title: Aortic Pulse-Wave Velocity and Its Relationship to Mortality in Diabetes and Glucose Intolerance: An Integrated Index of Vascular Function? Implications of diabetes in patients with acute coronary syndromes. The Global Registry of Acute Coronary Events. The effect of empagliflozin on arterial stiffness and heart rate variability in subjects with uncomplicated type 1 diabetes mellitus Renal Hemodynamic Effect of Sodium-Glucose Cotransporter 2 Inhibition in Patients With Type 1 Diabetes Mellitus Cardiovascular and renal burdens of prediabetes in the USA: analysis of data from serial cross-sectional surveys, 1988-2014. Impact of Diabetes on Long-Term Prognosis in Patients With Unstable Angina and Non–Q-Wave Myocardial Infarction: Results of the OASIS (Organization to Assess Strategies for Ischemic Syndromes) Registry Social network targeting to maximise population behaviour change: a cluster randomised controlled trial The answer to diabetes prevention: science, surgery, service delivery, or social policy? Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four-year results of the Look AHEAD trial. Pathways to professionalism? Quality improvement, care pathways, and the interplay of standardisation and clinical autonomy. False Dichotomies and Health Policy Research Designs: Randomized Trials Are Not Always the Answer Summarizing systematic reviews: methodological development, conduct and reporting of an umbrella review approach 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). Admission glucose concentrations independently predict early and late mortality in patients with acute myocardial infarction treated by primary or rescue percutaneous coronary intervention. Glycated hemoglobin measurement and prediction of cardiovascular disease. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study Pharmacist Interventions in the Management of Type 2 Diabetes Mellitus: A Systematic Review of Randomized Controlled Trials. Effect of the sodium glucose co-transporter 2 inhibitor canagliflozin on plasma volume in patients with type 2 diabetes mellitus. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. What determines the cost-effectiveness of diabetes screening? Community-Based Lifestyle Intervention in Patients With Coronary Artery Disease: The RESPONSE-2 Trial. Slowing Down the Progression of Type 2 Diabetes: We Need Fair, Innovative, and Disruptive Action on Environmental and Policy Levels!
abstract: 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 % , + 33·6 percentage points [ 30·2 - 37·0 ] , p<0·0001 ) ; and increased goal achievements for blood pressure ( 25·8 % to 62·0 % , + 36·2 percentage points [ 30·7 - 41·8 ] , p<0·0001 ) and lipids ( 1·0 % to 32·8 % , + 31·8 percentage points [ 29·1 - 34·4 , p<0·0001 ] ) . People with prediabetes also showed decreases in cardiovascular risk ( ASCVD -1·9 percentage points [ -2·5 to -1·3 ] to UKPDS -2·7 [ -3·5 to -1·9 ] , p<0·0001 ) ; but no change in prevalence of albuminuria , reduced eGFR , myocardial infa rct ion , or stroke . Prevalence and patterns were consistent across all prediabetes definitions examined . Compared with adults with prediabetes , adults with diagnosed diabetes showed much larger improvements in cardiovascular and renal risk treatments , apart from smoking , which did not decline . INTERPRETATION Over 25 years , cardiovascular and renal risks and disease have become highly prevalent in adults with prediabetes , irrespective of the definitions used . Identification of people with prediabetes might increase the opportunity for cardiovascular and renal risk reduction . FUNDING None Background Although unstable coronary artery disease is the most common reason for admission to a coronary care unit , the long-term prognosis of patients with this diagnosis is unknown . This is particularly true for patients with diabetes mellitus , who are known to have a high morbidity and mortality after an acute myocardial infa rct ion . Methods and Results Prospect ively collected data from 6 different countries in the Organization to Assess Strategies for Ischemic Syndromes ( OASIS ) registry were analyzed to determine the 2-year prognosis of diabetic and nondiabetic patients who were hospitalized with unstable angina or non – Q-wave myocardial infa rct ion . Overall , 1718 of 8013 registry patients ( 21 % ) had diabetes . Diabetic patients had a higher rate of coronary bypass surgery  than nondiabetic patients ( 23 % versus 20 % , P < 0.001 ) but had similar rates of catheterization and angioplasty . Diabetes independently predicted mortality ( relative risk [ RR ] , 1.57 ; 95 % CI , 1.38 to 1.81;P < 