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: OBJECTIVE Insulin resistance is a key characteristic of first-degree relatives of patients with type 2 diabetes . We therefore treated young , glucose-tolerant relatives with the insulin action enhancer troglitazone in order to determine the effects on insulin sensitivity , glucose metabolism , and glycogen synthase activity . RESEARCH DESIGN AND METHODS Relatives were r and omized in a double-blind manner and treated for 12 weeks with either 200 mg troglitazone or placebo . Before and after treatment , an oral glucose tolerance test ( OGTT ) and a euglycemic-hyperinsulinemic clamp ( 40 mU. m(-2 ) . min(-1 ) ) were performed , including 3-(3)H glucose infusion , glycolytic flux calculations , indirect calorimetry , and muscle biopsies . RESULTS Twelve relatives received troglitazone and 12 placebo ( aged 30.8 + /- 2.0 vs. 30.3 + /- 1.6 years , BMI 29.6 + /- 0.8 vs. 30.5 + /- 1.3 kg/m(2 ) ; means + /- SE ) . Area under the curve ( AUC ) for plasma glucose at the second OGTT was unchanged after troglitazone . In contrast , troglitazone reduced fasting ( from 70.3 + /- 6.9 to 52.2 + /- 5.8 vs. 73.6 + /- 11.0 to 73.3 + /- 6.5 pmol/l , P < 0.02 ) and AUC plasma insulin ( mean [ CI ] from 335.7 [ 230.9 - 488.1 ] to 277.4 [ 179.4 - 428.8 ] vs. 313.8 [ 218.2 - 451.2 ] to 353.9 [ 208.3 - 601.3 ] pmol/l , P < 0.05 ) . Additionally , fasting plasma triglycerides were reduced by troglitazone ( from 1.86 + /- 0.33 to 1.38 + /- 0.27 vs. 2.22 + /- 0.44 to 2.35 + /- 0.46 mmol/l , P < 0.01 ) . Insulin-stimulated glucose disposal increased in the troglitazone group ( from 208.3 + /- 23.7 to 263.5 + /- 30.4 vs. 197.1 + /- 20.0 to 200.8 + /- 20.8 mg . m(-2 ) . min(-1 ) , P < 0.02 ) mainly due to increased glucose storage ( from 99.9 + /- 17.9 to 146.0 + /- 25.3 vs. 87.1 + /- 16.7 to 87.9 + /- 15.7 mg . m(-2 ) . min(-1 ) , P < 0.02 ) , which took place without altering insulin-stimulated glycogen synthase activity . CONCLUSIONS In glucose-tolerant first-degree relatives , treatment with troglitazone improved insulin sensitivity almost 50 % , primarily due to increased glucose storage . It is suggested that the use of insulin action enhancers can be especially valuable in this group of subjects with a known high risk for developing type 2 diabetes Rosiglitazone , a thiazolidinedione , enhances peripheral insulin sensitivity in patients with type 2 diabetes . Because the synergic action of insulin and exercise has been shown to be decreased in insulin resistance , the aim of this study was to compare the effects of rosiglitazone and metformin on muscle insulin responsiveness at rest and during exercise in patients with type 2 diabetes . Therefore , 45 patients with newly diagnosed or diet-treated type 2 diabetes were r and omized for treatment with rosiglitazone ( 4 mg b.i.d . ) , metformin ( 1 g b.i.d . ) , or placebo in a 26-week double-blind trial . Skeletal muscle glucose uptake was measured using fluorine-18-labeled fluoro-deoxy-glucose and positron emission tomography ( PET ) during euglycemic-hyperinsulinemic clamp and one-legged exercise before and after the treatment period . Rosiglitazone ( P < 0.05 ) and metformin ( P < 0.0001 ) treatment lowered the mean glycosylated hemoglobin . The skeletal muscle glucose uptake was increased by 38 % ( P < 0.01 ) and whole-body glucose uptake by 44 % in the rosiglitazone group . Furthermore , the exercise-induced increment during insulin stimulation was enhanced by 99 % ( P < 0.0001 ) . No changes were observed in skeletal muscle or whole-body insulin sensitivity in the metformin group . In conclusion , rosiglitazone but not metformin 1 ) improves insulin responsiveness in resting skeletal muscle and 2 ) doubles the insulin-stimulated glucose uptake rate during physical exercise in patients with type 2 diabetes . Our results suggest that rosiglitazone improves synergic action of insulin and exercise OBJECTIVE To examine the effect of rosiglitazone on insulin resistance and blood