Prevention of type 2 diabetes - where is the evidence? Hemoglobin A1c predicts diabetes but not cardiovascular disease in nondiabetic women. Cost-effectiveness of interventions to control cardiovascular diseases and type 2 diabetes mellitus in South Asia: protocol for a systematic review Rosiglitazone evaluated for cardiovascular outcomes--an interim analysis. Gender difference in the impact of type 2 diabetes on coronary heart disease risk. Aspirin resistance and diabetes mellitus Does metformin improve vascular heath in children with type 1 diabetes? Protocol for a one year, double blind, randomised, placebo controlled trial Primary prevention of cardiovascular events with low-dose aspirin and vitamin E in type 2 diabetic patients: results of the Primary Prevention Project (PPP) trial. Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Disease Risk in Adults: Synopsis of the 2013 American College of Cardiology/American Heart Association Cholesterol Guideline Does smoking increase the risk of progression of nephropathy and/or cardiovascular disease in type 2 diabetic patients with albuminuria and those without albuminuria? Effect of symbiotic supplementation on glycemic control, lipid profiles and microalbuminuria in patients with non-obese type 2 diabetes: a randomized, double-blind, clinical trial Effect of population screening for type 2 diabetes and cardiovascular risk factors on mortality rate and cardiovascular events: a controlled trial among 1,912,392 Danish adults Thailand Diabetic Registry cohort: predicting death in Thai diabetic patients and causes of death. Mendelian randomization studies of biomarkers and type 2 diabetes No effects of oral vitamin D supplementation on non-alcoholic fatty liver disease in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial Fried-food consumption and risk of type 2 diabetes and coronary artery disease: a prospective study in 2 cohorts of US women and men. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. Electrocardiography and outcome in patients with diabetes mellitus on maintenance hemodialysis. Screening for type 2 diabetes in a high-risk population: study design and feasibility of a population-based randomized controlled trial Hyperhomocysteinemia increases risk of death, especially in type 2 diabetes : 5-year follow-up of the Hoorn Study. Serum and dietary magnesium and the risk for type 2 diabetes mellitus: the Atherosclerosis Risk in Communities Study. The kidney and cardiovascular outcome trials. The effectiveness of yoga to prevent diabetes mellitus type 2
Diabetes is an “ old disease ” . The first description of diabetes written on papyrus about 3500 years ago is found in the Ebers papyrus  , which was discovered in Egypt in 1873 by the German archeologist Georg Ebers . Humans , like most mammals , may develop diabetes , if sufficient environmental exposure to physical inactivity , unhealthy diet and obesity are present . Genetic effects are important for the individual risk of type 2 diabetes ( T2D ) but twin studies have shown that the genetic effects combined explain less than 50 % of the risk of T2D ( 1 ) . Today we know almost 100 susceptibility genes associated with T2D but the relative importance of each of these genes is low ( 2 ) , and together they explain only a small part of the disease risk . Thus , genetic screening can not be used for the prediction of T2D for individuals . On the other h and , healthy lifestyle can also prevent T2D in people who are genetically at high risk , e.g. those with positive family history ( 3 ) . Thus , the importance of lifestyle factors for the development and prevention of T2D is overwhelming . The strongest evidence in medicine is considered to come from r and omized controlled trials ( RCTs ) . They are also important in providing the link to causal inference that in most observational studies can not be derived . At the same time , observational studies are necessary for the identification of factors associated with an increased or decreased risk of a disease , and for generation of hypotheses on potential means for prevention based on modifiable risk factors . Observational studies have by now identified a large number of factors that are associated with the development of T2D or with the protection against it . Most of them are related to physical activity , diet and obesity . It has also been shown unequivocally that exposures ( poor nutrition , infections , smoking , etc . ) during fetal life and early infancy result ing in insufficient development ( often shown as low birth weight ) also predict T2D later in life ( 4 ) . Traditionally , T2D has been considered to be a disease of the elderly . However , with increasing obesity and sedentary lifestyle in children , there are increasing numbers of cases of T2D already occurring at a young age in many population s ( 5 ) . In the past two decades several innovative RCTs have repeatedly shown that interventions on modifiable risk factors can reduce the incidence of diabetes in high-risk groups . The evidence has been summarized in several systematic review s and meta-analyses ( 6,7 ) . There is compelling scientific evidence from RCTs that T2D can be prevented or its onset delayed . The key for prevention is a multimodal package of lifestyle changes that is a sum outcome of dietary and physical activity behaviours . The power of lifestyle was dramatically illustrated by the Finnish Diabetes Prevention Study ( DPS ) that explicitly showed that when the study participants with impaired glucose tolerance reached all five modest lifestyle intervention targets , none of them progressed to T2D ( 8) . Importantly , lifestyle intervention lasting for 3–6 years has been shown to have a carry-over effect on T2D incidence that lasts for several years ; up to 15 in the Finnish Diabetes Prevention Study ( 9 ) and 20 years in the China Da Qing Diabetes Prevention Study ( 10 ) . The observed sustained risk reduction seems to be a result of sustained lifestyle changes , but the legacy effect of improved glycaemia during the early intervention may also have contributed to the long-term effect . The follow-up data from the Chinese study indicate moreover that vascular risks are also reduced by lifestyle management . Several prognostic question naires exist for detecting people at risk of T2D ( 11 ) . One of the screening tools with an adequately high sensitivity and specificity is the Finnish Diabetes Risk Score ( FINDRISC ) developed in Finl and ( 12 ) . The FINDRISC has been successfully implemented in the Finnish primary health care system and used also in many other countries . The FINDRISC was also tested in the Omani population and as a result a slightly modified Omani Diabetes Risk Score was developed ( 13 ) which may be a suitable screening tool for the Arab population s in the Middle East . Lifestyle interventions aim ing at translating evidence from efficacy RCTs on T2D prevention into “ real world ” intervention programmes have also been carried out in various population s. Such data were recently combined in a meta- analysis considering the relationship between intervention effectiveness and adherence to guidelines ( 14 ) . The primary meta- analysis included 22 studies with outcome data for weight loss at 12 months . The pooled result of the direct pairwise meta- analysis shows that BACKGROUND Hemoglobin A1c ( HbA1c ) is a marker of cumulative glycemic exposure over the preceding 2- to 3-month period . Whether mild elevations of this biomarker provide prognostic information for development of clinical ly evident type 2 diabetes and cardiovascular disease among individuals at usual risk for these disorders is uncertain . METHODS We examined baseline HbA1c levels as a predictor of incident clinical diabetes and cardiovascular disease ( nonfatal myocardial infa rct ion , coronary revascularization procedure , ischemic stroke , or death from cardiovascular causes ) in a prospect i ve cohort study beginning in 1992 of 26,563 US female health professionals aged 45 years or more without diagnosed diabetes or vascular disease ( median follow-up 10.1 years ) . RESULTS During follow-up , 1238 cases of diabetes and 684 cardiovascular events occurred . In age-adjusted analyses using quintiles of HbA1c , a risk gradient was observed for both incident diabetes and cardiovascular disease . After multivariable adjustment , HbA1c remained a strong predictor of diabetes but was no longer significantly associated with incident cardiovascular disease . In analyses of threshold effects , adjusted relative risks for incident diabetes in HbA1c categories of less than 5.0 % , 5.0 % to 5.4 % , 5.5 % to 5.9 % , 6.0 % to 6.4 % , 6.5 % to 6.9 % , and 7.0 % or more were 1.0 , 2.9 , 12.1 , 29.3 , 28.2 , and 81.2 , respectively . Risk associations persisted after additional adjustment for C-reactive protein and after excluding individuals developing diabetes within 2 and 5 years of follow-up . CONCLUSIONS These prospect i ve findings suggest that HbA1c levels are elevated well in advance of the clinical development of type 2 diabetes , supporting recent recommendations for lowering of diagnostic thresholds for glucose metabolic disorders . In contrast , the association of HbA1c with incident cardiovascular events is modest and largely attributable to coexistent traditional risk factors Introduction While a number of strategies are being implemented to control cardiovascular diseases ( CVDs ) and type 2 diabetes mellitus ( T2DM ) , the cost-effectiveness of these in the South Asian context has not been systematic ally evaluated . We aim to systematic ally review the economic ( cost-effectiveness ) evidence available on the individual- , group- and population -level interventions for control of CVD and T2DM in South Asia . Methods and analysis This review will consider all relevant economic evaluations , either conducted alongside r and omised controlled trials or based on decision modelling estimates . These studies must include participants at risk of developing CVD/T2DM or with established disease in one or more of the South Asian countries ( India , Bangladesh , Pakistan , Sri Lanka , Nepal , Maldives , Bhutan and Afghanistan ) . We will identify relevant papers by systematic ally search ing all major data bases and registries . Selected articles will be screened by two independent research ers . Method ological quality of the studies will be assessed using a modified Drummond and a Phillips checklist . Cochrane guidelines will be followed for bias assessment in the effectiveness studies . Results Results will be presented in line with the PRISMA ( Preferred Reporting Items for Systematic review and Meta- analysis ) checklist , and overall quality of evidence will be presented as per the GRADE ( Grade s of Recommendation , Assessment , Development and Evaluation ) approach . Ethics and dissemination The study has received ethics approval from the All India Institute of Medical Sciences , New Delhi , India . The results of this review will provide policy-relevant recommendations for the uptake of cost-effectiveness evidence in prioritising decisions on essential chronic disease care packages for South Asia . Study registration number PROSPERO CRD42013006479 BACKGROUND A recent meta- analysis raised concern regarding an increased risk of myocardial infa rct ion and death from cardiovascular causes associated with rosiglitazone treatment of type 2 diabetes . METHODS We conducted an unplanned interim analysis of a r and omized , multicenter , open-label , noninferiority trial involving 4447 patients with type 2 diabetes who had inadequate glycemic control while receiving metformin or sulfonylurea , in which 2220 patients were assigned to receive add-on rosiglitazone ( rosiglitazone group ) , and 2227 to receive a combination of metformin plus sulfonylurea ( control group ) .  The primary end point was hospitalization or death from cardiovascular causes . RESULTS Because the mean follow-up was only 3.75 years , our interim analysis had limited statistical power to detect treatment differences . A total of 217 patients in the rosiglitazone group and 202 patients in the control group had the adjudicated primary end point ( hazard ratio , 1.08 ; 95 % confidence interval [ CI ] , 0.89 to 1.31 ) . After the inclusion of end points pending adjudication , the hazard ratio was 1.11 ( 95 % CI , 0.93 to 1.32 ) . There were no statistically significant differences between the rosiglitazone group and the control group regarding myocardial infa rct ion and death from cardiovascular causes or any cause . There were more patients with  heart failure  in the rosiglitazone group than in the control group ( hazard ratio , 2.15 ; 95 % CI , 1.30 to 3.57 ) . CONCLUSIONS Our interim findings from this ongoing study were inconclusive regarding the effect of rosiglitazone on the overall risk of hospitalization or death from cardiovascular causes . There was no evidence of any increase in death from either cardiovascular causes or all causes . Rosiglitazone was associated with an increased risk of heart failure . The data were insufficient to determine whether the drug was associated with an increase in the risk of myocardial infa rct ion . ( Clinical Trials.gov number , NCT00379769 [ Clinical Trials.gov ] . ) OBJECTIVE To explain the stronger effect of type 2 diabetes on the risk of coronary heart disease ( CHD ) in women compared with men . RESEARCH DESIGN AND METHODS The study population consisted of 1,296 nondiabetic subjects and 835 type 2 diabetic subjects aged 45 - 64 years without cardiovascular disease . The end points were CHD death and a major CHD event ( CHD death or nonfatal myocardial infa rct ion ) . The follow-up time was 13 years . RESULTS Major CHD event rate per 1,000 person-years was 11.6 in nondiabetic men , 1.8 in nondiabetic women , 36.3 in diabetic men , and 31.6 in diabetic women . The diabetes-related hazard ratio for a major CHD event from the Cox model , adjusted for age and area of residence , was 2.9 ( 95 % CI 2.2 - 3.9 ) in men and 14.4 ( 8.4 - 24.5 ) in women , and after further adjustment for cardiovascular risk factors , 2.8 ( 2.0 - 3.7 ) and 9.5 ( 5.5 - 16.9 ) , respectively . The burden of conventional risk factors in the presence of diabetes was greater in women than in men at baseline . Prospect ively , elevated blood pressure , low HDL cholesterol , and high triglycerides contributed to diabetes-related CHD risk more in women than in men . However , after adjusting for conventional risk factors , a substantial proportion of diabetes-related CHD risk remained unexplained in both genders . CONCLUSIONS The stronger effect of type 2 diabetes on the risk of CHD in women compared with men was in part explained by a heavier risk factor burden and a greater effect of blood pressure and atherogenic dyslipidemia in diabetic women Despite multiple interventions to reduce the risk of cardiovascular disease , the majority of people with diabetes develop macrovascular complications , and mortality following myocardial infa rct ion remains unacceptably high [ 1 ] . Antiplatelet agents are used for both the primary and secondary prevention of cardiovascular disease , although current guidelines are not consistent in their recommendation for the use of aspirin in diabetes [ 2 ] . In fact , there is little direct evidence supporting its efficacy in this group of patients . Instead , there is convincing data in the literature to suggest inadequate cardiovascular protection by aspirin in diabetes . In a meta- analysis of 287 r and omised trials , antiplatelet treatment ( aspirin in most studies ) reduced the risk of ischaemic events by 22 % , but the risk reduction in the subgroup with diabetes was only 7 % , which was not statistically significant [ 3 ] . This outcome was mirrored in the Primary Prevention Project trial , which reported that cardiovascular risk reduction with aspirin was marginal and non-significant in the presence of diabetes [ 4 ] . Despite this , there are no published studies specifically design ed to evaluate the clinical efficacy of aspirin in individuals with diabetes , a surprising omission in the era of ‘ evidence based ’ medicine . These findings from clinical trials raise the question as to why there should