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: Background —Arterial distensibility measures , generally from pulse-wave velocity ( PWV ) , are widely used with little knowledge of relationships to patient outcome . We tested whether aortic PWV predicts cardiovascular and all-cause mortality in type 2 diabetes and glucose-tolerance – tested ( GTT ) multiethnic population sample s. Methods and Results — Participants were r and omly sample d from ( 1 ) a type 2 diabetes outpatient clinic and ( 2 ) primary care population registers , from which nondiabetic control subjects were given a GTT .  Brachial blood pressures  and Doppler-derived aortic PWV  were measured . Mortality data over 10 years ’ follow-up were obtained . At any level of systolic blood pressure ( SBP ) , aortic PWV was greater in subjects with diabetes than in controls . Mortality risk doubled in subjects with diabetes ( hazard ratio 2.34 , 95 % CI 1.5 to 3.74 ) and in those with glucose intolerance ( 2.12 , 95 % CI 1.11 to 4.0 ) compared with controls . For all groups combined , age , sex , and SBP predicted mortality ; the addition of PWV independently predicted all-cause and cardiovascular mortality ( hazard ratio 1.08 , 95 % CI 1.03 to 1.14 for each 1 m/s increase ) but displaced SBP . Glucose tolerance status and smoking were other independent contributors , with African-Caribbeans experiencing reduced mortality risk ( hazard ratio 0.41 , 95 % CI 0.25 to 0.69 ) . Conclusions —Aortic PWV is a powerful independent predictor of mortality in both diabetes and GTT population sample s. In displacing SBP as a prognostic factor , aortic PWV is probably further along the causal pathway for arterial disease and may represent a useful integrated index of vascular status and hence cardiovascular risk BACKGROUND There are limited data describing the presenting characteristics , management , and outcomes of diabetic and nondiabetic patients with an acute coronary syndrome ( ACS ) . OBJECTIVE To examine differences in these factors , patients with ST-segment elevation acute myocardial infa rct ion , non-ST-segment elevation acute myocardial infa rct ion , and unstable angina were enrolled in a large multinational coronary disease registry . METHODS The Global Registry of Acute Coronary Events is a prospect i ve observational study of patients hospitalized with an ACS at 94 hospitals in 14 countries . The study sample consisted of 5403 patients with ST-segment elevation acute myocardial infa rct ion , 4725 with non-ST-segment elevation acute myocardial infa rct ion , and 5988 with unstable angina . RESULTS Approximately 1 in 4 patients presented to participating hospitals with a history of diabetes . Patients with diabetes were older , more often women , with a greater prevalence of comorbidities , and they were less likely to be treated with effective cardiac therapies than nondiabetic patients . Patients with diabetes who developed an ACS were at increased risk for each hospital outcome examined including heart failure , renal failure , cardiogenic shock , and death . These differences remained after adjustment for potentially confounding prognostic factors . CONCLUSIONS A considerable proportion of patients with an ACS has diabetes and is at increased risk for adverse outcomes compared with patients without diabetes . There are certain proven therapeutic strategies that remain underused in the diabetic population . A more widespread awareness of this increased risk and a more diligent use of proven cardiac treatment approaches are indicated for patients with diabetes who develop an ACS Background Individuals with type 1 diabetes mellitus are at high risk for the development of hypertension , contributing to cardiovascular complications . Hyperglycaemia-mediated neurohormonal activation increases arterial stiffness , and is an important contributing factor for hypertension . Since the sodium glucose cotransport-2 ( SGLT2 ) inhibitor empagliflozin lowers blood pressure and HbA1c in type 1 diabetes mellitus , we hypothesized that this agent would also reduce arterial stiffness and markers of sympathetic nervous system activity . Methods Blood pressure , arterial stiffness , heart rate variability ( HRV ) and circulating adrenergic mediators were measured during