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

Insulin resistance and consecutive hyperinsulinemia in individuals with the metabolic syndrome are associated with dyslipidemia. This latter is characterised by hypertriglyceridemia and a diminishment of high-density lipoprotein (HDL) cholesterol in the plasma. In severe forms of insulin resistance, low density lipoprotein (LDL) cholesterol may also be elevated. Hypertriglyceridemia is due to an increase in the rate of synthesis of very low density lipoproteins (VLDL) in the liver, and a reduction in their breakdown by the lipoprotein lipase in non-hepatic tissue. Changes in VLDL metabolism are associated with a reduction in HDL concentrations. In addition, direct effects of insulin on the lipid metabolism have been described. Changes in lipid metabolism due to insulin resistance and hyperinsulinemia may be of significance for the atherosclerosis risk in patients with the metabolic syndrome.
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PMID:[Dyslipoproteinemia and metabolic syndrome. Effects of insulin resistance and hyperinsulinemia on lipid metabolism]. 148 17

Insulin resistance with consecutive hyperinsulinemia is associated with dyslipidemia in individuals with metabolic syndrome or "syndrome x". This dyslipidemia is characterized by a hypertriglyceridemia and reduced levels of HDL-(high density lipoprotein)cholesterol in plasma. Table 1 summarizes the alterations of lipoproteins in insulin resistance. In severe forms of insulin resistance LDL-(low density lipoprotein)cholesterol can be elevated as well. The hypertriglyceridemia is caused by an elevated synthesis and secretion of VLDL (very low density lipoprotein) in the liver and by reduced metabolism, mediated e.g. by lipoprotein lipase. The alterations of VLDL-metabolism are associated with a reduced concentration of HDL-cholesterol. In addition the composition of lipoprotein particles can be altered, which might interfere with their normal metabolism. Furthermore addition direct effects of insulin on cellular cholesterol metabolism have been described. These alterations in lipid metabolism which are due to an insulin resistance and hyperinsulinemia might be related to the increased coronary risk which has been observed in patients with metabolic syndrome. Therefore the diagnostic approach in patients with hypertriglyceridemia should consider the possibility of an underlying glucose intolerance or Type 2 diabetes. Therapeutic aims and strategies are discussed. In accordance to guidelines of the American Heart Association the goals of lipid-lowering therapy take into account the prevalence of various cardiovascular risk factors in an individual patient (Table 2). Principle actions of lipid-lowering drugs on plasma lipids are outlined in Table 3. Table 4 summarizes the effect of antihypertensive drugs on plasma lipids and lipoproteins, which should be considered in the treatment of patients with dyslipidemia.
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PMID:[Disorders of lipid metabolism in insulin resistance]. 771 75

Major cardiovascular risk factors, such as hypertension, hyperlipidemia, and diabetes, often cluster in the same individuals. It has been claimed that obesity, hyperinsulinemia, insulin resistance, and a deranged intracellular handling of ions have pathogenetic importance in the development of this metabolic syndrome. However, a decrease in peripheral blood flow is another factor found in all the different facets of this syndrome. An increased peripheral resistance and a rarefaction of skeletal vessels are often seen in hypertensive subjects. Also, the insulin resistance so commonly seen in hypertension may be a consequence of a decreased blood flow because insulin resistance is associated with a decreased capillarization in skeletal muscle. Furthermore, the activity of skeletal muscle lipoprotein lipase, the key enzyme involved in the removal of triglycerides from the circulation, is known to be related to skeletal muscle vascularization. Because enhanced sympathetic activity has been associated with vascular hypertrophy and rarefaction of vascularization, overactivity in this part of the autonomic nervous system may lead to structural changes that will decrease the blood flow in peripheral tissues and thereby induce the metabolic syndrome of cardiovascular risk factors, particularly in individuals who, for genetic reasons, have decreased capillarization at the onset.
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PMID:Decreased peripheral blood flow in the pathogenesis of the metabolic syndrome comprising hypertension, hyperlipidemia, and hyperinsulinemia. 848 Jun 20

For better comprehension of the metabolic syndrome, it is necessary to differentiate the effect of insulin on glucose metabolism on the one hand, and on other metabolic activities on the other hand. Whereas glucose utilization is affected by insulin resistance, the effect of insulin on lipid metabolism, ion and aminoacid transport does not seem to be diminished. Lipid metabolism, however, seems to play a crucial role in the induction of the vicious cycle. Increased energy and fat ingestion may be due to an increased number of galanin secreting cells in the hypothalamus. The excessive fat intake results in an increased rate of release of insulin and increased influx of triglycerides into the blood. From these triglycerides an excess of free fatty acids is released by the action of lipoprotein lipase. The increased plasma free fatty acid level then results in insulin resistance affecting glucose metabolism. Also, these free fatty acids may impair the secretion of insulin. Induction of insulin resistance results in higher glucose levels, which may cause hyperinsulinemia. Hyperinsulinemia maintains the elevation of triglycerides. When diabetes becomes overt and elevated glucose levels prevail, the hyperinsulinism acts on the metabolic pathways which are still sensitive to insulin, namely lipid metabolism, aminoacid transport and ion transport.
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PMID:Hyperinsulinemia, hyperproinsulinemia and insulin resistance in the metabolic syndrome. 864 79