be a reduction in the clinical efficacy of  aspirin  in patients with diabetes compared with a nondiabetic population . Diabetes is intrinsically associated with particular biochemical abnormalities that may have the capacity to diminish the effects of aspirin on platelet function and cardiovascular risk — a possibility that has led to the hotly debated concept of aspirin resistance [ 5 , 6 ] . Unfortunately , aspirin resistance suffers from a lack of a st and ardised definition , although now generally thought of as either ( 1 ) reflecting clinical aspirin resistance ( or perhaps , more accurately , treatment failure ) , characterised by the occurrence of a thrombotic episode despite treatment with aspirin ; or ( 2 ) biochemical aspirin resistance where platelet responses persist despite platelet exposure to aspirin . Controversy remains as to the cause of biochemical aspirin resistance , its relevance to clinical outcomes , and the place of aspirin treatment in the management of cardiovascular risk in diabetes patients . All of this highlights the urgent need to underst and the mechanisms that underpin the interactions between diabetes and aspirin , to establish the role of aspirin in particular , and antiplatelet therapy in general , in the amelioration of cardiovascular events in individuals with diabetes . Diabetologia ( 2008 ) 51:385–390 DOI 10.1007/s00125 - 007 - 0898 - Background Cardiovascular disease is the leading cause of mortality in Type 1 diabetes ( T1D ) . Vascular dysfunction is an early and critical event in the development of cardiovascular disease . Children with T1D have vascular dysfunction therefore early interventions to improve vascular health are essential to reduce cardiovascular mortality in T1D . Metformin is an insulin sensitising agent which is known to improve vascular health outcomes in type 2 diabetes ( T2D ) and other individuals with insulin resistance . It has been used safely in children and adolescents with T2D for over 10 years . This study aims to assess the effect of metformin on vascular health in children with T1D . Methods / Design This study is a 12 month , double blind , r and omised , placebo controlled trial to determine the effect of metformin on vascular health in children ( age 8–18 ) with T1D . The sample size is 76 with 38 children in the metformin group and 38 children in the placebo group . Vascular health and biochemical markers will be measured at baseline , 3 , 6 and 12 months . Vascular function will be measured using flow mediated dilatation and glyceryl trinitrate mediated dilatation of the brachial artery and vascular structure will be measured with carotid and aortic intima media thickness , using st and ardised protocol s. Discussion This study will be the first to investigate the effect of metformin on vascular health in children with T1D . It will provide important information on a potential intervention to improve cardiovascular morbidity and mortality in this population at high risk from cardiovascular disease . Trial registration Australia New Zeal and Clinical Trials Registry OBJECTIVE We investigated in general practice the efficacy of antiplatelets and antioxidants in primary prevention of cardiovascular events in people with type 2 diabetes . RESEARCH DESIGN AND METHODS The Primary Prevention Project ( PPP ) is a r and omized , open trial with a two-by-two factorial design aim ed to investigate low-dose aspirin ( 100 mg/day ) and vitamin E ( 300 mg/day ) in the prevention of cardiovascular events in patients with one or more cardiovascular risk factors . The primary end point was a composite end point of cardiovascular death , stroke , or myocardial infa rct ion . A total of 1,031 people with diabetes in the PPP , aged > /=50 years , without a previous cardiovascular event were enrolled by 316 general practitioners and 14 diabetes outpatient clinics . RESULTS The PPP trial was prematurely stopped ( after a median of 3.7 years ) by the independent data safety and monitoring board because of a consistent benefit of aspirin compared with the control group in a population of 4,495 patients with one or more major cardiovascular risk factors . In diabetic patients , aspirin treatment was associated with a nonsignificant reduction in the main end point ( relative risk [ RR ] = 0.90 , 95 % CI 0.50 - 1.62 ) and in total cardiovascular events ( 0.89 , 0.62 - 1.26 ) and with a nonsignificant increase in cardiovascular deaths ( 1.23 , 0.69 - 2.19 ) . In nondiabetic subjects , RRs for the main end point , total cardiovascular events , and cardiovascular deaths were 0.59 ( 0.37 - 0.94 ) , 0.69 ( 0.53 - 0.90 ) , and 0.32 ( 0.14 - 0.72 ) , respectively . No significant reduction in any of the end points considered could be found with vitamin E in either diabetic or nondiabetic subjects . CONCLUSIONS Our data suggest a lower effect of primary prevention of cardiovascular disease ( CVD ) with low-dose aspirin in diabetic patients as opposed to subjects with other cardiovascular risk factors . If confirmed , these findings might indicate that the antiplatelet effects of aspirin in diabetic patients are overwhelmed by aspirin-insensitive mechanisms of platelet activation and thrombus formation , thus making the balance between benefits and harms of aspirin treatment unfavorable . Further large-scale trials investigating the role of aspirin in the primary prevention of CVD in diabetic patients are urgently needed Atherosclerotic cardiovascular disease ( ASCVD ) is the leading cause of death , decreased quality of life , and medical costs in the United States . Nearly 1 in 3 Americans die of heart disease and stroke ( 1 ) . Most ASCVD is preventable through a healthy lifestyle and effective treatment of cholesterol and blood pressure . The 2013 Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults from the American College of Cardiology and American Heart Association ( ACC/AHA ) provides an evidence -based approach to reducing ASCVD risk ( 2 ) . Guideline Development Process In 2008 , the National Heart , Lung , and Blood Institute ( NHLBI ) convened the Adult Treatment Panel ( ATP ) IV to up date the 2001 ATP-III cholesterol guidelines using a rigorous systematic process to identify and review r and omized , controlled trials ( RCTs ) with cardiovascular outcomes and meta-analyses of these RCTs . The panel comprised experts and clinicians from the fields of cardiology , epidemiology , primary care , and endocrinology ( 2 ) and received support from the Lifestyle Management and Risk Assessment Work Groups ( 3 , 4 ) . Systematic evidence review s conducted according to principles recommended by the Institute of Medicine ( 5 ) were performed to answer 3 questions relevant to clinical care . Two questions focused on the evidence supporting low-density lipoprotein cholesterol ( LDL-C ) and nonhigh-density lipoprotein cholesterol ( HDL-C ) levels as targets of treatment . One question examined the reduction in ASCVD events and adverse effects for each cholesterol-lowering drug class . The panel synthesized the evidence from these 3 review s as well as from Lifestyle Management and Risk Assessment Work Groups review s ( 3 , 4 ) that addressed 5 additional critical questions . Systematic electronic search es of relevant data bases of the peer- review ed English- language literature published from 1 January 1995 through 1 December 2009 for each critical question were conducted by an NHLBI-selected independent contractor and focused on RCTs and systematic review s and meta-analyses of RCTs assessed as fair to good quality . In addition , RCTs with ASCVD outcomes that included coronary heart disease , stroke , and cardiovascular deaths published after that date were eligible for consideration through July 2013 . Evidence tables were constructed , and the strength of evidence was rated according to the NHLBI ( Table 1 of the Supplement ) . Recommendations were grade d according to criteria from the NHLBI ( Table 2 of the Supplement ) and ACC/AHA ( Table 3 of the Supplement ) . Because of the inherent differences in grading systems and the clinical questions driving the recommendations , alignment between the NHLBI and ACC/AHA formats was imperfect . A complete description of the methods used and results of the evidence review are provided in the guideline ( 2 ) and the NHLBI evidence report ( www.nhlbi.nih.gov/ guidelines /cholesterol/ser/index.htm ) . Supplement . NHLBI and ACC/AHA Criteria for Rating Strength of Evidence To help clinicians estimate ASCVD risk , the risk assessment working group developed the Pooled Cohort Equations using data from 5 NHLBI-sponsored longitudinal , population -based cohorts of African American and non-Hispanic white men and women to estimate risk for a first myocardial infa rct ion , coronary heart disease death , or fatal or nonfatal stroke on the basis of age , sex , race , smoking status , total cholesterol level , HDL-C level , systolic blood pressure , antihypertensive therapy , and diabetes ( 4 , 6 ) . These equations significantly advance ASCVD risk estimation by providing sex- and race-specific estimates and including stroke as an outcome . The earlier Framingham equations calculated only coronary heart disease risk for non-Hispanic whites . The draft recommendations were review ed by 23 experts and representatives of federal agencies identified by the NHLBI . In September 2013 , the recommendations developed by the panel were transitioned to the ACC/AHA and had additional review by 4 experts nominated by the ACC Foundation and the AHA . The governing bodies of the ACC and AHA approved the guideline , which also received endorsement from the American Association of Cardiovascular and Pulmonary Rehabilitation , American Pharmacists Association , American Society for Preventive Cardiology , Association of Black Cardiologists , Preventive Cardiovascular Nurses Association , and WomenHeart : The National Coalition for Women with Heart Disease . Recommendations The guideline focuses on treatment of blood cholesterol to reduce ASCVD risk in adults . Major recommendations are summarized here and in Table 1 . The guideline report provides a complete listing of recommendations and supporting evidence behind each recommendation ( 2 ) . Table 1 . Major Recommendations for the Treatment of Blood Cholesterol to Reduce ASCVD Risk in Adults * 1 . Encourage Adherence to a Healthy Lifestyle A healthy lifestyle is the foundation for cardiovascular health . The panel endorsed the 2013 ACC/AHA Lifestyle Management Guideline ( 3 ) for a diet that is low in saturated fat , trans fat , and sodium ; emphasizes vegetables , fruits , whole grains , low-fat dairy products , poultry , fish , legumes , nontropical vegetable oils , and nuts ; and limits sweets , sugar-sweetened beverages , and red meats and engage in regular aerobic physical activity . Adults also should maintain a healthy body weight , avoid smoking , and control hypertension and diabetes when present . 2 . Statin Therapy Is Recommended for Adults in Groups Demonstrated to Benefit Strong RCT evidence shows that reduction in ASCVD events from statin therapy exceeds adverse events for 4 patient groups : those with clinical ASCVD ( acute coronary syndromes , myocardial infa rct ion , stable angina , coronary or other arterial revascularization , stroke , transient ischemic attack , or peripheral arterial disease of atherosclerotic origin ) when  statins are used for secondary prevention , and those with LDL-C levels 190 mg/dL ; those aged 40 to 75 years with diabetes and LDL-C levels 70 to 189 mg/dL ; and those aged 40 to 75 years without diabetes and with a 10-year ASCVD risk 7.5 % when statins are used for primary prevention . Moderate evidence supports consideration of statin therapy for primary prevention in individuals with a 10-year ASCVD risk of 5 % to < 7.5 % . Routine initiation of statin therapy is not recommended in adults with New York Heart Association heart failure class II to IV or those receiving maintenance hemodialysis . R and omized , controlled trials in these groups showed no reduction in ASCVD . 3 . Statins have an Acceptable Margin of Safety When Used in Properly Selected Individuals and Appropriately Monitored Strong RCT evidence supports safety of statins when they are used as directed in conjunction with regular follow-up assessment s in properly selected patients . Adjustment of statin intensity is recommended in individuals older than 75 years with a history of statin intolerance or other characteristics ( 2 ) or those receiving drug therapy that may increase statin adverse events . Routine monitoring of hepatic aminotransferase level or creatine kinase level is not recommended unless clinical ly indicated by symptoms suggesting hepatotoxicity or myopathy . Given the potential for decreasing ASCVD events and death , the relationship of muscle and other symptoms to statin treatment must be confirmed . Therefore , eliciting a history of muscle symptoms before statin initiation and carefully monitoring symptoms during statin discontinuation and rechallenge is recommended . Severe myopathy , rhabdomyolysis , and possibly hemorrhagic stroke are rare complications of statin therapy . Although statin therapy modestly increases the risk for type 2 diabetes , ASCVD risk reduction outweighs the excess risk for diabetes for high-intensity statins in secondary prevention or for 10-year ASCVD risk 7.5 % . Similarly , ASCVD risk reduction outweighs the excess risk for diabetes for moderate-intensity statin therapy in adults with a 10-year ASCVD risk 5 % . 4 . Engage in a ClinicianPatient Discussion Before Initiating Statin Therapy , Especially for Primary Prevention in Patients With Lower ASCVD Risk Decisions to initiate statin therapy in primary prevention should be based on clinical judgment and preferences of informed patients . In adults without clinical ASCVD or diabetes whose LDL-C level is < 190 mg/dL , calculating the estimated 10-year ASCVD risk should be the start of the clinicianpatient discussion and should not automatically lead to statin initiation . As the absolute risk for ASCVD events decreases , so does the net benefit of the intervention . Therefore , discussion of the potential for ASCVD event reduction , adverse effects , drugdrug interactions , and patient preferences is especially important for lower-risk primary prevention . The discussion provides the opportunity to encourage healthy lifestyle habits and control other risk factors . Additional factors may be considered when a risk-based decision is uncertain , including LDL-C levels 160 mg/dL , family history of premature ASCVD , elevated  lifetime ASCVD risk  , high-sensitivity C-reactive protein level 2.0 mg/L ,  coronary artery calcification score  > 300 Agatston units , and anklebrachial index < 0.9 . After age 75 years , comorbid conditions , anticipated longevity , safety considerations , and patient preferences should play a large role in decision making . 5 . Use the Newly Developed Pooled Cohort Equations for Estimating 10-Year ASCVD Risk The Pooled Cohort Equations are currently the best available method for estimating 10-year ASCVD risk to guide statin initiation ( 4 , 6 ) . Application of the inclusion and exclusion criteria from RCTs is cumbersome and results in underidentifying high-risk and overidentifying low-risk individuals for statin treatment . The Pooled Cohort Equations were developed using recent data from 5 NHLBI-sponsored , longitudinal , population -based cohorts of African American and white men and women ( ARIC [ UNLABELLED Diabetic nephropathy is the primary cause of chronic kidney disease and is associated with increased cardiovascular mortality .  