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: Aims /hypothesisThe aim of the present study was to investigate the effect of blood pressure lowering and intensive glucose control on the incidence and progression of retinopathy in type 2 diabetic patients . Methods The Action in Diabetes and Vascular Disease : Preterax and Diamicron MR Controlled Evaluation ( ADVANCE ) Retinal Measurements study , a sub study of ADVANCE , is a r and omised ( using a central , computer-based procedure ) controlled 2 × 2 factorial trial comprising a double-blind comparison of blood pressure lowering with perindopril – indapamide vs placebo , and an open comparison of st and ard vs intensive glucose control targeting a HbA1c of ≤ 6.5 % in 1,602 diabetic patients from ADVANCE centres with access to retinal cameras conducted from 2001 to 2008 . At baseline and the final visit , seven-field stereoscopic retinal photographs were taken and grade d by blinded readers ( grade able baseline and final photographs from 1,241 patients ) . Progression of ≥2 steps in the Early Treatment of Diabetic Retinopathy Study classification ( using the eye with worst grading ) was the primary outcome . Results Retinopathy progressed in 59 ( 4.8 % ) patients and developed in 128 ( 10.3 % ) patients over 4.1 years . Fewer patients on blood pressure-lowering treatment ( n = 623 ) experienced incidence or progression of retinopathy compared with patients on placebo ( n = 618 ) , but the difference was not significant ( OR 0.78 ; 95 % CI 0.57–1.06 ; p = 0.12 ) . Blood pressure-lowering treatment reduced the occurrence of macular oedema ( OR 0.50 ; 95 % CI 0.29–0.88 ; p = 0.016 ) and arteriovenous nicking compared with placebo ( OR 0.60 ; 95 % CI 0.38–0.94 ; p = 0.025 ) . Compared with st and ard glucose control ( n = 611 ) , intensive glucose control ( n = 630 ) did not reduce ( p = 0.27 ) the incidence and progression of retinopathy ( OR 0.84 ; 95 % CI 0.61–1.15 ) . Lower , borderline significant risks of microaneurysms , hard exu date s and macular oedema were observed with intensive glucose control , adjusted for baseline retinal haemorrhages . These effects of the two treatments were independent and additive . Adverse events in the ADVANCE study are reported elsewhere . Conclusions /interpretationBlood pressure lowering or intensive glucose control did not significantly reduce the incidence and progression of retinopathy , although consistent trends towards a benefit were observed , with significant reductions in some lesions observed with both interventions .Trial registration : Clinical Trials.gov ID no. NCT00145925 . Funding : Grants from Servier and the National Health and Medical Research Council of Background —This study sought to determine whether tight glycemic control with a modified glucose-insulin-potassium ( GIK ) solution in diabetic coronary artery bypass graft ( CABG ) patients would improve perioperative outcomes . Methods and Results —One hundred forty-one diabetic patients undergoing CABG were prospect ively r and omized to tight glycemic control ( serum glucose , 125 to 200 mg/dL ) with GIK or st and ard therapy ( serum glucose < 250 mg/dL ) using intermittent subcutaneous insulin beginning before anesthesia and continuing for 12 hours after surgery . GIK patients had lower serum glucose levels ( 138±4 versus 260±6 mg/dL ; P < 0.0001 ) , a lower incidence of atrial fibrillation ( 16.6 % versus 42 % ; P = 0.0017 ) , and a shorter postoperative length of stay ( 6.5±0.1 versus 9.2±0.3 days ; P = 0.003 ) . GIK patients also showed a survival advantage over the initial 2 years after surgery ( P = 0.04 ) and decreased episodes of recurrent ischemia ( 5 % versus 19 % ; P = 0.01 ) and developed fewer recurrent wound infections ( 1 % versus 10 % , P = 0.03 ) . Conclusions —Tight glycemic control with GIK  in diabetic CABG patients  improves perioperative outcomes , enhances survival , and decreases the incidence of ischemic events and wound complications A prospect i ve , stratified , r and omized 3-year clinical trial was conducted on the effect of rigorous versus conventional glucose control on peripheral nerve function in 33 insulin-treated diabetic patients with a duration of diabetes of less than 2 years . The goals for conventional glucose control were the mean of fasting and 80-minute postpr and ial plasma glucose of 150 mg/dl for non-insulin-dependent diabetes and 200 mg/dl for insulin-dependent diabetes . The goal of rigorous glucose control was an approximation of nondiabetic glucose control . No significant difference in glucose control or peripheral nerve function was observed between the rigorously and the conventionally controlled groups . Eight patients in the conventional-control group spontaneously achieved glucose control in the range that was the objective for the