0.001 ) , as well as cardiovascular death , new myocardial infa rct ion , stroke , and new congestive heart failure . Moreover , compared with their nondiabetic counterparts , women had a significantly higher risk than men ( RR , 1.98 ; 95 % CI , 1.60 to 2.44 ; and RR , 1.28 ; 95 % CI , 1.06 to 1.56 , respectively ) . Interestingly , diabetic patients without prior cardiovascular disease had the same event rates for all outcomes as nondiabetic patients with previous vascular disease . Conclusions Hospitalization for unstable angina or non – Q-wave myocardial infa rct ion predicts a high 2-year morbidity and mortality ; this is especially evident for patients with diabetes . Diabetic patients with no previous cardiovascular disease have the same long-term morbidity and mortality as nondiabetic patients with established cardiovascular disease after hospitalization for unstable coronary artery disease BACKGROUND Information and behaviour can spread through interpersonal ties . By targeting influential individuals , health interventions that harness the distributive properties of social networks could be made more effective and efficient than those that do not . Our aim was to assess which targeting methods produce the greatest cascades or spillover effects and hence maximise population -level behaviour change . METHODS In this cluster r and omised trial , participants were recruited from villages of the Department of Lempira , Honduras . We blocked villages on the basis of network size , socioeconomic status , and baseline rates of water purification , for delivery of two public health interventions : chlorine for water purification and multivitamins for micronutrient deficiencies . We then r and omised villages , separately for each intervention , to one of three targeting methods , introducing the interventions to 5 % sample s composed of either : r and omly selected villagers ( n=9 villages for each intervention ) ; villagers with the most social ties ( n=9 ) ; or nominated friends of r and om villagers ( n=9 ; the last strategy exploiting the so-called friendship paradox of social networks ) . Participants and data collectors were not aware of the targeting methods . Primary endpoints were the proportions of available products redeemed by the entire population under each targeting method . This trial is registered with Clinical Trials.gov , number NCT01672580 . FINDINGS Between Aug 4 , and Aug 14 , 2012 , 32 villages in rural Honduras ( 25 - 541 participants each ; total study population of 5773 ) received public health interventions . For each intervention , nine villages ( each with 1 - 20 initial target individuals ) were r and omised , using a blocked design , to each of the three targeting methods . In nomination-targeted villages , 951 ( 74·3 % ) of 1280 available multivitamin tickets were redeemed compared with 940 ( 66·2 % ) of 1420 in r and omly targeted villages and 744 ( 61·0 % ) of 1220 in indegree-targeted villages . All pairwise differences in redemption rates were significant ( p<0·01 ) after correction for multiple comparisons . Targeting nominated friends increased adoption of the nutritional intervention by 12·2 % compared with r and om targeting ( 95 % CI 6·9 - 17·9 ) . Targeting the most highly connected individuals , by contrast , produced no greater adoption of either intervention , compared with r and om targeting . INTERPRETATION Introduction of a health intervention to the nominated friends of r and om individuals can enhance that intervention 's diffusion by exploiting intrinsic properties of human social networks . This method has the additional advantage of scalability because it can be implemented without mapping the network . Deployment of certain types of health interventions via network targeting , without increasing the number of individuals targeted or the re sources used , could enhance the adoption and efficiency of those interventions , thereby improving population health . FUNDING National Institutes of Health , The Bill & Melinda Gates Foundation , Star Family Foundation , and the Canadian Institutes of Health Research The diabetes and obesity epidemics are closely intertwined . International r and omized controlled trials demonstrate that , in high-risk individuals , type 2 diabetes  can be prevented or at least delayed through lifestyle modification and , to a lesser degree , medication . We explored the relative roles of science , surgery , service delivery , and social policy in preventing diabetes . Although it is clear that there is a role for all , diabetes is a complex problem that dem and s commitment across a