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

The discovery of a new class of oral antidiabetic drugs was stimulated by difficulties with the treatment currently available for patients with type 2 diabetes mellitus. Thiazolidinediones can lower blood glucose values due to their special insulin-sensitiser effect. In this way, these drugs seem to be very effective in the treatment of type 2 diabetic patients with characteristics of metabolic syndrome. The intracellular action caused by thiazolidinediones differs markedly from that of other oral antidiabetic drugs available. Apart from antihyperglycaemic effect, thiazolidinediones have further beneficial effects in experimental diabetes which require corroboration by clinical studies. Troglitazone was the first drug which reached the market. Unfortunately, this drug was withdrawn soon due to its hepatotoxicity. Rosiglitazone proved to be much safer in clinical studies. Pioglitazone is being tested nowadays in clinical studies. Thiazolidinediones have been already listed among oral antidiabetic drugs in international therapeutical guidelines. Nevertheless, further clinical studies and experiences are needed to determine the final exact indication of thiazolidinediones for the treatment of type 2 diabetic patients.
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PMID:[Thiazolidinediones--a new class of oral antidiabetic drugs]. 1149 46

Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease for which there is no known effective therapy. A proportion of patients with NASH progress to advanced fibrosis and cirrhosis. NASH is considered one of the clinical features of the metabolic syndrome in which insulin resistance plays a central role. This prospective study evaluates the role of insulin-sensitizing agent in treatment of NASH. Eighteen nondiabetic patients with biopsy-proven NASH were treated with pioglitazone (30 mg daily) for 48 weeks. Tests of insulin sensitivity and body composition as well as liver biopsies were performed before and at the end of treatment. By 48 weeks, serum alanine aminotransferase values fell to normal in 72% of patients. Hepatic fat content and size as determined by magnetic resonance imaging decreased, and glucose and free fatty acid sensitivity to insulin were uniformly improved. Histological features of steatosis, cellular injury, parenchymal inflammation, Mallory bodies, and fibrosis were significantly improved from baseline (all P < 0.05). Using strict criteria, histological improvement occurred in two-thirds of patients. Pioglitazone was well tolerated; the main side effects were weight gain (averaging 4%) and an increase in total body adiposity. In conclusion, these results indicate that treatment with an insulin-sensitizing agent can lead to improvement in biochemical and histological features of NASH and support the role of insulin resistance in the pathogenesis of this disease. The long-term safety and benefits of pioglitazone require further study.
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PMID:A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. 1475 37

Pioglitazone monotherapy and combinations were assessed in patients with type 2 diabetes and metabolic syndrome (Adult Treatment Panel III criteria) from four worldwide randomised, multicentre, double-blind studies. Patients were treated for 52 weeks with pioglitazone (PIO, n = 1040), sulphonylurea (SU, n = 535) or metformin (MET, n = 500) PIO + SU (n = 277) or MET + SU (n = 273); or PIO + MET (n = 286) or SU + MET (n = 275). Pooled week 52 glycaemic and lipid changes were compared using analysis of covariance. Haemoglobin A(1c) decreased significantly with pioglitazone compared with sulphonylurea (p < 0.05). Fasting, 2- and 3-h plasma glucose, insulin and homeostasis model assessment for insulin resistance decreased significantly with pioglitazone compared with other monotherapies (p < 0.05) and decreased significantly with PIO + MET compared with SU + MET (p < 0.05). Pioglitazone, alone and with metformin, improved lipid components of diabetic dyslipidaemia more than did their respective comparison groups. Pioglitazone was associated with weight increase. In conclusion, pioglitazone provided effective glycaemic control and lipid profile improvements in patients with type 2 diabetes and metabolic syndrome.
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PMID:Pioglitazone in a subgroup of patients with type 2 diabetes meeting the criteria for metabolic syndrome. 1585 87

