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: Obese AT ( adipose tissue ) exhibits increased macrophage number . Pro-inflammatory CD16 + peripheral monocyte numbers are also reported to increase with obesity . The present study was undertaken to simultaneously investigate obesity-associated changes in CD16 + monocytes and ATMs ( AT macrophages ) . In addition , a pilot r and omized placebo controlled trial using the PPAR ( peroxisome-proliferator-activated receptor ) agonists , pioglitazone and fenofibrate was performed to determine their effects on CD14+/CD16 + monocytes , ATM and cardiometabolic and adipose dysfunction indices . Obese glucose-tolerant men ( n=28 ) were r and omized to placebo , pioglitazone ( 30 mg/day ) and fenofibrate ( 160 mg/day ) for 12 weeks . A blood sample was taken to assess levels of serum inflammatory markers and circulating CD14+/CD16 + monocyte levels via flow cytometry . A subcutaneous AT biopsy was performed to determine adipocyte cell surface and ATM number , the latter was determined via assessment of CD68 expression by IHC ( immunohistochemistry ) and real-time PCR . Subcutaneous AT mRNA expression of CEBPβ ( CCAAT enhancer-binding protein β ) , SREBP1c ( sterol-regulatory-element-binding protein 1c ) , PPARγ2 , IRS-1 ( insulin receptor substrate-1 ) , GLUT4 ( glucose transporter type 4 ) and TNFα ( tumour necrosis factor α ) were also assessed . Comparisons were made between obese and lean controls ( n=16 ) at baseline , and pre- and post-PPAR agonist treatment . Obese individuals had significantly increased adipocyte cell surface , percentage CD14+/CD16 + monocyte numbers and ATM number ( all P=0.0001 ) . Additionally , serum TNF-α levels were significantly elevated ( P=0.017 ) and adiponectin levels reduced ( total : P=0.0001 ; high : P=0.022 ) with obesity . ATM number and percentage of CD14+/CD16 + monocytes correlated significantly ( P=0.05 ) . Pioglitazone  improved adiponectin levels significantly ( P=0.0001 ) , and result ed in the further significant enlargement of adipocytes ( P=0.05 ) , without effect on the percentage CD14+/CD16 + or ATM number  . Pioglitazone treatment also significantly increased subcutaneous AT expression of CEBPβ mRNA . The finding that improvements in obesity-associated insulin resistance following pioglitazone were associated with increased adipocyte cell surface and systemic adiponectin levels , supports the central ity of AT to the cardiometabolic derangement underlying the development of T2D ( Type 2 diabetes ) and CVD ( cardiovascular disease ) The insulin-sensitizing effects of thiazolidinediones are thought to be mediated through peroxisome proliferator-activated receptor-gamma , a nuclear receptor that is highly abundant in adipose tissue . It has been reported that adipocytes secrete a variety of proteins , including tumor necrosis factor-alpha , resistin , plasminogen activator inhibitor-1 , and adiponectin . Adiponectin is a fat cell-secreted protein that has been reported to increase fat oxidation and improve insulin sensitivity . Our aim was to study the effects of troglitazone on adiponectin levels in lean , obese , and diabetic subjects . Ten diabetic and 17 nondiabetic subjects ( 8 lean , BMI < 27 kg/m(2 ) and 9 obese , BMI > 27 kg/m(2 ) ) participated in the study . All subjects underwent an 80 mU. m(-2 ) . min(-1 ) hyperinsulinemic-euglycemic glucose clamp before and after 3 months ' treatment with the thiazolidinedione ( TZD ) troglitazone ( 600 mg/day ) . Fasting plasma glucose significantly decreased in the diabetic group after 12 weeks of treatment compared with baseline ( 9.1 + /- 0.9 vs. 11.1 + /- 0.9 mmol/l , P < 0.005 ) but was unchanged in the lean and obese subjects . Fasting insulin for the entire group was significantly lower than baseline ( P = 0.02 ) after treatment . At baseline , glucose disposal rate ( R(d ) ) was lower in the diabetic subjects ( 3.4 + /- 0.5 mg . kg(-1 ) . min(-1 ) ) than in the lean ( 12.3 + /- 0.4 ) or obese subjects ( 6.7 + /- 0.7 ) ( P < 0.001 for both ) and was significantly improved in the diabetic and obese groups ( P < 0.05 ) after treatment , and it remained unchanged in the lean subjects . Baseline adiponectin levels were significantly lower in the diabetic than the lean subjects ( 9.0 + /- 1.7 vs. 16.7 + /- 2.7 micro g/ml , P = 0.03 ) and rose uniformly in all subjects ( 12.2 + /- 2.3 vs. 25.7 + /- 2.6 micro g/ml , P < 10(-4 ) ) after treatment , with no significant difference