range of government and nongovernment agencies to be effectively controlled . Accordingly , we argue that social policy is the key to achieving and sustaining social and physical environments required to achieve widespread reductions in both the incidence and prevalence of diabetes BACKGROUND Lifestyle interventions produce short-term improvements in glycemia and cardiovascular disease ( CVD ) risk factors in individuals with type 2 diabetes mellitus , but no long-term data are available . We examined the effects of lifestyle intervention on changes in weight , fitness , and CVD risk factors during a 4-year study . METHODS The Look AHEAD ( Action for Health in Diabetes ) trial is a multicenter r and omized clinical trial comparing the effects of an intensive lifestyle intervention ( ILI ) and diabetes support and education ( DSE ; the control group ) on the incidence of major CVD events in 5145 overweight or obese individuals ( 59.5 % female ; mean age , 58.7 years ) with type 2 diabetes mellitus . More than 93 % of participants provided outcomes data at each annual assessment . RESULTS Averaged across 4 years , ILI participants had a greater percentage of weight loss than DSE participants ( -6.15 % vs -0.88 % ; P < .001 ) and greater improvements in treadmill fitness ( 12.74 % vs 1.96 % ; P < .001 ) , hemoglobin A(1c ) level ( -0.36 % vs -0.09 % ; P < .001 ) , systolic ( -5.33 vs -2.97 mm Hg ; P < .001 ) and diastolic ( -2.92 vs -2.48 mm Hg ; P = .01 ) blood pressure , and levels of high-density lipoprotein cholesterol ( 3.67 vs 1.97 mg/dL ; P < .001 ) and triglycerides ( -25.56 vs -19.75 mg/dL ; P < .001 ) . Reductions in low-density lipoprotein cholesterol levels were greater in DSE than ILI participants ( -11.27 vs -12.84 mg/dL ; P = .009 ) owing to greater use of medications to lower lipid levels in the DSE group . At 4 years , ILI participants maintained greater improvements than DSE participants in weight , fitness , hemoglobin A(1c ) levels , systolic blood pressure , and high-density lipoprotein cholesterol levels . CONCLUSIONS Intensive lifestyle intervention can produce sustained weight loss and improvements in fitness , glycemic control , and CVD risk factors in individuals with type 2 diabetes . Whether these differences in risk factors translate to reduction in CVD events will ultimately be addressed by the Look AHEAD trial . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00017953 Care pathways are a prominent feature of efforts to improve healthcare quality , outcomes and accountability , but sociological studies of pathways often find professional resistance to st and ardisation . This qualitative study examined the  adoption and adaptation of a novel pathway  as part of a r and omised controlled trial in an unusually complex , non-linear field - emergency general surgery - by teams of surgeons and physicians in six theoretically sample d sites in the UK . We find near-universal receptivity to the concept of a  pathway  as a means of improving peri-operative processes and outcomes , but concern about the impact on appropriate professional judgement . However , this concern translated not into resistance and implementation failure , but into a nuancing of the pathways-as-realised in each site , and their use as a means of enhancing professional decision-making and inter-professional collaboration . We discuss our findings in the context of recent literature on the interplay between managerialism and professionalism in healthcare , and highlight practical and theoretical implication Some medical scientists argue that only data from r and omized controlled trials ( RCTs ) are trustworthy . They cl aim data from natural experiments and administrative data sets are always spurious and can not be used to evaluate health policies and other population -wide phenomena in the real world . While many acknowledge biases caused by poor study design s , in this article we argue that several valid design s using administrative data can produce strong findings , particularly the interrupted time series ( ITS ) design . Many policy studies neither permit nor require an RCT for cause- and -effect inference . Framing our arguments using Campbell and Stanley ’s classic research design monograph , we show that several “ quasi-experimental ” design s , especially interrupted time series ( ITS ) , can estimate valid effects ( or non-effects ) of health interventions and policies as diverse as public insurance coverage , speed limits , hospital safety programs , drug abuse regulation and withdrawal of drugs from the market . We further note the recent rapid uptake