Risk Of New-onset Diabetes Mellitus Research Articles

Diabetes Mellitus and Cardiovascular Events in Older Patients With Myocardial Infarction Prescribed Intensive-Dose and Moderate-Dose Statins

Practice guidelines recommend intensive-dose statins for patients with acute coronary syndrome, but recent data about the risk of new-onset diabetes mellitus have raised concerns about its use. Our main objective was to evaluate the association between intensive statin therapy and new-onset diabetes mellitus in patients with myocardial infarction and to evaluate the association of intensive statin therapy with long-term adverse clinical outcomes. A propensity score-matched cohort was created consisting of 17 080 patients with myocardial infarction aged >65 years old, hospitalized in Ontario, Canada, from 2004 to 2010. Clinical outcomes were compared in patients prescribed intensive-dose versus moderate-dose statins at hospital discharge. At 5 years, 13.6% of patients receiving intensive-dose statins and 13.0% of patients receiving moderate-dose statins had new-onset diabetes, which was not significantly different (P=0.19). By contrast, the 5-year rate of death or acute coronary syndrome was significantly lower at 44.8% in the intensive-dose statin group compared with 46.5% in the moderate-dose group (P=0.044). The reduction in combined clinical outcome was driven mainly by a significantly lower rate of acute coronary syndrome (P=0.039) associated with intensive-dose statins. No significant difference in mortality rates (34.8% in both groups) was observed between the treatment groups during the study period (P=0.89). In older patients with myocardial infarction, we found intensive-dose statin therapy to be effective in reducing repeat hospitalization for acute coronary syndrome. The rate of new-onset diabetes mellitus at long term was not significantly different between intensive-dose and moderate-dose statins.

Meta-Analysis of Impact of Different Types and Doses of Statins on New-Onset Diabetes Mellitus

Recent reports indicate that statins are associated with an increased risk for new-onset diabetes mellitus (DM) compared with placebo and that this relation is dose dependent. The aim of this study was to perform a comprehensive network meta-analysis of randomized controlled trials (RCTs) investigating the impact of different types and doses of statins on new-onset DM. RCTs comparing different types and doses of statins with placebo were searched for using the MEDLINE, Embase, and Cochrane databases. A search of RCTs pertinent to this meta-analysis covering the period from November 1994 to October 2012 was conducted by 2 independent investigators using the MEDLINE, Cochrane, Google Scholar, and Embase databases as well as abstracts and presentations from major cardiovascular meetings. Seventeen RCTs reporting the incidence of new-onset DM during statin treatment and including a total of 113,394 patients were identified. The RCTs compared either a statin versus placebo or high-dose versus moderate-dose statin therapy. Among different statins, pravastatin 40 mg/day was associated with the lowest risk for new-onset DM compared with placebo (odds ratio 1.07, 95% credible interval 0.86 to 1.30). Conversely, rosuvastatin 20 mg/day was numerically associated with 25% increased risk for DM compared with placebo (odds ratio 1.25, 95% credible interval 0.82 to 1.90). The impact on DM appeared to be intermediate with atorvastatin 80 mg/day compared with placebo (odds ratio 1.15, 95% credible interval 0.90 to 1.50). These findings were replicated at moderate doses. In conclusion, different types and doses of statins show different potential to increase the incidence of DM.

A pilot study of reduced dose cyclosporine and corticosteroids to reduce new onset diabetes mellitus and acute rejection in kidney transplant recipients

BackgroundNew onset diabetes mellitus (NODM) and acute rejection (AR) are important causes of morbidity and risk factors for allograft failure after kidney transplantation.MethodsIn this multi-center, open label, single-arm pilot study, 49 adult (≥18 years of age), low immunologic risk, non-diabetic recipients of a first deceased or living donor kidney transplant received early steroid reduction to 5 mg/day combined with Thymoglobulin® (Genzyme Transplant, Cambridge, MA, USA) induction, low dose cyclosporine (2-hour post-dose (C2) target of 600 to 800 ng/ml) and mycophenolic acid (MPA) therapy.ResultsSix months after transplantation, two patients (4%) developed NODM and one patient (2%) developed AR. Four patients had impaired fasting glucose tolerance based on 75-g oral glucose tolerance testing (OGTT). There was one patient death. There were no episodes of cytomegalovirus (CMV) infection or BK virus nephritis. In contrast, in a historical cohort of n = 27 patients treated with Thymoglobulin induction, and conventional doses of cyclosporine and corticosteroids, the incidence of NODM and AR was 18% and 15%.ConclusionsThe pilot study results suggest that Thymoglobulin induction combined with early steroid reduction, reduced cyclosporine exposure and MPA, may reduce the incidence of both NODM and AR in low immunological risk patients. A future controlled study enriched for patients at high risk for NODM is under consideration.Trial registrationClinicalTrials.gov: http://NCT00706680