clamped euglycaemia ( blood glucose 4–6 mmol/L ) and hyperglycaemia ( blood glucose 9–11 mmol/L ) in 40 normotensive type 1 diabetes mellitus patients . Studies were repeated after 8 weeks of empagliflozin ( 25 mg once daily ) . Results In response to empagliflozin during clamped euglycaemia , systolic blood pressure ( 111 ± 9 to 109 ± 9 mmHg , p = 0.02 ) and augmentation indices at the radial ( -52 % ± 16 to -57 % ± 17 , p = 0.0001 ) , carotid ( + 1.3 ± 1 7.0 to -5.7 ± 17.0 % , p < 0.0001 ) and aortic positions ( + 0.1 ± 13.4 to -6.2 ± 14.3 % , p < 0.0001 ) declined . Similar effects on arterial stiffness were observed during clamped hyperglycaemia without changing blood pressure under this condition . Carotid-radial pulse wave velocity decreased significantly under both glycemic conditions ( p ≤ 0.0001 ) , while declines in carotid-femoral pulse wave velocity were only significant during clamped hyperglycaemia ( 5.7 ± 1.1 to 5.2 ± 0.9 m/s , p = 0.0017 ) . HRV , plasma noradrenalin and adrenaline remained unchanged under both clamped euglycemic and hyperglycemic conditions . Conclusions Empagliflozin is associated with a decline in arterial stiffness in young type 1 diabetes mellitus subjects . The underlying mechanisms may relate to pleiotropic actions of SGLT2 inhibition , including glucose lowering , antihypertensive and weight reduction effects . Trial registration Clinical trial registration : Background — The primary objective of this mechanistic open-label , stratified clinical trial was to determine the effect of 8 weeks ’ sodium glucose cotransporter 2 inhibition with empagliflozin 25 mg QD on renal hyperfiltration in subjects with type 1 diabetes mellitus ( T1D ) . Methods and Results — Inulin ( glomerular filtration rate ; GFR ) and paraaminohippurate ( effective renal plasma flow ) clearances were measured in individuals stratified based on having hyperfiltration ( T1D-H , GFR ≥ 135 mL/min/1.73m2 , n=27 ) or normal GFR ( T1D-N , GFR 90–134 mL/min/1.73m2 , n=13 ) at baseline . Renal function and circulating levels of renin-angiotensin-aldosterone system mediators and NO were measured under clamped euglycemic ( 4–6 mmol/L ) and hyperglycemic ( 9–11 mmol/L ) conditions at baseline and end of treatment . During clamped euglycemia , hyperfiltration was attenuated by −33 mL/min/1.73m2 with empagliflozin in T1D-H , ( GFR 172±23–139±25 mL/min/1.73 m2 , P<0.01 ) . This effect was accompanied by declines in plasma NO and effective renal plasma flow and an increase in renal vascular resistance ( all P<0.01 ) . Similar significant effects on GFR and renal function parameters were observed during clamped hyperglycemia . In T1D-N , GFR , other renal function parameters , and plasma NO were not altered by empagliflozin . Empagliflozin reduced hemoglobin A1c significantly in both groups , despite lower insulin doses in each group ( P⩽0.04 ) . Conclusions — In conclusion , short-term treatment with the sodium glucose cotransporter 2 inhibitor empagliflozin  attenuated renal hyperfiltration in subjects with T1D , likely by affecting tubular-glomerular feedback mechanisms . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01392560 BACKGROUND There is controversy over the usefulness of prediabetes as a diagnostic label . Using data from US National Health and Nutrition Examination Surveys ( NHANES ) between 1988 and 2014 , we examined the cardiovascular and renal burdens in adults with prediabetes over time and compared patterns with other glycaemic status groups . METHODS We analysed  cross-sectional survey data from non-pregnant adults aged 20 years and older from the NHANES survey periods 1988 - 94 , 1999 - 2004 , 2005 - 10 , and 2011 - 14 . We defined diagnosed diabetes as patients ' self-report that they had been previously diagnosed by a physician or health professional ; among those with no self-reported diabetes , prediabetes was defined as a fasting plasma glucose ( FPG ) concentration of 100 - 125 mg/dL ( 5·6 - 6·9 mmol/L ) or an HbA1c of 5·7 - 6·4 % ( 39 - 47 mmol/mol ) ; undiagnosed diabetes as an FPG of 126 mg/dL ( 7·0 mmol/L ) or higher or an HbA1c of 6·5 % ( 48 mmol/mol ) or higher ; and normal glycaemic status as an FPG of less than 100 mg/dL ( 5·6 mmol/L ) and an HbA1c of less than 5·7 % ( 39 mmol/mol ) . We