Metabolic syndrome as a cardiovascular risk factor in patients with type 2 diabetes

INTRODUCTION AND OBJECTIVES: To assess the cardiovascular risk associated with the presence of metabolic syndrome in patients with type 2 diabetes.Patients and method. Prospective cohort study of patients with type 2 diabetes. The baseline presence of components of metabolic syndrome as defined by the World Health Organization was determined. The main dependent variable was a combination of coronary events (onset angina, fatal or nonfatal myocardial infarction) and cerebrovascular events (transient ischemic attack, fatal or nonfatal stroke and lower limb amputation). Secondary end points were coronary events and stroke. We calculated the predictive power of the presence of metabolic syndrome and of different numbers of its component features. RESULTS: 318 patients were included. Mean duration of follow-up was 4.6 years (SD 1.5 years). The prevalence of metabolic syndrome was 77.0%. The rates of cardiovascular events, coronary events and stroke, expressed per 1000 patient-years, were 14.0, 5.6, and 8.4 respectively in patients without metabolic syndrome, and 33.3, 20.7, and 11.7 respectively in patients with metabolic syndrome (P=.058 cardiovascular events; P=.05 coronary events). In the multivariate analysis, the simultaneous presence of all four metabolic syndrome components significantly increased the global cardiovascular disease risk (RR=5.0; 95% CI, 1.6-15.9; P=.006) and the risk of coronary heart disease (RR=7.4; 95% CI, 1.3-41.1; P=.02), but not the risk of stroke. CONCLUSIONS: The simultaneous presence of all four metabolic syndrome components is associated with an increase in the risk of cardiovascular events in patients with type 2 diabetes.     

Residual risk in statin-treated patients: Future therapeutic options

Statin therapy for aggressive low-density lipoprotein cholesterol (LDL-C) reduction reduces cardiovascular morbidity and mortality. However, even on maximal statin therapy, high-risk patients have substantial residual risk of coronary heart disease (CHD). Certain subgroups, such as individuals with diabetes mellitus, low high-density lipoprotein cholesterol (HDL-C), metabolic syndrome, or other comorbidities, have a particularly high residual risk. Patients at high risk for future CHD events often require multiple aggressive risk-reduction therapies (eg, antiplatelet agents, an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, beta-blockade, cholesterol and/or diabetes management, and lifestyle interventions) to further lower their overall cardiovascular risk. For cholesterol management, combination therapy may be required to attain optimal levels of LDL-C, HDL-C, and non-HDL-C.     

Metabolic syndrome, diabetes and cardiovascular events: current controversies and recommendations

Metabolic syndrome is now present in up to 40% of the United States adult population and is associated with a nearly a two fold increase in cardiovascular events, independent of the presence of diabetes mellitus. The concept of the metabolic syndrome as clinical syndrome has recently been challenged, however, and controversy exists as to whether the metabolic syndrome adds to cardiovascular risk above and beyond the sum of its independent metabolic components. Given the epidemic of obesity in both industrialized and third world countries, this issue is of great importance. The current article puts this controversy into perspective and explores the association of metabolic syndrome with both accelerated cardiovascular risk and the risk of development of type 2 diabetes. The pathophysiology of the increased risk of cardiovascular disease in diabetes associated with metabolic syndrome is discussed and the importance of early recognition of metabolic syndrome and potential role of addressing insulin resistance is stressed. Clearly more data is needed, but it is safe to say that metabolic syndrome is a worldwide epidemic in association with central obesity and underlying insulin resistance, which will propel a marked increase in cardiovascular events and diabetes mellitus in the years to come. Further research is needed to understand the role of more aggressive therapy in preventing type 2 diabetes and cardiovascular events in the population.     