IGF2 ApaI A/G Polymorphism Evaluated in ESRD Individuals as a Biomarker to Identify Patients with New Onset Diabetes Mellitus after Renal Transplant in Asian Indians

Insulin like growth factors2 (IGF2) regulates pancreatic β-cell renewal and apoptosis, which in turn plays a role in altering insulin activity and glucose homeostasis. Polymorphisms in IGF2 gene have been associated with altered levels of IGF2. Hence, ApaI polymorphism in exon 9 of IGF2 (rs#680) gene was assessed in patients with end stage renal disease (ESRD) to identify individuals at risk of developing new onset diabetes mellitus (NODM) in Asian Indians. Isolated DNA was used for PCR&RFLP based genotyping of IGF2 ApaI polymorphism which was carried out in 364 individuals these included 140 patients who had undergone renal transplant, 42 of which developed new onset diabetes mellitus after renal transplant and 224 healthy control volunteers. In the present study NODM or post transplant diabetes mellitus (PTDM) showed a significant association with G allele and AG genotype when compared with the Non-NODM ESRD patients after transplant (OR 2.081, 95% CI = 1.191 - 3.634, p = 0.01 and OR 3.188, 95% CI = 1.498 - 6.785, p = 0.002) ESRD patients with healthy controls also showed an association with G allele and AG genotype (OR 1.512, 95% CI = 1.060 - 2.155, p = 0.02 and OR 2.235, 95% CI = 1.453 - 3.438, p = 0.0002). IGF2 could be used as a biomarker to identify individuals at high risk of developing NODM, it would be a valuable asset in selecting appropriate immunosuppressive regimens for individuals undergoing transplant. Present study shows the importance of IGF2 ApaI polymorphism in assessing the risk of NODM in ESRD individuals in Asian Indians with ESRD.

Statins and Risk of New-Onset Diabetes Mellitus

For any prescription drug, the potential benefits to health must be balanced against potential risks. Understanding these potential risks can help physicians and patients make informed decisions on whether to use a medication. Recently, statins, a class of medications prescribed to treat high cholesterol levels, have been found to modestly increase the risk of developing diabetes mellitus. It is clear that statins can prevent future major cardiovascular events, such as heart attack, stroke, and deaths from cardiovascular causes, in patients who have had a previous heart attack or those with multiple cardiovascular risk factors. However, the associations between diabetes mellitus and statin use have raised concerns over the widespread use of statin medications in patients at lower risk for cardiovascular disease. In this Patient Page, we describe the indications for statin therapy, the most common adverse effects, and recent concerns about new-onset diabetes mellitus to help patients and providers make more informed decisions about the use of this important class of medications in at-risk individuals. Cardiovascular disease is a major cause of illness and death worldwide. Elevated blood cholesterol levels (specifically the low-density lipoprotein [LDL] cholesterol) are associated with a higher risk of heart attack, stroke, and heart failure. It has become clear that elevated LDL cholesterol levels predict future events, and modern risk scores such as the Framingham Risk Score use LDL cholesterol level as an important predictor of future cardiac events.1 In addition, as new large trials shed light on the important role of LDL in cardiac disease, the optimal LDL cholesterol level has been progressively lowered in national guidelines. Statins are a class of medications called 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. These drugs block a critical …

Association between donor and recipient TCF7L2 gene polymorphisms and the risk of new-onset diabetes mellitus after liver transplantation in a Han Chinese population