pressure in patients with essential hypertension , classified based on abnormalities of their renin-angiotensin system . RESEARCH DESIGN AND METHODS A total of 24 hypertensive nondiabetic patients ( age 58 + /- 6 years , BMI 30 + /- 5 kg/m2 ) were studied before and after rosiglitazone treatment . After 2 weeks off antihypertensive medication , subjects received a euglycemic-hyperinsulinemic clamp ( 40 mU. m(-2 ) . min(-1 ) ) with 6,6-[2H2]glucose infusion , ambulatory blood pressure monitoring , and blood tests for cardiovascular risk factors . Subjects were then placed on rosiglitazone ( 4 mg orally b.i.d . ) and their usual antihypertensive medications ( but not ACE inhibitors ) for 16 weeks , and baseline tests were repeated . RESULTS There was no change in fasting plasma glucose ( 83 + /- 2 vs. 82 + /- 2 mg/dl , P = 0.60 ) , but fasting insulin decreased ( 16.1 + /- 1.4 vs. 12.5 + /- 0.9 micro U/ml , P < 0.01 ) . Total glucose disposal during the clamp increased ( 5.0 + /- 0.4 vs. 5.9 + /- 0.5 mg . kg(-1 ) . min(-1 ) , P < 0.001 ) , with no change in suppression of hepatic glucose output . There were significant decreases in mean 24-h systolic ( 138 + /- 2 vs. 134 + /- 2 mmHg , P < 0.02 ) and diastolic ( 85 + /- 2 vs. 80 + /- 2 mmHg , P < 0.0001 ) blood pressure , and the decline in systolic blood pressure was correlated with the improvement in insulin sensitivity ( r = 0.59 , P < 0.005 ) . Triglycerides ( 135 + /- 16 vs. 89 + /- 8 mg/dl , P < 0.01 ) , LDL cholesterol ( 129 + /- 6 vs. 122 + /- 8 mg/dl , P = 0.18 ) , and HDL cholesterol ( 51 + /- 3 vs. 46 + /- 3 mg/dl , P < 0.02 ) all decreased , with no change in the LDL-to-HDL ratio . Plasminogen activator inhibitor-1 and C-reactive protein also declined significantly . CONCLUSIONS Rosiglitazone treatment of nondiabetic hypertensive patients improves insulin sensitivity , reduces systolic and diastolic blood pressure , and induces favorable changes in markers of cardiovascular risk . Insulin sensitizers may provide cardiovascular benefits when used in the treatment of patients with hypertension Troglitazone and metformin lower glucose levels in diabetic patients without increasing plasma insulin levels . We compared the insulin sparing actions of these two agents and their effects on insulin sensitivity and insulin secretion in 20 type 2 diabetic patients . To avoid the confounding effect of improved glycemic control on insulin action and secretion , patients were first rendered euglycemic with 4 weeks of continuous subcutaneous insulin infusion ( CSII ) before r and omization to CSII plus troglitazone ( n = 10 ) or CSII plus metformin ( n = 10 ) ; euglycemia was maintained for another 6 - 7 weeks . Insulin sensitivity was assessed by a hyperinsulinemic-euglycemic clamp 1 ) at baseline , 2 ) after 4 weeks of CSII , and 3 ) after CSII plus either troglitazone or metformin . The 24-h glucose , insulin , and C-peptide profiles were performed on the day before the second and third glucose clamps . Good glycemic control was achieved with CSII alone and was maintained with CSII plus an oral agent ( mean 24-h glucose : troglitazone , 6.2+/-0.6 mmol/l ; metformin , 6.2 + /-0.3 mmol/l ) . Insulin requirements decreased 53 % with troglitazone compared with CSII alone ( 48+/-4 vs. 102+/-13 U/day , P < 0.001 ) , but only 31 % with metformin ( 76+/-13 vs. 110+/-18 U/day , P < 0.005 ) . The 24-h C-peptide profiles were similar . Normal fasting hepatic glucose output was maintained with both agents despite lower insulin levels than on CSII alone . Insulin sensitivity did not change significantly with CSII alone or with CSII plus metformin , but improved 29 % with CSII plus troglitazone ( P < 0.005 vs. CSII alone ) and was then 45 % higher than in the CSII plus metformin patients ( P < 0.005 ) . In conclusion , metformin has no effect on insulin-stimulated glucose disposal independent of glycemic control in type 2 diabetes . Troglitazone ( 600 mg/day ) has greater insulin-sparing effects than metformin ( 1,700 