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Metabolic syndrome (MS) refers to the clustering of cardiometabolic risk factors - including abdominal obesity, hyperglycaemia, dyslipidaemia and elevated blood pressure - that are thought to be linked to insulin resistance. MS is associated with increased risk of cardiovascular disease and type 2 diabetes. MS is common, affecting a quarter to a third of adults, and its prevalence is rising, in parallel with increasing obesity and population ageing. Operational definitions of MS have been proposed by the World Health Organization and the National Cholesterol Education Program. Recently, the International Diabetes Federation proposed a global definition that emphasised the importance of central adiposity. In cardiovascular risk assessment, MS encapsulates the contribution of non-traditional risk factors and provides a clinically useful framework for early identification of people at increased long-term risk. It should be used in conjunction with standard algorithms based on conventional risk factors, which better predict short-term risk. Management of MS should emphasise lifestyle interventions (eg, physical activity, healthy diet and weight reduction) to reduce long-term risk of cardiovascular disease and diabetes. Those at increased short-term risk should also have individual risk factors treated according to established guidelines.
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PMID:Revisiting the metabolic syndrome. 1760 19

Increase in patients with central obesity and insulin resistance is an important cause for the worldwide increased incidence of type 2 diabetes. Several risk factors such as glucose intolerance, hyperinsulinemia, obesity, dyslipidemia, and hypertension, but also endothelial dysfunction and inflammation, have been found to cluster and often precede type 2 diabetes mellitus. Seeing the importance of early identification, the US National Cholesterol Education Program created a readily applicable definition of the metabolic syndrome for daily clinical practice. It is assumed that the cardiovascular risk for patients belonging to the metabolic syndrome can just be calculated out of the sum of the separate cardiovascular risk factors dyslipidemia and hypertension. However, there are also data pointing toward a higher risk than expected from these separate cardiovascular risk factors because of possible direct vascular effects of insulin resistance and obesity. Awareness of the underlying disorders of insulin resistance and its associated (non-) traditional risk factors such as endothelial dysfunction and inflammation is important for understanding the pathophysiology and thus coherent treatment.
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PMID:The operative risk factors in the metabolic syndrome: is it lipids and high BP or are there direct vascular effects of insulin resistance and obesity. 1725 21

Identifying patients with cardiovascular risks was once the simple process of recognizing the traditional risk factors. However, since the National Cholesterol Educational Program Adult Treatment Panel III guidelines were released in 2001, and again revised in 2004, identification of cardiovascular risk has become more complicated. This article provides both an overview and an update on the metabolic syndrome as a cluster of risk factors for both type 2 diabetes and cardiovascular disease (CVD). Specific issues are discussed as they relate to African-American women and their prevalence of the metabolic syndrome and cardiometabolic risk. Nurses are optimally prepared to identify the early signs of cardiometabolic risk by testing for and assessing the metabolic syndrome. Likewise, nursing is in a position to provide teaching and counsel regarding the needed lifestyle alterations for patients with metabolic syndrome in order to reduce the risk of type 2 diabetes, cardiovascular disease, and/or stroke.
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PMID:An overview and update on the metabolic syndrome: implications for identifying cardiometabolic risk among African-American women. 1741 Jul 59

Elevations in alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), markers of liver dysfunction and nonalcoholic fatty liver, are considered as part of the metabolic syndrome and related diseases. However, information is limited regarding the persistence (tracking) in levels of these enzymes over time and their influence on cardiovascular (CV) risk in young adults. The study sample consisted of white and black subjects (N = 489, 40% male, 73% white; baseline age, 18-32 years) followed over a period of 12 years as part of the Bogalusa Heart Study, with repeat measurements of CV risk factor variables and liver enzymes. Both at baseline and follow-up, males vs females had higher ALT (P < .01 to .0001) and GGT (P < .0001); blacks vs whites had higher GGT (P < .0001). With respect to persistence in enzyme levels over time, of those individuals who had ALT and GGT at the top quintile specific for age, race, and sex at baseline, about 50% of them continued to remain so with high values after 12 years. Individuals with levels persistently in the highest quintile vs those in the lowest quintile showed higher (P < .0001) body mass index, waist circumference, triglycerides, low-density lipoprotein cholesterol, glucose, insulin, insulin resistance index, and systolic and diastolic blood pressures; lower (P < .0001) high-density lipoprotein cholesterol; and higher (P < .05 to .001) prevalence of obesity, hypertension, dyslipidemia, metabolic syndrome as defined by the National Cholesterol Education Program Adult Treatment Panel III, positive parental history of type 2 diabetes, and coronary heart disease. In addition, based on a multivariate analysis using 2 separate models for ALT and GGT, baseline levels of both enzymes were independent predictors of follow-up; insulin resistance index and baseline GGT were also predictive of follow-up systolic blood pressure. Elevations in liver enzymes ALT and GGT, within "reference" range, persist over time and relate to clinically relevant adverse CV risk profile in young adults.
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PMID:Persistent elevation of liver function enzymes within the reference range is associated with increased cardiovascular risk in young adults: the Bogalusa Heart Study. 1751 12