New-onset diabetes mellitus (NODM) is a frequent and serious complication arising after liver transplantation (LT). Transcription factor 7-like 2 (TCF7L2) polymorphisms have been reported to strongly associate with type 2 diabetes. In addition, the donor liver plays a vital role in regulating blood glucose levels. In this study, we aim at evaluating the association between donor and recipient TCF7L2 gene polymorphisms with NODM after LT. A total of 125 patients undergoing primary LT, without a history of diabetes were included. Four single nucleotide polymorphisms (rs290487, rs7903146, rs11196205, and rs12255372), closely associated with type 2 diabetes in the Eastern Asia population, were genotyped and analyzed. Both donor and recipient rs290487 polymorphisms (CC vs. TT genotype) were found to be significantly associated with NODM. In multivariate analysis, donor rs290487 genetic variation (OR = 2.172 per each C allele, p = 0.015), blood tacrolimus levels at 1 month post-LT >10 ng/ml (OR = 3.264, p = 0.017), and recipient age >55 years (OR = 2.638, p = 0.043) were identified as independent risk factors of NODM. Furthermore, donor rs290487 CC genotype could predict a high probability (>40%) of the onset of NODM. Predictive model containing donor rs290487 polymorphism showed a significantly higher prognostic ability on NODM than the model with only clinical parameters (p = 0.031). Donor TCF7L2 rs290487 polymorphism is associated with an increased risk of NODM after LT and has a potential clinical value for the prediction of NODM.

Statins and risk of diabetes mellitus

New analyses have assessed the link between statin use and the risk of new-onset diabetes mellitus in the 'real world' and in the setting of a randomized, controlled trial, respectively. Investigators from both studies concluded that the cardiovascular and mortality benefits of statins outweigh the increased risk of diabetes in some groups of patients.

Statins and the Risk of Diabetes: The Debate

We read with interest the report by Culver et al1 that statin use increases the risk of new-onset diabetes mellitus (NOD) in postmenopausal women participating in the Women's Health Initiative. This association remained significant after multivariate adjustments and for all statins evaluated.1

Early Steroid Withdrawal Regimen Prevents New‐Onset Diabetes Mellitus in Old‐Age Recipients After Living Donor Liver Transplantation

Steroid use after liver transplantation is known to increase the risk of new-onset diabetes mellitus (NODM). In this study, we tried to identify a patient subgroup who would benefit with regard to NODM by an early steroid withdrawal regimen (ESWR) after living donor liver transplantation (LDLT) METHODS: Among 100 adult LDLT patients, 65 were on a conventional immunosuppressive regimen (CIR), and 35 were on an ESWR. With the ESWR, the steroid was tapered off mostly within 7 days with induction of basiliximab in combination with tacrolimus and mycophenolate mofetil (MMF). The CIR was a combination of tacrolimus and steroid. MMF was added in selected patients. Steroid was tapered off 2-6 months after LT. The presence of NODM was investigated cross-sectionally 6 months after LT. There was no significant difference in terms of acute cellular rejection, sepsis, or death during follow-up. NODM had developed in 13 patients (13 %). Old recipient age (≥ 55) and pretransplant history of hypertension were significant risk factors for NODM. The type of immunosuppression was the single risk factor for NODM in subgroup of old-age recipients (≥ 55 years) on the CIR (hazard ratio 13.34, p = 0.04). ESWR can safely reduce the incidence of NODM after LDLT in old-age recipients. Therefore, ESWR should be considered first in old-age recipients undergoing LDLT.

Statins and new-onset diabetes mellitus—a matter for debate

Statins are effective for cardiovascular disease prevention but have recently been associated with an increased risk of new-onset diabetes mellitus. However, until this association is confirmed, treatment discontinuation is not advisable. Lifestyle measures and treatment of risk factors that often cluster with dyslipidemia could ameliorate this potential adverse effect of statins.

The Long-Term Effect of Statins on the Risk of New-Onset Diabetes Mellitus in Elderly Taiwanese Patients with Hypertension and Dyslipidaemia

HMG-CoA reductase inhibitors (statins) have been linked to new-onset diabetes (NOD). Individual statins may differ in the extent to which they increase the risk for NOD; however, the effect of statins on the development of NOD in elderly hypertensive and dyslipidaemic patients has not been well studied. The aim of this study was to investigate the relative risk for NOD among elderly (age ≥65 years) hypertensive and dyslipidaemic Taiwanese patients who received different statins. This was a retrospective cohort study performed using data from claim forms provided to the central regional branch of the Bureau of National Health Insurance in Taiwan from July 2004 to December 2009. Prescriptions for statins before the index date were retrieved from a prescription database. We estimated the hazard ratios (HRs) of NOD associated with statin use. Non-diabetic subjects served as the reference group. A total of 2735 NOD cases were identified among 15,637 elderly hypertensive and dyslipidaemic patients during the study period. The risk of NOD after adjusting for sex, age, concomitant medication and mean dose of prescription was lower among users of atorvastatin (HR 0.77; 95% CI 0.71, 0.83) and rosuvastatin (HR 0.65; 95% CI 0.51, 0.82) than among non-users. Patients who took lovastatin (HR 1.38; 95% CI 1.26, 1.50) or simvastatin (HR 1.30; 95% CI 1.14, 1.48) were at higher risk of developing NOD than non-users. Pravastatin and fluvastatin were not associated with increased risk of NOD. The results of this study suggest that elderly hypertensive and dyslipidaemic patients who take atorvastatin or rosuvastatin are at lower risk of NOD. Lovastatin and simvastatin were associated with a significant increase in the risk of NOD.

