10-year follow-up of intensive glucose control in type 2 diabetes. Design of the cooperative study on glycemic control and complications in diabetes mellitus type 2: Veterans Affairs Diabetes Trial. WITHDRAWN: Targeting intensive glycaemic control versus targeting conventional glycaemic control for type 2 diabetes mellitus. Long-term effects of intensive glucose lowering on cardiovascular outcomes. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33) IV insulin during acute cerebral infarction in diabetic patients Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study Combined intensive blood pressure and glycemic control does not produce an additive benefit on microvascular outcomes in type 2 diabetic patients. Effect of the diabetes outpatient intensive management programme on glycaemic control for type 2 diabetic patients. The Hyperglycemia: Intensive Insulin Infusion in Infarction (HI-5) study: a randomized controlled trial of insulin infusion therapy for myocardial infarction. Intensive Glycemic Control and the Prevention of Cardiovascular Events: Implications of the ACCORD, ADVANCE, and VA Diabetes Trials A phase II randomised controlled trial of intensive insulin therapy in general intensive care patients. Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial--clinical implications. Impact of intensive glycemic control on the incidence of atrial fibrillation and associated cardiovascular outcomes in patients with type 2 diabetes mellitus (from the Action to Control Cardiovascular Risk in Diabetes Study). Effects of insulin treatment on cause-specific one-year mortality and morbidity in diabetic patients with acute myocardial infarction. DIGAMI Study Group. Diabetes Insulin-Glucose in Acute Myocardial Infarction.
BACKGROUND During the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) , patients with type 2 diabetes mellitus who received intensive glucose therapy  had a lower risk of microvascular complications than did those receiving conventional dietary therapy . We conducted post-trial monitoring to determine whether this improved glucose control persisted and whether such therapy had a long-term effect on macrovascular outcomes . METHODS Of 5102 patients with newly diagnosed type 2 diabetes , 4209 were r and omly assigned to receive either conventional therapy ( dietary restriction ) or intensive therapy ( either sulfonylurea or insulin or , in overweight patients , metformin ) for glucose control . In post-trial monitoring , 3277 patients were asked to attend annual UKPDS clinics for 5 years , but no attempts were made to maintain their previously assigned therapies . Annual question naires were used to follow patients who were unable to attend the clinics , and all patients in years 6 to 10 were assessed through question naires . We examined seven prespecified aggregate clinical outcomes from the UKPDS on an intention-to-treat basis , according to previous r and omization categories . RESULTS Between-group differences in glycated hemoglobin levels were lost after the first year . In the sulfonylurea-insulin group , relative reductions in risk persisted at 10 years for any diabetes-related end point ( 9 % , P=0.04 ) and microvascular disease ( 24 % , P=0.001 ) , and risk reductions for myocardial infa rct ion ( 15 % , P=0.01 ) and death from any cause ( 13 % , P=0.007 ) emerged over time , as more events occurred . In the metformin group , significant risk reductions persisted for any diabetes-related end point ( 21 % , P=0.01 ) , myocardial infa rct ion ( 33 % , P=0.005 ) , and death from any cause ( 27 % , P=0.002 ) . CONCLUSIONS Despite an early loss of glycemic differences , a continued reduction in microvascular risk and emergent risk reductions for myocardial infa rct ion and death from any cause were observed during 10 years of post-trial follow-up . A continued benefit after metformin therapy was evident among overweight patients . ( UKPDS 80 ; Current Controlled Trials number , IS RCT N75451837 . INTRODUCTION Long-term glycemic control trials in type 2 diabetes show as the main clinical benefit a difference in retinal photocoagulation ( 3/1000 in the UK Prospect i ve Diabetes Study [ UKPDS ] ) , but no effect on visual acuity or renal failure . No intensive glycemic control trial has yet affected cardiovascular ( CV ) events , the main cause of morbidity and mortality . By contrast , modest blood pressure reduction has protective effects on visual acuity , renal function , CV events , and mortality . Optimal glycemic control goals are not established in elderly , obese persons with advanced complications , the most common patients in the Veterans Affairs ( VA ) system . The earlier feasibility trial in such patients ( VA-CSDM ) suggested potentially worse CV outcomes with lower attained hemoglobin A1c ( HbA1c ) levels . OBJECTIVES The primary objective of the Veterans Affairs Diabetes Trial ( VADT ) is the assessment of the effect of intensive glycemic treatment on CV events . Other objectives are effects on microangiopathy , quality of life , and cost effectiveness . RESEARCH DESIGN AND METHODS The VADT , started in December 2000 , is enrolling 1700 men and women previously uncontrolled on insulin or maximum doses of oral agents at 20 VA medical centers . Accrual is 2 years and follow-up is 5 - 7 years , with visits every 1.5 months . The study has a power of 86 % to detect a 21 % relative reduction in major CV events ( CV death , myocardial infa rct ion [ MI ] , cerebrovascular accident [ CVA ] , congestive heart failure [ CHF ] , revascularization and amputation for ischemia ) . Subjects are r and omized to an intensive arm aim ing at normal HbA1c levels or to a st and ard arm with usual , improved glycemic control . An HbA1c separation of > 1.5 % is to be maintained ( expected 2 % ) . Both arms receive step therapy : glimepiride or metformin plus rosiglitazone and addition of insulin or other oral agents to achieve goals . Strict control of blood pressure and dyslipidemia , daily aspirin , diet , and education are identical in both arms . Plasma fibrinogen , plasminogen-activating inhibitor I ( PAI-I ) , lipids , renal function parameters , and ECG are measured throughout . Stereo retinal photographs are obtained at entry and 5 years , eye examinations yearly , and intervention as needed to prevent visual deterioration . Recruitment is proceeding on schedule : the current mean HbA1c at entry is 9.4+/-1.6 % and mean duration of diagnosed diabetes 11+/-8 years Background Patients with type 2 diabetes mellitus ( T2D ) have an increased risk of cardiovascular disease and mortality compared to the background population . Observational studies report an association between reduced blood glucose and reduced risk of both micro- and macrovascular complications in patients with T2D . Our previous systematic review of intensive glycaemic control versus conventional glycaemic control was based on 20 r and omised clinical trials that r and omised 29 , 986 participants with T2D . We now report our up date d review . Objectives To assess the effects of targeted intensive glycaemic control compared with conventional glycaemic control in patients with T2D . Search methods Trials were obtained from search es of The Cochrane Library , MEDLINE , EMBASE , Science Citation Index Exp and ed , LILACS , and CINAHL ( all until December 2012 ) . Selection criteria We included r and omised clinical trials that prespecified targets of intensive glycaemic control versus conventional glycaemic control targets in adults with T2D . Data collection and analysis Two authors independently assessed the risk of bias and extracted data . Dichotomous outcomes were assessed by risk ratios ( RR ) and 95 % confidence intervals ( CI ) . Health-related quality of life and costs of intervention were assessed with st and ardized mean differences ( SMD ) and 95 % Cl . Main results Twenty-eight trials with 34,912 T2D participants r and omised 18,717 participants to intensive glycaemic control  versus 16,195 participants to  conventional glycaemic control . Only two trials had low risk of bias on all risk of bias domains assessed . The duration of the intervention ranged from three days to 12.5 years . The number of participants in the included trials ranged from 20 to 11,140 . There were no statistically significant differences between targeting intensive versus conventional glycaemic control for all-cause mortality ( RR 1.00 , 95 % CI 0.92 to 1.08 ; 34,325 participants , 24 trials ) or cardiovascular mortality ( RR 1.06 , 95 % CI 0.94 to 1.21 ; 34,177 participants , 22 trials ) . Trial sequential analysis showed that a 10 % relative risk reduction could be refuted for all-cause mortality . Targeting intensive glycaemic control did not show a statistically significant effect on the risks of macrovascular complications as a composite outcome in the r and om-effects model , but decreased the risks in the fixed-effect model ( r and om RR 0.91 , 95 % CI 0.82 to 1.02 ; and