rigorous-control group , and five patients in the rigorous-control group never achieved the desired glucose control . In the remaining 20 patients , with similar baseline glucose control and peripheral nerve function characteristics , observed over a median of 2 years , improved blood glucose control ( P less than 0.01 ) was not associated with any significant improvement in peripheral nerve function . Nevertheless , a significant ( P less than 0.05 ) correlation was found between the degree of abnormal nerve function at entry into the study and change in nerve function during the study . If control of hyperglycemia benefits peripheral nerve function of diabetic patients , its demonstration may require a closer approximation of normoglycemia , a larger difference in glucose control between the two study groups , a longer duration of treatment , and the use of patients with more advanced  peripheral nerve function  abnormalities than those in this study maintaining near-normal glycemia . 5 Group B patients were treated using the usual protocol s , with oral hy- poglycemic drugs or 2 daily doses of intermediate- acting insulin . Supplementary small doses of short- acting insulin were administered subcutaneously only if glucose levels were 250 mg/dl . Mean daily plasma glucose levels were assessed in each patient in both groups by employing all the measured glucose values obtained during the study . The mean glucose level in the conservative treatment group was assessed by the 3 st and ard prepr and ial glucose values ( at 7 A.M. , 1 P.M. , 6 P.M. ) , 1 measurement at 12 A.M. hours and any additional measurements that were performed accord- ing to the discretion of the attending physician . All patients were treated with an optimal antianginal reg- imen . Complete 2-dimensional , spectral , and color-fl ow Doppler echocardiographic examinations were per- formed by 2 examiners not involved in the fi nal anal- ysis of data , with a Hewlett-Packard Sonos 1000 Ul- trasound Machine ( And over , Massachusetts ) with a 2.5-MHz transducer , while the patients were asymp- tomatic . Images were obtained within 3 hours from ad- mission and 72 hours later and stored on high- quality videotapes for later blinded analysis . A DI design ed to determine the combined systolic and diastolic myocar- dial performance , and defi ned as the sum of isovolumet- ric contraction time plus isovolumetric relaxation time divided by ejection time , was estimated from LV outfl ow and mitral infl ow velocity patterns ( ( IVCT IVRT)/ ET).6 Videotape recordings were analyzed by 1 BACKGROUND Patients with type 2 diabetes are at high risk of fatal and non-fatal myocardial infa rct ion and stroke . There is indirect evidence that agonists of peroxisome proliferator-activated receptor gamma ( PPAR gamma ) could reduce macrovascular complications . Our aim , therefore , was to ascertain whether pioglitazone reduces macrovascular morbidity and mortality in high-risk patients with type 2 diabetes . METHODS We did a prospect i ve , r and omised controlled trial in 5238 patients with type 2 diabetes who had evidence of macrovascular disease .  We recruited patients from primary -care practice s and hospitals . We assigned patients to oral pioglitazone titrated from 15 mg to 45 mg ( n=2605 ) or matching placebo ( n=2633 ) , to be taken in addition to their glucose-lowering drugs and other medications . Our primary endpoint was the composite of all-cause mortality , non fatal myocardial infa rct ion ( including silent myocardial infa rct ion ) , stroke , acute coronary syndrome , endovascular or surgical intervention in the coronary or leg arteries , and amputation above the ankle . Analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N NCT00174993 . FINDINGS Two patients were lost to follow-up , but were included in analyses . The average time of observation was 34.5 months . 514 of 2605 patients in the pioglitazone group and 572 of 2633 patients in the placebo group had at least one event in the primary composite endpoint ( HR 0.90 , 95 % CI 0.80 - 1.02 , p=0.095 ) . The main secondary endpoint was the composite of all-cause mortality , non-fatal myocardial infa rct ion , and stroke . 301 patients in the pioglitazone group and 358 in the placebo group reached this endpoint ( 0.84 , 0.72 - 0.98 , p=0.027 ) . Overall safety and tolerability was good with no change in the safety profile of pioglitazone identified . 