline ( all p < 0.05 by paired t test ) or placebo ( p = 0.009 for insulin and p = 0.008 for glycated hemoglobin by ANOVA ) . Atorvastatin 10 , 20 , 40 , and 80 mg decreased insulin sensitivity ( 1 % , 3 % , 3 % , and 4 % , respectively ) when compared with either baseline ( p = 0.312 , p = 0.008 , p < 0.001 , and p = 0.008 , respectively , by paired t test ) or placebo ( p = 0.033 by ANOVA ) . CONCLUSIONS Despite beneficial reductions in LDL cholesterol and apolipoprotein B , atorvastatin treatment result ed in significant increases in fasting insulin and glycated hemoglobin levels consistent with insulin resistance and increased ambient glycemia in hypercholesterolemic patients . ( Effects of Atorvastatin on Adiponectin Levels and Insulin Sensitivity In Hypercholesterolemic Patients ; NCT00745836 ) Little is known about the effect of exercise training on the expression of adiponectin receptor genes in peripheral blood mononuclear cells ( P BMC s ) . In this study , we investigated the effects of aerobic training on the expression of AdipoR1 and AidpoR2 mRNAs in P BMC s , whole body insulin sensitivity , and circulating adiponectins in men . Thirty young men were r and omly assigned to either a control ( n=15 ) or an exercise ( n=15 ) group . Subjects assigned to the exercise group underwent a 12-week jogging and /or running programme on a motor-driven treadmill at an intensity of 60%-75 % of the age-based maximum heart rate with duration of 40 minutes per session and a frequency of 5 days per week . Two-way mixed ANOVA with repeated measures was used to test any significant time-by-group interaction effects for the measured variables at p=0.05 . We found significant time-by-group interaction effects for waist circumference ( p=0.001 ) , VO2max ( p<0.001 ) , fasting insulin ( p=0.016 ) , homeostasis model assessment for insulin resistance ( HOMA-IR ) ( p=0.010 ) , area under the curve ( AUC ) for insulin response during the 75-g oral glucose tolerance test ( p=0.002 ) , high-molecular weight ( HMW ) adiponectin ( p=0.016 ) , and the P BMC mRNA levels of AdipoR1 ( p<0.001 ) and AdipoR2 ( p=0.001 ) . The exercise group had significantly increased mRNA levels of AdipoR1 and AdipoR2 in P BMC s , along with increased whole body insulin sensitivity and HMW adiponectin , decreased waist circumference , and increased VO2max compared with the control group . In summary , the current findings suggest that exercise training modulates the expression of AdipoR1 and AdipoR2 mRNAs in P BMC s , implying that manipulation of the expression of these genes could be a potential surrogate for lifestyle intervention-mediated improvements of whole body insulin sensitivity and glucose homeostasis Reduction of serum cholesterol levels with statin therapy decreases the risk of coronary heart disease . Inhibition of HMG-CoA reductase by statin results in decreased synthesis of cholesterol and other products downstream of mevalonate , which may produce adverse effects in statin therapy . We studied the reductions of serum ubiquinol-10 and ubiquinone-10 levels in hypercholesterolemic patients treated with atorvastatin . Fourteen patients were treated with 10 mg/day of atorvastatin  , and serum lipid , ubiquinol-10 and ubiquinone-10 levels were measured before and after 8 weeks of treatment . Serum total cholesterol and LDL-cholesterol levels decreased significantly . All patients showed definite reductions of serum ubiquinol-10 and ubiquinone-10 levels , and mean levels of serum ubiquinol-10 and ubiquinone-10 levels decreased significantly from 0.81 + /- 0.21 to 0.46 + /- 0.10 microg/ml ( p < 0.0001 ) , and from 0.10 + /- 0.06 to 0.06 + /- 0.02 microg/ml ( p = 0.0008 ) , respectively . Percent reductions of ubiquinol-10 and those of total cholesterol showed a positive correlation ( r = 0.627 , p = 0.0165 ) . As atorvastatin reduces serum ubiquinol-10 as well as serum cholesterol levels in all patients , it is imperative that physicians are forewarned about the risks associated with ubiquinol-10 depletion OBJECTIVE Pravastatin has been reported to elevate circulating adiponectin levels in patients with various insulin resistant state , hypertension , coronary artery disease , and hypercholesterolemia . This study aim ed to evaluate whether pravastatin increase serum total and high molecular weight adiponectin levels and improve insulin sensitivity in female patients with type 2 diabetes mellitus and hypercholesterolemia . PATIENTS AND DESIGN This study was design ed as a multicenter , double-blind , placebo-controlled , factorial r and omized trial ( placebo and pravastatin at 20 or 40 mg per day ) . A total of 73 female patients with type 2 diabetes and hypercholesterolemia were enrolled . Changes in total and high molecular weight ( HMW ) serum adiponect 
    Output:
    
agent
The meta- analysis showed a significant increase in plasma adiponectin levels following statin therapy .