of ITS and argue for exp and ed training in quasi-experimental design s in medical and graduate schools and in post-doctoral curricula Aims : With the increase in the number of systematic review s available , a logical next step to provide decision makers in healthcare with the evidence they require has been the conduct of review s of existing systematic review s. Syntheses of existing systematic review s are referred to by many different names , one of which is an umbrella review . An umbrella review allows the findings of review s relevant to a review question to be compared and contrasted . An umbrella review 's most characteristic feature is that this type of evidence synthesis only considers for inclusion the highest level of evidence , namely other systematic review s and meta-analyses . A methodology working group was formed by the Joanna Briggs Institute to develop method ological guidance for the conduct of an umbrella review , including diverse types of evidence , both quantitative and qualitative . The aim of this study is to describe the development and guidance for the conduct of an umbrella review . Methods : Discussion and testing of the elements of methods for the conduct of an umbrella review were held over a 6-month period by members of a methodology working group . The working group comprised six participants who corresponded via teleconference , e-mail and face-to-face meeting during this development period . In October 2013 , the methodology was presented in a workshop at the Joanna Briggs Institute Convention . Workshop participants , review authors and method ologists provided further testing , critique and feedback on the proposed methodology . Results : This study describes the methodology and methods developed for the conduct of an umbrella review that includes published systematic review s and meta-analyses as the analytical unit of the review . Details are provided regarding the essential elements of an umbrella review , including presentation of the review question in a Population , Intervention , Comparator , Outcome format , nuances of the inclusion criteria and search strategy . A critical appraisal tool with 10 questions to help assess risk of bias in systematic review s and meta-analyses was also developed and tested . Relevant details to extract from included review s and how to best present the findings of both quantitative and qualitative systematic review s in a reader friendly format are provided . Conclusions : Umbrella review s provide a ready means for decision makers in healthcare to gain a clear underst and ing of a broad topic area . The umbrella review methodology described here is the first to consider review s that report other than quantitative evidence derived from r and omized controlled trials . The methodology includes an easy to use and informative summary of evidence table to readily provide decision makers with the available , highest level of evidence relevant to the question posed 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 BACKGROUND In patients with acute myocardial infa rct ion ( MI ) , increased plasma glucose levels at hospital admission are associated with worse outcome . We aim ed to assess the predictive value of admission glucose concentrations on short- and long-term mortality in patients with acute MI undergoing primary or rescue percutaneous coronary intervention ( PCI ) .  METHODS We analyzed the 30-day and long-term ( mean follow-up 3.7 years ) outcome of 978 patients prospect ively included in a single-center registry of patients with acute MI treated with PCI within 24 hours after onset of symptoms . Patients were classified according to plasma glucose levels at admission : < 7.8 mmol/L ( group I , n = 322 ) , 7.8 to 11 mmol/L ( group II , n = 348 ) , and > 11.0 mmol/L ( group III , n = 308 ) . RESULTS Mortality at 30 days was 1.2 % in group I , 6.3 % in group II , and 16.6 % in group III ( P < .001 ) . After multivariate adjustment for age , the presence of cardiogenic shock , and TIMI 3 flow after PCI , the association of mortality with glucose classification remained significant ( P value for trend = .003 ) . The relative risk of death at 30 days for group III versus group I was 3.9 ( 95 % CI 1.2 - 13.2 ) . During long-term follow-up , mortality was similar in groups I and II . However , in group III adjusted mortality remained significantly increased compared with group I ( relative risk 1.76 , CI 1.01 - 3.08 ) . CONCLUSIONS In patients undergoing emergency PCI for acute MI , glucose levels at hospital admission are predictive for short- and long-term survival . Knowledge of