6 % ( 149 of 2065 ) and 4 % ( 108 of 2633 ) of those in the pioglitazone and placebo groups , respectively , were admitted to hospital with heart failure ; mortality rates from heart failure did not differ between groups . INTERPRETATION Pioglitazone reduces the composite of all-cause mortality , non-fatal myocardial infa rct ion , and stroke in patients with type 2 diabetes who have a high risk of macrovascular events BACKGROUND Intensified multifactorial intervention - with tight glucose regulation and the use of renin-angiotensin system blockers , aspirin , and lipid-lowering agents - has been shown to reduce the risk of nonfatal cardiovascular disease among patients with type 2 diabetes mellitus and microalbuminuria . We evaluated whether this approach would have an effect on the rates of death from any cause and from cardiovascular causes . METHODS In the Steno-2 Study , we r and omly assigned 160 patients with type 2 diabetes and persistent microalbuminuria to receive either intensive therapy or conventional therapy ;  the mean treatment period was 7.8 years . Patients were subsequently followed observationally for a mean of 5.5 years , until December 31 , 2006 . The primary end point at 13.3 years of follow-up was the time to death from any cause . RESULTS Twenty-four patients in the intensive-therapy group died , as compared with 40 in the conventional-therapy group ( hazard ratio , 0.54 ; 95 % confidence interval [ CI ] , 0.32 to 0.89 ; P=0.02 ) . Intensive therapy was associated with a lower risk of death from cardiovascular causes ( hazard ratio , 0.43 ; 95 % CI , 0.19 to 0.94 ; P=0.04 ) and of cardiovascular events ( hazard ratio , 0.41 ; 95 % CI , 0.25 to 0.67 ; P<0.001 ) . One patient in the intensive-therapy group had progression to end-stage renal disease , as compared with six patients in the conventional-therapy group ( P=0.04 ) . Fewer patients in the intensive-therapy group required retinal photocoagulation ( relative risk , 0.45 ; 95 % CI , 0.23 to 0.86 ; P=0.02 ) . Few major side effects were reported . CONCLUSIONS In at-risk patients with type 2 diabetes , intensive intervention with multiple drug combinations and behavior modification had sustained beneficial effects with respect to vascular complications and on rates of death from any cause and from cardiovascular causes . ( Clinical Trials.gov number , NCT00320008 . OBJECTIVE To investigate whether long-term intensive glycemic and lipid control would ameliorate the carotid intima medial thickness ( IMT ) in patients with type 2 diabetes mellitus ( T2DM ) . METHODS IMT was evaluated on B-mode ultrasonography in 116 patients with T2DM .  Body mass index ( BMI ) , waist-to-hip ratio ( WHR ) , fasting blood glucose ( FBG ) , 2 hour post 
    Output:
    
agent
Intensive glycaemic control does not seem to reduce all cause mortality in patients with type 2 diabetes .
***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: Aims /hypothesisThe aim of the present study was to investigate the effect of blood pressure lowering and intensive glucose control on the incidence and progression of retinopathy in type 2 diabetic patients . Methods The Action in Diabetes and Vascular Disease : Preterax and Diamicron MR Controlled Evaluation ( ADVANCE ) Retinal Measurements study , a sub study of ADVANCE , is a r and omised ( using a central , computer-based procedure ) controlled 2 × 2 factorial trial comprising a double-blind comparison of blood pressure lowering with perindopril – indapamide vs placebo , and an open comparison of st and ard vs intensive glucose control targeting a HbA1c of ≤ 6.5 % in 1,602 diabetic patients from ADVANCE centres with access to retinal cameras conducted from 2001 to 2008 . At baseline and the final visit , seven-field stereoscopic retinal photographs were taken and grade d by blinded readers ( grade able baseline and final photographs from 1,241 patients ) . Progression of ≥2 steps in the Early Treatment of Diabetic Retinopathy Study classification ( using the eye with worst grading ) was the primary outcome . Results Retinopathy progressed in 59 ( 4.8 % ) patients and developed in 128 ( 10.3 % ) patients over 4.1 years . Fewer patients on blood pressure-lowering treatment ( n = 623 ) experienced incidence or progression of retinopathy compared with patients on placebo ( n = 618 ) , but the difference was not significant ( OR 0.78 ; 95 % CI 0.57–1.06 ; p = 0.12 ) . Blood pressure-lowering treatment reduced the occurrence of macular oedema ( OR 0.50 ; 95 % CI 0.29–0.88 ; p = 0.016 ) and arteriovenous nicking compared with placebo ( OR 0.60 ; 95 % CI 0.38–0.94 ; p = 0.025 ) . Compared with st and ard glucose control ( n = 611 ) , intensive glucose control ( n = 630 ) did not reduce ( p = 0.27 ) the incidence and progression of retinopathy ( OR 0.84 ; 95 % CI 0.61–1.15 ) . Lower , borderline significant risks of microaneurysms , hard exu date s and macular oedema were observed with intensive glucose control , adjusted for baseline retinal haemorrhages . These effects of the two treatments were independent and additive . Adverse events in the ADVANCE study are reported elsewhere . Conclusions /interpretationBlood pressure lowering or intensive glucose control did not