Although statins are known to increase the risk for new onset diabetes mellitus , our data might suggest that the mechanism for this is unlikely to be due to a reduction in adiponectin expression
***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: We investigated the effect of pioglitazone in comparison with and in combination with simvastatin on insulin resistance , plasma adiponectin , postpr and ial plasma glucose , insulin , and intact proinsulin levels in a nondiabetic population at cardiovascular risk . One hundred twenty-five nondiabetic patients at cardiovascular risk were r and omized to pioglitazone ( PIO ) , pioglitazone and simvastatin ( PIO/SIM ) , or simvastatin ( SIM ) treatments . Blood sample s were taken for the measurement of adiponectin and lipid levels . In addition , an oral glucose load with the measurements of glucose , insulin , and intact proinsulin levels was performed . Adiponectin levels increased from 14.0+/-8.2 to 27.6+/-14.5 microg/mL ( P<.0001 ) during PIO treatment and from 11.7+/-10.0 to 26.7+/-15.7 microg/mL ( P<.0001 ) during PIO/SIM treatment . A decrease in adiponectin levels from 15.5+/-12.7 to 11.6+/-7.0 microg/mL ( P<.05 ) was observed during SIM treatment . Although fasting intact proinsulin levels remained unchanged , the increase in postpr and ial intact proinsulin levels could be reduced from 29.5+/-21.4 to 22.1+/-17.5 pmol/L ( P<.01 ) during PIO treatment and from 24.3+/-27.4 to 21.1+/-16.5 mmol/L ( P<.05 ) during PIO/SIM treatment . Lipid parameters improved during SIM treatment but not during PIO treatment . Combined treatment with PIO/SIM was superior in improving overall cardiovascular risk profile than every single drug Background —Biological mechanisms underlying statin and angiotensin II type 1 receptor blocker therapies differ . Therefore , we compared vascular and metabolic responses to these therapies either alone or in combination in hypercholesterolemic , hypertensive patients . Methods and Results —This was a r and omized , double-blind , placebo-controlled crossover trial with 3 treatment arms ( each 2 months ) and 2 washout periods ( each 2 months ) . Forty-seven hypertensive , hypercholesterolemic patients were given simvastatin 20 mg and placebo , simvastatin 20 mg and losartan 100 mg , or losartan 100 mg and placebo daily during each 2-month treatment period . Losartan alone or combined therapy significantly reduced blood pressure compared with simvastatin alone . Compared with losartan alone , simvastatin alone or combined therapy significantly changed lipoproteins . All 3 treatment arms significantly improved flow-mediated dilator response to hyperemia and decreased plasma malondialdehyde and monocyte chemoattractant protein-1 levels relative to baseline measurements . However , these parameters were changed to a greater extent with combined therapy compared with simvastatin or losartan alone ( both P<0.001 and P=0.030 for monocyte chemoattractant protein-1 by ANOVA ) . Combined therapy or losartan alone significantly increased plasma adiponectin levels and insulin sensitivity ( determined by QUICKI ) relative to baseline measurements . These changes were significantly greater than in the group treated with simvastatin alone ( P<0.001 for adiponectin , P=0.029 for QUICKI by ANOVA ) . Conclusions —Simvastatin combined with losartan improves endothelial function and reduces inflammatory markers to a greater extent than monotherapy with either drug in hypercholesterolemic , hypertensive patients OBJECTIVES Statins and fibrates alter lipids , apolipoproteins and inflammatory markers in persons without HIV . The objective of this study was to evaluate changes in lipoproteins , apolipoproteins and other markers of inflammation with the use of pravastatin and fenofibrate . DESIGN Evaluation