fixed RR 0.93 , 95 % CI 0.87 to 0.99 ; P = 0.02 ; 32,846 participants , 14 trials ) . Targeting intensive versus conventional glycaemic control seemed to reduce the risks of non-fatal myocardial infa rct ion ( RR 0.87 , 95 % CI 0.77 to 0.98 ; P = 0.02 ; 30,417 participants , 14 trials ) , amputation of a lower extremity ( RR 0.65 , 95 % CI 0.45 to 0.94 ; P = 0.02 ; 11,200 participants , 11 trials ) , as well as the risk of developing a composite outcome of microvascular diseases ( RR 0.88 , 95 % CI 0.82 to 0.95 ; P = 0.0008 ; 25,927 participants , 6 trials ) , nephropathy ( RR 0.75 , 95 % CI 0.59 to 0.95 ; P = 0.02 ; 28,096 participants , 11 trials ) , retinopathy ( RR 0.79 , 95 % CI 0.68 to 0.92 ; P = 0.002 ; 10,300 participants , 9 trials ) , and the risk of retinal photocoagulation ( RR 0.77 , 95 % CI 0.61 to 0.97 ; P = 0.03 ; 11,212 participants , 8 trials ) . No statistically significant effect of targeting intensive glucose control could be shown on non-fatal stroke , cardiac revascularization , or peripheral revascularization . Trial sequential analyses did not confirm a reduction of the risk of non-fatal myocardial infa rct ion but confirmed a 10 % relative risk reduction in favour of intensive glycaemic control on the composite outcome of microvascular diseases . For the remaining microvascular outcomes , trial sequential analyses could not establish firm evidence for a 10 % relative risk reduction . Targeting intensive glycaemic control significantly increased the risk of mild hypoglycaemia , but substantial heterogeneity was present ; severe hypoglycaemia ( RR 2.18 , 95 % CI 1.53 to 3.11 ; 28,794 participants , 12 trials ) ; and serious adverse events ( RR 1.06 , 95 % CI 1.02 to 1.10 ; P = 0.007 ; 24,280 participants , 11 trials ) . Trial sequential analysis for a 10 % relative risk increase showed firm evidence for mild hypoglycaemia and serious adverse events and a 30 % relative risk increase for severe hypoglycaemia when targeting intensive versus conventional glycaemic control . Overall health-related quality of life , as well as the mental and the physical components of health-related quality of life did not show any statistical significant differences . Authors ' conclusions Although we have been able to exp and the number of participants by 16 % in this up date , we still find paucity of data on outcomes and the bias risk of the trials was mostly considered high . Targeting intensive glycaemic control compared with conventional glycaemic control did not show significant differences for all-cause mortality and cardiovascular mortality . Targeting intensive glycaemic control seemed to reduce the risk of microvascular complications , if we disregard the risks of bias , but increases the risk of hypoglycaemia and serious adverse events BACKGROUND Intensive glucose lowering has previously been shown to increase mortality among persons with advanced type 2 diabetes and a high risk of cardiovascular disease . This report describes the 5-year outcomes of a mean of 3.7 years of intensive glucose lowering on mortality and key cardiovascular events . METHODS We r and omly assigned participants with type 2 diabetes and cardiovascular disease or additional cardiovascular risk factors to receive intensive therapy ( targeting a glycated hemoglobin level below 6.0 % ) or st and ard therapy ( targeting a level of 7 to 7.9 % ) . After termination of the intensive therapy , due to higher mortality in the intensive-therapy group , the target glycated hemoglobin level was 7 to 7.9 % for all participants , who were followed until the planned end of the trial . RESULTS Before the intensive therapy was terminated , the intensive-therapy group did not differ significantly from the st and ard-therapy group in the rate of the primary outcome ( a composite of nonfatal myocardial infa rct ion , nonfatal stroke , or death from cardiovascular causes ) ( P=0.13 ) but had more deaths from any cause ( primarily cardiovascular ) ( hazard ratio , 1.21 ; 95 % confidence interval [ CI ] , 1.02 to 1.44 ) and fewer nonfatal myocardial infa rct ions ( hazard ratio , 0.79 ; 95 % CI , 0.66 to 0.95 ) . These trends persisted during the entire follow-up period ( hazard ratio for death , 1.19 ; 95 % CI , 1.03 to 1.38 ; and hazard ratio for nonfatal myocardial infa rct ion , 0.82 ; 95 % CI , 0.70 to 0.96 ) . After the intensive intervention was terminated , the median glycated hemoglobin level in the intensive-therapy group rose from 6.4 % to 7.2 % , and