Diagnosis and management of the metabolic syndrome in obesity

The metabolic syndrome is a constellation of interrelated abnormalities that increase the risk for cardiovascular disease and progression to type 2 diabetes. The prevalence of this syndrome is increasing because of the 'obesity epidemic'. The National Cholesterol Education Program Adult Treatment Panel III defined practical criteria for the diagnosis of the metabolic syndrome and established the basic principles for its management. Also, the International Diabetes Federation recently proposed another definition. The metabolic syndrome is a secondary target for cardiovascular risk reduction. Clinicians should identify individuals with this condition, assess their cardiovascular risk and treat them by an aggressive and multifaceted approach. The most effective therapeutic intervention in patients with the metabolic syndrome should focus on modest weight reduction and regular physical activity. Adoption of a healthier diet and smoking cessation are necessary. Drug therapy may be needed to achieve recommended goals if therapeutic lifestyle changes are not sufficient. Low-density lipoprotein cholesterol is the primary target of therapy (new aggressive goals should be achieved). Statins are probably the drugs of choice. Fibrates and nicotinic acid are also useful options. Hypertension should be managed aggressively probably starting with an inhibitor of the renin-angiotensin system or a calcium channel blocker and adding a low dose of a thiazide diuretic if necessary. Aspirin should be administered if the cardiovascular risk is high. In the future acarbose, metformin, meglitinides and thiazolidinediones may be used in patients with the metabolic syndrome to delay the onset of type 2 diabetes and reduce cardiovascular risk. Such an intense and multifactorial approach is likely to reverse the bad prognosis associated with the metabolic syndrome.     

Impaired Glucose Tolerance

Impaired glucose tolerance (IGT) is determined by measuring plasma glucose levels 2 hours after glucose loading in the oral glucose tolerance test. There is good evidence from epidemiologic and prospective trials [e.g. Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Europe (DECODE)] linking IGT with the development of type 2 diabetes mellitus and cardiovascular disease (CVD). IGT is characterized by an increase in postprandial glucose levels, which is considered the earliest metabolic abnormality in type 2 diabetes mellitus. It is one of a series of risk factors for CVD (hypertension, high triglyceride levels, low high-density lipoprotein-cholesterol and central obesity), known as the metabolic syndrome. The different factors making up this syndrome are intimately related. An impaired lipid profile can contribute to insulin resistance, as IGT may play a pathogenic role on other cardiovascular risk factors. IGT is the first easily identifiable step in the pathophysiology of type 2 diabetes mellitus. It is associated with high risk for type 2 diabetes mellitus and subsequent vascular morbidity and mortality. It is currently unknown whether treating IGT will reduce the incidence of macrovascular complications, as studies addressing this issue have yet to be conducted. Therefore, the main reason to identify and treat IGT is to prevent or delay the onset of type 2 diabetes mellitus. It has been demonstrated that lifestyle intervention with diet and exercise can reduce the incidence of type 2 diabetes mellitus. Pharmacologic intervention with metformin and acarbose is also effective. Other drugs, such as those indicated to treat other parameters of the metabolic syndrome, may also be useful. We can now be assured that prevention or delay of onset of type 2 diabetes mellitus is possible in individuals with IGT, either by changes in lifestyle or by pharmacotherapy.     

Value of Angiotensin receptor blocker therapy in diabetes

There are more clinical trials investigating angiotensin receptor blockers (ARBs) in diabetes than any other drug class, ranging from early "prevention" trials to the treatment of individuals with advanced organ damage. In its earliest manifestations, visceral adiposity predisposes to hypertension and hyperglycemia (metabolic syndrome). In these individuals, ARB therapy delays the progression to chronic hypertension and may also delay the progression to overt diabetes. Based on the increased cardiovascular disease risk of the metabolic syndrome, which is similar to stage 1 hypertension, both lifestyle modification and ARB therapy are justifiable. ARB therapy has also been found to delay the onset of microalbuminuria and retinopathy. In established diabetic nephropathy, ARB therapy is recommended as a standard alternative to angiotensin-converting enzyme inhibition to reduce macroalbuminuria and delay the progression to end-stage disease. Finally, large trials in ischemic heart disease, heart failure, and stroke have demonstrated clear benefits of ARB therapy. Because ARBs have side effect rates equal to placebo and far lower than any other antihypertensive drug class, the benefit/risk ratio is highly favorable across the entire spectrum of diabetic disease. Thus, ARB therapy is a highly attractive alternative for individuals at any stage of diabetes and with any pattern of complications.     

