***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: In patients with diabetes and coronary artery disease , the potential negative role of sulfonylurea drugs is under intensive investigation . We assessed the effects of treatment with glibenclamide or insulin on the extension of left ventricular myocardial dysfunction induced by acute ischemia . Nineteen consecutive patients with type 2 diabetes and coronary artery disease entered the study . Each patient was r and omly assigned to either insulin or glibenclamide therapy . Treatment was crossed over after 12 weeks and maintained for another 12 weeks . At the end of each treatment , left ventricular myocardial function at rest and during dipyridamole infusion was studied by  two-dimensional echocardiography under the same conditions of metabolic control . Glibenclamide or insulin treatment did not influence the rest values of left ventricular dimensions , left ventricular ejection fraction ( LVEF ) , or wall motion score index ( WMSI ) . Dipyridamole infusion , in patients receiving glibenclamide treatment , decreased LVEF ( 43 + /- 7 vs. 37 + /- 12 % , P < 0.005 ) and increased WMSI ( 1.4 + /- 0.28 vs. 1.98 + /- 0.24 , P < 0.001 ) compared with baseline values ; during insulin treatment , LVEF ( 46 + /- 8 vs. 45 + /- 11 % , NS ) and WMSI ( 1.4 + /- 0.29 vs. 1.6 + /- 0.4 , NS ) did not change significantly . Peak stress LVEF was higher ( 45 + /- 11 vs. 37 + /- 12 % , P < 0.001 ) and WMSI lower ( 1.6 + /- 0.4 vs. 1.98 + /- 0.24 , P < 0.001 ) in patients receiving insulin . The results indicate that in patients with type 2 diabetes and coronary artery disease , ischemic myocardial dysfunction induced by dipyridamole infusion is less severe during treatment with insulin than with glibenclamide . Restitution of a preconditioning mechanism in insulin-treated patients may be the potential beneficial mechanism Background Brief episodes of ischemia render the heart more resistant to subsequent ischemia ; this phenomenon has been called ischemic preconditioning . In some animal species , myocardial preconditioning appears to be due to activation of ATP-sensitive K+ ( KATP ) channels . The role played by KATP channels in preconditioning in humans remains unknown . The aim of this study was to establish whether glibenclamide , a selective KATP channel blocker , abolishes the ischemic preconditioning observed in humans during coronary angioplasty following repeated balloon inflations . Methods and Results Twenty consecutive patients undergoing one-vessel coronary angioplasty were r and omized to receive 10 mg oral glibenclamide or placebo . Sixty minutes after glibenclamide or placebo administration , patients were given an infusion of 10 % dextrose ( 8 mL/min ) to correct glucose plasma levels or , respectively , an infusion of saline at the same infusion rate . Thirty minutes after the beginning of the infusion , both patient groups underwent coronary angioplasty . The mean values ( ± 1 SD ) of ST-segment shifts on the surface 12-lead ECG and the intracoronary ECG were measured at the end of the first and second balloon inflations , both 2 minutes long . In glibenclamide-treated patients , the mean ST-segment shift during the second balloon inflation was similar to that observed during the first inflation ( 23± 13 versus 20±8 mm , P = NS ) , and the severity of cardiac pain was greater ( 55±21 versus 43±23 mm on a scale of 0 to 100 , P<.05 ) . Conversely , in placebo-treated patients the mean ST-segment shift during the second inflation was less than that during the first inflation ( 9±5 versus 23±13 mm , P<.001 ) , as was the severity of cardiac pain ( 15±15 versus 42±19 mm , P<.01 ) . Blood glucose levels were significantly reduced 60 minutes after glibenclamide compared with those at baseline ( 53±9 versus 102±10 mg/100 mL , P<.001 ) in the glibenclamide group ; however , before coronary angioplasty , blood glucose levels increased to 95±19 mg/100 mL , a value similar to that found in placebo group ( 96±11 mg/100 mL , P = NS ) . Conclusions In humans , ischemic preconditioning during brief repeated coronary occlusions is completely abolished by pretreatment with glibenclamide , thus suggesting that it is mainly mediated by KATP channels