***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: Basic fibroblast growth factor ( bFGF ) is a potent endothelial cell mitogen that does not normally circulate , but increases in microalbuminuric adult type 2 diabetes mellitus . Earlier work indicated an unexpected association between low levels of plasma bFGF immunoreactivity and the subsequent 4-year need for laser treatment in 172 patients from the Veterans Affairs Diabetes Trial ( mean : age , 59 years ; diabetes duration , 11 years ; baseline hemoglobin A(1c ) , 9.5 % ) . In the present study , we tested for an association between endothelial cell inhibitory autoantibodies in plasma and the need for  laser treatment .  Inhibitory activity in endothelial cells from the immunoglobulin G fractions of plasma was significantly associated ( P = .002 ) with low plasma bFGF immunoreactivity . There was a significant association ( P = .003 ) between endothelial cell inhibitory autoantibodies in baseline plasma and the time to occurrence of first laser treatment  after 4 years of study treatment . After adjusting for other risk factors , endothelial cell inhibitory activity greater than 90 % vs less than or equal to 90 % ( hazard ratio , 0.2 ; P = .003 ) and low-density lipoprotein cholesterol concentration ( hazard ratio , 0.98 ; P = .02 ) were each significant predictors of the time to first postr and omization laser occurrence . These results suggest that circulating autoantibodies inhibitory in endothelial cells may contribute to the need for laser treatment  in adult men with advanced type 2 diabetes mellitus . Among the possible risk factors evaluated , baseline insulin use was the only variable significantly inversely ( P = .02 ) associated with the baseline occurrence of inhibitory endothelial cell autoantibodies . It could not be determined whether insulin use may decrease the occurrence of endothelial cell inhibitory autoantibodies in advancing adult type 2 diabetes mellitus Type 2 diabetes mellitus and cognitive impairment are 2 of the most common chronic conditions found in persons aged > or = 60 years . Clinical studies have shown a greater prevalence of global cognitive impairment , incidence of cognitive decline , and incidence of Alzheimer disease in patients with type 2 diabetes . To date , there have been no r and omized trials of the effects of long-term glycemic control on cognitive function and structural brain changes in patients with type 2 diabetes . The primary aim of the Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) Memory in Diabetes Study ( ACCORD-MIND ) is to test whether there is a difference in the rate of cognitive decline and structural brain change in patients with diabetes treated with st and ard-care guidelines  compared with those treated with intensive-care guidelines .  This comparison will be made in a sub sample of 2,977 patients with diabetes participating in the ongoing ACCORD trial , a clinical trial sponsored by the National Heart , Lung , and Blood Institute ( NHLBI ) with support from the National Institute on Aging ( NIA ) . Data from this ACCORD sub study on the possible beneficial or adverse effects of intensive treatment on cognitive function will be obtained from a 30-minute test battery , administered at baseline and 20-month and 40-month visits . In addition , full-brain magnetic resonance imaging will be performed on 630 participants at baseline and at 40 months to assess the relation between the ACCORD treatments and structural brain changes . The general aim of ACCORD-MIND is to determine whether the intensive treatment of diabetes , a major risk factor for Alzheimer disease and vascular dementia , can reduce the early decline in cognitive function that could later evolve into more cognitively disabling conditions . This report presents the design , rationale , and methods of the ACCORD-MIND sub study CONTEXT Macular edema contributes to visual impairment , and albuminuria is associated with increased cardiovascular mortality in adults with type 2 diabetes mellitus . These microvascular complications result from increased capillary leakage of plasma proteins whose causation is not completely understood . OBJECTIVE The objective of the present study was to test whether plasma from type 2 diabetes with maculopathy/albuminuria or control subjects contains autoantibodies that can