detected among the three groups . During the glucose clamps , adiponectin levels were suppressed below basal levels in all groups ( 10.2 + /- 2.3 vs. 12.2 + /- 2.3 micro g/ml , P < 0.01 ) . Adiponectin levels correlated with R(d ) ( r = 0.46 , P = 0.016 ) and HDL cholesterol levels ( r = 0.59 , P < 0.001 ) and negatively correlated with fasting insulin ( r = -0.39 , P = 0.042 ) and plasma triglyceride ( r = -0.61 , P < 0.001 ) . Our findings show that TZD treatment increased adiponectin levels in all subjects , including normal subjects in which no other effects of TZDs are observed . Insulin also appears to suppress adiponectin levels . We have confirmed these results in normal rats . These findings suggest that adiponectin can be regulated by obesity , diabetes , TZDs , and insulin , and it may play a physiologic role in enhancing insulin sensitivity OBJECTIVE Improvement in endothelial function is predicted to improve insulin sensitivity , and this may be one mechanism by which fenofibrate decreases the incidence of coronary heart disease . We hypothesize fenofibrate improves endothelial function by enhancing insulin sensitivity . RESEARCH DESIGN AND METHODS We administered placebo or fenofibrate 200 mg daily for 8 weeks to 46 patients with primary hypertriglyceridemia ( 24 had metabolic syndrome ) . This study was r and omized , double blind , placebo controlled , and crossover in design . RESULTS Compared with placebo , fenofibrate decreased total cholesterol , non-HDL cholesterol , apolipoprotein B , and triglycerides and increased HDL cholesterol and apolipoprotein A-I ( all P < 0.001 ) while tending to decrease LDL cholesterol ( P = 0.069 ) . Fenofibrate significantly improved percent flow-mediated dilator response to hyperemia by 48 + /- 5 % ( P < 0.001 ) and lowered plasma levels of high-sensitivity C-reactive protein ( hsCRP ) relative to baseline measurements from 0.80 to 0.70 mg/l ( P = 0.001 ) and fibrinogen levels by 16 + /- 3 % ( P < 0.001 ) . Compared with placebo , fenofibrate therapy significantly increased plasma levels of adiponectin by 14 + /- 5 % ( P = 0.008 ) and increased insulin sensitivity ( assessed by quantitative insulin sensitivity check index [ QUICKI ] ) by 6 + /- 2 % ( P = 0.048 ) . There were significant correlations between percent changes in adiponectin levels and percent changes in flow-mediated dilation ( r = 0.401 , P = 0.006 ) , hsCRP ( r = -0.443 , P = 0.002 ) , or QUICKI ( r = 0.292 , P = 0.049 ) . Multivariate regression analysis showed that only changes in adiponectin levels persisted as an independent predictor of changes in flow-mediated dilation ( r = 0.504 , P = 0.013 ) . Overall , we observed similar results in 24 patients with metabolic syndrome . CONCLUSIONS Fenofibrate therapy significantly improved percent flow-mediated dilator response to hyperemia , reduced inflammation marker levels , increased adiponectin levels , and improved insulin sensitivity in hypertriglyceridemic or metabolic syndrome patients Objective . To examine the effect of acute and short-term ( ~1 week ) aerobic exercise training on plasma adiponectin levels in inactive , abdominally obese men . Material s and Methods . Inactive and abdominally obese men ( n = 38 , waist circumference ≥102 cm ) recruited from Kingston , Canada were r and omly allocated to perform three bouts of aerobic treadmill exercise at either low ( 50 % VO2 peak ) or high ( 75 % VO2 peak ) intensity during a 1-week period  . Blood sample s were taken before and after the first exercise session and 24–72 hours following the completion of the final exercise session . Results . Adiponectin levels were elevated immediately following an acute bout of exercise at both high and low intensities ( High : 5.79 ± 0.42 versus 5.05 ± 0.41 ug/mL ; Low : 5.24 ± 0.44 versus 4.37 ± 0.44 ug/mL , P < 0.05 ) and remained elevated following 30 minutes of rest . In comparison to baseline , adiponectin levels were also elevated 24–72 hours following the final exercise session ( High : 5.47 ± 0.48 versus 4.88 ± 0.48 ug/mL ; Low : 5.18 ± 0.49 versus 4.47 ± 0.49 ug/mL , P < 0.05 ) . Conclusion . Both acute and short-term aerobic exercise result in a significant increase in plasma adiponectin levels in inactive , abdominally obese men independent of intensity BACKGROUND We investigated whether combination therapy with a statin plus a fibrate , as compared with statin monotherapy , would reduce the risk of cardiovascular disease in patients with type 2 diabetes mellitus who were at high risk for cardiovascular disease . METHODS We r and omly assigned 5518 patients with type 2 diabetes who were being treated with open-label simvastatin to receive either masked fenofibrate or placebo .  