repeated the analyses using varying definitions of prediabetes ( FPG 110 - 125 mg/dL [ 6·1 - 6·9 mmol/L ] or HbA1c 5·7 - 6·4 % [ 39 - 47 mmol/mol ] , FPG 110 - 125 mg/dL [ 6·1 - 6·9 mmol/L ] or HbA1c 6·0 - 6·4 % [ 42 - 47 mmol/mol ] , and FPG 100 - 125 mg/dL [ 5·6 - 6·9 mmol/L ] and HbA1c 5·7 - 6·4 % [ 39 - 47 mmol/mol ] ) . For each group over time , we estimated the prevalences of hypertension and dyslipidaemia ; and among individuals with those conditions , we estimated the proportions who had been treated and who were achieving care goals . By glycaemic group , we estimated those who were current , former , and never smokers ; mean 10-year risk of cardiovascular disease ( using estimators from the Framingham Heart Study , the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) , and the ACC/AHA ASCVD guidelines ) ; albuminuria ( median and albumin-to-creatinine ratio ≥30 mg/g ) , estimated glomerular filtration rate ( eGFR ; mean and < 60 mL/min per 1·73m2 ) ; and prevalence of myocardial infa rct ion and stroke . For all estimates , we calculated predicted changes between 1988 - 94 and 2011 - 14 using logistic regression models adjusted for age , sex , and race or ethnic group . FINDINGS We obtained data for 27 971 eligible individuals . In 2011 - 14 , in the population of adults with prediabetes , 36·6 % ( 95 % CI 32·8 - 40·5 ) had hypertension , 51·2 % ( 47·0 - 55·3 ) had dyslipidaemia , 24·3 % ( 21·7 - 27·3 ) smoked ; 7·7 % ( 6·8 - 8·8 ) had albuminuria ; 4·6 % ( 3·7 - 5·9 ) had reduced eGFR ; and 10-year cardiovascular event risk ranged from 5 % to 7 % . From 1988 - 94 to 2011 - 14 , adults with prediabetes showed significant increases in hypertension ( + 9·7 percentage points [ 95 % CI 5·4 - 14·0 ] ) ; no change in dyslipidaemia ; decreases in smoking ( -6·4 percentage points [ -10·7 to -2·1 ] ) ; increased use of treatment to lower blood pressure ( 54·2 % [ 49·0 - 59·3 ] to 81·4 % [ 76·7 - 85·3 ] , + 27·2 percentage points [ 20·5 - 33·8 ] p<0·0001 ) and to reduce lipids ( 6·6 % to 40·2 % , + 33· 
    Output:
    
agent
Identified evidence suggests that cardiovascular disease ( CVD ) prevention services should consider regulation of blood glucose as a key target for intervention .
***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: Background —Arterial distensibility measures , generally from pulse-wave velocity ( PWV ) , are widely used with little knowledge of relationships to patient outcome . We tested whether aortic PWV predicts cardiovascular and all-cause mortality in type 2 diabetes and glucose-tolerance – tested ( GTT ) multiethnic population sample s. Methods and Results — Participants were r and omly sample d from ( 1 ) a type 2 diabetes outpatient clinic and ( 2 ) primary care population registers , from which nondiabetic control subjects were given a GTT .  Brachial blood pressures  and Doppler-derived aortic PWV  were measured . Mortality data over 10 years ’ follow-up were obtained . At any level of systolic blood pressure ( SBP ) , aortic PWV was greater in subjects with diabetes than in controls . Mortality risk doubled in subjects with diabetes ( hazard ratio 2.34 , 95 % CI 1.5 to 3.74 ) and in those with glucose intolerance ( 2.12 , 95 % CI 1.11 to 4.0 ) compared with controls . For all groups combined , age , sex , and SBP predicted mortality ; the addition of PWV independently predicted all-cause and cardiovascular mortality ( hazard ratio 1.08 , 95 % CI 1.03 to 1.14 for each 1 m/s increase ) but displaced SBP . Glucose tolerance status and smoking were other independent contributors , with African-Caribbeans experiencing reduced mortality risk ( hazard ratio 0.41 , 95 % CI 0.25 to 0.69 ) . Conclusions —Aortic PWV is a powerful independent predictor of mortality in both diabetes and GTT population sample s. In displacing SBP as a prognostic factor , aortic PWV is probably further along the causal pathway for arterial disease and may represent a useful integrated index of vascular status and hence cardiovascular risk BACKGROUND There are limited data describing the presenting characteristics , management , and outcomes of diabetic and nondiabetic patients with an acute coronary syndrome ( ACS ) . OBJECTIVE To examine differences in these factors , patients with ST-segment elevation