Obesity and cardiovascular disease. Pathogenetic role of the metabolic syndrome and therapeutic implications

Since obesity is a major risk factor for cardiovascular disease (CVD), the increasing prevalence and degree of obesity in all developed countries has the potential to significantly offset the current efforts to decrease CVD burden in our population. Obesity is pathogenetically related to several clinical and sub-clinical abnormalities that contribute to the development of atherosclerotic placks and their complication, leading to the onset of cardiovascular events. Obesity seems to interact with inheritable factors in determining the onset of insulin resistance, a metabolic abnormality that is responsible for altered glucose metabolism and predisposition to type 2 diabetes, but that also has a major role in the development of dyslipidemia, hypertension and many other sub-clinical abnormalities that contribute to the atherosclerotic process and onset of cardiovascular events. Inheritable factors seem to modulate the onset of type 2 diabetes, dyslipidemia, hypertension and various insulin resistance-related sub-clinical abnormalities, often in a clustering pattern that is commonly referred to as the "metabolic syndrome." Inheritable factors also are involved in the onset of CVD in a given population or individuals with various components of the metabolic syndrome. Intense research is currently undergoing to better understand the molecular mechanisms that could explain the relationship between environmental and inheritable factors that lead from obesity to atherosclerosis and cardiovascular event. The elucidation of these mechanisms will provide improved therapeutic strategies to reduce cardiovascular risk in the obese patients. However, effective therapeutic tools that control each of the known pathophysiological steps mediating CVD in obese patients are already available and should be used more aggressively. Patient education and coordinated approach of physicians, nurses and other health care providers in a multidisciplinary treatment of the obese patient is of fundamental importance to reduce CVD burden in our population.     

Cardiovascular events in type 2 diabetes: comparison with nondiabetic individuals without and with prior cardiovascular disease. 10-year follow-up of the Hoorn Study.

AIMS: We questioned whether prior cardiovascular disease has the same impact on risk of cardiovascular events as type 2 diabetes, and whether this differed between men and women. METHODS AND RESULTS: To address these issues we compared the 10-year risk of cardiovascular events among 208 Caucasian individuals with diabetes to that of 2253 Caucasian individuals without diabetes, in a population-based cohort study. Gender significantly modified the association between type 2 diabetes and cardiovascular events (p=0.01). The hazard ratio of cardiovascular events associated with the presence of diabetes was higher in women (adjusted hazard ratio, 1.8; 95% CI, 1.2 to 2.7) than in men (adjusted hazard ratio, 1.3; 0.9 to 2). As compared to men without diabetes but with prior cardiovascular disease, risk of cardiovascular events was significantly lower in men with diabetes but without prior cardiovascular disease (adjusted hazard ratio, 0.5; 0.3 to 0.9). In contrast, this risk was equal in women with diabetes but without prior cardiovascular disease and women without diabetes but with prior cardiovascular disease (adjusted hazard ratio, 1.0; 0.6 to 1.7; P for interaction between gender and diabetes=0.05). CONCLUSIONS: Women with diabetes but without prior cardiovascular disease have a risk of cardiovascular events that is similar to that of women without diabetes but with prior cardiovascular disease, whereas in men the presence of prior cardiovascular disease conferred a higher risk. These data emphasise the necessity of aggressive treatment of cardiovascular risk factors in women with type 2 diabetes.     