Increasing evidence suggests that the quality-rather than just the quantity-of low-density lipoproteins (LDLs) exerts a great influence on cardiovascular risk. LDLs comprise multiple subclasses with discrete size and density, and different physicochemical composition, metabolic behaviors, and atherogenicity. Individuals generally cluster into 2 broad subgroups. Most have a predominance of large LDLs, and some have a higher proportion of small particles. Small, dense LDLs are good predictors of cardiovascular events and progression of coronary artery disease. Their predominance has been accepted as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel III. Several studies have shown that therapeutic modulation of LDL size and subclass is of great benefit in reducing the risk of cardiovascular events. This seems particularly true for statins and fibrates when they are administered to higher-risk patients, such as those with type 2 diabetes or vascular disease. Data reporting outcomes with the use of rosuvastatin, the latest statin molecule introduced to the market, and ezetimibe, a cholesterol absorption inhibitor, are promising.
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PMID:Effects of statins, fibrates, rosuvastatin, and ezetimibe beyond cholesterol: the modulation of LDL size and subclasses in high-risk patients. 1766 Jan 66

Patients with type 2 diabetes have a marked increase in the risk of premature coronary heart disease (CHD). One of the underlying reasons for this increased risk is atherogenic dyslipidaemia, which is common in this patient group and characterized by low plasma levels of high-density lipoprotein cholesterol (HDL-C), increased levels of serum triglycerides, specifically very low-density lipoprotein triglycerides, and an increase in small, dense low-density lipoprotein (LDL) particles. Current management strategies focus on the initial use of statin or fibrate therapy (the latter approach indicated in patients with pronounced hypertriglyceridaemia). Recent treatment guidelines also emphasize the need for reduction in LDL-cholesterol (LDL-C) below 100 mg/dl (2.6 mmol/l) in diabetic patients, as this patient group has a clustering of cardiovascular risk factors that collectively lead to an excess risk of premature mortality. Multidrug lipid-modifying therapy has been proposed to further reduce CHD risk in diabetic patients. Adding nicotinic acid to primary statin therapy would be a logical approach based on the complementary therapeutic benefits of these treatments. Nicotinic acid is the most potent agent currently available for raising HDL-C and is also effective in reducing triglycerides and LDL-C. Moreover, clinical trial data have shown that nicotinic acid can be safely used in diabetic patients. Data from the Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER 2) study in patients with established CHD and low HDL-C (27% of whom had type 2 diabetes) show the atheroprotective effects of nicotinic acid/statin combination therapy. The clinical benefits of this combination therapy are indicated by subgroup analyses from the HDL-Atherosclerosis Treatment Study, which showed 40% reduction in coronary event frequency in patients with impaired glucose tolerance. Together, these data support the proposed strategy of aggressive multidrug treatment of diabetic dyslipidaemia to improve patient outcome.
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PMID:Dyslipidaemia in diabetic patients: time for a rethink. 1769 54

In population-based studies, a cluster of cardiovascular risk factors comprising the metabolic syndrome (MetS) has been documented as predictive of cardiovascular disease events and type 2 diabetes. Currently, there are several proposed definitions of the MetS, although data support some advantages of using the 2005 National Cholesterol Education Program Adult Treatment Panel III definition, which is considered superior to most others, including the one from the 2005 International Diabetes Federation study. One controversial issue is that some of the conventional cardiovascular risk factors included in the MetS cluster appear to be equally predictive of cardiovascular outcomes as the syndrome itself (eg, the influence of smoking habits). Further observational and intervention studies are needed to explore this issue and target the core problem of the syndrome, which is proposed to be insulin resistance. Useful therapies for the metabolic syndrome include lifestyle modification and drugs that lower conventional cardiovascular risk factors, such as metformin, the "glitazones," and evidence-based drugs.
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PMID:Cardiovascular risk in the metabolic syndrome: fact or fiction? 1799 73

