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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The National Cholesterol Education Program recognizes the importance of the metabolic syndrome and has published guidelines for its diagnosis. Weight loss, physical activity, and treatment of the individual risk factors constitute the main strategies for treatment. For now, the goals and methods of treating hypertension and dyslipidemia are the same in people with the metabolic syndrome as in the general population. Thiazolidinedione drugs increase insulin sensitivity, but their use in the metabolic syndrome is only speculative at present. We recommend they be used only as indicated to treat diabetes mellitus.
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PMID:A truly deadly quartet: obesity, hypertension, hypertriglyceridemia, and hyperinsulinemia. 1254 72

The metabolic syndrome is intended to identify patients who have increased risk of diabetes and/or a cardiac event due to the deleterious effects of weight gain, sedentary lifestyle, and/or an atherogenic diet. The National Cholesterol Education Program's Adult Treatment Panel III definition uses easily measured clinical findings of increased abdominal circumference, elevated triglycerides, low high-density lipoprotein-cholesterol, elevated fasting blood glucose and/or elevated blood pressure. Three of these five are required for diagnosis. The authors also note that other definitions of metabolic syndrome focus more on insulin resistance and its key role in this syndrome. This review focuses on how treatment might affect each of the five components. Abdominal obesity can be treated with a variety of lower calorie diets along with regular exercise. Indeed, all of the five components of the metabolic syndrome are improved by even modest amounts of weight loss achieved with diet and exercise. For those with impaired fasting glucose tolerance, there is good evidence that a high fiber, low saturated fat diet with increased daily exercise can reduce the incidence of diabetes by almost 60%. Of note, subjects who exercise the most, gain the most benefit. Metformin has also been shown to be helpful in these subjects. Thiazolidinedione drugs may prove useful, but further studies are needed. Although intensified therapeutic lifestyle change will help the abnormal lipid profile, some patients may require drug therapy. This review also discusses the use of statins, fibrates, and niacin. Likewise, while hypertension in the metabolic syndrome benefits from therapeutic lifestyle change, physicians should also consider angiotensin converting enzyme inhibitor drugs or angiotensin receptor blockers, due to their effects on preventing complications of diabetes, such as progression of diabetic nephropathy and due to their effects on regression of left ventricular hypertrophy. Aspirin should be considered in those with at least a 10% risk of a coronary event over 10 years. Finally, three related conditions, nonalcoholic fatty liver disease, polycystic ovary syndrome and protease inhibitor associated lipodystrophy improve with therapeutic lifestyle change. Although metformin is shown to be useful with polycystic ovary syndrome, the data supporting drug therapy for the other syndromes is less convincing. More robust studies are needed before any firm recommendations can be made.
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PMID:Treatment of metabolic syndrome. 1515 70

Insulin resistance is a characteristic feature of obesity and type 2 diabetes mellitus, but it is also present in up to 25% of healthy nonobese individuals. The molecular mechanisms causing insulin resistance are not yet fully understood. Recently, overexpression of several potential inhibitors of the insulin receptor tyrosine-kinase activity, a key step in insulin signaling, has been described in insulin-resistant subjects . PC-1 is expressed in many tissues and inhibits insulin signaling either at the level of the insulin receptor or downstream at a postreceptor site. An elevated PC-1 content in insulin target tissues may play an important role in the development of insulin resistance in obesity and type 2 diabetes mellitus. A polymorphism in PC-1 has been demonstrated to be associated with insulin resistance. This was a DNA polymorphism in exon 4 that causes an amino acid change from lysine to glutamine at codon 121 (K121Q). PC-1 121Q allele might predispose independently of other well established risk factors for early myocardial infarction. Testing for the PC-1 K121Q polymorphism might be valuable in patients with a family history of atherosclerotic vascular disease and myocardial infarction. There is growing evidence that genetic factors play an important role in the development of diabetic nephropathy (DN). Efforts to identify these factors rely primarily on the candidate gene approach; candidate genes for insulin resistance may be considered candidates for DN as well. In a stratified analysis according to duration of diabetes, the risk of early-onset end-stage renal disease (ESRD) for carriers of the Q variant was 2.3 times that for noncarriers. The cellular mechanisms for the insulin resistance of pregnancy and gestational diabetes mellitus (GDM) are unknown. Women with GDM have an increased PC-1 content and excessive phosphorylation of serine/threonine residues in muscle insulin receptors. The postreceptor defects in insulin signaling may contribute to the pathogenesis of GDM and the increased risk for type 2 diabetes later in life. Although widely explored, the true cause of insulin resistance in uremic patients is not entirely elucidated yet. During the last decade it was found that erythropoietin (EPO) therapy, used for correction of anemia in patients with end stage renal failure, ameliorates insulin resistance. An increased lymphocyte PC-1 activity over control was found in hemodialysis patients. A two-month EPO therapy significantly decreased PC-1 activity to the control values, suggesting that an effect on PC-1 expression could be implicated in the amelioration of insulin resistance in uremic patients treated with EPO. Current investigations implicate that therapeutic modification of PC-1 expression would be of great benefit for insulin-resistant type 2 diabetics. Metformin, a biguanide oral antidiabetic agent, was shown to affect insulin resistance by decreasing enzymatic activity of overexpressed PC-1 molecules in obese type 2 diabetics. Thiazolidinedione (TZD) insulin-sensitizing drugs are a class of compounds that improve insulin action in vivo. Treatment of patients with TZDs seems to have a beneficial effect on most, if not all, components of metabolic syndrome. TZDs have also been used in the treatment of nondiabetic human insulin-resistant states, and have demonstrated an improvement in insulin sensitivity. Although much remains to be learned about PPAR gamma receptor and TZD action, the advent of TZD insulin-sensitizing agents has an enormous impact on our understanding of insulin resistance. The great potential of insulin resistance therapy illuminated by the TZDs will continue to catalyze research in this area directed toward the discovery of new insulin-sensitizing agents that work through other mechanisms.
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PMID:Plasma cell membrane glycoprotein 1 (PC-1): a marker of insulin resistance in obesity, uremia and diabetes mellitus. 1520 35

The metabolic syndrome leads to cardiovascular disease and type 2 diabetes mellitus, through multiple risks, such as insulin resistance, dyslipidemia, hyperinsulinemia, and hypertension. It also represents a disorder of partial genetic background as mutations of the peroxisome proliferator-activated receptor-gamma (PPAR-g). Thiazolidinedione agonists for the PPAR-g system are effective in control of insulin resistance and diabetes. Telmisartan has a molecular structure that imparts partial agonist properties with the PPAR-g molecule, which results in reductions in glucose and lipid metabolism. Administration of telmisartan to rats on a high-fat, high-carbohydrate diet leads to reductions in glucose, insulin, and triglyceride levels. The results imply that the ARB agent, telmisartan, could treat both the hemodynamic and metabolic aberrations seen in subjects with the metabolic syndrome, such as insulin resistance, glucose intolerance, and hypertension.
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PMID:Angiotensin-receptor blocking agents and the peroxisome proliferator-activated receptor-gamma system. 1606 Oct 40