mg/day ) in CSII-treated euglycemic patients . This is probably explained by the peripheral tissue insulin-sensitizing effects of troglitazone UNLABELLED Nine obese patients with Type II diabetes mellitus were examined in a double-blind cross-over study . Metformin 0.5 g trice daily or placebo were given for 4 weeks . At the end of each period fasting and day-time postpr and ial values of plasma glucose , insulin , C-peptide and lactate were determined , and in vivo insulin action was assessed using the euglycemic clamp in combination with [3 - 3H]glucose tracer technique . Metformin treatment significantly reduced mean day-time plasma glucose levels ( 10.2 + /- 1.2 vs 11.4 + /- 1.2 mmol/l , P less than 0.01 ) without enhancing mean day-time plasma insulin ( 43 + /- 4 vs 50 + /- 7 mU/l , NS ) or C-peptide levels ( 1.26 + /- 0.12 vs 1.38 + /- 0.18 nmol/l , NS ) . Fasting plasma lactate was unchanged ( 1.57 + /- 0.16 vs 1.44 + /- 0.11 mmol/l , NS ) , whereas mean day-time plasma lactate concentrations were slightly increased ( 1.78 + /- 0.11 vs 1.38 + /- 0.11 mmol/l , P less than 0.01 ) . The clamp study revealed that metformin treatment was associated with an enhanced insulin-mediated glucose utilization ( 370 + /- 38 vs 313 + /- 33 mg.m-2.min-1 , P less than 0.01 ) , whereas insulin-mediated suppression of hepatic glucose production was unchanged . Also basal glucose clearance was improved ( 61.0 + /- 5.8 vs 50.6 + /- 2.8 ml.m-2.min-1 , P less than 0.05 ) , whereas basal hepatic glucose production was unchanged ( 81 + /- 6 vs 77 + /- 4 mg.m-2.min-1 , NS ) . CONCLUSIONS 1 ) Metformin treatment in obese Type II diabetic patients reduces hyperglycemia without changing the insulin secretion . ( ABSTRACT TRUNCATED AT 
    Output:
    
agent
Results Both TZDs and metformin  enhance insulin suppression of endogenous glucose production and fasting plasma glucose clearance .
TZDs , but not metformin , also improve insulin-mediated glucose uptake at all insulin levels .
Conclusions /interpretationIn patients with type 2 diabetes , metformin improves fasting hepatic insulin sensitivity and glucose clearance ; TZDs improve fasting hepatic insulin sensitivity and glucose clearance , and potentiate glucose disposal under insulinised conditions
***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: OBJECTIVE Insulin resistance is a key characteristic of first-degree relatives of patients with type 2 diabetes . We therefore treated young , glucose-tolerant relatives with the insulin action enhancer troglitazone in order to determine the effects on insulin sensitivity , glucose metabolism , and glycogen synthase activity . RESEARCH DESIGN AND METHODS Relatives were r and omized in a double-blind manner and treated for 12 weeks with either 200 mg troglitazone or placebo . Before and after treatment , an oral glucose tolerance test ( OGTT ) and a euglycemic-hyperinsulinemic clamp ( 40 mU. m(-2 ) . min(-1 ) ) were performed , including 3-(3)H glucose infusion , glycolytic flux calculations , indirect calorimetry , and muscle biopsies . RESULTS Twelve relatives received troglitazone and 12 placebo ( aged 30.8 + /- 2.0 vs. 30.3 + /- 1.6 years , BMI 29.6 + /- 0.8 vs. 30.5 + /- 1.3 kg/m(2 ) ; means + /- SE ) . Area under the curve ( AUC ) for plasma glucose at the second OGTT was unchanged after troglitazone . In contrast , troglitazone reduced fasting ( from 70.3 + /- 6.9 to 52.2 + /- 5.8 vs. 73.6 + /- 11.0 to 73.3 + /- 6.5 pmol/l , P < 0.02 ) and AUC plasma insulin ( mean [ CI ] from 335.7 [ 230.9 - 488.1 ] to 277.4 [ 179.4 - 428.8 ] vs. 313.8 [ 218.2 - 451.2 ] to 353.9 [ 208.3 - 601.3 ] pmol/l , P < 0.05 ) . Additionally , fasting plasma triglycerides were reduced by troglitazone ( from 1.86 + /- 0.33 to 1.38 + /- 0.27 vs. 2.22 + /- 0.44 to 2.35 + /- 0.46 mmol/l , P < 0.01 ) . Insulin-stimulated glucose disposal increased in the troglitazone group ( from 208.3 + /- 23.7 to 263.5 + /- 30.4 vs. 197.1 + /- 20.0 to 200.8 + /- 20.8 mg . m(-2 ) . min(-1 ) , P < 0.02 ) mainly due