the use of glucose-lowering medications and rates of severe hypoglycemia and other adverse events were similar in the two groups . CONCLUSIONS As compared with st and ard therapy , the use of intensive therapy for 3.7 years to target a glycated hemoglobin level below 6 % reduced 5-year nonfatal myocardial infa rct ions but increased 5-year mortality . Such a strategy can not be recommended for high-risk patients with advanced type 2 diabetes . ( Funded by the National Heart , Lung and Blood Institute ; Clinical Trials.gov number , NCT00000620 . ) Abstract Objectives : To test the hypothesis that intensive metabolic treatment with insulin-glucose infusion followed by multidose insulin treatment in patients with diabetes mellitus and acute myocardial infa rct ion improves the prognosis . Design : Patients with diabetes mellitus and acute myocardial infa rct ion were r and omly allocated st and ard treatment plus insulin-glucose infusion for at least 24 hours followed by multidose insulin treatment or st and ard treatment ( controls ) . Subjects : 620 patients were recruited , of whom 306 received intensive insulin treatment and 314 served as controls .  Main outcome measure : Long term all cause mortality . Results : The mean ( range ) follow up was 3.4 ( 1.6 - 5.6 ) years . There were 102 ( 33 % ) deaths in the treatment group compared with 138 ( 44 % ) deaths in the control group ( relative risk ( 95 % confidence interval ) 0.72 ( 0.55 to 0.92 ) ; P=0.011).The effect was most pronounced among the predefined group that included 272 patients without previous insulin treatment and at a low cardiovascular risk ( 0.49 ( 0.30 to 0.80 ) ; P=0.004 ) . Conclusion : Insulin-glucose infusion followed by intensive subcutaneous insulin in diabetic patients with acute myocardial infa rct ion improves long term survival , and the effect seen at one year continues for at least 3.5 years , with an absolute reduction in mortality of 11 % . This means that one life was saved for nine treated patients . The effect was most apparent in patients who had not previously received insulin treatment and who were at a low cardiovascular risk . Key messages Diabetes mellitus is common among patients with acute myocardial infa rct ion Diabetic patients with myocardial infa rct ion have a poor short and long term prognosis Poor metabolic control is common among diabetic patients with myocardial infa rct ion Improved metabolic control by means of acute insulin-glucose infusion followed by long term intensive insulin treatment improves long term prognosis among these 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 Although hyperglycemia can be a nonspecific response to stress , tight glycemic control during acute myocardial infa rct ion1 and in postoperative ventilated patients 2 has been shown to significantly reduce mortality . Animal3 and human4 - 6 ⇓ ⇓ studies suggest that hyperglycemia also augments acute cerebral ischemia , and clinical efficacy of tight glycemic control during acute cerebral infa rct ion is being investigated.7 Good glycemic control during acute cerebral infa rct ion in nondiabetic patients appears feasible and safe , but this has not been reported in patients with diabetes mellitus.7 Our Institutional Review Board approved this study , and all subjects signed a valid informed consent . We prospect ively administered an IV insulin protocol initiated within 12 hours after onset of cerebral infa rct ion to 24 consecutive patients with admission hyperglycemia ( 9.4 to 22.2 mmol/L or 170 to 400 mg/dL ) . Nurses supervised closely by the principal investigator administered the insulin protocol in an open-label fashion . We modified our insulin protocol after each three to seven treated subjects to improve glycemic control and minimize hypoglycemia while keeping the protocol practical . We adjusted the insulin BACKGROUND In patients with type 2 diabetes , the effects of intensive glucose control on vascular outcomes remain uncertain . METHODS We r and omly assigned 11,140 patients with type 2 diabetes to undergo either  st and ard glucose control or intensive glucose control , defined as the use of gliclazide ( modified release ) plus other drugs as required to achieve a glycated hemoglobin value of 6.5 % or less . Primary end points were composites of major macrovascular events ( death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke ) and major microvascular events ( new or worsening nephropathy or retinopathy ) , assessed both