A Neutral Risk on the Development of New-Onset Diabetes Mellitus (NODM) in Taiwanese Patients with Dyslipidaemia Treated with Fibrates

There are no data on the incidence of new-onset diabetes mellitus (NODM ) in nondiabetic dyslipidaemia patients treated with fibrates. The aim of our study was to clarify these issues, to investigate the relationship between NODM and fibrate and whether the fibrates lead to increased risk for developing NODM. A retrospective cohort study was conducted by analyzing the Longitudinal Health Insurance Database (LHID 2005) of the National Health Insurance Research Database (NHIRD) from 2005 to 2010 to investigate all fibrate prescriptions for patients with dyslipidaemia. We estimated the hazard ratios (HRs) of NODM associated with fibrate use. We identified 145 NODM patients among 3,815 dyslipidaemic patients in the database for the study period. The risk estimates for NODM for users of fenofibrate (HR 1.30; 95% CI 0.82, 2.05) and gemfibrozil (HR 0.771; 95% CI 0.49, 1.22) were not associated with an increased risk of developing NODM (P > 0.05). Our results revealed that patients with dyslipidaemia who took fenofibrate and gemfibrozil had a neutral risk of NODM. The reasons may be associated with the fibrates have the properties that activate PPARα and in some cases also activated PPARγ, leading to showing a neutral risk of NODM.

Implications of high-dose statin link with incident diabetes

According to a meta-analysis of five clinical trials, high-dose statin therapy is associated with increased risk of new-onset diabetes mellitus. When treating patients with excessive levels of non-HDL cholesterols despite moderate-dose statin therapy, should we prescribe a strategy known to be efficacious, but associated with safety concerns, or should we prescribe combination therapy that has no proven effects on outcomes?

Opposing Effects of β Blockers and Angiotensin-Converting Enzyme Inhibitors on Development of New-Onset Diabetes Mellitus in Patients With Stable Coronary Artery Disease

We used data from patients with stable coronary artery disease (CAD) to assess the risk of new-onset diabetes mellitus (NOD) with β blockers and to determine whether angiotensin-converting enzyme (ACE) inhibition would modify this risk. The Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) trial randomized 8,290 patients with stable CAD to trandolapril or placebo. Presence of NOD was assessed at each study visit over a median follow-up time of 4.8 years. We examined the risk of NOD associated with β-blocker use with Cox regression models adjusting for 25 baseline covariates and tested whether this risk was modified by randomization to the ACE inhibitor. Of 6,910 patients without diabetes mellitus at enrollment (1,179 women and 5,731 men, mean age 64 ± 8 years), 4,147 (60%) were taking β blockers and 733 (8.8%) developed NOD. We observed a significant interaction between β-blocker use and randomization to ACE inhibitor with respect to NOD (p = 0.028). Participants taking β blockers assigned to the placebo group (n = 2,090) were at increased risk for NOD adjusting for baseline covariates (hazard ratio 1.63, 95% confidence interval 1.29 to 2.05, p <0.001), and this risk was attenuated in those assigned to trandolapril (n = 2,057, hazard ratio 1.11, 95% confidence interval 0.87 to 1.42, p = 0.39). β blocker use was associated with increased risk for NOD in patients with stable CAD, and this risk was decreased in patients treated concurrently with an ACE inhibitor. In conclusion, these data suggest that ACE inhibition may attenuate the risk for glucose abnormalities observed in patients taking β blockers.