admission glucose levels may improve initial bedside risk stratification IMPORTANCE The value of measuring levels of glycated hemoglobin ( HbA1c ) for the prediction of first cardiovascular events is uncertain . OBJECTIVE To determine whether adding information on HbA1c values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease ( CVD ) risk . DESIGN , SETTING , AND PARTICIPANTS Analysis of individual-participant data available from 73 prospect i ve studies involving 294,998 participants without a known history of diabetes mellitus or CVD at the baseline assessment . MAIN OUTCOMES AND MEASURES Measures of risk discrimination for CVD outcomes ( eg , C-index ) and reclassification ( eg , net reclassification improvement ) of participants across predicted 10-year risk categories of low ( < 5 % ) , intermediate ( 5 % to < 7.5 % ) , and high ( ≥ 7.5 % ) risk . RESULTS During a median follow-up of 9.9 ( interquartile range , 7.6 - 13.2 ) years , 20,840 incident fatal and nonfatal CVD outcomes ( 13,237 coronary heart disease and 7603 stroke outcomes ) were recorded . In analyses adjusted for several conventional cardiovascular risk factors , there was an approximately J-shaped association between HbA1c values and CVD risk . The association between HbA1c values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate , but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein . The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 ( 95 % CI , 0.7350 to 0.7517 ) . The addition of information on HbA1c was associated with a C-index change of 0.0018 ( 0.0003 to 0.0033 ) and a net reclassification improvement of 0.42 ( -0.63 to 1.48 ) for the categories of predicted 10-year CVD risk . The improvement provided by HbA1c assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting , r and om , or postload plasma glucose levels . CONCLUSIONS AND RELEVANCE In a study of individuals without known CVD or diabetes , additional assessment of HbA1c values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk 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 % ) BACKGROUND Intensive lifestyle interventions can reduce the incidence of  type 2 diabetes in people with impaired glucose tolerance , but how long these benefits extend beyond the period of active intervention , and whether such interventions reduce the risk of cardiovascular disease ( CVD ) and mortality , is unclear . We aim ed to assess whether intensive lifestyle interventions have a long-term effect on the risk of diabetes , diabetes-related macrovascular and microvascular complications , and mortality . METHODS In 1986 , 577 adults with impaired glucose tolerance from 33 clinics in China were r and omly assigned to either the  control group or to one of three lifestyle intervention groups ( diet , exercise , or diet plus exercise ) . Active intervention took place over 6 years until 1992 . In 2006 , study participants were followed-up to assess the long-term effect of the interventions . The primary outcomes were diabetes incidence , CVD incidence and mortality , and all-cause mortality . FINDINGS Compared with control participants , those in the combined lifestyle intervention groups had a 51 % lower incidence of diabetes ( hazard rate ratio [ HRR ] 0.49 ; 95 % CI 0.33 - 0.73 ) during the active intervention period and a 43 % lower incidence ( 0.57 ; 0.41 - 0.81 ) over the 20 year period , controlled for age and clustering by clinic . The average annual incidence of diabetes was 7 % for intervention participants versus 11 % in control participants , with 20-year cumulative incidence of 80 % in the intervention groups and 93 % in the control group . Participants in the intervention group spent an average of 3.6 fewer years with diabetes than those in the control group . There was no significant difference between the intervention and control groups in the rate of first CVD events ( HRR 0.98 ; 95 % CI 0.71 - 1.37 ) , CVD mortality ( 0.83 ; 0.48 - 1.40 ) , and all-cause mortality ( 0.96 ; 0.65 - 1.41 ) , but our study had limited statistical power to detect differences for these outcomes . INTERPRETATION Group-based lifestyle interventions over 6 years can prevent or delay diabetes for up to 14 years after the active intervention . However , whether lifestyle intervention also leads to reduced CVD and mortality remains unclear BACKGROUND Diabetes mellitus is a major health problem that is growing rapidly worldwide . A collaborative and integrated team approach in which pharmacists can play a pivotal role should be sought when managing patients with diabetes . OBJECTIVE To identify and summarize the main outcomes of pharmacist interventions in the management of type 2 diabetes .  