jointly and separately . RESULTS After a median of 5 years of follow-up , the mean glycated hemoglobin level was lower in the intensive-control group ( 6.5 % ) than in the st and ard-control group ( 7.3 % ) . Intensive control reduced the incidence of combined major macrovascular and microvascular events ( 18.1 % , vs. 20.0 % with st and ard control ; hazard ratio , 0.90 ; 95 % confidence interval [ CI ] , 0.82 to 0.98 ; P=0.01 ) , as well as that of major microvascular events ( 9.4 % vs. 10.9 % ; hazard ratio , 0.86 ; 95 % CI , 0.77 to 0.97 ; P=0.01 ) , primarily because of a reduction in the incidence of nephropathy ( 4.1 % vs. 5.2 % ; hazard ratio , 0.79 ; 95 % CI , 0.66 to 0.93 ; P=0.006 ) , with no significant effect on retinopathy ( P=0.50 ) . There were no significant effects of the type of glucose control on major macrovascular events ( hazard ratio with intensive control , 0.94 ; 95 % CI , 0.84 to 1.06 ; P=0.32 ) , death from cardiovascular causes ( hazard ratio with intensive control , 0.88 ; 95 % CI , 0.74 to 1.04 ; P=0.12 ) , or death from any cause ( hazard ratio with intensive control , 0.93 ; 95 % CI , 0.83 to 1.06 ; P=0.28 ) . Severe hypoglycemia , although uncommon , was more common in the intensive-control group ( 2.7 % , vs. 1.5 % in the st and ard-control group ; hazard ratio , 1.86 ; 95 % CI , 1.42 to 2.40 ; P<0.001 ) . CONCLUSIONS A strategy of intensive glucose control , involving gliclazide ( modified release ) and other drugs as required , that lowered the glycated hemoglobin value to 6.5 % yielded a 10 % relative reduction in the combined outcome of major macrovascular and microvascular events , primarily as a consequence of a 21 % relative reduction in nephropathy . ( Clinical Trials.gov number , NCT00145925 . Abstract Objective : To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes . Design : Prospect i ve observational study . Setting : 23 hospital based clinics in Engl and , Scotl and , and Northern Irel and . Participants : 4585 white , Asian Indian , and Afro-Caribbean UKPDS patients , whether r and omised or not to treatment , were included in analyses of incidence ; of these , 3642 were included in analyses of relative risk . Outcome measures : Primary predefined aggregate clinical outcomes : any end point or deaths related to diabetes and all cause mortality . Secondary aggregate outcomes : myocardial infa rct ion , stroke , amputation ( including death from peripheral vascular disease ) , and microvascular disease ( predominantly retinal photo-coagulation ) . Single end points : non-fatal heart failure and cataract extraction . Risk reduction associated with a 1 % reduction in up date d mean HbA1c adjusted for possible confounders at diagnosis of diabetes . Results : The incidence of clinical complications was significantly associated with glycaemia . Each 1 % reduction in up date d mean HbA1c was associated with reductions in risk of 21 % for any end point related to diabetes ( 95 % confidence interval 17 % to 24 % , P<0.0001 ) , 21 % for deaths related to diabetes ( 15 % to 27 % , P<0.0001 ) , 14 % for myocardial infa rct ion ( 8 % to 21 % , P<0.0001 ) , and 37 % for microvascular complications ( 33 % to 41 % , P<0.0001 ) . No threshold of risk was observed for any end point . Conclusions : In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia . Any reduction in HbA1c is likely to reduce the risk of complications , with the lowest risk being in those with HbA1c values in the normal range ( < 6.0 % ) A reduction of either blood pressure or glycemia decreases some microvascular complications of type 2 diabetes , and we studied here their combined effects . In total , 4733 older adults with established type 2 diabetes and hypertension were r and omly assigned to intensive ( systolic blood pressure less than 120 mm Hg ) or st and ard ( systolic blood pressure less than 140 mm Hg ) blood pressure control , and separately to intensive ( HbA1c less than 0.060 ) or st and ard ( HbA1c 0.070 - 0.079 ) glycemic control . Prespecified microvascular outcomes were a composite of renal failure and retinopathy and nine single outcomes . Proportional hazard regression models were used without correction for type I error due to multiple tests . During a mean follow-up of 4.7 years , the primary outcome occurred in 11.4 % of intensive and 10.9 % of st and ard blood pressure patients ( hazard ratio 1.08 ) , and in 11.1 % of intensive and 11.2 % of st and ard glycemia control patients . Intensive blood