Risk of new-onset diabetes mellitus associated with beta-blocker treatment for hypertension

Background:This study investigated the risk of new-onset diabetes (NOD) among hypertensive patients initiating carvedilol therapy vs other beta-blocker (BB) therapy in a clinical practice setting.Methods:Patients aged ≥18 years with ≥1 pharmacy claim for a BB of interest (carvedilol immediate-release [IR]/controlled-release [CR], atenolol, metoprolol succinate, or metoprolol tartrate) were identified in the IMS LifeLink Health Plan Claims Database. Index date was the first chronologically occurring prescription for any BB during the enrollment period (July 1, 2000–December 31, 2007). Patients had to be continuously eligible to receive healthcare services 6 months prior to and a minimum of 3 months after index date and have ≥1 diagnostic code for hypertension (ICD-9-CM: 401.xx–405.xx) during this time frame. Patients were excluded for having a diagnosis of diabetes mellitus (ICD-9-CM: 250.xx) and/or prescription for antidiabetic therapy in the 6 months prior to and/or 3 months after index date. Eligible patients were propensity-score matched in a 1:3 ratio (carvedilol : other BBs). Mean duration of follow-up was 12.8 and 14.8 months for the carvedilol group and other BB group, respectively. Primary outcome of interest was presence and timing of NOD.Results:Among 3084 patients in the carvedilol group and 9252 in the other BB group, mean age was 56 years, with 54% male. NOD rate was 3.16 per 100 person-years for carvedilol patients vs 3.36 for patients in the other BB group (NS). Risk of NOD was similar between groups (HR 0.971, 95% CI: 0.78, 1.21; P = 0.792).Conclusions:Findings suggest the risk of NOD among hypertensive patients is similar between carvedilol and other BB agents (i.e., atenolol, metoprolol succinate, or metoprolol tartrate).Limitations:The use of administrative claims data and relatively short follow-up period may limit the generalizability of results.

Short-term metabolic changes achieved by weight loss in hypertensive patients

Introduction Glucose and lipid metabolism abnormalities of hypertensive patients are highly relevant due to its increase in cardiovascular risk; moreover, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) have a high risk of new-onset diabetes mellitus (DM) development. The objective of the study was to describe glucose metabolism abnormalities and the impact of mid-term weight loss. Methods A six-month prospective, observational and multicentre study of patients with hypertension was conducted. Clinical antecedents, physical examination, blood test and treatments were collected in two separated visits; conventional advice was the only intervention planned. Results A total of 1957 patients were included, mean age 66.3 (10.9) years and 59.9% males. A previous diagnosis of glucose metabolism alteration was present in 43.9% (25.5% type-2 DM, 14.8% IFG, 1.6% IFG and IGT, 1.0% IGT and 1.0% type-1 DM). An increasing pattern of cardiovascular risk and target organ damage was observed according to the categories of fasting glucose. Oral glucose tolerance test (OGTT) was carried out in 234 patients (11.9%) patients and yielded the diagnosis of IGT in 44.7% or DM in 22.4% of patients with fasting glucose > 100 mg/dl. Six months follow-up was achieved in 85.9% patients. A slight reduction in fasting glucose was observed in the whole cohort and patients who achieved ≥ 5% weight loss experienced the highest reduction in fasting glucose, LDL-c and triglycerides; moreover, 15.8% normalized their IFG. Conclusions Glucose and lipid metabolism abnormalities are highly prevalent in hypertensive patients and improve with 5% of weight lost at 6 months follow-up. OGTT is not currently extended in daily clinical practise .

Telmisartan Effects on Insulin Resistance in Obese or Overweight Adults Without Diabetes or Hypertension

Angiotensin receptor blockers (ARBs) are antihypertensive agents associated with reduced risk of new-onset diabetes mellitus. The ARB telmisartan is a partial agonist of peroxisome proliferator-activated receptor-gamma (PPAR-γ). This study evaluated the effect of telmisartan on insulin resistance, a known target of PPAR-γ agonism. Overweight/obese persons with body mass index ≥28 kg/m2, waist circumference≥35 inches, and components of the metabolic syndrome without hypertension or diabetes who were not preselected for insulin resistance were enrolled. Patients were randomized to telmisartan or matching placebo for 16 weeks. The primary efficacy measure was changed from baseline in the insulin sensitivity index (SI), calculated from oral glucose tolerance testing. SI was also evaluated in a subset of patients using a hyperinsulinemic euglycemic clamp. Secondary end points included measures of insulin sensitivity and glucose and lipid metabolism. A total of 138 patients were randomized and received ≥1 dose of study medication; 128 completed the study. At end point, no significant difference was found between telmisartan and placebo groups regarding change from baseline in SI or in glucose area under the curve. No significant between-group differences were found regarding glucose metabolism or lipoprotein levels. In the population with abdominal obesity and components of the metabolic syndrome, telmisartan did not increase insulin sensitivity.