Atherogenic dyslipidemia is one of the major components of the metabolic syndrome, a complex cluster of several risk factors within a single patient that according to the National Cholesterol Education Program (NCEP) Adult Treatment Panel III includes at least 3 of the following: large waist circumference, elevated triglyceride levels, low levels of high-density lipoprotein cholesterol (HDL-C), hypertension, and elevated fasting glucose levels, which are directly related to the incidence of coronary heart disease. Atherogenic dyslipidemia clinically presents as elevated serum triglyceride levels, increased levels of small dense low-density lipoprotein (sdLDL) particles, and decreased levels of HDL-C. An important component of atherogenic dyslipidemia is central obesity, which is defined as increased waist circumference and has recently been identified as a chief predictor of the metabolic syndrome in certain patients. Another recent study found that both body mass index and waist circumference were highly predictive of eventual development of the metabolic syndrome. Because atherogenic dyslipidemia usually precedes the clinical manifestation of the metabolic syndrome, strategies to treat it are the focus of pharmacologic intervention. For example, the 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors, commonly known as statins, benefit hypercholesterolemic patients who have atherogenic dyslipidemia that is associated with the metabolic syndrome. Pioglitazone, an antidiabetic agent that acts primarily by decreasing insulin resistance, improves sensitivity to insulin in muscle and adipose tissue and inhibits hepatic gluconeogenesis. Pioglitazone improves glycemic control while reducing circulating insulin levels. The investigational agent, rimonabant--a centrally and peripherally acting, selective cannabinoid type-1 receptor blocker--is the first therapy developed for managing several cardiovascular risk factors at one time. Rimonabant has shown promise in attacking atherogenic dyslipidemia from several vantage points by affecting glucose, HDL-C, triglycerides, and waist circumference in patients who are prone to atherogenic dyslipidemia.
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PMID:The metabolic basis of atherogenic dyslipidemia. 1647 58

Thiazolidinediones (TZDs) are peroxisomal proliferator-activated receptor (PPAR)-gamma agonists. They increase insulin action through several mechanisms including: stimulation of the expression of genes that increase fat oxidation and lower plasma free fatty acid levels; increased expression, synthesis and release of adiponectin; and stimulation of adipocyte differentiation resulting in more and smaller fat cells. TZDs lower blood sugar comparably to sulfonylureas and metformin. The clinical use of TZDs is limited due to the long duration of time required before they reach their full blood sugar-lowering action (3-4 months) and adverse effects such as fluid retention, resulting in excessive weight gain and occasionally in peripheral and/or pulmonary oedema and congestive heart failure. Troglitazone, a TZD that has since been removed from the market because of hepatoxicity, has been demonstrated to decrease the progression from normal or impaired glucose tolerance to overt Type 2 diabetes mellitus. Pioglitazone, another TZD, marginally decreased the incidence of cardiovascular complications in patients with Type 2 diabetes mellitus (PROactive trial). Other, as yet, unapproved uses of TZDs include: non-alcoholic fatty liver disease, in which TZDs reduced hepatic fat accumulation and improved liver function tests; polycystic ovary syndrome, where TZDs improved ovulation, hirsutism and endothelial dysfunction; and lipodystrophies, where TZDs increased body fat (marginally) and decrease liver size. Lastly, because PPAR-alpha and -gamma agonists improve atherosclerotic vascular disease and insulin sensitivity, respectively, dual PPAR-alpha/gamma agonists, which are currently undergoing clinical trials, may be useful in treating patients with the metabolic syndrome.
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PMID:Recent findings concerning thiazolidinediones in the treatment of diabetes. 1650 61