acute myocardial infa rct ion , non-ST-segment elevation acute myocardial infa rct ion , and unstable angina were enrolled in a large multinational coronary disease registry . METHODS The Global Registry of Acute Coronary Events is a prospect i ve observational study of patients hospitalized with an ACS at 94 hospitals in 14 countries . The study sample consisted of 5403 patients with ST-segment elevation acute myocardial infa rct ion , 4725 with non-ST-segment elevation acute myocardial infa rct ion , and 5988 with unstable angina . RESULTS Approximately 1 in 4 patients presented to participating hospitals with a history of diabetes . Patients with diabetes were older , more often women , with a greater prevalence of comorbidities , and they were less likely to be treated with effective cardiac therapies than nondiabetic patients . Patients with diabetes who developed an ACS were at increased risk for each hospital outcome examined including heart failure , renal failure , cardiogenic shock , and death . These differences remained after adjustment for potentially confounding prognostic factors . CONCLUSIONS A considerable proportion of patients with an ACS has diabetes and is at increased risk for adverse outcomes compared with patients without diabetes . There are certain proven therapeutic strategies that remain underused in the diabetic population . A more widespread awareness of this increased risk and a more diligent use of proven cardiac treatment approaches are indicated for patients with diabetes who develop an ACS Background Individuals with type 1 diabetes mellitus are at high risk for the development of hypertension , contributing to cardiovascular complications . Hyperglycaemia-mediated neurohormonal activation increases arterial stiffness , and is an important contributing factor for hypertension . Since the sodium glucose cotransport-2 ( SGLT2 ) inhibitor empagliflozin lowers blood pressure and HbA1c in type 1 diabetes mellitus , we hypothesized that this agent would also reduce arterial stiffness and markers of sympathetic nervous system activity . Methods Blood pressure , arterial stiffness , heart rate variability ( HRV ) and circulating adrenergic mediators were measured during clamped euglycaemia ( blood glucose 4–6 mmol/L ) and hyperglycaemia ( blood glucose 9–11 mmol/L ) in 40 normotensive type 1 diabetes mellitus patients . Studies were repeated after 8 weeks of empagliflozin ( 25 mg once daily ) . Results In response to empagliflozin during clamped euglycaemia , systolic blood pressure ( 111 ± 9 to 109 ± 9 mmHg , p = 0.02 ) and augmentation indices at the radial ( -52 % ± 16 to -57 % ± 17 , p = 0.0001 ) , carotid ( + 1.3 ± 1 7.0 to -5.7 ± 17.0 % , p < 0.0001 ) and aortic positions ( + 0.1 ± 13.4 to -6.2 ± 14.3 % , p < 0.0001 ) declined . Similar effects on arterial stiffness were observed during clamped hyperglycaemia without changing blood pressure under this condition . Carotid-radial pulse wave velocity decreased significantly under both glycemic conditions ( p ≤ 0.0001 ) , while declines in carotid-femoral pulse wave velocity were only significant during clamped hyperglycaemia ( 5.7 ± 1.1 to 5.2 ± 0.9 m/s , p = 0.0017 ) . HRV , plasma noradrenalin and adrenaline remained unchanged under both clamped euglycemic and hyperglycemic conditions . Conclusions Empagliflozin is associated with a decline in arterial stiffness in young type 1 diabetes mellitus subjects . The underlying mechanisms may relate to pleiotropic actions of SGLT2 inhibition , including glucose lowering , antihypertensive and weight reduction effects . Trial registration Clinical trial registration : Background — The primary objective of this mechanistic open-label , stratified clinical trial was to determine the effect of 8 weeks ’ sodium glucose cotransporter 2 inhibition with empagliflozin 25 mg QD on renal hyperfiltration in subjects with type 1 diabetes mellitus ( T1D ) . Methods and Results — Inulin ( glomerular filtration rate ; GFR ) and paraaminohippurate ( effective renal plasma flow ) clearances were measured in individuals stratified based on having hyperfiltration ( T1D-H , GFR ≥ 135 mL/min/1.73m2 , n=27 ) or normal GFR ( T1D-N , GFR 90–134 mL/min/1.73m2 , n=13 ) at baseline . Renal function and circulating levels