pressure control only reduced the incidence of microalbuminuria ( hazard ratio 0.84 ) , and intensive glycemic control reduced the incidence of macroalbuminuria and a few other microvascular outcomes . There was no interaction between blood pressure and glycemic control , and neither treatment prevented renal failure . Thus , in older patients with established type 2 diabetes and hypertension , intensive blood pressure control improved only 1 of 10 prespecified microvascular outcomes . None of the outcomes were significantly reduced by simultaneous intensive treatment of glycemia and blood pressure , signifying the lack of an additional beneficial effect from combined treatment AIM The purpose of this study was to examine the effect of the diabetes outpatient intensive management programme ( DOIMP ) on glycaemic control over a 12 week follow-up period for type 2 diabetic patients in Korea . BACKGROUND Diabetic complications can be prevented if the glycaemic status of diabetes patients is maintained within a nearly normal range . Patient education is critical in controlling blood glucose levels of patients with diabetes within the optimal range . METHODS DOIMP was composed of multidisciplinary education , complication monitoring and telephone counselling .  Twenty-five patients in the intervention group participated in the DOIMP and 24 patients in the control group were briefed on the conventional description of diabetes mellitus by diabetes education nurses . RESULTS Patients in the intervention group had a mean decrease of 2.3 % , which those in the control group having a mean decrease 0.4 % in glycosylated haemoglobin ( HbA(1)c ) . There was no difference between the two groups in the change in fasting blood glucose ( FBG ) and two-hour postpr and ial blood glucose ( 2-h PBG ) . The proportion of the patients with HbA(1)c < 7 % was higher in the intervention group than in the control group at the post-test compare with the pretest . CONCLUSION DOIMP can reduce HbA(1)c in type 2 diabetes patients . RELEVANCE TO CLINICAL PRACTICE These findings indicated that DOIMP could be effective in glycaemic control in type 2 diabetes patients OBJECTIVE There is conflicting evidence regarding the benefit of intravenous insulin therapy on mortality following acute myocardial infa rct ion ( AMI ) . The goal of the current study was to determine whether improved glycemic control , achieved through an insulin/dextrose infusion with a variable rate of insulin , reduces mortality among hyperglycemic patients with AMI . RESEARCH DESIGN AND METHODS Subjects suffering AMI with either known diabetes or without diabetes but blood glucose level ( BGL ) > or = 7.8 mmol/l were r and omized to receive  insulin/dextrose infusion therapy  for at least 24 h to maintain a BGL < 10 mmol/l or conventional therapy . RESULTS A total of 240 subjects were recruited .  Insulin/dextrose infusion did not reduce mortality at the inpatient stage ( 4.8 vs. conventional 3.5 % , P = 0.75 ) , 3 months ( 7.1 vs 4.4 % , P = 0.42 ) , or 6 months ( 7.9 vs. 6.1 % , P = 0.62 ) . There was , however , a lower incidence of cardiac failure ( 12.7 vs. 22.8 % , P = 0.04 ) and reinfa rct ion within 3 months ( 2.4 vs. 6.1 % , P = 0.05 ) . When analyzed by mean BGL achieved during the first 24 h , mortality was lower among subjects with a mean BGL < or = 8 mmol/l , compared with subjects with a mean BGL > 8 mmol/l ( 2 vs. 11 % at 6 months , P = 0.02 ) . CONCLUSIONS We did not find a reduction in mortality among patients who received insulin/dextrose infusion therapy . However , it remains possible that tight glycemic control with insulin therapy following AMI improves outcomes Diabetes is defined by its association with hyperglycemia-specific microvascular complications ; however , it also imparts a two- to fourfold risk of cardiovascular disease ( CVD ) . Although microvascular complications can lead to significant morbidity and premature mortality , by far the greatest cause of death in people with diabetes is CVD . Results from r and omized controlled trials have demonstrated conclusively that the risk of microvascular complications can be reduced by intensive glycemic control in patients with type 1 ( 1,2 ) and type 2 diabetes ( 3–5 ) . In the Diabetes Control and Complications Trial ( DCCT ) , there was an ∼60 % reduction in development or progression of diabetic retinopathy , nephropathy , and neuropathy between the intensively treated group ( goal A1C < 6.05 % , mean achieved A1C ∼7 % ) and the st and ard group ( A1C ∼9 % ) over an average of 6.5 years . The relationship between glucose control ( as reflected by the mean on- study A1C value ) and risk of complications was log-linear and extended down to the normal A1C range ( < 6 % ) with no threshold noted . In the UK Prospect i ve Diabetes Study ( UKPDS ) , participants newly diagnosed with type 2 diabetes were followed for 10 years , and intensive control ( median A1C 7.0 % ) was found to reduce the overall microvascular complication rate by 25 % compared with conventional treatment ( median A1C 7.9 % ) . Here , too , secondary analyses showed a continuous relationship between the risk of microvascular complications and glycemia extending into the normal range of A1C , with no glycemic threshold . On the basis of these two large controlled trials , along with smaller studies and numerous epidemiologic reports , the consistent findings related to microvascular risk reduction with intensive glycemic control have led the American Diabetes Association ( ADA ) to recommend an A1C goal of < 7 % for most adults with diabetes ( 6 ) , recognizing that more or less stringent goals may be appropriate for certain patients . Whereas many epidemiologic studies and meta-analyses OBJECTIVE To determine the safety and efficacy of an intensive insulin regimen compared with a conventional insulin regimen in general intensive care unit patients . METHODS A phase II , r and omised controlled trial was conducted in 70 critically ill patients in a closed multidisciplinary ICU of a university-affiliated tertiary hospital . We assessed patient characteristics at baseline . Trial process measures included number of blood glucose measurements per day and number in target range , type and quantity of caloric intake , patient outcome and insulin dosing . The primary outcome was the median blood glucose concentration . Secondary outcome measures were incidence of hypoglycaemia ( blood glucose level < 2.2 mmol/L ) , clinical sequelae of hypoglycaemia and hospital mortality . RESULTS Thirty-five patients were r and omised to each of the two groups . More blood glucose sample s were taken per day in the intensive insulin group ( 16 versus 9 ) , but the number of sample s in the normoglycaemic range was 48.5 % , compared with 79.8 % within the target glucose range in the conventional insulin group . The median ( interquartile range ) blood glucose concentrations in the intensive and conventional insulin therapy groups were 5.4 ( 5.1 - 5.7 ) mmol/L and 7.9 ( 7.2 - 9.0 ) mmol/L , respectively ( difference , 2.5 mmol/L ; P < 0.0001 ) . Five patients ( 14.3 % ) in the intensive insulin therapy group became hypoglycaemic versus none in the conventional insulin therapy group . There were no detected clinical sequelae of hypoglycaemia . CONCLUSION The intensive insulin regimen was effective in achieving the target blood glucose concentration , with clear separation from the conventional insulin regimen . Although the incidence of hypoglycaemia was increased , there was no detectable harm Patients with type 2 diabetes are at high risk for several serious health problems , including premature death , cardiovascular disease (CVD),2 blindness , and kidney failure . Moreover , there is a strong positive association between the degree of glycemia , measured as plasma glucose or glycated hemoglobin ( Hb A1c ) , and the above outcomes . Hence , it has been hypothesized that the mortality and morbidity of type 2 diabetes can be reduced with intensive control of glycemia . The Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) trial tested this hypothesis by determining whether a therapeutic strategy that targeted a typical Hb A1c value of < 6.0 % , compared with a strategy that targeted an Hb A1c value of 7.0%–7.9 % , would reduce CVD ( 1 ) . The primary outcome was a composite of CVD death , nonfatal myocardial infa rct ion , and nonfatal stroke . Secondary outcomes included all-cause mortality , development and progression of microvascular disease , frequency of severe hypoglycemia , and progression of retinopathy . The trial also tested the effects of intensive blood pressure ( BP ) control and the addition of a fibrate in selected patients . The study r and omized 10 251 participants with well-established type 2 diabetes . Entry criteria included a history of a cardiovascular event or at least 2 risk factors for CVD , and a normal serum creatinine concentration . The trial was not design ed to test