induce apoptosis or activate Rho kinase ( ROCK ) in endothelial cells . DESIGN A cohort of Veterans Affairs Diabetes Trial adults ( > 40 yr of age ) was r and omized  to st and ard vs. intensive glycemic treatment lasting 5 - 7.5 yr . SETTING The study was conducted in outpatient clinics . PATIENTS Case and age-matched control subjects who differed for the baseline presence of significant diabetic maculopathy and /or progression to macro-albuminuria were included in the study . INTERVENTION Pharmacological and lifestyle interventions in the Veterans Affairs Diabetes Trial generally result ed in substantially improved glycemic , blood pressure , and lipid levels . RESULTS Autoantibodies from patients with macular edema or progression to albuminuria potently induced caspase-dependent apoptosis in endothelial cells ( up to 60 % ) , whereas IgG from age-matched normal plasma caused much less apoptosis ( < 10 % ; P < 0.0001 ) . The active inhibitory autoantibodies triggered stress fiber formation in endothelial cells likely through the activation of Rho guanosine 5'-triphosphatase , which could be nearly completed inhibited by 10 microm Y27632 , a specific ROCK inhibitor . CONCLUSIONS These results suggest that autoantibodies from a subset of advanced type 2 diabetes may contribute to diabetic vascular complications by activating ROCK , inducing stress fiber formation and apoptosis in endothelial cells OBJECTIVE We explore the effect of r and omized treatment , comparing intensive to st and ard glucose-lowering strategies on major cardiovascular outcomes , death , and severe adverse events in older versus younger participants in the Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) trial . RESEARCH DESIGN AND METHODS Participants with type 2 diabetes ( n = 10,251 ) with a mean age of 62 years , a median duration of diabetes of 10 years , and a median A1C of 8.1 % ( 65 mmol/mol ) were r and omized to treatment strategies targeting either A1C < 6.0 % ( 42 mmol/mol ) or 7.0–7.9 % ( 53–63 mmol/mol ) and followed for a mean of 3.7 years . Outcomes were analyzed within subgroups defined by baseline age ( < 65 vs. ≥65 years ) . RESULTS Older and younger ACCORD participants achieved similar intensive-arm A1C levels and between-arm A1C differences . Within the older subgroup , similar hazards of the cardiovascular primary outcome and total mortality were observed in the two arms . While there was no intervention effect on cardiovascular mortality in the older subgroup , there was an increased risk in the intensive arm for the younger subgroup ( older hazard ratio [ HR ] = 0.97 ; younger HR = 1.71 ; P = 0.03 ) . Regardless of intervention arm , the older subgroup experienced higher annualized rates of severe hypoglycemia ( 4.45 % intensive and 1.36 % st and ard ) than the younger subgroup ( 2.45 % intensive and 0.80 % st and ard ) .  CONCLUSIONS Intensive glucose lowering  increased the risk of cardiovascular disease and total mortality in younger participants , whereas it had a neutral effect in older participants . The intensive to st and ard relative risk of severe hypoglycemia was similar in both age subgroups , with higher absolute rates in older participants within both treatment arms Urinary albumin was studied in 45 patients with insulin-dependent diabetes in a 4-year prospect i ve r and omized trial , comparing continuous sc insulin infusion ( CSII ) , multiple insulin injections , and conventional treatment with twice daily injections . Strict blood glucose control was obtained with CSII and multiple injections , better than with conventional treatment ( 2P less than 0.01 ) : mean glycosylated haemoglobin ( % HbA1 + /- SEM ) after 4 years : CSII 9.0 + /- 0.4 % ; multiple injections 9.4 + /- 0.4 % ; conventional treatment 10.5 + /- 0.5 . A total of 696 24-h urine specimens were collected . After 4 years of CSII from the time of r and omization , urinary albumin excretion was reduced ( 26 + /- 5 to 16 + /- 4 mg/24 h , mean + /- SEM , 2P less than 0.01 ) , when compared with conventional treatment ( 2P = 0.01 ) , when compared with conventional treatment ( 2P = 0.01 ) where no change was observed ( 21 + /- 4 to 22 + /- 6 mg/24 h , n.s . ) . The reduction observed during  multiple injection treatment was not significant ( 17 + /- 3 to 14 + /- 3 mg/24 h ) . Long-term near-normoglycaemia may influence the