Statins frequently do not control all of the lipid abnormalities found in patients with the metabolic sydrome. Pioglitizone (PIO), an insulin sensitizing agent, has been shown to have favorable lipid effects in diabetic patients. Little information is available regarding the effect of combined statin and PIO therapy in non-diabetic patients with the metabolic syndrome. We report our experience of adding PIO to statin therapy in non-diabetic patients with the metabolic syndrome. Pioglitazone was administered to 24 non-diabetic patients in our lipid clinic who were already on a statin yet continued to have significant lipid abnormalities. All patients had characteristic lipid abnormalities and clinical features of the metabolic syndrome. The treatment period was 59+/-29 (range 7-123) weeks. Lipid profiles, fasting glucose, and alanine aminotransferase were assessed before and at least 6 weeks after pioglitazone was added to statin. Triglyceride levels decreased from 307+/-295mg/dL to 173+/-129mg/dL (P=0.003), non-high-density lipoprotein cholesterol (non-HDL) decreased from 151+/-53mg/dL to 130+/-49mg/dL, (P=0.003), and high-density lipoprotein cholesterol (HDL) levels increased from 42+/-11mg/ dL to 45+/-12mg/dL, (P=0.039). The addition of PIO to statin in non-diabetic patients with metabolic sydrome produced significant additional benefits in the lipid profile over statin monotherapy. Favorable effects were seen in triglycerides, HDL, and non-HDL levels. Study limitations include: this is a small non-blinded observational study in which patients served as their own controls. The duration of combination therapy and type of statin employed were variable.
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PMID:Benefit of adding pioglitazone to statin therapy in non-diabetic patients with the metabolic syndrome. 1693 9

Peroxisome Proliferator-Activate Receptors (PPARs) are transcription factors belonging to the nuclear receptor superfamily. The three PPARs (alpha, beta/delta, and gamma) are distributed differently in the different organs. PPARalpha is most common in the liver, but also found in kidney, gut, skeletal muscle and adipose tissue, while PPARbeta/delta, is fairly ubiquitous; it may be found in body tissues and brain (for myelination process and lipid metabolism in the brain). PPARgamma has 3 isoforms, such as PPARgamma 1, PPARgamma 2, and PPARgamma 3. The syndrome-X was firstly coined by Reaven in 1988 and then to be provided in 1999 by the name : the metabolic syndrome-X. This metabolic syndrome represents a "Cluster" of metabolic disorders and cardiovascular risk factors which has been collected and summarized by the author and such a cluster includes: insulin resistance/hyperinsulinemia, central obesity, glucose intolerance/DM, atherogenic dyslipidemia (increase TG, decrease HDL-cholesterol, increase Apo-B, increase small dense LDL), hypertension, prothrombotic state (increase PAI-1, increase F-VII, increase fibrinogen, increase vWF, increase adhesion molecules), endothelial dysfunction, hyperuricemia, and increased hsC-RP and cytokines. The metabolic syndrome-X may lead to the development of T2DM and coronary heart disease (CHD); insulin resistance plays pivotal roles in the progression of such a syndrome and cardiovascular diseases. Improvement of Insulin Resistance, therefore, is most likely to reduce the high cardiovascular event rate in T2DM. It has been generally accepted that Insulin Resistance (detected by HOMA-R) and Acute Insulin Response = AIR (by HOMA-B) are both usually present in T2DM. The Thiazolidinedions (TZDs) are Insulin Sensitizers (e.g Rosiglitazone = ROS, Pioglitazone = PIO) introduced into clinical practice in 1997; clinical evidence data showed that TZDs improved both HOMA-R, and HOMA-B. PPARgamma can be activated by TZDs and it appears to be fundamental to the pathophysiology of diabetes mellitus i.e increase GLUT-4, increase glucokinase, decrease PEPCK, increase GLUT-4, and decreases production by fat cell of several mediators that may cause insulin resistance, such as TNFalpha and resistin. PPARgamma also mediates increased production of Adiponectin and the insulin signaling intermediate PI3K, and both actions lead to increase insulin sensitivity. A "dual PPARgamma-PPARalpha agonists" (e.g PIO, but ROS poorly activate PPARalpha) might lower glucose and modulate lipids. Thus, PIO, as a stronger "dual PPARgamma-PPARalpha agonists", shows an important therapeutic pathway in diabetes mellitus and cardiovascular diseases, even in metabolic syndrome. Current evidence suggests a close relationship between activation of PPARgamma and restoration of insulin sensitivity by reductions in TNFalpha and FFAs, and the enhancement of insulin stimulation of PI3-K Pathway and also increase adiponectin & decrease resistin.
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PMID:New approach in the treatment of T2DM and metabolic syndrome (focus on a novel insulin sensitizer). 1711 68