METHODS PubMed , Cochrane Central Register of Controlled Trials , and Web of Science were search ed for r and omized controlled trials evaluating the effectiveness of any pharmacist intervention directed at patients with type 2 diabetes in comparison with usual care . Outcome measures of interest included glycosylated hemoglobin ( Alc ) , blood glucose , blood pressure , lipid profile , body mass index ( BMI ) , 10-year coronary heart disease ( CHD ) risk , medication adherence , health-related quality of life ( HRQoL ) , and economic outcomes . The risk of bias in included studies was assessed using the Cochrane risk of bias tool . RESULTS Thirty-six studies were included in this systematic review , involving 5,761 participants . The studies evaluated the effects of several pharmacist interventions carried out in various countries and in different health care facilities , such as community pharmacies , primary care clinics , and hospitals . The number of studies reporting each outcome of interest varied . Alc was evaluated in 26 studies , of which 24 reported a greater reduction in this outcome in the intervention group compared with the control group , with the difference in change between groups ranging from -0.18 % to -2.1 % . Eighteen studies assessed change in systolic blood pressure , of which 17 studies reported a greater improvement in this outcome in the intervention group , with the difference in change between groups varying between -3.3 mmHg and -23.05 mmHg . For diastolic blood pressure , a greater effect was also observed in the intervention group in 14 out of 15 studies , with the difference in change between groups varying between -0.21 mmHg and -9.1 mmHg . Thirteen studies described total cholesterol as an outcome measure , of which 10 reported a greater improvement in this outcome in the intervention group , with the difference in change between groups ranging from + 18.95 mg dL(-1 ) to -32.48 mg dL(-1 ) . With regard to low-density lipoprotein cholesterol , a greater reduction in this parameter in the intervention group was documented in 12 out of 15 studies , with the difference in change between groups varying between + 7.35 mg dL(-1 ) and -30 mg dL(-1 ) . Similarly , favorable data were reported on high-density lipoprotein cholesterol in the intervention group in 9 out of 12 studies that assessed this outcome , with the difference in change between groups ranging from -5.8 mg dL(-1 ) to + 11 mg dL(-1 ) . Data on triglycerides were also reported in 12 studies , of which 9 reported a greater reduction in triglycerides levels in the intervention group , with the difference in change between groups varying between + 12 mg dL(-1 ) and -62 mg dL(-1 ) . Overall , a beneficial effect on BMI was also described in the intervention group in 12 out of 14 studies . Of note , in all 6 studies that estimated the 10-year CHD risk among study patients , a greater improvement in the intervention group versus the control group was found . In addition , pharmacist interventions also had a positive impact on medication adherence and HRQoL in most studies that ascertained these outcomes . Finally , although only 3 studies conducted a cost-effectiveness analysis , pharmacist interventions proved to be cost-effective . CONCLUSIONS The findings from this review clearly support the involvement of pharmacists as members of health care teams in the management of patients with type 2 diabetes . DISCLOSURES This systematic review was not funded . The authors declare that they have no conflicts of interest . Concept and study design were created by Pousinho , Morgado , and Alves . Pousinho took the lead in data collection , along with Alves , and data interpretation was performed by Pousinho , Falcão , and Alves . The manuscript was primarily written by Pousinho , along with Alves , and revised by Alves , Morgado , and Falcão AIM To evaluate the effects of canagliflozin on plasma volume , urinary glucose excretion ( UGE ) , fasting plasma glucose ( FPG ) , glycated haemoglobin ( HbA1c ) and additional measures of fluid/electrolyte balance in patients with type 2 diabetes on background therapy with metformin and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers . METHODS Patients ( N = 36 ) were r and omized ( 1:1 ) to receive canagliflozin 300 mg or placebo for 12 weeks .  