Prevention of Type 2 Diabetes Mellitus to Reduce Cardiovascular Morbidity and Mortality: A Review of the Evidence

Cardiovascular disease accounts for the majority of deaths in patients with type 2 diabetes mellitus. Lifestyle interventions aimed at weight loss and increased physical activity and therapy with antidiabetic drugs have proven effective in reducing the risk of new-onset diabetes in high-risk individuals. Substantial evidence also suggests that drugs that inhibit the renin-angiotensin system, namely angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, also prolong the time to onset of clinical diabetes. An open question is whether delay of new-onset diabetes with antidiabetic or antihypertensive agents reduces cardiovascular morbidity and mortality. A large ongoing study is investigating whether therapy with an oral antidiabetic drug or an angiotensin II receptor blocker reduces the incidence of new-onset diabetes and cardiovascular events in high-risk patients.     

Abdominal obesity and dyslipidemia in the metabolic syndrome: importance of type 2 diabetes and familial combined hyperlipidemia in coronary artery disease risk

Regional body fat distribution has an important influence on metabolic and cardiovascular risk factors. Increased abdominal (visceral) fat accumulation is a risk factor for coronary artery disease (CAD), dyslipidemia, hypertension, stroke, and type 2 diabetes. The recent emphasis on treatment of the dyslipidemia of the metabolic syndrome (hypertriglyceridemia, reduced high-density lipoprotein, and increased small, dense low-density lipoprotein particle number) has compelled practitioners to consider lipid-lowering therapy in a greater number of their patients, as one in two individuals over age 50 has the metabolic syndrome. Individuals with the metabolic syndrome typically have normal low-density lipoprotein cholesterol levels, and current lipid-lowering guidelines may underestimate their cardiovascular risk. Two subgroups of patients with the metabolic syndrome are at particularly high risk for premature CAD. One, individuals with type 2 diabetes, accounts for 20-30% of early cardiovascular disease. The second, familial combined hyperlipidemia, accounts for an additional 10-20% of premature CAD. Familial combined hyperlipidemia is characterized by the metabolic syndrome in addition to a disproportionate elevation of apolipoprotein B levels. The measurement of fasting glucose and apolipoprotein B, in addition to the fasting lipid profile, can help to estimate CAD risk in patients with the metabolic syndrome.     

The association of hypertension and diabetes: prevalence, cardiovascular risk and protection by blood pressure reduction

Diabetes and hypertension frequently coexist, and their combination provides additive increases in the risk of life-threatening cardiovascular events. Recent guidelines agree on the need for early, aggressive reduction of blood pressure, with a goal of <130/80 mmHg, in patients with diabetes. The mechanism that underpins the increased sensitivity of diabetic subjects to hypertension is not known, but may involve impaired autoregulation or attenuated nocturnal decrease of blood pressure. All classes of antihypertensive agents are effective in reducing blood pressure in diabetic subjects, and all show evidence of a concomitant reduction in cardiovascular risk. Although there is some evidence that agents that interrupt the renin-angiotensin system (RAS) provide greater protective effects, the data are not conclusive. However, most diabetic subjects will require combination therapy to reach goal blood pressure. Antihypertensive drugs can also significantly influence the probability that otherwise healthy individuals will develop metabolic syndrome or type 2 diabetes. While diuretics and betablockers have a prodiabetic effect, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers may prevent diabetes more effectively than the metabolically neutral calcium channel blockers. Given that diabetes is an important cardiovascular risk factor, there is the potential for reductions in risk due to reduced blood pressure to be offset by an increased risk due to the development of diabetes. Such concerns should be considered in the selection of antihypertensive therapy.     