of participants in ACTG A5087 , a r and omized trial of pravastatin 40 mg/day or fenofibrate 200 mg/day for the treatment of dyslipidemia . Participants that failed single-agent therapy at week 12 were given the combination . METHODS Participants with available specimens were tested for apolipoproteins A1 and B , adiponectin , plasminogen-activator inhibitor type 1 ( PAI-1 ) , P-selectin , and high-sensitivity C-reactive protein ( hs-CRP ) . RESULTS 74 participants ( 37 per r and omized arm ) received either pravastatin or fenofibrate for 12 weeks with 60 receiving combination treatment from weeks 12 - 48 . There were no significant changes in hs-CRP , PAI-1 , and P-selectin . From baseline to week 12 , the median Apo B levels (-8 mg/dL , P=0.01 for fenofibrate and -27 mg/dL , P<0.01 for pravastatin ) and ApoB/A1 ratios ( -0.16 , P<0.01 for both arms ) significantly decreased . From baseline to week 48 , median adiponectin ( -1 ng/dL , P<0.01 ) , Apo B ( -22 mg/dL , P<0.01 ) and Apo B/A1 ratios ( -0.2 , P<0.01 ) all decreased in those who went on combination therapy , whereas Apo A1 ( 9.5 mg/dL , P=0.01 ) levels increased . CONCLUSION Treatment with pravastatin or fenofibrate improves the atherogenic lipid profile within the first 12 weeks and is sustained through 48 weeks with combination therapy . Adiponectin levels decrease with lipid-lowering therapy . However , markers of inflammation and platelet activation were not appreciably changed suggesting that the biologic properties of these agents differ in persons with HIV infection OBJECTIVES We investigated whether atorvastatin might decrease insulin sensitivity and increase ambient glycemia in hypercholesterolemic patients . BACKGROUND Clinical trials suggest that some statin treatments might increase the incidence of diabetes despite reductions in low-density lipoprotein ( LDL ) cholesterol and improvement in endothelial dysfunction . METHODS A r and omized , single-blind , placebo-controlled parallel study was conducted in 44 patients taking placebo and in 42 , 44 , 43 , and 40 patients given daily atorvastatin 10 , 20 , 40 , and 80 mg , respectively , during a 2-month treatment period . RESULTS Atorvastatin 10 , 20 , 40 , and 80 mg significantly reduced LDL cholesterol ( 39 % , 47 % , 52 % , and 56 % , respectively ) and apolipoprotein B levels ( 33 % , 37 % , 42 % , and 46 % , respectively ) after 2 months of therapy when compared with either baseline ( all p < 0.001 by paired t test ) or placebo ( p < 0.001 by analysis of variance [ ANOVA ] ) . Atorvastatin 10 , 20 , 40 , and 80 mg significantly increased fasting plasma insulin ( mean changes : 25 % , 42 % , 31 % , and 45 % , respectively ) and glycated hemoglobin levels ( 2 % , 5 % , 5 % , and 5 % , respectively ) when compared with either baseline ( all p < 0.05 by paired t test ) or placebo ( p = 0.009 for insulin and p = 0.008 for glycated hemoglobin by ANOVA ) . Atorvastatin 10 , 20 , 40 , and 80 mg decreased insulin sensitivity ( 1 % , 3 % , 3 % , and 4 % , respectively ) when compared with either baseline ( p = 0.312 , p = 0.008 , p < 0.001 , and p = 0.008 , respectively , by paired t test ) or placebo ( p = 0.033 by ANOVA ) . CONCLUSIONS Despite beneficial reductions in LDL cholesterol and apolipoprotein B , atorvastatin treatment result ed in significant increases in fasting insulin and glycated hemoglobin levels consistent with insulin resistance and increased ambient glycemia in hypercholesterolemic patients . ( Effects of Atorvastatin on Adiponectin Levels and Insulin Sensitivity In Hypercholesterolemic Patients ; NCT00745836 ) Little is known about the effect of exercise training on the expression of adiponectin receptor genes in peripheral blood mononuclear cells ( P BMC s ) . In this study , we investigated the effects of