The diagnosis of the metabolic syndrome (MS) according to the National Cholesterol Education Program Adult Treatment Panel III does not reflect necessarily the presence of insulin resistance (IR), a potential therapeutical target for type 2 diabetes and cardiovascular disease prevention. Based on previous prevalence data, a cross-sectional study was conducted to determine the HOMA-IR relationship to the MS and some associated abnormalities. HOMA-IR > was higher in individuals with the MS (2.8+/-1.6 vs. 1.8+/-1.4) (p < 0.001). HOMA-IR >or= 2.5 allied good specificity and sensitivity levels for the association of MS and IR. Hyperglycemia, hypertrigliceridemia, and abdominal obesity, the MS components best related to IR, were statistically associated with HOMA-IR > 2.5, but not hypertension neither low HDL-c. The demonstration that some of MS phenotypes or associated abnormalities were more predictive for IR could point out to the possibility of the use of the index as a marker of the presence of IR associated to MS.
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PMID:[Metabolic syndrome, its phenotypes, and insulin resistance by HOMA-IR]. 1820 94

We sought to assess the relationship between the metabolic syndrome, abdominal obesity, and glucose deterioration amongst patients with type 2 diabetes. Our prospective cohort consisted of 164 adult patients with established diabetes who have a history of poor glycemic control, have just completed an intensive intervention aimed at improved control, and have demonstrated reduced HbA1c prior to enrollment. Waist circumference and presence of metabolic syndrome were assessed at baseline, and patients were followed up (median 24 months) for assessment of the study outcome, namely, time-to-hyperglycemic relapse, predefined as HbA1c >8% and >1% rise over baseline. Kaplan-Meier estimates of relapse-free glucose maintenance and multivariable Cox regression models were used for quantifying the independent effects of the metabolic syndrome and waist circumference on risk of glucose deterioration. The mean baseline waist circumference was 42.9 5.5 inches. Prevalence of the metabolic syndrome was 80%. During follow-up, 39 patients (24%) experienced hyperglycemic relapse. The metabolic syndrome was not associated with time-to-relapse (P = 0.15). The waist circumference component by itself, however, was associated with increased likelihood of hyperglycemic relapse with an unadjusted hazard ratio of 3.4 (95% confidence interval (CI) 1.2-9.7) and a hazard ratio of 3.2 (95% CI 1.1-9.1) after adjusting for age, gender, insulin use, weight change, and physical activity level. The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII) metabolic syndrome had limited ability to predict glucose deterioration in this type 2 diabetes cohort. Waist circumference by itself, however, is a strong predictor of future glucose control, and may be a parsimonious tool for risk stratification. BMI may also be a useful predictive tool.
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PMID:Waist circumference, not the metabolic syndrome, predicts glucose deterioration in type 2 diabetes. 1827 89

In the circulation, cholesterol and triglycerides are enveloped in apolipoproteins and phospholipids, and transported as complex particles called lipoproteins. Abnormal levels of lipoproteins occur in children either because of a genetic defect in lipid metabolism pathways (primary lipid disorders, e.g. familial hypercholesterolemia [FH]) or secondary to other diseases or conditions (e.g. insulin resistance) and can be clinically significant; for example, elevated low-density lipoprotein cholesterol levels are a major risk factor for future cardiovascular disease. Patients with primary lipid disorders in childhood such as FH can exhibit early atherosclerotic lesions in childhood. Other risk factors for cardiovascular disease, such as obesity and type 2 diabetes mellitus, are increasingly common in the pediatric population, and are often associated with dyslipidemia. Thus, pediatricians should be aware of how to screen, diagnose and treat dyslipidemia. The majority of lipid disorders in children can be managed with diet and lifestyle modification. Pharmacologic therapy (e.g. statins) may be added if target lipoprotein levels are not achieved. Clinicians may be guided in patient management by recent scientific statements from the American Heart Association; however, existing National Cholesterol Education Program treatment guidelines should be urgently updated to incorporate new evidence regarding atherosclerosis pathophysiology, obesity and the metabolic syndrome, emerging cardiovascular risk factors, and pharmacologic therapy in pediatric patients.
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PMID:Primary and secondary disorders of lipid metabolism in pediatrics. 1831 44


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