The primary outcome was the first occurrence of nonfatal myocardial infa rct ion , nonfatal stroke , or death from cardiovascular causes . The mean follow-up was 4.7 years . RESULTS The annual rate of the primary outcome was 2.2 % in the fenofibrate group and 2.4 % in the placebo group ( hazard ratio in the fenofibrate group , 0.92 ; 95 % confidence interval [ CI ] , 0.79 to 1.08 ; P=0.32 ) . There were also no significant differences between the two study groups with respect to any secondary outcome . Annual rates of death were 1.5 % in the fenofibrate group and 1.6 % in the placebo group ( hazard ratio , 0.91 ; 95 % CI , 0.75 to 1.10 ; P=0.33 ) . Prespecified subgroup analyses suggested heterogeneity in treatment effect according to sex , with a benefit for men and possible harm for women ( P=0.01 for interaction ) , and a possible interaction according to lipid subgroup , with a possible benefit for patients with both a high baseline triglyceride level and a low baseline level of high-density lipoprotein cholesterol ( P=0.057 for interaction ) . CONCLUSIONS The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events , nonfatal myocardial infa rct ion , or nonfatal stroke , as compared with simvastatin alone . These results do not support the routine use of combination therapy with fenofibrate and simvastatin to reduce cardiovascular risk in the majority of high-risk patients with type 2 diabetes . ( Clinical Trials.gov number , NCT00000620 . CONTEXT HIV patients on antiretroviral therapy ( ART ) have a unique dyslipidemia [ elevated triglycerides and non-high-density lipoprotein-cholesterol ( HDL-C ) , low HDL-C ] with insulin resistance ( characterized by hypoadiponectinemia ) . OBJECTIVE The aim was to test a targeted , comprehensive , additive approach to treating the dyslipidemia . DESIGN AND SETTING We conducted a r and omized , double-blind , 
    Output:
    
agent
The observed effect was robust in sensitivity analyses and independent of fibrate dose .
The present meta- analysis suggests that fibrate therapy increases circulating levels of adiponectin .
***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: Obese AT ( adipose tissue ) exhibits increased macrophage number . Pro-inflammatory CD16 + peripheral monocyte numbers are also reported to increase with obesity . The present study was undertaken to simultaneously investigate obesity-associated changes in CD16 + monocytes and ATMs ( AT macrophages ) . In addition , a pilot r and omized placebo controlled trial using the PPAR ( peroxisome-proliferator-activated receptor ) agonists , pioglitazone and fenofibrate was performed to determine their effects on CD14+/CD16 + monocytes , ATM and cardiometabolic and adipose dysfunction indices . Obese glucose-tolerant men ( n=28 ) were r and omized to placebo , pioglitazone ( 30 mg/day ) and fenofibrate ( 160 mg/day ) for 12 weeks . A blood sample was taken to assess levels of serum inflammatory markers and circulating CD14+/CD16 + monocyte levels via flow cytometry . A subcutaneous AT biopsy was performed to determine adipocyte cell surface and ATM number , the latter was determined via assessment of CD68 expression by IHC ( immunohistochemistry ) and real-time PCR . Subcutaneous AT mRNA expression of CEBPβ ( CCAAT enhancer-binding protein β ) , SREBP1c ( sterol-regulatory-element-binding protein 1c ) , PPARγ2 , IRS-1 ( insulin receptor substrate-1 ) , GLUT4 ( glucose transporter type 4 ) and TNFα ( tumour necrosis factor α ) were also assessed . Comparisons were made between obese and lean controls ( n=16 ) at baseline , and pre- and post-PPAR agonist treatment . Obese individuals had significantly increased adipocyte cell surface , percentage CD14+/CD16 + monocyte numbers and ATM number ( all P=0.0001 ) . Additionally , serum TNF-α levels were significantly elevated ( P=0.017 ) and adiponectin levels reduced ( total : P=0.0001 ; high : P=0.022 ) with obesity . ATM number and percentage of CD14+/CD16 + monocytes correlated significantly ( P=0.05 ) . Pioglitazone  improved adiponectin levels significantly ( P=0.0001 ) , and result ed in the further significant enlargement of adipocytes ( P=0.05 ) , without effect on the percentage CD14+/CD16 + or ATM number  . Pioglitazone treatment also significantly increased subcutaneous AT expression of CEBPβ mRNA . The finding that improvements in obesity-associated insulin resistance following pioglitazone were associated with increased adipocyte cell surface and systemic adiponectin levels , supports the central ity of AT to the cardiometabolic derangement underlying the development of T2D ( Type 2 diabetes ) and CVD ( cardiovascular disease ) The insulin-sensitizing effects of thiazolidinediones are thought to be mediated through peroxisome proliferator-activated receptor-gamma , a nuclear receptor that is highly abundant in adipose tissue . It has been reported that adipocytes secrete a variety of proteins , including tumor necrosis factor-alpha , resistin , plasminogen activator inhibitor-1 , and adiponectin . Adiponectin is a fat cell-secreted protein that has been reported to increase fat oxidation and improve insulin sensitivity . Our aim was to study the effects of troglitazone on adiponectin levels in lean , obese , and diabetic subjects . Ten diabetic and 17 nondiabetic subjects ( 8 lean , BMI < 27 kg/m(2 ) and 9 obese , BMI > 27 kg/m(2 ) ) participated in the study . All subjects underwent an 80 mU. m(-2 ) . min(-1 ) hyperinsulinemic-euglycemic glucose clamp before and after 3 months ' treatment with the thiazolidinedione ( TZD ) troglitazone ( 600 mg/day ) . Fasting plasma glucose significantly decreased in the diabetic group after 12 weeks of treatment compared with baseline ( 9.1 + /- 0.9 vs. 11.1 + /- 0.9 mmol/l , P < 0.005 ) but was unchanged in the lean and obese subjects . Fasting insulin for the entire group was significantly lower than baseline ( P = 0.02 ) after treatment . At baseline , glucose disposal rate ( R(d ) ) was lower in the diabetic subjects ( 3.4 + /- 0.5 mg . kg(-1 ) . min(-1 ) ) than in the lean ( 12.3 + /- 0.4 ) or obese subjects ( 6.7 + /- 0.7 ) ( P < 0.001 for both ) and was significantly improved in the diabetic and obese groups ( P < 0.05 ) after treatment , and it remained unchanged in the lean subjects . Baseline adiponectin levels were significantly lower in the diabetic than the lean subjects ( 9.0 + /- 1.7 vs. 16.7 + /- 2.7 micro g/ml , P = 0.03 ) and rose uniformly in all subjects ( 12.2 + /- 2.3 vs. 25.7 + /- 2.6 micro g/ml , P < 10(-4 ) ) after treatment , with no significant difference detected among the three groups . During the glucose clamps , adiponectin levels were suppressed below basal levels in all groups ( 10.2 + /- 2.3 vs. 12.2 + /- 2.3 micro g/ml , P < 0.01 ) . Adiponectin levels correlated with R(d ) ( r = 0.46 , P = 0.016 ) and HDL cholesterol levels ( r = 0.59 , P < 0.001 ) and negatively correlated with fasting insulin ( r = -0.39 , P = 0.042 ) and plasma triglyceride ( r = -0.61 , P < 0.001 ) . Our findings show that TZD treatment increased adiponectin levels in all subjects , including normal subjects in which no other effects of TZDs are observed . Insulin also appears to suppress adiponectin levels . We have confirmed these results in normal rats . These findings suggest that adiponectin can be regulated by obesity , diabetes , TZDs , and insulin , and it may play a physiologic role in enhancing insulin sensitivity OBJECTIVE Improvement in endothelial function is predicted to improve insulin sensitivity , and this may be one mechanism by which fenofibrate decreases the incidence of coronary heart disease . We hypothesize fenofibrate improves endothelial function by enhancing insulin sensitivity . RESEARCH DESIGN AND METHODS We administered placebo or fenofibrate 200 mg daily for 8 weeks to 46 patients with primary hypertriglyceridemia ( 24 had metabolic syndrome ) . This study was r and omized , double blind , placebo controlled , and crossover in design . RESULTS Compared with placebo , fenofibrate decreased total cholesterol , non-HDL cholesterol , apolipoprotein B , and triglycerides and increased HDL cholesterol and apolipoprotein A-I ( all P < 0.001 ) while tending to decrease LDL cholesterol ( P = 0.069 ) . Fenofibrate significantly improved percent flow-mediated dilator response to hyperemia by 48 + /- 5 % ( P < 0.001 ) and lowered plasma levels of high-sensitivity C-reactive protein ( hsCRP ) relative to baseline measurements from 0.80 to 0.70 mg/l ( P = 0.001 ) and fibrinogen levels by 16 + /- 3 % ( P < 0.001 ) . Compared with placebo , fenofibrate therapy significantly increased plasma levels of adiponectin by 14 + /- 5 % ( P = 0.008 ) and increased insulin