the efficacy of any particular medication or combination of medications . What differed between the 2 arms was the glycemic target and consequently the frequency of use of glycemia medications and , to a lesser extent , the dosage . All participants made frequent clinic visits , during which lifestyle education and hypoglycemia prevention were emphasized . Within 8 months after enrollment , the median Hb A1c values in the intensive and st and ard glycemia arms reached 6.4 % and 7.5 % , respectively , and remained stable with a difference between the medians of 1.1 % Atrial  fibrillation ( AF )  is prevalent in patients with type 2 diabetes mellitus ( DM ) and is associated with markers of poor glycemic control ; however , the impact of glycemic control on incident AF and outcomes is unknown . The aims of this study were to prospect ively evaluate if intensive glycemic control in patients with DM affects incident AF and to evaluate morbidity and mortality in patients with DM and incident AF . A total of 10,082 patients with DM from the Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) cohort were studied in a r and omized , double-blind fashion . Participants were r and omized to an intensive therapeutic strategy targeting a glycated hemoglobin level of < 6.0 % or a st and ard strategy targeting a glycated hemoglobin level of 7.0 % to 7.9 % . Incident AF occurred in 159 patients ( 1.58 % ) over the follow-up period , at a rate of 5.9 per 1,000 patient-years in the intensive-therapy group and a rate of 6.37 per 1,000 patient-years in the st and ard-therapy group ( p = 0.52 ) . In a multivariate model , predictors of incident AF were age , weight , diastolic blood pressure , heart rate , and heart failure history .  Patients with DM and new-onset AF  had a hazard ratio of 2.65 for all-cause mortality ( 95 % confidence interval 1.8 to 3.86 , p < 0.0001 ) , a hazard ratio of 2.1 for myocardial infa rct ion ( 95 % confidence interval 1.33 to 3.31 , p = 0.0015 ) , and a hazard ratio of 3.80 for the development of heart failure ( 95 % confidence interval 2.48 to 5.84 , p < 0.0001 ) . In conclusion , intensive glycemic control did not affect the rate of new-onset AF .  Patients with DM and incident AF had an increased risk for morbidity and mortality compared with those without AF Diabetic patients with acute myocardial infa rct ion have a poor prognosis , which has been attributed to a higher incidence of congestive heart failure and fatal reinfa rct ion . This study reports on the one-year morbidity and mortality in a r and omized study with the aim of testing whether insulin-glucose infusion initiated as soon as possible after onset of myocardial infa rct ion and followed by long-term subcutaneous insulin treatment may have a beneficial effect on outcome in diabetic patients . In all , 306 patients were recruited to the insulin-treated group , while 314 patients served as controls .  The overall mortality after one year was 19 % in the insulin group compared to 26 % among controls ( P < 0.05 ) . The treatment effect was most pronounced in patients without prior insulin medication and at low cardiovascular risk . In this stratum the in-hospital mortality was reduced by 58 % ( P < 0.05 ) and the one-year mortality by 52 % ( P < 0.02 ) . The most frequent cause of death in all patients was congestive heart failure ( 66 % ) , but cardiovascular mortality ( congestive heart failure , fatal reinfa rct ion , sudden death and stroke ) tended to be decreased in insulin-treated patients . However , this difference did not reach the level of statistical significance . The number of reinfa rct ions was 53 ( 28 % fatal ) in the insulin group compared to 55 ( 45 % fatal ) in the control group . The two groups did not differ as regards need for hospital care or coronary revascularization during the year of follow-up . In summary , left ventricular failure and fatal reinfa rct ions contribute to increased mortality in diabetic patients following acute myocardial infa rct ion . Intensive insulin treatment lowered this mortality during one year of follow-up
Intensive glycaemic control does not seem to reduce all cause mortality in patients with type 2 diabetes .
OBJECTIVE To assess the effect of targeting intensive glycaemic control versus conventional glycaemic control on  all cause mortality and cardiovascular mortality , non-fatal myocardial infa rct ion , microvascular complications , and severe hypoglycaemia in patients with type 2 diabetes .