to increased glucose storage ( from 99.9 + /- 17.9 to 146.0 + /- 25.3 vs. 87.1 + /- 16.7 to 87.9 + /- 15.7 mg . m(-2 ) . min(-1 ) , P < 0.02 ) , which took place without altering insulin-stimulated glycogen synthase activity . CONCLUSIONS In glucose-tolerant first-degree relatives , treatment with troglitazone improved insulin sensitivity almost 50 % , primarily due to increased glucose storage . It is suggested that the use of insulin action enhancers can be especially valuable in this group of subjects with a known high risk for developing type 2 diabetes Rosiglitazone , a thiazolidinedione , enhances peripheral insulin sensitivity in patients with type 2 diabetes . Because the synergic action of insulin and exercise has been shown to be decreased in insulin resistance , the aim of this study was to compare the effects of rosiglitazone and metformin on muscle insulin responsiveness at rest and during exercise in patients with type 2 diabetes . Therefore , 45 patients with newly diagnosed or diet-treated type 2 diabetes were r and omized for treatment with rosiglitazone ( 4 mg b.i.d . ) , metformin ( 1 g b.i.d . ) , or placebo in a 26-week double-blind trial . Skeletal muscle glucose uptake was measured using fluorine-18-labeled fluoro-deoxy-glucose and positron emission tomography ( PET ) during euglycemic-hyperinsulinemic clamp and one-legged exercise before and after the treatment period . Rosiglitazone ( P < 0.05 ) and metformin ( P < 0.0001 ) treatment lowered the mean glycosylated hemoglobin . The skeletal muscle glucose uptake was increased by 38 % ( P < 0.01 ) and whole-body glucose uptake by 44 % in the rosiglitazone group . Furthermore , the exercise-induced increment during insulin stimulation was enhanced by 99 % ( P < 0.0001 ) . No changes were observed in skeletal muscle or whole-body insulin sensitivity in the metformin group . In conclusion , rosiglitazone but not metformin 1 ) improves insulin responsiveness in resting skeletal muscle and 2 ) doubles the insulin-stimulated glucose uptake rate during physical exercise in patients with type 2 diabetes . Our results suggest that rosiglitazone improves synergic action of insulin and exercise OBJECTIVE To examine the effect of rosiglitazone on insulin resistance and blood pressure in patients with essential hypertension , classified based on abnormalities of their renin-angiotensin system . RESEARCH DESIGN AND METHODS A total of 24 hypertensive nondiabetic patients ( age 58 + /- 6 years , BMI 30 + /- 5 kg/m2 ) were studied before and after rosiglitazone treatment . After 2 weeks off antihypertensive medication , subjects received a euglycemic-hyperinsulinemic clamp ( 40 mU. m(-2 ) . min(-1 ) ) with 6,6-[2H2]glucose infusion , ambulatory blood pressure monitoring , and blood tests for cardiovascular risk factors . Subjects were then placed on rosiglitazone ( 4 mg orally b.i.d . ) and their usual antihypertensive medications ( but not ACE inhibitors ) for 16 weeks , and baseline tests were repeated . RESULTS There was no change in fasting plasma glucose ( 83 + /- 2 vs. 82 + /- 2 mg/dl , P = 0.60 ) , but fasting insulin decreased ( 16.1 + /- 1.4 vs. 12.5 + /- 0.9 micro U/ml , P < 0.01 ) . Total glucose disposal during the clamp increased ( 5.0 + /- 0.4 vs. 5.9 + /- 0.5 mg . kg(-1 ) . min(-1 ) , P < 0.001 ) , with no change in suppression of hepatic glucose output . There were significant decreases in mean 24-h systolic ( 138 + /- 2 vs. 134 + /- 2 mmHg , P < 0.02 ) and diastolic ( 85 + /- 2 vs. 80 + /- 2 mmHg , P < 0.0001 ) blood pressure , and the decline in systolic blood pressure was correlated with the improvement in insulin sensitivity ( r = 0.59 , P < 0.005 ) . Triglycerides ( 135 + /- 16 vs. 89 + /- 8 mg/dl , P < 0.01 ) , LDL cholesterol ( 129 + /- 6 vs. 122 + /- 8 mg/dl , P = 0.18 ) , and HDL cholesterol ( 51 + /- 3 vs. 46 + /- 3 mg/dl , P < 0.02 ) all decreased , with no change in the LDL-to-HDL ratio . Plasminogen activator inhibitor-1 and C-reactive protein also declined significantly . CONCLUSIONS Rosiglitazone treatment of nondiabetic hypertensive patients improves insulin sensitivity , reduces systolic and diastolic blood pressure , and induces favorable changes in markers of cardiovascular risk . Insulin sensitizers may provide cardiovascular benefits when used in the treatment of patients with hypertension Troglitazone and metformin lower glucose levels in diabetic patients without increasing plasma insulin levels . We compared the insulin sparing actions of these two agents and their effects on insulin sensitivity and insulin secretion in 20 type 2 diabetic patients . To avoid the confounding effect of improved glycemic control on insulin action and secretion , patients were first rendered euglycemic with 4 weeks of continuous subcutaneous insulin infusion ( CSII ) before r and omization to CSII plus troglitazone ( n = 10 ) or CSII plus metformin ( n = 10 ) ; euglycemia was maintained for another 6 - 7 weeks . Insulin sensitivity was assessed by a hyperinsulinemic-euglycemic clamp 1 ) at baseline , 2 ) after 4 weeks of CSII , and 3 ) after CSII plus either troglitazone or metformin . The 24-h glucose , insulin , and C-peptide profiles were performed on the day before the second and third glucose clamps . Good glycemic control was achieved with CSII alone and was maintained with CSII plus an oral agent ( mean 24-h glucose : troglitazone , 6.2+/-0.6 mmol/l ; metformin , 6.2 + /-0.3 mmol/l ) . Insulin requirements decreased 53 % with troglitazone compared with CSII alone ( 48+/-4 vs. 102+/-13 U/day , P < 0.001 ) , but only 31 % with metformin ( 76+/-13 vs. 110+/-18 U/day , P < 0.005 ) . The 24-h C-peptide profiles were similar . Normal fasting hepatic glucose output was maintained with both agents despite lower insulin levels than on CSII alone . Insulin sensitivity did not change significantly with CSII alone or with CSII plus metformin , but improved 29 % with CSII plus troglitazone ( P < 0.005 vs. CSII alone ) and was then 45 % higher than in the CSII plus metformin patients ( P < 0.005 ) . In conclusion , metformin has no effect on insulin-stimulated glucose disposal independent of glycemic control in type 2 diabetes . Troglitazone ( 600 mg/day ) has greater insulin-sparing effects than metformin ( 1,700 mg/day ) in CSII-treated euglycemic patients . This is probably explained by the peripheral tissue insulin-sensitizing effects of troglitazone UNLABELLED Nine obese patients with Type II diabetes mellitus were examined in a double-blind cross-over study . Metformin 0.5 g trice daily or placebo were given for 4 weeks . At the end of each period fasting and day-time postpr and ial values of plasma glucose , insulin , C-peptide and lactate were determined , and in vivo insulin action was assessed using the euglycemic clamp in combination with [3 - 3H]glucose tracer technique . Metformin treatment significantly reduced mean day-time plasma glucose levels ( 10.2 + /- 1.2 vs 11.4 + /- 1.2 mmol/l , P less than 0.01 ) without enhancing mean day-time plasma insulin ( 43 + /- 4 vs 50 + /- 7 mU/l , NS ) or C-peptide levels ( 1.26 + /- 0.12 vs 1.38 + /- 0.18 nmol/l , NS ) . Fasting plasma lactate was unchanged ( 1.57 + /- 0.16 vs 1.44 + /- 0.11 mmol/l , NS ) , whereas mean day-time plasma lactate concentrations were slightly increased ( 1.78 + /- 0.11 vs 1.38 + /- 0.11 mmol/l , P less than 0.01 ) . The clamp study revealed that metformin treatment was associated with an enhanced insulin-mediated glucose utilization ( 370 + /- 38 vs 313 + /- 33 mg.m-2.min-1 , P less than 0.01 ) , whereas insulin-mediated suppression of hepatic glucose production was unchanged . Also basal glucose clearance was improved ( 61.0 + /- 5.8 vs 50.6 + /- 2.8 ml.m-2.min-1 , P less than 0.05 ) , whereas basal hepatic glucose production was unchanged ( 81 + /- 6 vs 77 + /- 4 mg.m-2.min-1 , NS ) . CONCLUSIONS 1 ) Metformin treatment in obese Type II diabetic patients reduces hyperglycemia without changing the insulin secretion . ( ABSTRACT TRUNCATED AT 
    Output:
    