Pharmacodynamic parameters were assessed at baseline and at weeks 1 and 12 . RESULTS Increased 24-h UGE was seen in the canagliflozin group compared with a reduction in the placebo group at both week 1 ( 91.8 vs. -2.4 g ) and week 12 ( 82.6 vs. -0.4 g ) . Canagliflozin also reduced both FPG and HbA1c . Reductions in body weight and blood pressure were observed at weeks 1 and 12 . Canagliflozin decreased plasma volume compared with an increase with placebo at week 1 ( -5.4 vs. 4.3 % ; p = 0.02 ) , but this was largely attenuated at week 12 ( 4.6 vs. 5.8 % ; p = 0.76 ) . A modest numerical increase in urine volume was observed with canagliflozin at week 1 that was attenuated at week 12 ; other measures of volume status ( i.e. blood urea nitrogen , serum creatinine and haematocrit ) remained modestly increased with canagliflozin at week 12 . CONCLUSION Canagliflozin provided sustained effects on UGE and FPG over 12 weeks and a transient reduction in plasma volume that was largely attenuated by week 12 BACKGROUND Cardiovascular morbidity is a major burden in patients with type 2 diabetes . In the Steno-2 Study , we compared the effect of a targeted , intensified , multifactorial intervention with that of conventional treatment on modifiable risk factors for cardiovascular disease in patients with type 2 diabetes and microalbuminuria . METHODS The primary end point of this open , parallel trial was a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , nonfatal stroke , revascularization , and amputation .  Eighty patients were r and omly assigned to receive conventional treatment in accordance with national guidelines and 80 to receive intensive treatment , with a stepwise implementation of behavior modification and pharmacologic therapy that targeted hyperglycemia , hypertension , dyslipidemia , and microalbuminuria , along with secondary prevention of cardiovascular disease with aspirin . RESULTS The mean age of the patients was 55.1 years , and the mean follow-up was 7.8 years . The decline in glycosylated hemoglobin values , systolic and diastolic blood pressure , serum cholesterol and triglyceride levels measured after an overnight fast , and urinary albumin excretion rate were all significantly greater in the intensive-therapy group than in the conventional-therapy group . Patients receiving intensive therapy also had a significantly lower risk of cardiovascular disease ( hazard ratio , 0.47 ; 95 percent confidence interval , 0.24 to 0.73 ) , nephropathy ( hazard ratio , 0.39 ; 95 percent confidence interval , 0.17 to 0.87 ) , retinopathy ( hazard ratio , 0.42 ; 95 percent confidence interval , 0.21 to 0.86 ) , and autonomic neuropathy ( hazard ratio , 0.37 ; 95 percent confidence interval , 0.18 to 0.79 ) . CONCLUSIONS A target-driven , long-term , intensified intervention aim ed at multiple risk factors in patients with type 2 diabetes and microalbuminuria reduces the risk of cardiovascular and microvascular events by about 50 percent Aims /hypothesisThe cost-effectiveness of screening for diabetes is unknown but has been modelled previously . None of these models has taken account of uncertainty . We aim ed to describe these uncertainties in a model where the outcome was CHD risk . Subjects and methods Our model used population data from the Danish Inter99 study , and simulations were run in a theoretical population of 1,000,000 individuals . CHD risk was estimated using the UK Prospect i ve Diabetes Study ( UKPDS ) risk engine , and risk reduction from published r and omised clinical trials . Probabilistic sensitivity analysis was used to provide confidence intervals for modelled outputs . Uncertain parameter values were independently simulated from distributions derived from existing literature and deterministic sensitivity analysis performed using multiple model runs under different strategy choices and using extreme parameter estimates . Results In the least conservative model ( low costs and multiplicative risk reduction for combined treatments ) , the 95 % confidence interval of the incremental cost-effectiveness ratio varied from £ 23,300–82,000 . The major contributors to this uncertainty were treatment risk reduction model parameters : the risk reduction for hypertension treatment and UKPDS risk model intercept . Overall cost-effectiveness ratio was not sensitive to decisions about which groups to screen , nor the costs of screening or treatment . It was strongly affected by assumptions about how treatments combine to reduce risk . Conclusions /interpretationOur model suggests that there is considerable uncertainty about whether or not screening for diabetes would be cost-effective . The most important but uncertain parameter is the effect of treatment . In addition to directly influencing current policy decisions , health care modelling can identify important unknown