Cigarette smoking is probably the most complex and the least understood among the risk factors for chronic kidney disease and cardiovascular disease in diabetic patients . The aim of this study was to determine the impact of smoking on progression of nephropathy and cardiovascular disease in type 2 diabetic patients with albuminuria and those without albuminuria . METHODS This is a prospect i ve study . The Ethics Committee of Morocco 's Mohammed V University in Rabat approved the study protocol . Inclusion criteria targeted patients who were type 2 diabetics and who had nephrology follow up for at least 36 months . RESULTS A total of 671 cases of T2D were included . Mean age of all patients was 65 ± 11 years and 12.1 % were smokers . There was no statistically significant difference between T2D patients with albuminuria according to absence of presence of smoking at the time of enrollment , at 1 year and 3 years of follow-up , concerning the median albumin excretion rate ( mg/day ) : 98 [ 56 - 281 ] vs. 124 [ 56 - 323 ] ( p=0.59 ) ; 98 [ 56 - 281 ] vs. 124 [ 56 - 323 ] ( p=0.15 ) and 98 [ 56 - 281 ] vs. 124 [ 56 - 323 ] ( p=0.52 ) respectively . There was a statistically significant difference between T2D patients with albuminuria according to absence or presence of smoking at the time of enrollment and the end of follow-up , concerning cardiovascular events : 56 ( 12.3 % ) vs. 19 ( 28.4 % ) ( p<0.001 ) and 66 ( 14.5 % ) vs. 19 ( 28.4 % ) ( p=0.004 ) respectively . CONCLUSION Smoking remains one of the most important modifiable risk factors for progression of renal and cardiovascular disease in diabetic patients , thus adding to the burden of morbimortality Background The prevalent raise of type 2 diabetes ( T2D ) around the globe , are creating higher risk for cardiovascular diseases ( CVDs ) and increasing strain on each country ’s health care budget in the world . Microalbuminuria has appeared as a key parameter in diabetic patients . Microalbuminuria is also related to increased cardiovascular morbidity in people who are non-obese diabetic . Some studies have suggested that consumption of symbiotic foods might help improve the metabolic profile , inflammatory factors and biomarkers of oxidative stress . The aim of trial was to determine the effect of symbiotic supplementation on glycemic control , lipid profiles and microalbuminuria in non-obese T2D . Methods In this r and omized , double-blind , clinical ly controlled trial , 70 patients with T2D ( 28 females , 42 males ) were r and omly divided into two groups ( n = 35 for each group ) . The symbiotic group ( SG ) consumed 500 mg/d of symbiotic supplementations containing probiotics ( Lactobacillus family , Bifidobacterium family , Streptococus thermophilus ) , Prebiotics ( Fructo oligosaccharide ) and B group vitamins ( 1 mg ) , lactose ( 0.5 mg ) , malt-dextrin , magnesium saturate and the placebo group ( PG ) consumed capsules filled with row starch and also B group vitamins ( 1 mg ) , lactose ( 0.5 mg ) , malt-dextrin , magnesium saturate for 9 weeks . Fasting blood glucose ( FBG ) , hemoglobin A1c ( HbA1c ) , blood lipid profiles , 24-h dietary recalls , and anthropometric measurements were measured at the baseline and at the end of trial . SPSS software , version 16 was used to test the data and the results were expressed as mean ± st and ard deviation . Paired sample s T-Test were used to compare continuous variables within groups . Comparison between different groups was performed through two independent sample s T-Test . In the absence of normal distribution , the comparison between the groups was made using non-parametric Wilcoxon on signed ranks and Mann – Whitney tests . P values < 0.05 was considered significant . Results Symbiotic supplementation decreased significantly , FBG ( P = 0.05 ) and HbA1c ( P < 0.01 ) . There were no significant differences in lipid profiles within and between the groups at the end of study ( P > 0.05 ) . Microalbuminuria ( P < 0.05 ) and HbA1c ( P < 0.05 ) are increased significantly in PG at the end of the study . Furthermore , the mean changes of microalbuminuria and HbA1c experienced significant between the two groups . There was significant reduction in urea between two groups from baseline ( P = 0.051 ) . No significant changes in baseline were shown in creatinine among the two groups or within either groups ( P > 0.05 ) . Conclusion The consumption of 500 mg/d symbiotic supplementation for 9 weeks could improve the HbA1c , BMI and Microalbuminuria in T2D . Although , No effect has been indicated on FBS , lipid profiles , urea and creatinine . Trial Registration The trial has been registered in the Iranian Registry of Clinical Trials I RCT 2015072223284N1 , identifier . Registered 21 May 2016 “ retrospectively registered ” Aims /hypothesisHealth check programmes for chronic disease have been introduced in a number of countries . However , there are few trials assessing the benefits and harms of these screening programmes at the population level . In a post hoc analysis , we evaluated the effect of population -based screening for type 2 diabetes and cardiovascular risk factors on mortality rates and cardiovascular events . Methods This register-based , non-r and omised , controlled trial included men and women aged 40–69 years without known diabetes who were registered with a general practice in Denmark ( n = 1,912,392 ) . Between 2001 and 2006 , 153,107 individuals registered with 181 practice s participating in the Anglo – Danish – Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION)-Denmark study were sent a diabetes risk score question naire . Individuals at moderate-to-high risk were invited to visit their GP for assessment of diabetes status and cardiovascular risk ( screening group ) . The 1,759,285 individuals registered with all other general practice s in Denmark constituted the retrospectively constructed no-screening ( control ) group . Outcomes were mortality rate and cardiovascular events ( cardiovascular disease death , non-fatal ischaemic heart disease or stroke ) . The analysis was performed according to the intention-to-screen principle . Results Among the screening group , 27,177 ( 18 % ) individuals attended for assessment of diabetes status and cardiovascular risk . Of these , 1,533 were diagnosed with diabetes . During a median follow-up of 9.5 years , there were 11,826 deaths in the screening group and 141,719 in the no-screening group ( HR 0.99 [ 95 % CI 0.96 , 1.02 ] , p = 0.66 ) . There were 17,941 cardiovascular events in the screening group and 208,476 in the no-screening group ( HR 0.99 [ 0.96 , 1.02 ] , p = 0.49 ) . Conclusions /interpretationA population -based stepwise screening programme for type 2 diabetes and cardiovascular risk factors among all middle-aged adults in Denmark was not associated with a reduction in rate of mortality or cardiovascular events between 2001 and 2012 INTRODUCTION The prevalence of type 2 diabetes in Thail and is 9.8 percent which is double the number forecast by World Health Organization . There is inadequate information to statistically represent all Thai diabetic patients for their causes of death . OBJECTIVE To determine the clinical characteristics that predicted death and causes of death in Thai diabetic patients . MATERIAL AND METHOD This prospect i ve cohort was a 3-year follow-up study of the Thai Diabetes Registry project done between April , 2003 , and February , 2006 , which registered 9,419 diabetic patients attending 11 diabetic clinics in tertiary medical centers in Bangkok and major provinces of Thail and . The dead or alive status ( 99.5 % ) was determined . The causes of death were defined by review ing the medical records . RESULTS Of the 9,370 diabetic patients registered , 425 patients  died , 1.84 percent per year . There was an increased risk of death associated with age , type of healthcare plan , lower education , insulin use , smoking , history of coronary artery disease and cerebrovascular disease , serum creatinine and high HbA1c . Lipid-lowering medication and metformin decreased the risk of death . Cardiovascular disease , infection and cancer were the prevalent causes of death . CONCLUSION The present study showed risk factors that influenced death and causes of death in Thai diabetics Many biomarkers are associated with type 2 diabetes ( T2D ) risk in epidemiological observations . The aim of this study was to identify and summarize current evidence for causal effects of biomarkers on T2D . A systematic literature search in PubMed and EMBASE ( until April 2015 ) was done to identify Mendelian r and omization studies that examined potential causal effects of biomarkers on T2D . To replicate the