aerobic training on the expression of AdipoR1 and AidpoR2 mRNAs in P BMC s , whole body insulin sensitivity , and circulating adiponectins in men . Thirty young men were r and omly assigned to either a control ( n=15 ) or an exercise ( n=15 ) group . Subjects assigned to the exercise group underwent a 12-week jogging and /or running programme on a motor-driven treadmill at an intensity of 60%-75 % of the age-based maximum heart rate with duration of 40 minutes per session and a frequency of 5 days per week . Two-way mixed ANOVA with repeated measures was used to test any significant time-by-group interaction effects for the measured variables at p=0.05 . We found significant time-by-group interaction effects for waist circumference ( p=0.001 ) , VO2max ( p<0.001 ) , fasting insulin ( p=0.016 ) , homeostasis model assessment for insulin resistance ( HOMA-IR ) ( p=0.010 ) , area under the curve ( AUC ) for insulin response during the 75-g oral glucose tolerance test ( p=0.002 ) , high-molecular weight ( HMW ) adiponectin ( p=0.016 ) , and the P BMC mRNA levels of AdipoR1 ( p<0.001 ) and AdipoR2 ( p=0.001 ) . The exercise group had significantly increased mRNA levels of AdipoR1 and AdipoR2 in P BMC s , along with increased whole body insulin sensitivity and HMW adiponectin , decreased waist circumference , and increased VO2max compared with the control group . In summary , the current findings suggest that exercise training modulates the expression of AdipoR1 and AdipoR2 mRNAs in P BMC s , implying that manipulation of the expression of these genes could be a potential surrogate for lifestyle intervention-mediated improvements of whole body insulin sensitivity and glucose homeostasis Reduction of serum cholesterol levels with statin therapy decreases the risk of coronary heart disease . Inhibition of HMG-CoA reductase by statin results in decreased synthesis of cholesterol and other products downstream of mevalonate , which may produce adverse effects in statin therapy . We studied the reductions of serum ubiquinol-10 and ubiquinone-10 levels in hypercholesterolemic patients treated with atorvastatin . Fourteen patients were treated with 10 mg/day of atorvastatin  , and serum lipid , ubiquinol-10 and ubiquinone-10 levels were measured before and after 8 weeks of treatment . Serum total cholesterol and LDL-cholesterol levels decreased significantly . All patients showed definite reductions of serum ubiquinol-10 and ubiquinone-10 levels , and mean levels of serum ubiquinol-10 and ubiquinone-10 levels decreased significantly from 0.81 + /- 0.21 to 0.46 + /- 0.10 microg/ml ( p < 0.0001 ) , and from 0.10 + /- 0.06 to 0.06 + /- 0.02 microg/ml ( p = 0.0008 ) , respectively . Percent reductions of ubiquinol-10 and those of total cholesterol showed a positive correlation ( r = 0.627 , p = 0.0165 ) . As atorvastatin reduces serum ubiquinol-10 as well as serum cholesterol levels in all patients , it is imperative that physicians are forewarned about the risks associated with ubiquinol-10 depletion OBJECTIVE Pravastatin has been reported to elevate circulating adiponectin levels in patients with various insulin resistant state , hypertension , coronary artery disease , and hypercholesterolemia . This study aim ed to evaluate whether pravastatin increase serum total and high molecular weight adiponectin levels and improve insulin sensitivity in female patients with type 2 diabetes mellitus and hypercholesterolemia . PATIENTS AND DESIGN This study was design ed as a multicenter , double-blind , placebo-controlled , factorial r and omized trial ( placebo and pravastatin at 20 or 40 mg per day ) . A total of 73 female patients with type 2 diabetes and hypercholesterolemia were enrolled . Changes in total and high molecular weight ( HMW ) serum adiponect 
    Output:
    