Hyperinsulinemia secondary to insulin resistance in type-II diabetes or in the metabolic syndrome is associated with the "atherogenetic lipoprotein phenotype": high triglycerides, small, dense low-density lipoprotein (LDL) cholesterol, and low high-density lipoprotein (HDL) cholesterol. In contrast, hyperinsulinemia in pancreas-kidney transplant recipients (PKT-R), secondary to systemic venous drainage of the heteropically implanted pancreas graft, leads to high lipoprotein lipase (LPL) activity and a presumably antiatherogenic lipoprotein profile with very attenuated postprandial lipemia, high HDL cholesterol, and a preponderance of large-sized HDL (HDL(2)) and large buoyant LDL particles. We interpret these findings to suggest that in PKT-R, peripheral hyperinsulinemia upregulates LPL activity in peripheral tissues, which induces rapid clearance of chylomicron triglycerides from plasma and, thus, attenuates postprandial lipemia. Low postprandial lipemia allows little net cholesteryl ester transfer from HDL to triglyceride-rich lipoproteins, keeping the levels of the antiatherogenic lipoprotein HDL high and potentially increasing, thereby reverse cholesterol transport. The type of lipoprotein metabolism and pattern present in PKT-R is associated with a low cardiovascular risk in the general population; it cannot be excluded, however, that hyperinsulinemia as found in PKT-R may contribute to atherosclerosis by effects unrelated to lipoprotein metabolism.
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PMID:Pancreas transplantation modulates reverse cholesterol transport. 1055 2

We examined the effects of the potassium channel opener KRN4884 (5-amino-N-[2-(2-chlorophenyl)ethyl]-N'-cyano-3-pyridinecarboxamidine ) on cardiovascular metabolic syndrome (i.e., syndrome X), in rats. High-fructose diet rats developed hypertension, hypertriglyceridemia, increased total cholesterol/HDL (high-density lipoprotein)-cholesterol ratio, and hyperinsulinemia, KRN4884 (0.3-3.0 mg/kg, twice a day for 14 days, p.o.) alleviated the risk factors in fructose-fed rats. Furthermore, fructose-fed rats exhibited impairment of glucose tolerance and excess insulin secretion when loaded with glucose orally. Treatment with KRN4884 (1.0 mg/kg, twice a day for 14 days, p.o.) improved the glucose intolerance and inhibited hypersecretion of insulin in the glucose-loaded, fructose-fed rats. In contrast, KRN4884 (0.3-1.0 mg/kg, twice a day for 10 days, p.o.) did not affect serum triglyceride, cholesterol, glucose, or insulin concentrations in normal rats. LPL (lipoprotein lipase) activities in skeletal muscle and adipose tissue, and HTGL (hepatic triglyceride lipase) activity in liver were measured after administration of KRN4884 or vehicle twice a day for 14 days in fructose-fed rats. KRN4884 caused a significant increase in LPL activity in muscle and tended to increase LPL activity in adipose tissue in fructose-fed rats. HTGL was decreased in fructose-fed rats as compared with normal controls and was unaffected by KRN4884. These findings suggested that KRN4884 enhances insulin sensitivity and LPL activity, which are related to glucose and lipid metabolism and may be useful for the treatment of syndrome X.
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PMID:Effects of the K+ channel opener KRN4884 on the cardiovascular metabolic syndrome model in rats. 1067 63

The clustering of cardiovascular risk factors such as abdominal obesity, hypertension, dyslipidaemia and glucose intolerance in the same persons has been called the metabolic or insulin-resistance syndrome. In 1998 WHO proposed a unifying definition for the syndrome and chose to call it the metabolic syndrome rather than the insulin-resistance syndrome. Although insulin resistance has been considered as a common denominator for the different components of the syndrome, there is still debate as to whether it is pathogenically involved in all of the different components of the syndrome. Clustering of the syndrome in families suggests a genetic component. It is plausible that so-called thrifty genes, which have ensured optimal storage of energy during periods of fasting, could contribute to the phenotype of the metabolic syndrome. Common variants in a number of candidate genes influencing fat and glucose metabolism can probably, together with environmental triggers, increase susceptibility to the syndrome. Among these, the genes for beta 3-adrenergic receptor, hormone-sensitive lipase, lipoprotein lipase, IRS-1, PC-1, skeletal muscle glycogen synthase, etc. appear to increase the risk of the metabolic syndrome. In addition, novel genes may be identified by genome-wide searches.
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PMID:Genetics of the metabolic syndrome. 1088 91