findings of identified studies , data from two large-scale , genome-wide association studies ( GWAS ) were used : DIAbetes  Genetics Replication And Meta- analysis  ( DIAGRAMv3 ) for T2D and the Meta-Analyses of Glucose and Insulin-related traits Consortium ( MAGIC ) for glycaemic traits . GWAS summary statistics were extracted for the same genetic variants ( or proxy variants ) , which were used in the original Mendelian r and omization studies . Of the 21 biomarkers ( from 28 studies ) , ten have been reported to be causally associated with T2D in Mendelian r and omization . Most biomarkers were investigated in a single cohort study or population . Of the ten biomarkers that were identified , nominally significant associations with T2D or glycaemic traits were reached for those genetic variants related to bilirubin , pro-B-type natriuretic peptide , delta-6 desaturase and dimethylglycine based on the summary data from DIAGRAMv3 or MAGIC . Several Mendelian r and omization studies investigated the nature of associations of biomarkers with T2D . However , there were only a few biomarkers that may have causal effects on T2D . Further research is needed to broadly evaluate the causal effects of multiple biomarkers on T2D and glycaemic traits using data from large-scale cohorts or GWAS including many different genetic variants Background Non-alcoholic fatty liver disease ( NAFLD ) is the most common hepatic disorder worldwide , reaching prevalence up to 90 % in obese patients with type 2 diabetes ( T2D ) , and representing an independent risk factor for cardiovascular mortality . Furthermore , the coexistence of T2D and NAFLD leads to higher incidence of diabetes ’ complications and additive detrimental liver outcomes . The existence of a close association between NAFLD and hypovitaminosis D , along with the anti-inflammatory and insulin-sensitizing properties of vitamin D , have been largely described , but vitamin D effects on hepatic fat content have never been tested in a r and omized controlled trial . We assessed the efficacy and safety of 24-week oral high-dose vitamin D supplementation in T2D patients with NAFLD . Methods This r and omized , double-blind , placebo-controlled trial was carried out at the Diabetes Centre of Sapienza University , Rome , Italy , to assess oral treatment with cholecalciferol ( 2000 IU/day ) or placebo in T2D patients with NAFLD . The primary endpoint was reduction of hepatic fat fraction ( HFF ) measured by magnetic resonance ; as hepatic outcomes , we also investigated changes in serum transaminases , CK18-M30 , N-terminal Procollagen III Propeptide ( P3NP ) levels , and Fatty Liver Index ( FLI ) . Secondary endpoints were improvement in metabolic ( fasting glycaemia , HbA1c , lipids , HOMA-IR , HOMA-β , ADIPO-IR , body fat distribution ) and cardiovascular ( ankle-brachial index , intima-media thickness , flow-mediated dilatation ) parameters from baseline to end of treatment . Results Sixty-five patients were r and omized , 26 ( cholecalciferol ) and 29 ( placebo ) subjects completed the study . 25(OH ) vitamin D significantly increased in the active treated group ( 48.15 ± 23.7 to 89.80 ± 23.6 nmol/L , P < 0.001 ) ; however , no group differences were found in HFF , transaminases , CK18-M30 , P3NP levels or FLI after 24 weeks . Vitamin D neither changed the metabolic profile nor the cardiovascular parameters . Conclusions Oral high-dose vitamin D supplementation over 24 weeks did not improve hepatic steatosis or metabolic/cardiovascular parameters in T2D patients with NAFLD . Studies with a longer intervention period are warranted for exploring the effect of long time exposure to vitamin D.Trial registration This trial was approved on July 2011 by the Ethics Committee of Policlinico Umberto I , Sapienza University of Rome , Italy , and registered at www . clinical trialsregister.eu number 2011 - 003010 - 17 BACKGROUND Through the processes of oxidation , polymerization , and hydrogenation , the cooking method of frying modifies both foods and their frying medium . However , it remains unknown whether the frequent consumption of fried foods is related to long-term cardiometabolic health . OBJECTIVE We examined fried-food consumption and risk of developing incident type 2 diabetes ( T2D ) or coronary artery disease ( CAD ) . DESIGN Fried-food consumption was assessed by using a question naire in 70,842 women from the Nurses ' Health Study ( 1984 - 2010 ) and 40,789 men from the Health Professionals Follow-Up Study ( 1986 - 2010 ) who were free of diabetes , cardiovascular disease , and cancer at baseline . Time-dependent Cox proportional hazards models were used to estimate RRs and 95 % CIs for T2D and CAD adjusted for demographic , diet , lifestyle , and other cardiometabolic risk factors . Results were pooled by using an inverse variance-weighted r and om-effects meta- analysis . RESULTS We documented 10,323 incident T2D cases and 5778 incident CAD cases .  Multivariate-adjusted RRs ( 95 % CIs ) for individuals who consumed fried foods < 1 , 1 - 3 , 4 - 6 , or ≥7 times/wk were 1.00 ( reference ) , 1.15 ( 0.97 , 1.35 ) , 1.39 ( 1.30 , 1.49 ) , and 1.55 ( 1.32 , 1.83 ) , respectively , for T2D and 1.00 ( reference ) , 1.06 ( 0.98 , 1.15 ) , 1.23 ( 1.14 , 1.33 ) , and 1.21 ( 1.06 , 1.39 ) , respectively , for CAD . Associations were largely attenuated when we further controlled for biennially up date d hypertension , hypercholesterolemia , and body mass index . CONCLUSIONS  Frequent fried-food consumption was significantly associated with risk of incident T2D and moderately with incident CAD , and these associations were largely mediated by body weight and comorbid hypertension and hypercholesterolemia BACKGROUND The cardiovascular effect of liraglutide , a glucagon-like peptide 1 analogue , when added to st and ard care in patients with type 2 diabetes , remains unknown . METHODS In this double-blind trial , we r and omly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo . The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome , with a margin of 1.30 for the upper boundary of the 95 % confidence interval of the hazard ratio . No adjustments for multiplicity were performed for the prespecified exploratory outcomes . RESULTS A total of 9340 patients underwent r and omization . The median follow-up was 3.8 years . The primary outcome occurred in significantly fewer patients in the liraglutide group ( 608 of 4668 patients [ 13.0 % ] ) than in the placebo group ( 694 of 4672 [ 14.9 % ] ) ( hazard ratio , 0.87 ; 95 % confidence interval [ CI ] , 0.78 to 0.97 ; P<0.001 for noninferiority ; P=0.01 for superiority ) . Fewer patients died from cardiovascular causes in the liraglutide group ( 219 patients [ 4.7 % ] ) than in the placebo group ( 278 [ 6.0 % ] ) ( hazard ratio , 0.78 ; 95 % CI , 0.66 to 0.93 ; P=0.007 ) . The rate of death from any cause was lower in the liraglutide group ( 381 patients [ 8.2 % ] ) than in the placebo group ( 447 [ 9.6 % ] ) ( hazard ratio , 0.85 ; 95 % CI , 0.74 to 0.97 ; P=0.02 ) . The rates of nonfatal myocardial infa rct ion , nonfatal stroke , and hospitalization for heart failure were nonsignificantly lower in the liraglutide group than in the placebo group . The most common adverse events leading to the discontinuation of liraglutide were gastrointestinal events . The incidence of pancreatitis was nonsignificantly lower in the liraglutide group than in the placebo group . CONCLUSIONS In the time-to-event analysis , the rate of the first occurrence of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo . ( Funded by Novo Nordisk and the National Institutes of Health ; LEADER Clinical Trials.gov number , NCT01179048 . ) BACKGROUND AND OBJECTIVES In hemodialysis , applicable guidelines recommend regular electrocardiogram ( ECG ) recordings . However , respective systematic evaluations are absent . Thus , the authors investigated whether routine ECG findings add prognostic information to st and ard risk assessment in hemodialysis . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS The relationship between nine common baseline ECG variables and a combined cardiovascular endpoint ( CVE ; cardiac death , myocardial infa rct ion , stroke ) , sudden death , stroke , MI , and all-cause death in 1253 patients from the German Diabetes and Dialysis Study was evaluated . All patients were on maintenance hemodialysis , had type 2 diabetes mellitus , and received r and omized treatment with atorvastatin or placebo .  RESULTS During 4 yr of follow-up ( March 1998 to March 2004 ) , 469 patients reached the CVE , and 617 died . After adjustment for demographics , comorbidities , and biomarkers in multivariate analysis , patients presenting without sinus rhythm were 89 % more likely to die , and the risk of CVE and stroke increased by 75 % and 164 % , respectively , compared with patients with preserved sinus rhythm . Left ventricular hypertrophy was associated with > 2-fold increase in the risk of stroke and a 60 % increase in the risk of sudden death . CONCLUSIONS In hemodialysis patients with type 2 diabetes mellitus , the absence of sinus rhythm is a risk indicator for CVE , stroke , and all-cause death , and left ventricular hypertrophy is associated with stroke and sudden death . Thus , routine ECG recording adds prognostic information to st and ard risk assessment Background We describe the design and present the results of the first year of a population -based study of screening for type 2 diabetes in individuals at high risk of developing the disease . High risk is defined as having abdominal obesity . Methods Between 2006 and 2007 , 79,142 inhabitants of two Dutch municipalities aged 40–74 years were approached to participate in screening . Eligible participants had a self-reported waist circumference of ≥80 cm for women and ≥94 cm for men , and no known pre-existing diabetes . Of the respondents ( n = 20,578 ; response rate 26 % ) , 16,135 were abdominally obese . In total , 10,609 individuals gave written informed consent for participation and were r and omized into either the screening ( n = 5305 ) or the control arm ( n = 5304 ) . Participants in the screening arm were invited to have  their fasting plasma glucose ( FPG ) measured and were referred to their general practitioner ( GP ) if it was ≥6.1 mmol/L. In addition , blood lipids were determined in the screening arm , because abdominal obesity is often associated with cardiovascular risk factors . Participants in both arms received written healthy lifestyle information . Between-group differences were analyzed with Chi-square tests and logistic regression ( categorical variables ) and unpaired t-tests ( continuous variables ) . Results The screening attendance rate was 84.1 % . Attending screening was associated with age at r and omization ( OR = 1.03 , 95 % CI 1.02 - 1.04 ) , being married ( OR = 1.57 , 95 % CI 1.33 - 1.83 ) and not-smoking currently ( OR = 0.52 , 95 % CI 0.44 - 0.62 ) . Of the individuals screened , 5.6 % had hyperglycemia , and a further 11.6 % had an estimated absolute cardiovascular disease risk of 5 % or higher , according to the Systematic Coronary Risk Evaluation risk model . These participants were referred to their GP . Conclusions Self-reported home-assessed waist circumference could feasibly detect persons at high risk of hyperglycemia or cardiovascular disease . Continuation of the large-scale RCT is warranted to test the hypothesis that targeted population -based screening for type 2 diabetes leads to a significant reduction in cardiovascular morbidity and mortality . Trial registration IS RCT BACKGROUND A high serum total homocysteine ( tHcy ) concentration is a risk factor for death , but the strength of the relation in patients with type 2 ( non-insulin-dependent ) diabetes mellitus compared with nondiabetic subjects is not known . A cross-sectional study suggested that the association between tHcy and cardiovascular disease is stronger in diabetic than in nondiabetic subjects . We therefore prospect ively investigated the combined effect of hyperhomocysteinemia and type 2 diabetes on mortality . METHODS AND RESULTS Between October 1 , 1989 , and December 31 , 1991 , serum was saved from 2484 men and women , 50 to 75 years of age , who were r and omly selected from the town of Hoorn , The Netherl and s.  Fasting serum tHcy concentration was measured in 171 subjects who died ( cases ; 76 of cardiovascular disease ) and in a stratified r and om sample of 640 survivors ( control subjects ) .  Mortality risks were calculated over 5 years of follow-up by means of logistic regression . The prevalence of hyperhomocysteinemia ( tHcy > 14 micromol/L ) was 25 . 8 % . After adjustment for major cardiovascular risk factors , serum albumin , and HbA(1c ) , the odds ratio ( 95 % CI ) for 5-year mortality was 1.56 ( 1.07 to 2.30 ) for hyperhomocysteinemia and 1.26 ( 1.02 to 1 . 55 ) per 5-micromol/L increment of tHcy . The odds ratio for 5-year mortality for hyperhomocysteinemia was 1.34 ( 0.87 to 2.06 ) in nondiabetic subjects and 2.51 ( 1.07 to 5.91 ) in diabetic subjects ( P=0.08 for interaction ) . CONCLUSIONS Hyperhomocysteinemia is related to 5-year mortality independent of other major risk factors and appears to be a stronger ( 1.9-fold ) risk factor for mortality in type 2 diabetic patients than in nondiabetic subjects BACKGROUND Experimental studies in animals and cross-sectional studies in humans have suggested that low serum magnesium levels might lead to type 2 diabetes ; however , this association has not been examined prospect ively . METHODS We assessed the risk for type 2 diabetes associated with low serum magnesium level and low dietary magnesium intake in a cohort of nondiabetic middle-aged adults ( N = 12,128 ) from the Atherosclerosis Risk in Communities Study during 6 years of follow-up .  Fasting serum magnesium level  , categorized into 6 levels , and  dietary magnesium intake  , categorized into quartiles , were measured at the baseline examination . Incident type 2 diabetes was defined by self-report of physician diagnosis , use of diabetic medication , fasting glucose level of at least 7.0 mmol/L ( 126 mg/dL ) , or nonfasting glucose level of at least 11.1 mmol/L ( 200 mg/dL ) . RESULTS Among white participants , a grade d inverse relationship between serum magnesium levels and incident type 2 diabetes was observed . From the highest to the lowest serum magnesium levels , there was an approximate 2-fold increase in incidence rate ( 11.1 , 12.2 , 13.6 , 12.8 , 15.8 , and 22.8 per 1000 person-years ; P = .001 ) . This grade d association remained significant after simultaneous adjustment for potential confounders , including diuretic use . Compared with individuals with serum magnesium levels of 0.95 mmol/L ( 1.90 mEq/L ) or greater , the adjusted relative odds of incident type 2 diabetes rose progressively across the following lower magnesium categories : 1.13 ( 95 % CI , 0.79 - 1.61 ) , 1.20 ( 95 % CI , 0.86 - 1.68 ) , 1.11 ( 95 % CI , 0.80 - 1.56 ) , 1.24 ( 95 % CI , 0.86 - 1.78 ) , and 1.76 ( 95 % CI , 1.18 - 2.61 ) ( for trend , P = .01 ) . In contrast , little or no association was observed in black participants . No association was detected between  dietary magnesium intake  and the risk for incident type 2 diabetes in black or white participants . CONCLUSIONS Among white participants , low serum magnesium level is a strong , independent predictor of incident type 2 diabetes . That low dietary magnesium intake does not confer risk for type 2 diabetes implies that compartmentalization and renal h and ling of magnesium may be important in the relationship between low serum magnesium levels and the risk for type 2 diabetes Chronic kidney disease ( CKD ) affects a substantial minority of people with type 2 diabetes ( T2D ) . Analysis of US National Health and Nutrition Examination Survey ( NHANES ) data sets from 2007 through 2012 showed Stage 3 or worse disease ( estimated glomerular filtration rate [ eGFR ] < 60 mL/min per 1.73 m2 ) in nearly one in five patients , with increasing age , blood pressure , obesity , and levels of glycemia all associated with higher likelihood of Stage 3 or worse CKD , comparable to findings from surveys from many other areas , which also show micro- or