of renin-angiotensin-aldosterone system mediators and NO were measured under clamped euglycemic ( 4–6 mmol/L ) and hyperglycemic ( 9–11 mmol/L ) conditions at baseline and end of treatment . During clamped euglycemia , hyperfiltration was attenuated by −33 mL/min/1.73m2 with empagliflozin in T1D-H , ( GFR 172±23–139±25 mL/min/1.73 m2 , P<0.01 ) . This effect was accompanied by declines in plasma NO and effective renal plasma flow and an increase in renal vascular resistance ( all P<0.01 ) . Similar significant effects on GFR and renal function parameters were observed during clamped hyperglycemia . In T1D-N , GFR , other renal function parameters , and plasma NO were not altered by empagliflozin . Empagliflozin reduced hemoglobin A1c significantly in both groups , despite lower insulin doses in each group ( P⩽0.04 ) . Conclusions — In conclusion , short-term treatment with the sodium glucose cotransporter 2 inhibitor empagliflozin  attenuated renal hyperfiltration in subjects with T1D , likely by affecting tubular-glomerular feedback mechanisms . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01392560 BACKGROUND There is controversy over the usefulness of prediabetes as a diagnostic label . Using data from US National Health and Nutrition Examination Surveys ( NHANES ) between 1988 and 2014 , we examined the cardiovascular and renal burdens in adults with prediabetes over time and compared patterns with other glycaemic status groups . METHODS We analysed  cross-sectional survey data from non-pregnant adults aged 20 years and older from the NHANES survey periods 1988 - 94 , 1999 - 2004 , 2005 - 10 , and 2011 - 14 . We defined diagnosed diabetes as patients ' self-report that they had been previously diagnosed by a physician or health professional ; among those with no self-reported diabetes , prediabetes was defined as a fasting plasma glucose ( FPG ) concentration of 100 - 125 mg/dL ( 5·6 - 6·9 mmol/L ) or an HbA1c of 5·7 - 6·4 % ( 39 - 47 mmol/mol ) ; undiagnosed diabetes as an FPG of 126 mg/dL ( 7·0 mmol/L ) or higher or an HbA1c of 6·5 % ( 48 mmol/mol ) or higher ; and normal glycaemic status as an FPG of less than 100 mg/dL ( 5·6 mmol/L ) and an HbA1c of less than 5·7 % ( 39 mmol/mol ) . We repeated the analyses using varying definitions of prediabetes ( FPG 110 - 125 mg/dL [ 6·1 - 6·9 mmol/L ] or HbA1c 5·7 - 6·4 % [ 39 - 47 mmol/mol ] , FPG 110 - 125 mg/dL [ 6·1 - 6·9 mmol/L ] or HbA1c 6·0 - 6·4 % [ 42 - 47 mmol/mol ] , and FPG 100 - 125 mg/dL [ 5·6 - 6·9 mmol/L ] and HbA1c 5·7 - 6·4 % [ 39 - 47 mmol/mol ] ) . For each group over time , we estimated the prevalences of hypertension and dyslipidaemia ; and among individuals with those conditions , we estimated the proportions who had been treated and who were achieving care goals . By glycaemic group , we estimated those who were current , former , and never smokers ; mean 10-year risk of cardiovascular disease ( using estimators from the Framingham Heart Study , the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) , and the ACC/AHA ASCVD guidelines ) ; albuminuria ( median and albumin-to-creatinine ratio ≥30 mg/g ) , estimated glomerular filtration rate ( eGFR ; mean and < 60 mL/min per 1·73m2 ) ; and prevalence of myocardial infa rct ion and stroke . For all estimates , we calculated predicted changes between 1988 - 94 and 2011 - 14 using logistic regression models adjusted for age , sex , and race or ethnic group . FINDINGS We obtained data for 27 971 eligible individuals . In 2011 - 14 , in the population of adults with prediabetes , 36·6 % ( 95 % CI 32·8 - 40·5 ) had hypertension , 51·2 % ( 47·0 - 55·3 ) had dyslipidaemia , 24·3 % ( 21·7 - 27·3 ) smoked ; 7·7 % ( 6·8 - 8·8 ) had albuminuria ; 4·6 % ( 3·7 - 5·9 ) had reduced eGFR ; and 10-year cardiovascular event risk ranged from 5 % to 7 % . From 1988 - 94 to 2011 - 14 , adults with prediabetes showed significant increases in hypertension ( + 9·7 percentage points [ 95 % CI 5·4 - 14·0 ] ) ; no change in dyslipidaemia ; decreases in smoking ( -6·4 percentage points [ -10·7 to -2·1 ] ) ; increased use of treatment to lower blood pressure ( 54·2 % [ 49·0 - 59·3 ] to 81·4 % [ 76·7 - 85·3 ] , + 27·2 percentage points [ 20·5 - 33·8 ] p<0·0001 ) and to reduce lipids ( 6·6 % to 40·2 % , + 33· 
    Output:
    