The aim of this study was to determine if there is a relationship among skeletal muscle fiber composition, capillarization, blood pressure (BP) and/or the components of the metabolic syndrome. Two groups were compared: 8 recently diagnosed, untreated, hypertensive men (BP > or = 140/90) and 7 normotensive men as controls. Muscle biopsies were taken from the vastus lateralis part of quadriceps femoris muscle in order to assess: fiber type proportion, capillarization, hexokinase, citrate synthase, beta-hydroxyacyl CoA dehydrogenase activities; lipoprotein lipase mass and activity, free fatty acids and triglycerides. Serum levels of insulin, glucose, cholesterol, uric acid and triglycerides were also assayed. Hypertensive patients had higher insulin levels and insulin resistance [homeostasis model assessment (HOMA)], a decreased hexokinase activity and an increase of muscle lipoprotein lipase mass as compared to controls. Interestingly, correlations among values differ in each group. The percentage of type IIB fibers was related to diastolic BP (blood pressure) in control and to mean BP in hypertensive subjects. Serum cholesterol and glucose were inversely related to the percentage of type I fibers in the control subjects. Negative correlations between capillarization and glucose, cholesterol and uric acid levels were found in control subjects. In all subjects, a strong correlation was found between SBP (systolic BP) and DBP (diastolic BP), and insulin resistance (IR) and uric acid levels. Muscle fiber type proportion and capillarization were related to blood pressure and components of the metabolic syndrome.
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PMID:Muscle fiber composition and capillarization in relation to metabolic alterations in hypertensive men. 1132 89

Nonalcoholic steatohepatitis (NASH) is a syndrome frequently associated with obesity, diabetes mellitus, and dyslipidemia. Increased fasting insulinemia and blood glucose levels may trigger a reduced catabolism of lipoproteins rich in triglycerides by lipoprotein lipase (LPL) and an increase in their fasting and postprandial levels. An association between postprandial lipemia and coronary heart disease has been observed, and many studies now support this concept. The most important result of our study is the increase in triglyceride-rich lipoproteins response after a fat load in NASH patients, the increase of incremental area under the postprandial curve, and the duration of the hypertriglyceridemic peaks. The persisting postprandial plasma triglyceride elevation in NASH patients was mostly due to the elevated plasma level of large triglyceride-rich particles. These data are coupled with lower plasma HDL2-cholesterol levels. As for lipoprotein analyses, the number of apolipoprotein B100 (ApoB100) particles is not significantly different between the two groups, and the higher content of triglycerides in NASH very low density lipoproteins (VLDL) increases the triglyceride-to-ApoB ratio and the particle size. A decreased enzymatic activity of LPL or a defective assembly and secretion of VLDL from hepatocytes due to a moderate reduction in microsomal triglyceride transfer protein could be involved in the overloading of VLDL. Moreover, the undetectable levels of ApoB48 in triglyceride-rich lipoproteins fraction A could be related to the synthesis of smaller and denser chylomicrons. NASH patients not only are insulin resistant but also tend to present alterations in fatty meal delivery, suggesting that an increase in fasting plasma insulin and glucose, with insulin resistance, joins with depressed metabolism of triglyceride-rich lipoproteins. An increase in postprandial triglyceride levels with production of large VLDL suggests an atherogenic behavior of lipid metabolism, in accordance with the high prevalence of the metabolic syndrome in NASH patients. This paper suggests that a fat load may be useful in early detection of atherogenic risk in the presence of otherwise normal fasting plasma lipids.
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PMID:Postprandial triglyceride-rich lipoprotein metabolism and insulin sensitivity in nonalcoholic steatohepatitis patients. 1176 56

Type 2 diabetes is characterised by both impaired insulin secretion and insulin resistance but their relative contribution to the development of hyperglycaemia may differ due to heterogeneity of the disease. Under most circumstances, insulin resistance is the earliest detectable defect in pre-diabetic individuals but it is not known whether this is the primary defect or secondary to other abnormalities such as abdominal obesity with excessive free fatty acid turnover and increased lipid deposits in muscle. Initially, enhanced insulin secretion can compensate for the insulin resistance but early phase insulin secretion is impaired. In the transition from normal to impaired and diabetic glucose tolerance, insulin sensitivity deteriorates about 40% whereas insulin secretion deteriorates 3-4 fold. In addition to insulin resistance, the metabolic syndrome includes hypertension, dyslipidaemia, obesity and microalbuminuria. In patients with manifest diabetes, chronic hyperglycaemia can result in further deterioration of insulin sensitivity and secretion (glucotoxicity), which is aggravated by elevated free fatty acids (lipotoxicity). Abdominal obesity and insulin resistance are strongly correlated and studies have aimed at understanding the genetic basis. Candidate genes for the metabolic syndrome include those for the beta 3-adrenergic receptor, lipoprotein lipase, hormone sensitive lipase, peroxisome proliferator-activated receptor-gamma, insulin receptor substrate-1 and glycogen synthase. Therefore, type 2 diabetes is multigenic and appears to represent a collision between thrifty genes and an affluent society. Successful management will require treatments targeted at defects of both insulin secretion and insulin resistance.
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PMID:Pathogenesis of type 2 diabetes: the relative contribution of insulin resistance and impaired insulin secretion. 1196 29


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