or uncertain parameters that may be the target of future research BACKGROUND Among patients with coronary artery disease ( CAD ) , improvement of lifestyle-related risk factors ( LRFs ) reduces cardiovascular morbidity and mortality . However , modification of LRFs is highly challenging . OBJECTIVES This study sought to evaluate the impact of combining community-based lifestyle programs with regular hospital-based secondary prevention . METHODS The authors performed a r and omized controlled trial of nurse-coordinated referral of patients and their partners to 3 widely available community-based lifestyle programs , in 15 hospitals in the Netherl and s. Patients admitted for acute coronary syndrome and /or revascularization , with ≥1 LRF ( body mass index > 27 kg/m2 , self-reported physical inactivity , and /or smoking ) were included . All patients received guideline -based usual care . The intervention was based on 3 lifestyle programs for weight reduction , increasing physical activity , and smoking cessation . The primary outcome was the proportion of success at 12 months , defined as improvement in ≥1 qualifying LRF using weight ( ≥5 % reduction ) , 6-min-walking distance ( ≥10 % improvement ) , and urinary cotinine ( 200 ng/ml detection limit ) without deterioration in the other 2 . RESULTS The authors r and omized 824 patients . Complete data on the primary outcome were available in 711 patients .  The proportion of successful patients in the intervention group was 37 % ( 133 of 360 ) compared with 26 % ( 91 of 351 ) in the control group ( p = 0.002 ; risk ratio : 1.43 ; 95 % confidence interval : 1.14 to 1.78 ) . In the intervention group , partner participation was associated with a significantly greater success rate ( 46 % vs. 34 % ; p = 0.03 ) . CONCLUSIONS Among patients with coronary artery disease , nurse-coordinated referral to a comprehensive set of community-based , widely available lifestyle interventions , with optional partner participation , leads to significant improvements in LRFs . ( RESPONSE-2 : R and omised Evaluation of Secondary Prevention by Outpatient Nurse SpEcialists 2 ; NTR3937 ) Over the past decades , we have observed an increase of prevalence of diabetes  in many countries along with significant differences in prevalence trends between countries worldwide ( 1 ) . In Europe and other Western countries , the prevalence rate reaches a plateau or has slowed down on the level of ∼8–10 % . In Asia , a continuous rise in prevalence has been monitored , similar to that in Africa , and an explosion of diabetes prevalence can be observed in the Arabic region . Surprisingly , in each of the countries , there is a significant number of people who do not develop  diabetes  during their lives despite living unhealthy lifestyles in similar environments — in Europe , an estimated 10 % of the population ( 2 ) . These people might be the secret answer to successful individual diabetes prevention , but we still do not underst and the detailed mechanisms of why some people develop diabetes— and why others do not . What we can do is observe individual lifestyle and environment as determinants for the development or prevention of diabetes and the respective risk factors including genetic susceptibility . The interplay between these determinants , influencing the probability of the individual staying healthy or how a person learns or chooses a healthy lifestyle , will define success in diabetes prevention ( 3 ) . Innovative actions are needed to slow down the progression of type 2 diabetes . The purpose of this article is to offer innovative policy and environmental strategic activities design ed to enable sustainable diabetes prevention with scalability on national level . # # # Why Do We Need Environmental and Policy Changes in Diabetes Prevention ? Diabetes prevention is a success story , but it generates new challenges . Throughout the past 15 years , a number of r and omized controlled trials have sought to test various interventions to prevent diabetes ( 4 ) . The results are overwhelmingly positive on an individual level , with a significant relative diabetes risk reduction attributed to lifestyle and pharmacological intervention ( 5
target: Identified evidence suggests that cardiovascular disease ( CVD ) prevention services should consider regulation of blood glucose as a key target for intervention .
background: The primary objective of this study was to analyze the most up-to- date evidence regarding whether and how blood sugar regulation influences cardiovascular health promotion and disease prevention by carrying out an umbrella review .