significantly reduce the incidence and progression of retinopathy , although consistent trends towards a benefit were observed , with significant reductions in some lesions observed with both interventions .Trial registration : Clinical Trials.gov ID no. NCT00145925 . Funding : Grants from Servier and the National Health and Medical Research Council of Background —This study sought to determine whether tight glycemic control with a modified glucose-insulin-potassium ( GIK ) solution in diabetic coronary artery bypass graft ( CABG ) patients would improve perioperative outcomes . Methods and Results —One hundred forty-one diabetic patients undergoing CABG were prospect ively r and omized to tight glycemic control ( serum glucose , 125 to 200 mg/dL ) with GIK or st and ard therapy ( serum glucose < 250 mg/dL ) using intermittent subcutaneous insulin beginning before anesthesia and continuing for 12 hours after surgery . GIK patients had lower serum glucose levels ( 138±4 versus 260±6 mg/dL ; P < 0.0001 ) , a lower incidence of atrial fibrillation ( 16.6 % versus 42 % ; P = 0.0017 ) , and a shorter postoperative length of stay ( 6.5±0.1 versus 9.2±0.3 days ; P = 0.003 ) . GIK patients also showed a survival advantage over the initial 2 years after surgery ( P = 0.04 ) and decreased episodes of recurrent ischemia ( 5 % versus 19 % ; P = 0.01 ) and developed fewer recurrent wound infections ( 1 % versus 10 % , P = 0.03 ) . Conclusions —Tight glycemic control with GIK  in diabetic CABG patients  improves perioperative outcomes , enhances survival , and decreases the incidence of ischemic events and wound complications A prospect i ve , stratified , r and omized 3-year clinical trial was conducted on the effect of rigorous versus conventional glucose control on peripheral nerve function in 33 insulin-treated diabetic patients with a duration of diabetes of less than 2 years . The goals for conventional glucose control were the mean of fasting and 80-minute postpr and ial plasma glucose of 150 mg/dl for non-insulin-dependent diabetes and 200 mg/dl for insulin-dependent diabetes . The goal of rigorous glucose control was an approximation of nondiabetic glucose control . No significant difference in glucose control or peripheral nerve function was observed between the rigorously and the conventionally controlled groups . Eight patients in the conventional-control group spontaneously achieved glucose control in the range that was the objective for the rigorous-control group , and five patients in the rigorous-control group never achieved the desired glucose control . In the remaining 20 patients , with similar baseline glucose control and peripheral nerve function characteristics , observed over a median of 2 years , improved blood glucose control ( P less than 0.01 ) was not associated with any significant improvement in peripheral nerve function . Nevertheless , a significant ( P less than 0.05 ) correlation was found between the degree of abnormal nerve function at entry into the study and change in nerve function during the study . If control of hyperglycemia benefits peripheral nerve function of diabetic patients , its demonstration may require a closer approximation of normoglycemia , a larger difference in glucose control between the two study groups , a longer duration of treatment , and the use of patients with more advanced  peripheral nerve function  abnormalities than those in this study maintaining near-normal glycemia . 5 Group B patients were treated using the usual protocol s , with oral hy- poglycemic drugs or 2 daily doses of intermediate- acting insulin . Supplementary small doses of short- acting insulin were administered subcutaneously only if glucose levels were 250 mg/dl . Mean daily plasma glucose levels were assessed in each patient in both groups by employing all the measured glucose values obtained during the study . The mean glucose level in the conservative treatment group was assessed by the 3 st and ard prepr and ial glucose values ( at 7 A.M. , 1 P.M. , 6 P.M. ) , 1 measurement at 12 A.M. hours and any additional measurements that were performed accord- ing to the discretion of the attending physician . All patients were treated with an optimal antianginal reg- imen . Complete 2-dimensional , spectral , and color-fl ow Doppler echocardiographic examinations were per- formed by 2 examiners not involved in the fi nal anal- ysis of data , with a Hewlett-Packard Sonos 1000 Ul- trasound Machine ( And over , Massachusetts ) with a 2.5-MHz transducer , while the patients were asymp- tomatic . Images were obtained within 3 hours from ad- mission and 72 hours later and stored on high- quality videotapes for later blinded analysis . A DI design ed to determine the combined systolic and diastolic myocar- dial performance , and defi ned as the sum of isovolumet- ric