Management of Dyslipidemias in the Presence of the Metabolic Syndrome or Type 2 Diabetes

In the metabolic syndrome and type 2 diabetes, excess energy intake on the background of genetic predisposition and lifestyle factors leads to the dysregulation of fatty acid metabolism and acquired insulin resistance. These initial metabolic defects are reflected to both lipoprotein and glucose metabolism and contribute to increased risk for cardiovascular disease. However, even after controlling for the traditional cardiovascular risk factors, subjects with the metabolic syndrome and type 2 diabetes remain at high residual cardiovascular risk despite of low/normal LDL-cholesterol concentration. For 2 decades, statin therapy has been the cornerstone of treatment of dyslipidemia in these disorders. In the metabolic syndrome and type 2 diabetes, only statin treatment has demonstrated consistently a significant reduction in cardiovascular and all cause mortality in clinical trials. Lately, increased incidence of diabetes especially in the high-risk populations using statins has raised the debate whether statins are indicated for primary prevention especially in the metabolic syndrome. Guidelines recommend intensified lifestyle intervention to those in high risk groups on statin therapy to reduce the residual risk. Despite of the proven efficacy on plasma lipids, fibrate, or niacin as monotherapy, or in combination with statins has failed in reducing cardiovascular mortality. This underlies the fact that improvement in dyslipidemia or other biomarkers is not equal to the reduction in cardiovascular events. However, fibrates in combination with statins seem to be beneficial to reduce CVD events in subjects with low HDL-cholesterol (< 0.9?C1.1?mmol/L) and elevated triglycerides (> 2.3?mmol/L), but the data are derived from subgroup analysis of clinical trials. The position of niacin and ezetimibe and omega-3 fatty acids in treatment of dyslipidemia in the metabolic syndrome and type 2 diabetes is even less clear and remains to be established in future clinical trials.     

Clustering of silent cardiovascular risk factors in apparently healthy Hispanics

Ischaemic heart disease is one of the leading causes of cardiovascular morbidity and mortality. Because most factors leading to cardiovascular disease have a silent course, early screening is needed for prevention and for halting disease progression. In our centre, a programme was implemented in apparently healthy subjects for the early diagnosis and treatment of factors known to increment the risk of developing cardiovascular and metabolic disease. We present data from the first 153 individuals evaluated. The incidence of modifiable risk factors in our healthy population was as follows: overweight 33% (BMI: 25-30 kg/m(2)), obesity 45% (BMI >30 kg/m(2)), sedentarism 84%, arterial hypertension 15% (>140/90 mm Hg), hyperinsulinaemia 50%, glucose intolerance 14% (>160 mg/dl 120 min after 75 g glucose load), type 2 diabetes mellitus 5%, hypercholesterolaemia 50%, hypertriglyceridaemia 28%, and salt sensitivity 25%. Clustering of three or more cardiovascular risk factors was observed in 59% of the apparently healthy subjects. Obesity was associated with greater clustering of risk factors. The cardiovascular dysmetabolic syndrome was present in 72% of the obese individuals. These findings revealed a very high prevalence of cardiovascular risk factors in apparently healthy Hispanics. Even though these individuals were clinically asymptomatic, they are at increased risk for developing cardiovascular disease and type 2 diabetes mellitus. Mechanisms for the early detection and correction of modifiable risk factors in the healthy population must be implemented. Only through prevention will a reduction in the incidence of cardiovascular atherosclerotic disease and of type 2 diabetes mellitus be achieved.     

Effect of metabolic syndrome or type II diabetes mellitus on the occurrence of recurrent vascular events in hypertensive patients