macroalbuminuria to be present in one-sixth to one-third of diabetic people . Improvement in albuminuria has been shown in clinical trials of glycemic interventions , including the Action to Control Cardiovascular Disease in Diabetes ( ACCORD ) trial , the Action in Diabetes and Vascular Disease : Preterax and Diamicron MR Controlled Evaluation ( ADVANCE ) trial , in which the nephroprotective effect of blood pressure lowering was also demonstrated , and the UK Prospect i ve Diabetes Study ( UKPDS ) . However , over the past decade a host of cardiovascular outcome trials ( CVOTs ) have been performed with newer T2D therapeutic agents , and many of these have included intriguing information pertaining to renal disease and renal outcomes not necessarily related to changes in glycemia . It is of interest to review some of these findings . Glucagon-like peptide-1 ( GLP-1 ) has been reported to increase glomerular filtration rate ( GFR ) , renal blood flow , and the fractional excretion both of sodium and potassium , with renal GLP-1 receptors present in afferent arteriolar vascular smooth muscle cells , glomerular endothelial cells and macrophages , juxtaglomerular cells , and the proximal tubule , perhaps mediating the greater natriuresis seen after oral than intravenous sodium . In the Liraglutide Effect and Action in Diabetes : Evaluation of Cardiovascular Outcome Results ( LEADER ) trial , the significant 13 % reduction in the primary composite outcome of cardiovascular death , myocardial infa rct ion , and stroke was found on subgroup analysis to particularly occur among participants with Stage 3 CKD , having eGFR 30 - 59 mL/min per 1.73 m2 . No significant effect on eGFR was found with liraglutide , although both those receiving and not receiving the drug showed a decline in eGFR from approximately 75 to 65 mL/min per 1.73 m2 over the 48-month period of observation . Liraglutide administration was associated with a significant reduction in albuminuria , with nearly a 25 % lower likelihood of development of macroalbuminuria , and with the albumin : creatinine ratio ( ACR ) approximately 20 % lower among treated people , regardless of the baseline level of eGFR . Similarly , in the Evaluation of Lixisenatide in Acute Coronary Syndrome ( ELIXA ) trial , a 34 % increase in the urine ACR was reported among people receiving placebo , but the increase was 24 % among those receiving lixisenatide , and in the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes ( SUSTAIN-6 ) , persistent macroalbuminuria developed among 2.7 % of those receiving semaglutide , but among 4.9 % of those receiving placebo . The enzyme dipeptidyl peptidase (DPP)-4 is , like the GLP-1 receptor , present in multiple renal membrane-bound locations , including afferent arteriolar vascular smooth muscle cells , mesangial cells , podocytes , and proximal tubular cells , and DPP-4 inhibitors appear to have salutary effects on albuminuria similar to those of the GLP-1 agents . In the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR)-Thrombolysis in Myocardial Infa rct ion ( TIMI ) 53 trial , saxagliptin was associated with significantly less worsening and more improvement in microalbumin levels at 1 year , at 2 years , and by end-of-treatment . The reduction in microalbumin levels was similar in patients with and without renal impairment . Interestingly , there was no relationship between improvement in albuminuria and improvement in HbA1c . The other DPP4i CVOTs have not reported effects of these agents on renal function or albuminuria , but studies of sitagliptin and linagliptin suggest that these agents may also reduce albuminuria . Sodium-glucose cotransporter ( SGLT ) 2 inhibitors affect multiple sites , with the potential to affect renal function . The Canagliflozin Cardiovascular Assessment Study ( CANVAS ) showed a 27 % reduction in progression of albuminuria , with a 40 % reduction in eGFR , need for renal-replacement therapy , or death from renal causes associated with the use of canagliflozin . After a fall in mean eGFR with canagliflozin from 76 to 73 mL/min per 1.73 m2 at 3 months , eGFR remained stable through 6 years while gradually declining during the period of observation with placebo . Evidence of dual effects of SGLT2 inhibition on both albuminuria and GFR was even more strongly shown in the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients ( EMPA-REG OUTCOME ) ; in that CVOT , although there was an initial decline in eGFR with empagliflozin , from 94 mL/min per 1.73 m2 through 192 weeks , eGFR was consistently higher with empagliflozin , although this was less clear in trial participants with baseline eGFR < 60 mL/min per 1.73 m2 . Empagliflozin also reduced the development of acute renal failure . Further analysis showed empagliflozin to be associated with a reduction in albuminuria , regardless of the baseline urine albumin level . The CVOTs have offered the possibility that diabetes treatment may move beyond surrogate endpoints to actual cardiovascular outcome benefits . It appears that these drugs will also lead to a reduction in adverse renal outcomes . We should look with optimism at this potential approach to a major complication of diabetes Background : Type 2 diabetes mellitus ( T2DM ) is becoming a leading problem worldwide . Emerging reports reveal alarming evidence of increasing prevalence of T2DM that has reached p and emic levels . Despite the significant incidence , there are limited reliable data re sources and comprehensive systematic review and meta- analysis on the effects of yoga on people who are a prediabetic or high risk for developing T2DM . Objective : The objective of this protocol is to conduct a full-scale systematic review and meta-analyses on the effects of yoga on people who are prediabetes or high risk of developing T2DM . Methods : The articles enrolled in the study will be retrieved from the online data bases between 2002 and the date the search es are executed . The search es will be repeated just before the final analyses and further relevant studies for inclusion . We will conduct a bibliographic search in data bases : Medline / PubMed , Scopus , Cochrane Library , EBSCO , and IndMED using keywords including prediabetes state , high risk for diabetes , metabolic syndrome , and yoga . A defined search strategy will be implemented along with selection criteria to obtain full-text articles of relevant studies . This study protocol was prepared according to the Preferred Reporting Items for Systematic Review s and Meta- Analysis for Protocol s 2015 guidelines . There will be no language restrictions . Ethics and dissemination : The proposed study will be based on published studies and publicly available anonymized data without directly involving human participants and therefore requires neither formal human ethical review nor approval by a human research ethics committee . We published an outline of the protocol in the International Prospect i ve Register of Systematic Review s ( PROSPERO ) in 2018 . We plan to disseminate the findings of this systematic review and meta- analysis through publication in a peer- review ed journal and presentation at relevant conference proceedings . In addition , we believe the results of the systematic review will have implication s for policy and practice . We will prepare policymaker summary using a vali date d format , disseminate through social media and email discussion groups . Review registration number : PROSPERO registration number CRD
During subgroup analysis , a more beneficial effect of magnesium supplementation was observed in diabetic subjects with hypomagnesaemia .
CONCLUSIONS Magnesium supplementation can produce a favourable effect on FPG , HDL , LDL , TG and SBP .
BACKGROUND Cardiovascular disorders remain the leading cause of death in type 2 diabetic patients .
In the present study , a systematic review and a meta- analysis of r and omised controlled trials ( RCTs ) were conducted aim ing to evaluate the effect of magnesium supplementation on  type 2 diabetes ( T2D ) associated cardiovascular risk factors in both diabetic and nondiabetic individuals .