Patients with type 2 diabetes mellitus and/or the metabolic syndrome have considerable cardiovascular risk. Treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and with antihypertensive and some antihyperglycemic agents reduces this risk, but residual macrovascular morbidity and mortality persist, even in patients assigned to intensive multifactorial intervention programs. Therapeutic strategies that target inflammation and lipid abnormalities not well addressed by statins may offer additional opportunities for improving the prognosis of these patients. Inflammation, a key mechanism of atherogenesis, appears to have particular relevance to diabetic vascular complications, as well as in the development of diabetes itself. Oxidative stress and hyperglycemia also figure among the pathogenic factors that promote cardiovascular complications in patients with the metabolic syndrome and/or diabetes and may augment the ongoing inflammation. Peroxisome proliferator-activated receptor (PPAR)-alpha and PPAR-gamma, members of the nuclear receptor family, form ligand-activated transcription factors that regulate key important metabolic pathways. PPARs have become therapeutic targets through the use of the fibrate class of antidyslipidemic drugs (PPAR-alpha) and the insulin-sensitizing thiazolidinediones (PPAR-gamma). The activation of these PPARs may also suppress inflammation and atherosclerosis. Recent clinical trials (Fenofibrate Intervention and Event Lowering in Diabetes [FIELD], Prospective Pioglitazone Clinical Trial in Macrovascular Events [PROactive]) have considered the impact of these PPAR agonists on cardiovascular disease, with mixed effects that require careful analysis, especially given ongoing trials and additional PPAR agonists in development.
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PMID:Inflammation in diabetes mellitus: role of peroxisome proliferator-activated receptor-alpha and peroxisome proliferator-activated receptor-gamma agonists. 1730 56

Endothelial dysfunction is a key event in the development of renovascular complications in the metabolic syndrome. The aim of this study was to elucidate the pathogenetic mechanisms involved in renovascular injuries in the Zucker obese rat, a model of the metabolic syndrome, and to examine the therapeutic effects of pioglitazone, a thiazolidinedione. Obese rats fed high-protein diet (OHP) for 12 weeks exhibited nephropathy and endothelial dysfunction, which were improved by pioglitazone. Accumulation of nitrotyrosine, a tracer of nitrative stress, was increased in aorta of the OHP group. The mRNA expressions of NADPH oxidase components and inducible nitric oxide synthase in the aorta were enhanced in the OHP group. Pioglitazone reduced nitrotyrosine in the aorta of the OHP group, inhibiting the augmented expression levels of both. These results suggest that nitrative stress could cause endothelial dysfunction in the rat model of metabolic syndrome with nephropathy, and that pioglitazone ameliorates these injuries, presumably by reducing nitrative stress.
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PMID:Pioglitazone ameliorates endothelial dysfunction in obese rats with nephropathy. 1768 Dec 82

Insulin resistance, which precedes type 2 diabetes mellitus (T2DM), is a widespread pathology associated with the metabolic syndrome, myocardial ischemia, and hypertension. Finding an adequate treatment for this pathology is an important goal in medicine. The purpose of the present research was to investigate the effect of an extract from Aloe vera gel containing a high concentration of polyphenols on experimentally induced insulin resistance in mice. A polyphenol-rich Aloe vera extract (350 mg/kg) with known concentrations of aloin (181.7 mg/g) and aloe-emodin (3.6 mg/g) was administered orally for a period of 4 weeks to insulin resistant ICR mice. Pioglitazone (50 mg/kg) and bi-distilled water were used as positive and negative controls respectively. Body weight, food intake, and plasma concentrations of insulin and glucose were measured and insulin tolerance tests were performed. The insulin resistance value was calculated using the homeostasis model assessment for insulin resistance (HOMA-IR) formula. Results showed that the polyphenol-rich extract from Aloe vera was able to decrease significantly both body weight (p < 0.008) and blood glucose levels (p < 0.005) and to protect animals against unfavorable results on HOMA-IR, which was observed in the negative control group. The highest glucose levels during the insulin tolerance curve test were in the negative control group when compared to the Aloe vera extract and pioglitazone treated mice (p < 0.05). In conclusion, Aloe vera gel could be effective for the control of insulin resistance.
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PMID:Effect of a polyphenol-rich extract from Aloe vera gel on experimentally induced insulin resistance in mice. 1818 89


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