Patients with hypertension and manifest vascular disease are at high risk for recurrent cardiovascular diseases. It is unknown if the metabolic syndrome further increases the risk in these patients. This study aims to quantify the effect of metabolic syndrome and type II diabetes on cardiovascular events in hypertensive patients with vascular disease. A total of 2,196 hypertensive patients with vascular disease (cerebrovascular disease (34%), coronary heart disease (50%), peripheral arterial disease (28%), abdominal aortic aneurysm (13%)) from the Second Manifestations of Arterial Disease study were followed for up to 10 years (mean 3.9 years) for death, stroke and myocardial infarction. Age and sex adjusted hazard ratios (HR) were calculated for hypertensive patients with metabolic syndrome but without diabetes (n=775) and for hypertensive patients with type II diabetes (n=381), compared to merely hypertensive patients (n=1,040). Forty-nine percent had metabolic syndrome (NCEP ATPIII definition) and 17% had type II diabetes. Metabolic syndrome predicted vascular death (HR 1.41, 95% confidence interval (CI) 1.01-1.98), stroke (HR 1.36, 95% CI 0.85-2.16) and myocardial infarction (HR 1.40, 95% CI 0.97-2.01). Type II diabetes accounted for even higher risks of vascular end points (HR 1.41-1.64). The effect of metabolic syndrome on future events could not be explained by the presence of type II diabetes. Even in high-risk patients with hypertension and vascular disease, presence of metabolic syndrome or type II diabetes identifies patients at high risk for future cardiovascular events. Identifying metabolic syndrome patients may direct therapy focusing on treatment of insulin resistance by reducing weight and increasing physical activity.     

Insulin resistance is a cardiovascular risk factor in humans

Diabetes is a common metabolic disorder associated to elevated cardiovascular morbidity and mortality that is not explained by hyperglycemia or traditional cardiovascular risk factors such as smoking or hypercholesterolemia. Intensive glycemic control with insulin that achieves near-normal glycemia does not reduce significantly macrovascular complications compared with conventional glycemic control. Cardiovascular disease continues to develop in patients with diabetes despite adequate glycemic control. In contrast, intensive control with metformin (leading to insulin resistance improvement) reduces diabetes complications, including cardiovascular events, suggesting that enhancement of insulin sensitivity rather than plasma glucose level has a major role improving diabetes outcomes. Accordingly, insulin resistance estimated by glucose tolerance tests is better predictor of future cardiovascular events than fasting glucose level in nondiabetic individuals. Insulin resistance precedes for decades the clinical onset of type 2 diabetes and deteriorates metabolic control of type 1 diabetes. Numerous investigations including cross-sectional and prospective studies, meta-analyses, and systematic reviews provide compelling evidence that insulin resistance by itself is a cardiovascular risk factor in a variety of population groups, including the general population and patients with diabetes. Several estimations of insulin resistance have been consistently associated with elevated rate of cardiovascular events independently of other cardiovascular risk factors and diabetes status. The clinical expression of insulin resistance (the metabolic syndrome or any of its components including obesity, hyperinsulinemia, hypertension, and dyslipemia) has been related to cardiovascular disease as well. An estimation conducted by the Archimedes model confirms that insulin resistance is the most important single cause of coronary artery disease.     

Introduction: organ involvement in the cardiometabolic syndrome

The cardiometabolic syndrome is a construct associated with an increased risk of type 2 diabetes mellitus, cardiovascular disease (coronary artery disease, peripheral arterial disease, and stroke), chronic kidney disease, and the metabolic hepatopathy referred to as nonalcoholic fatty liver disease or nonalcoholic steatohepatitis. Thus, the term cardiometabolic syndrome includes all of these metabolic, islet, cardiovascular, renal, and hepatic disorders and clustering clinical syndromes. This overview of the cardiometabolic syndrome is designed to review the clinical complications and the end-organ cellular and extracellular matrix remodeling events that occur with the cardiometabolic syndrome. The MINER acronym will serve as an outline, representing: Myocardial and metabolic-hepatopathy, Intimal and islet, Neurovascular, Endothelial, and Renal oxidation-reduction (redox) stress and remodeling.     