mechanisms leading to albuminuria in diabetes , if introduced at an early stage of the disease OBJECTIVE To examine whether intensive glycemic control could decrease the frequency or severity of diabetic microvascular complications , an 8-year prospect i ve study of Japanese patients with type 2 diabetes was performed . RESEARCH DESIGN AND METHODS A total of 110 patients with type 2 diabetes ( 55 with no retinopathy [ the primary prevention cohort ] and 55 with simple retinopathy [ the secondary intervention cohort ] ) were r and omly assigned to multiple insulin injection therapy ( MIT ) groups and administered three or more daily insulin injections or assigned to conventional insulin injection therapy ( CIT ) groups and administered one or two daily intermediate-acting insulin injections . Worsening of microvascular complications was regularly assessed during 8 years . Two or more steps up in the 19 stages of the modified Early Treatment of Diabetic Retinopathy Study classification in retinopathy and one or more stages up among three stages in nephropathy ( normoalbuminuria , microalbuminuria , and albuminuria ) were defined as worsening of complications . RESULTS In both primary prevention and secondary intervention cohorts , the cumulative percentages of worsening in retinopathy and nephropathy were significantly lower ( P < 0.05 ) in the MIT group than in the CIT group . In neurological tests after 8 years , the MIT group showed significant improvement ( P < 0.05 ) in the median nerve conduction velocities ( motor and sensory nerves ) , whereas the CIT group showed significant deterioration ( P < 0.05 ) in the nerve conduction velocities and vibration threshold . From this study , the glycemic threshold to prevent the onset and progression of diabetic microvascular complications was as follows : HbA1c < 6.5 % , fasting blood glucose concentration < 110 mg/dl , and 2-h postpr and ial blood glucose concentration < 180 mg/dl . CONCLUSIONS Intensive glycemic control can delay the onset and progression of the early stages of diabetic microvascular complications in Japanese patients with type 2 diabetes Background — We report relationships between cardiovascular disease risk factors and myocardial structure , function , and scar in patients with type 1 diabetes mellitus in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications ( DCCT/EDIC ) study . Methods and Results — Cardiac magnetic resonance was obtained in 1017 patients with type 1 diabetes mellitus .  Gadolinium cardiac magnetic resonance was also obtained in 741 patients . The mean age was 49±7 years ; 52 % were men ; and mean duration of diabetes mellitus was 28±5 years . Associations of cardiovascular disease risk factors with cardiac magnetic resonance parameters were examined with linear and logistic regression models . History of macroalbuminuria was positively associated with left ventricular mass ( by 14.8 g ) , leading to a significantly higher ratio of left ventricular mass to end-diastolic volume ( by 8 % ) . Mean hemoglobin A1c levels over the preceding 22 years were inversely associated with end-diastolic volume ( −3.0 mL per unit mean hemoglobin A1c percent ) and stroke volume ( −2.3 mL per unit mean hemoglobin A1c percent ) and positively related to the ratio of elevated left ventricular mass to end-diastolic volume ( 0.02 g/mL per unit ) . The overall prevalence of myocardial scar was 4.3 % by cardiac magnetic resonance and 1.4 % by clinical adjudication of myocardial infa rct ion . Both mean hemoglobin A1c ( odds ratio , 1.5 [ 95 % confidence interval , 1.0–2.2 ] per unit ) and macroalbuminuria ( odds ratio , 3.5 [ 95 % confidence interval , 1.2–9.9 ] ) were significantly associated with myocardial scar and traditional cardiovascular disease risk factors . Conclusions — In addition to traditional cardiovascular disease risk factors , elevated mean hemoglobin A1c and macroalbuminuria were 
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AUTHORS ' CONCLUSIONS This review suggests that people who receive intensive glycaemic control for treatment of diabetes had comparable risks of kidney failure , death and major cardiovascular events as people who received less stringent blood glucose control , while experiencing small clinical benefits on the onset and progression of microalbuminuria and myocardial infa rct ion .