contraction time plus isovolumetric relaxation time divided by ejection time , was estimated from LV outfl ow and mitral infl ow velocity patterns ( ( IVCT IVRT)/ ET).6 Videotape recordings were analyzed by 1 BACKGROUND Patients with type 2 diabetes are at high risk of fatal and non-fatal myocardial infa rct ion and stroke . There is indirect evidence that agonists of peroxisome proliferator-activated receptor gamma ( PPAR gamma ) could reduce macrovascular complications . Our aim , therefore , was to ascertain whether pioglitazone reduces macrovascular morbidity and mortality in high-risk patients with type 2 diabetes . METHODS We did a prospect i ve , r and omised controlled trial in 5238 patients with type 2 diabetes who had evidence of macrovascular disease .  We recruited patients from primary -care practice s and hospitals . We assigned patients to oral pioglitazone titrated from 15 mg to 45 mg ( n=2605 ) or matching placebo ( n=2633 ) , to be taken in addition to their glucose-lowering drugs and other medications . Our primary endpoint was the composite of all-cause mortality , non fatal myocardial infa rct ion ( including silent myocardial infa rct ion ) , stroke , acute coronary syndrome , endovascular or surgical intervention in the coronary or leg arteries , and amputation above the ankle . Analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N NCT00174993 . FINDINGS Two patients were lost to follow-up , but were included in analyses . The average time of observation was 34.5 months . 514 of 2605 patients in the pioglitazone group and 572 of 2633 patients in the placebo group had at least one event in the primary composite endpoint ( HR 0.90 , 95 % CI 0.80 - 1.02 , p=0.095 ) . The main secondary endpoint was the composite of all-cause mortality , non-fatal myocardial infa rct ion , and stroke . 301 patients in the pioglitazone group and 358 in the placebo group reached this endpoint ( 0.84 , 0.72 - 0.98 , p=0.027 ) . Overall safety and tolerability was good with no change in the safety profile of pioglitazone identified . 6 % ( 149 of 2065 ) and 4 % ( 108 of 2633 ) of those in the pioglitazone and placebo groups , respectively , were admitted to hospital with heart failure ; mortality rates from heart failure did not differ between groups . INTERPRETATION Pioglitazone reduces the composite of all-cause mortality , non-fatal myocardial infa rct ion , and stroke in patients with type 2 diabetes who have a high risk of macrovascular events BACKGROUND Intensified multifactorial intervention - with tight glucose regulation and the use of renin-angiotensin system blockers , aspirin , and lipid-lowering agents - has been shown to reduce the risk of nonfatal cardiovascular disease among patients with type 2 diabetes mellitus and microalbuminuria . We evaluated whether this approach would have an effect on the rates of death from any cause and from cardiovascular causes . METHODS In the Steno-2 Study , we r and omly assigned 160 patients with type 2 diabetes and persistent microalbuminuria to receive either intensive therapy or conventional therapy ;  the mean treatment period was 7.8 years . Patients were subsequently followed observationally for a mean of 5.5 years , until December 31 , 2006 . The primary end point at 13.3 years of follow-up was the time to death from any cause . RESULTS Twenty-four patients in the intensive-therapy group died , as compared with 40 in the conventional-therapy group ( hazard ratio , 0.54 ; 95 % confidence interval [ CI ] , 0.32 to 0.89 ; P=0.02 ) . Intensive therapy was associated with a lower risk of death from cardiovascular causes ( hazard ratio , 0.43 ; 95 % CI , 0.19 to 0.94 ; P=0.04 ) and of cardiovascular events ( hazard ratio , 0.41 ; 95 % CI , 0.25 to 0.67 ; P<0.001 ) . One patient in the intensive-therapy group had progression to end-stage renal disease , as compared with six patients in the conventional-therapy group ( P=0.04 ) . Fewer patients in the intensive-therapy group required retinal photocoagulation ( relative risk , 0.45 ; 95 % CI , 0.23 to 0.86 ; P=0.02 ) . Few major side effects were reported . CONCLUSIONS In at-risk patients with type 2 diabetes , intensive intervention with multiple drug combinations and behavior modification had sustained beneficial effects with respect to vascular complications and on rates of death from any cause and from cardiovascular causes . ( Clinical Trials.gov number , NCT00320008 . OBJECTIVE To investigate whether long-term intensive glycemic and lipid control would ameliorate the carotid intima medial thickness ( IMT ) in patients with type 2 diabetes mellitus ( T2DM ) . METHODS IMT was evaluated on B-mode ultrasonography in 116 patients with T2DM .  Body mass index ( BMI ) , waist-to-hip ratio ( WHR ) , fasting blood glucose ( FBG ) , 2 hour post 
    Output:
    