sensitivity ( assessed by quantitative insulin sensitivity check index [ QUICKI ] ) by 6 + /- 2 % ( P = 0.048 ) . There were significant correlations between percent changes in adiponectin levels and percent changes in flow-mediated dilation ( r = 0.401 , P = 0.006 ) , hsCRP ( r = -0.443 , P = 0.002 ) , or QUICKI ( r = 0.292 , P = 0.049 ) . Multivariate regression analysis showed that only changes in adiponectin levels persisted as an independent predictor of changes in flow-mediated dilation ( r = 0.504 , P = 0.013 ) . Overall , we observed similar results in 24 patients with metabolic syndrome . CONCLUSIONS Fenofibrate therapy significantly improved percent flow-mediated dilator response to hyperemia , reduced inflammation marker levels , increased adiponectin levels , and improved insulin sensitivity in hypertriglyceridemic or metabolic syndrome patients Objective . To examine the effect of acute and short-term ( ~1 week ) aerobic exercise training on plasma adiponectin levels in inactive , abdominally obese men . Material s and Methods . Inactive and abdominally obese men ( n = 38 , waist circumference ≥102 cm ) recruited from Kingston , Canada were r and omly allocated to perform three bouts of aerobic treadmill exercise at either low ( 50 % VO2 peak ) or high ( 75 % VO2 peak ) intensity during a 1-week period  . Blood sample s were taken before and after the first exercise session and 24–72 hours following the completion of the final exercise session . Results . Adiponectin levels were elevated immediately following an acute bout of exercise at both high and low intensities ( High : 5.79 ± 0.42 versus 5.05 ± 0.41 ug/mL ; Low : 5.24 ± 0.44 versus 4.37 ± 0.44 ug/mL , P < 0.05 ) and remained elevated following 30 minutes of rest . In comparison to baseline , adiponectin levels were also elevated 24–72 hours following the final exercise session ( High : 5.47 ± 0.48 versus 4.88 ± 0.48 ug/mL ; Low : 5.18 ± 0.49 versus 4.47 ± 0.49 ug/mL , P < 0.05 ) . Conclusion . Both acute and short-term aerobic exercise result in a significant increase in plasma adiponectin levels in inactive , abdominally obese men independent of intensity BACKGROUND We investigated whether combination therapy with a statin plus a fibrate , as compared with statin monotherapy , would reduce the risk of cardiovascular disease in patients with type 2 diabetes mellitus who were at high risk for cardiovascular disease . METHODS We r and omly assigned 5518 patients with type 2 diabetes who were being treated with open-label simvastatin to receive either masked fenofibrate or placebo .  The primary outcome was the first occurrence of nonfatal myocardial infa rct ion , nonfatal stroke , or death from cardiovascular causes . The mean follow-up was 4.7 years . RESULTS The annual rate of the primary outcome was 2.2 % in the fenofibrate group and 2.4 % in the placebo group ( hazard ratio in the fenofibrate group , 0.92 ; 95 % confidence interval [ CI ] , 0.79 to 1.08 ; P=0.32 ) . There were also no significant differences between the two study groups with respect to any secondary outcome . Annual rates of death were 1.5 % in the fenofibrate group and 1.6 % in the placebo group ( hazard ratio , 0.91 ; 95 % CI , 0.75 to 1.10 ; P=0.33 ) . Prespecified subgroup analyses suggested heterogeneity in treatment effect according to sex , with a benefit for men and possible harm for women ( P=0.01 for interaction ) , and a possible interaction according to lipid subgroup , with a possible benefit for patients with both a high baseline triglyceride level and a low baseline level of high-density lipoprotein cholesterol ( P=0.057 for interaction ) . CONCLUSIONS The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events , nonfatal myocardial infa rct ion , or nonfatal stroke , as compared with simvastatin alone . These results do not support the routine use of combination therapy with fenofibrate and simvastatin to reduce cardiovascular risk in the majority of high-risk patients with type 2 diabetes . ( Clinical Trials.gov number , NCT00000620 . CONTEXT HIV patients on antiretroviral therapy ( ART ) have a unique dyslipidemia [ elevated triglycerides and non-high-density lipoprotein-cholesterol ( HDL-C ) , low HDL-C ] with insulin resistance ( characterized by hypoadiponectinemia ) . OBJECTIVE The aim was to test a targeted , comprehensive , additive approach to treating the dyslipidemia . DESIGN AND SETTING We conducted a r and omized , double-blind , 
    Output:
    