Dyslipidemia in the metabolic syndrome: clinical implications and management

Dyslipidemia is an important component of the metabolic syndrome. Dyslipidemia in the metabolic syndrome is characterized by hypertriglyceridemia, low serum levels of high density lipoprotein cholesterol (HDL-C) and an increase in the serum fraction of small dense low density lipoprotein cholesterol (LDL-C) particles. Serum LDL-C elevation is frequently present, but is not a criterion of the metabolic syndrome. A Medline search was conducted using the terms metabolic syndrome, dyslipidemia, hypertriglyceridemia and HDL cholesterol. The metabolic syndrome is a common and important risk factor for cardiovascular disease and progression to type 2 diabetes mellitus. Dyslipidemia is present in most patients with the metabolic syndrome and is treatable with therapeutic lifestyle changes and pharmacotherapy. Aggressive management of atherogenic dyslipidemia is justified by the very high cardiovascular risk associated with this disorder. Atherogenic dyslipidemia is frequently present in patients with the metabolic syndrome and requires aggressive treatment due to the very high risk for cardiovascular disease and progression to type 2 diabetes mellitus.     

Renin-angiotensin-system blockade in the prevention of diabetes

Type 2 diabetes often occurs in association with hypertension and cardiovascular disease, and markedly increases cardiovascular risk. Strategies to reduce the incidence of diabetes in patients with cardiovascular disease or at high risk for such disease are therefore important. Certain classes of antihypertensive agents, namely the thiazide diuretics and beta-blockers, have an adverse impact on the metabolic profile and increase the risk for new-onset diabetes in hypertensive subjects. In contrast, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), which are blockers of the renin-angiotensin system (RAS), have been shown to increase insulin sensitivity. They may also reduce the risk of diabetes in patients with hypertension or cardiovascular disorders. Some of the evidence in favour of ACE inhibitors and ARBs has come from studies with active comparators that have potential adverse metabolic effects. However, the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) programme demonstrated that the ARB candesartan reduced the incidence of diabetes in heart failure patients in comparison to placebo. The mechanisms responsible for the beneficial effects of RAS blockade remain to be established. Nevertheless, a treatment that can control hypertension and reduce the risk of onset of type 2 diabetes at the same time is certainly desirable.     

Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for prevention of type 2 diabetes: a meta-analysis of randomized clinical trials

OBJECTIVES: We sought to investigate the role of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) in preventing the new onset of type 2 diabetes mellitus. BACKGROUND: Diabetes is a public health problem of epidemic proportions and its prevalence is on the rise. The typical American born today has a one in three chance of developing type 2 diabetes. This diagnosis is associated with an adverse cardiovascular prognosis and is considered the risk equivalent of established coronary disease. Even in high-risk individuals, diabetes is a preventable disease. Several studies have shown that ACE inhibitors and ARBs decrease the incidence of new-onset type 2 diabetes. However, the exact role of these agents in diabetes prevention has not yet been fully elucidated. METHODS: We conducted a meta-analysis of 12 randomized controlled clinical trials of ACE inhibitors or ARBs, identified through a MEDLINE search and a review of reports from scientific meetings, to study the efficacy of these medications in diabetes prevention. RESULTS: This showed that ACE inhibitors and ARBs were associated with reductions in the incidence of newly diagnosed diabetes by 27% and 23%, respectively, and by 25% in the pooled analysis. CONCLUSIONS: The use of an ACE inhibitor or ARB should be considered in patients with pre-diabetic conditions such as metabolic syndrome, hypertension, impaired fasting glucose, family history of diabetes, obesity, congestive heart failure, or coronary heart disease.     

Cardiovascular risk associated with the metabolic syndrome

The term metabolic syndrome refers to a clustering of cardiovascular risk factors, most of which also share insulin resistance as an additional feature. Scientific effort has concentrated on understanding why these diverse cardiovascular risks co-occur in individuals and in determining the presumed common environmental or genetic factors that might underpin this. Clinically important developments include publication of standard definitions of the metabolic syndrome and recommendations for the use of type 2 diabetes and the presence of the metabolic syndrome as critical "risk stratifiers" in cardiovascular disease prevention. The remarkable recent secular increases in the prevalence of type 2 diabetes and obesity in many populations mean that the importance of the metabolic syndrome as a determinant of cardiovascular disease is likely to increase until these trends can be reversed.