Lipid-lowering agents and new onset diabetes mellitus

Statin treatment (and possibly niacin when given alone or in combination with statins) appears to be associated with a slightly increased risk of new onset diabetes mellitus (NODM). However, statin induced cardiovascular disease (CVD) risk reduction is greater in patients with DM than in non-diabetic patients in several survival studies. Thus, statin treatment outweighs any potential increase in CVD risk related to NODM and in high-risk Caucasian patients present clinical practice should not change. However, the risk/benefit ratio of treatment might not be as favourable in subjects with propensity to develop DM such as the elderly and in subjects of Asian ethnicity. Colesevelam was shown to improve both glycaemic control and lipid profile in inadequately controlled T2DM and might reduce the risk for NODM. There are no data on the incidence of NODM in fibrate-treated non-diabetic patients. Prospective studies are needed to clarify these issues.

Risk Factors for New-Onset Diabetes Mellitus in Adult Liver Transplant Recipients, an Analysis of the Organ Procurement and Transplant Network/United Network for Organ Sharing Database

OBJECTIVE.: To analyze the risk factors for new-onset diabetes mellitus (NODM) in liver transplant recipients using the Organ Procurement and Transplant Network/United Network for Organ Sharing database. METHODS.: Among 20,172 primary liver recipients (age > or =18 years) transplanted between July 2004 and December 2008 in Organ Procurement and Transplant Network/United Network for Organ Sharing databases, 15,463 recipients without pretransplant diabetes were identified. Risk factors for NODM were examined using multivariate Cox regression analysis. RESULTS.: NODM was reported in 26.4% of recipients (median follow-up, 685 days). Independent predictors of NODM development included recipient age (> or = 50 vs. <50 years, hazard ratio [HR]=1.241), African American race (HR=1.147), body mass index (> or = 25 vs. <25, HR=1.186), hepatitis C (HR=1.155), recipient cirrhosis history (HR=1.107), donor age (> or = 60 vs. <60 year, HR=1.152), diabetic donor (HR=1.151), tacrolimus (tacrolimus vs. cyclosporine, HR=1.236), and steroid at discharge (HR=1.594). Living donor transplant (HR=0.628) and induction therapy (HR=0.816) were associated with a decreased risk of NODM. CONCLUSION.: The incidence of NODM was 26.4% in liver recipients with a median follow-up time of 685 days. Identified risk factors for NODM in liver transplantation were similar to that in kidney transplantation. Some of the identified factors are potentially modifiable, including obesity and the choice of immunosuppressive regimens.

Impact of different definitions of the metabolic syndrome on the prevalence of organ damage, cardiometabolic risk and cardiovascular events

We compared definitions of metabolic syndrome performed by ATPIII [the National Cholesterol Education Program Adult Treatment Panel III; three criteria of the following: systolic blood pressure >or=130 mmHg and/or diastolic blood pressure >or=85 mmHg, fasting serum glucose >or=110 mg/dl, high-density lipoprotein plasma cholesterol <or=40 mg/dl (men) or <or=50 mg/dl (women), plasma triglycerides >or=150 mg/dl, waist circumference >or=102 cm (men) or 88 cm (women)], AHA (the American Heart Association; same cut-off of ATPIII except serum glucose >or= 100 mg/dl) and IDF [the International Diabetes Federation; mandatory criteria of visceral obesity with reduced cut-off of 94 cm (men) or 80 cm (women), and at least two criteria with the same cut-off as in AHA] for their impact on metabolic syndrome prevalence, cardiac organ damage, long-term risk of cardiovascular events and death for any cause and risk of developing diabetes mellitus, in-office and out-of-office hypertension and left ventricular hypertrophy (LVH). In 2051 participants, we measured office, home and ambulatory blood pressure as well as metabolic, anthropometric and echocardiographic variables. Measurements were performed between 1990 and 1992 and repeated 10 years later. Information on long-term incidence of cardiovascular events and all-cause deaths was also collected. Prevalence of metabolic syndrome was significantly greater when using the AHA and IDF as compared to the ATPIII definition. Prevalence of LVH was higher in participants with than without metabolic syndrome and similar for the three definitions. Over 12-year follow-up, there were 179 cardiovascular events and 233 deaths for any cause. The risk of cardiovascular events and death was markedly greater for participants with as compared with those without metabolic syndrome, regardless of the definition of metabolic syndrome. This was the case also for the risk of new-onset diabetes mellitus, office, home and ambulatory hypertension and new-onset LVH. Risks of fatal and nonfatal cardiovascular events, diabetes mellitus, hypertension and LVH were similar for the three definitions of metabolic syndrome. However, the AHA and IDF definitions are more sensitive than that of ATPIII in identifying metabolic syndrome condition.