BACKGROUND Improved blood-glucose control decreases the progression of diabetic microvascular disease , but the effect on macrovascular complications is unknown . There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation . We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a r and omised controlled trial . METHODS 3867 newly diagnosed patients with type 2 diabetes , median age 54 years ( IQR 48 - 60 years ) , who after 3 months ' diet treatment had a mean of two fasting plasma glucose ( FPG ) concentrations of 6.1 - 15.0 mmol/L were r and omly assigned intensive policy with a sulphonylurea ( chlorpropamide , glibenclamide , or glipizide ) or with insulin , or conventional policy with diet . The aim in the intensive group was FPG less than 6 mmol/L. In the conventional group , the aim was the best achievable FPG with diet alone ; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 15 mmol/L. Three aggregate endpoints were used to assess differences between conventional and intensive treatment :  any diabetes-related endpoint ( sudden death , death from hyperglycaemia or hypoglycaemia , fatal or non-fatal myocardial infa rct ion , angina , heart failure , stroke , renal failure , amputation [ of at least one digit ] , vitreous haemorrhage , retinopathy requiring photocoagulation , blindness in one eye , or cataract extraction ) ; diabetes-related death ( death from myocardial infa rct ion , stroke , peripheral vascular disease , renal disease , hyperglycaemia or hypoglycaemia , and sudden death ) ; all-cause mortality . Single clinical endpoints and surrogate sub clinical endpoints were also assessed . All analyses were by intention to treat and frequency of hypoglycaemia was also analysed by actual therapy . FINDINGS Over 10 years , haemoglobin A1c ( HbA1c ) was 7.0 % ( 6.2 - 8.2 ) in the intensive group compared with 7.9 % ( 6.9 - 8.8 ) in the conventional group -- an 11 % reduction . There was no difference in HbA1c among agents in the intensive group . Compared with the conventional group , the risk in the intensive group was 12 % lower ( 95 % CI 1 - 21 , p=0.029 ) for any diabetes-related endpoint ; 10 % lower ( -11 to 27 , p=0.34 ) for any diabetes-related death ; and 6 % lower ( -10 to 20 , p=0.44 ) for all-cause mortality . Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25 % risk reduction ( 7 - 40 , p=0.0099 ) in microvascular endpoints , including the need for retinal photocoagulation . There was no difference for any of the three aggregate endpoints between the three intensive agents ( chlorpropamide , glibenclamide , or insulin ) . Patients in the intensive group had more hypoglycaemic episodes than those in the conventional group on both types of analysis ( both p<0.0001 ) . The rates of major hypoglycaemic episodes per year were 0.7 % with conventional treatment , 1.0 % with chlorpropamide , 1.4 % with glibenclamide , and 1.8 % with insulin .  Weight gain was significantly higher in the intensive group ( mean 2.9 kg ) than in the conventional group ( p<0.001 ) , and patients assigned insulin had a greater gain in weight ( 4.0 kg ) than those assigned chlorpropamide ( 2.6 kg ) or glibenclamide ( 1.7 kg ) . INTERPRETATION Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications , but not macrovascular disease , in patients with type 2 diabetes . ( ABSTRACT TRUNCATED In a diabetes detection survey carried out between 1962 and 1965 , 2477 ( 1.1 % ) of 228,883 subjects had Clinistix-positive glucosuria after a carbohydrate-rich luncheon meal . Of these 2477 , 578 displayed impaired tolerance to oral glucose without having manifest diabetes . From this group , 267 men were divided into five groups and subjected to the following treatments and controls : ( a ) diet regulation and 0.5 g tolbutamide t.i.d . ( N = 49 ) , annual oral glucose tolerance test ( OGTT ) ; ( b ) diet regulation and one placebo tablet t.i.d . ( N = 48 ) , annual OGTT ; ( c ) diet regulation only ( N = 50 ) , annual OGTT ; ( d ) no treatment ( N = 61 ) , annual OGTT ; and ( e ) no treatment , OGTT at follow-up ( N = 59 at follow-up ) . In addition , a control group was included comprised of men with normal OGTT ( N = 52 ) . At follow-up , 29 % of those without diet regulation and medication ( group e ; N = 59 ) had developed diabetes . Of those on diet regulation , but without active medication ( group b plus group c , N = 98 ) , 13 % had diabetes . No individual maintaining tolbutamide  and diet regulation ( N = 23 ) had progressed to diabetes . In this group , 80 % of those later examined ( N = 11 ) had serum tolbutamide concentrations in the therapeutic range . No individual with initially normal OGTT developed diabetes or impaired OGTT . The findings suggest that normal oral glucose tolerance signifies little risk of progress to impaired glucose tolerance and manifest diabetes , whereas impaired glucose tolerance is associated with a high risk of progression to diabetes . In addition , it seems possible that treatment with diet regulation , in combination with tolbutamide , may prevent or postpone progression from impaired glucose tolerance to manifest diabetes Background —The ischemic preconditioning response among elderly patients is known to be lower than in adult patients . Since mitochondrial ATP-sensitive potassium ( KATP ) channels exert preconditioning effects , we undertook this study to determine whether this attenuated activation of KATP channels influences the reduced responsiveness of elderly patients to ischemic preconditioning . Methods and Results —Fifty-six patients undergoing angioplasty for a major epicardial coronary artery were r and omly allocated to either an ischemic preconditioning group , a nicor and il ( an agonist of KATP channels ) group , or a glibenclamide ( an antagonist of KATP channels ) , group based on their age : adult groups ( n=26 ; age , ≤55 years ; mean age , 45±5 years ) and elderly groups ( n=30 ; age , ≥65 years ; mean age , 71±3 years ) . Ischemic preconditioning with a 120-second coronary occlusion significantly lowered the ischemic burden assessed by ST-segment shift , chest pain score , and myocardial lactate extraction ratios in the adult group . This did not occur in the elderly group . The impaired preconditioning responsiveness in the elderly patients was reversed by nicor and il administration or an ischemic period lengthened to 180 seconds . However , nicor and il-induced cardioprotection was abolished by administering glibenclamide in both the adult and elderly groups . Conclusions —The present study demonstrates that preconditioning significantly enhances the tolerance of the heart to subsequent ischemia in adults but not in senescent patients . Since prolonged ischemia and nicor and il are able to mimic preconditioning and can reverse impaired responsiveness , impaired preconditioning of the aged heart appears to be due to an attenuated activation of KATP channels AIMS The increased tolerance to myocardial ischaemia observed during the second of two sequential exercise tests , i.e. the warm-up phenomenon , has been proposed as a clinical model of ischaemic preconditioning . As ATP-sensitive K+ channels appear to be a mediator of ischaemic preconditioning in both experimental and clinical studies , the aim of this study was to investigate the role of K(ATP ) channels in the warm-up phenomenon . METHODS AND RESULTS Twenty-six patients with coronary artery disease were r and omized to receive 10 mg oral 
    Output:
    
In vitro and in animal studies , GB is both deleterious for ischemic preconditionning ( IPC ) and protective for arrhythmia during acute ischemia .
Glimepiride ( GM ) and gliclazide ( GCZ ) do not seem to have effect on IPC .
In human , according to the investigations used , the GB seems nil or suppressing for IPC , it seems elsewhere decreases ventricular arrhythmias during periods of acute ischemia .
It is possible that these two actions account for the non-appearance of concordant deleterious effects between short and long-term studies .
With regards to other drugs , only the GM has been specifically studied in human and appears to be nil on IPC .
This trial demonstrates the absence of deleterious cardiac effects of GB compared to chlorpropamide and particularly compared to insulin .
CONCLUSION In conclusion , in experimental studies the cardiac effects of SU differ : both deleterious and protective for GB , nil for GM and GCZ on IPC .
In all cases the clinical consequences seems to be nil