Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are three peroxisome proliferator-activated receptors (PPARs) subtypes which are commonly designated PPAR alpha, PPAR gamma and PPAR beta/delta. PPAR alpha activation increases high density lipoprotein (HDL) cholesterol synthesis, stimulates "reverse" cholesterol transport and reduces triglycerides. PPAR gamma activation results in insulin sensitization and antidiabetic action. Until recently, the biological role of PPAR beta/delta remained unclear. However, treatment of obese animals by specific PPAR delta agonists results in normalization of metabolic parameters and reduction of adiposity. Combined treatments with PPAR gamma and alpha agonists may potentially improve insulin resistance and alleviate atherogenic dyslipidemia, whereas PPAR delta properties may prevent the development of overweight which typically accompanies "pure" PPAR gamma ligands. The new generation of dual-action PPARs--the glitazars, which target PPAR-gamma and PPAR-alpha (like muraglitazar and tesaglitazar) are on deck in late-stage clinical trials and may be effective in reducing cardiovascular risk, but their long-term clinical effects are still unknown. A number of glitazars have presented problems at a late stage of clinical trials because of serious side-effects (including ragaglitazar and farglitazar). The old and well known lipid-lowering fibric acid derivative bezafibrate is the first clinically tested pan--(alpha, beta/delta, gamma) PPAR activator. It is the only pan-PPAR activator with more than a quarter of a century of therapeutic experience with a good safety profile. Therefore, bezafibrate could be considered (indeed, as a "post hoc" understanding) as an "archetype" of a clinically tested pan-PPAR ligand. Bezafibrate leads to considerable raising of HDL cholesterol and reduces triglycerides, improves insulin sensitivity and reduces blood glucose level, significantly lowering the incidence of cardiovascular events and new diabetes in patients with features of metabolic syndrome. Clinical evidences obtained from bezafibrate-based studies strongly support the concept of pan-PPAR therapeutic approach to conditions which comprise the metabolic syndrome. However, from a biochemical point of view, bezafibrate is a PPAR ligand with a relatively low potency. More powerful new compounds with pan-PPAR activity and proven long-term safety should be highly effective in a clinical setting of patients with coexisting relevant lipid and glucose metabolism disorders.
Cardiovasc Diabetol 2005 Sep 16
PMID:Dual and pan-peroxisome proliferator-activated receptors (PPAR) co-agonism: the bezafibrate lessons. 1616 52

Elevated plasma homocysteine has been reported in individuals with diseases of the metabolic syndrome including vascular disease and insulin resistance. As homocysteine exerts detrimental effects on endothelial and neuronal cells, this study investigated effects of acute homocysteine exposure on beta-cell function and insulin secretion using clonal BRIN-BD11 beta-cells. Acute insulin release studies in the presence of various test reagents were performed using monolayers of BRIN-BD11 cells and samples assayed by insulin radioimmunoassay. Cellular glucose metabolism was assessed by nuclear magnetic resonance (NMR) analysis following 60-min exposure of BRIN-BD11 cell monolayers to glucose in either the absence or presence of homocysteine. Homocysteine dose-dependently inhibited insulin release at moderate and stimulatory glucose concentrations. This inhibitory effect was reversible at all but the highest concentration of homocysteine. 13C-glucose NMR demonstrated decreased labelling of glutamate from glucose at positions C2, C3 and C4, indicating that the tricarboxylic acid (TCA) cycle-dependent glucose metabolism was reduced in the presence of homocysteine. Homocysteine also dose-dependently inhibited insulinotropic responses to a range of glucose-dependent secretagogues including nutrients (alanine, arginine, 2-ketoisocaproate), hormones (glucagon-like peptide-1 (7-36)amide, gastric inhibitory polypeptide and cholecystokinin-8), neurotransmitter (carbachol), drug (tolbutamide) as well as a depolarising concentration of KCl or elevated Ca2+. Insulin secretion induced by activation of adenylate cyclase and protein kinase C pathways with forskolin and phorbol 12-myristate 13-acetate were also inhibited by homocysteine. These effects were not associated with any adverse action on cellular insulin content or cell viability, and there was no increase in apoptosis/necrosis following exposure to homocysteine. These data indicate that homocysteine impairs insulin secretion through alterations in beta-cell glucose metabolism and generation of key stimulus-secretion coupling factors. The participation of homocysteine in possible beta-cell demise merits further investigation.
 ...
PMID:Detrimental actions of metabolic syndrome risk factor, homocysteine, on pancreatic beta-cell glucose metabolism and insulin secretion. 1664 97

Lowering of low-density lipoprotein cholesterol with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) is clearly efficacious in the treatment and prevention of coronary artery disease. However, despite increasing use of statins, a significant number of coronary events still occur and many of such events take place in patients presenting with type 2 diabetes and metabolic syndrome. More and more attention is being paid now to combined atherogenic dyslipidemia which typically presents in patients with type 2 diabetes and metabolic syndrome. This mixed dyslipidemia (or "lipid quartet"): hypertriglyceridemia, low high-density lipoprotein cholesterol levels, a preponderance of small, dense low-density lipoprotein particles and an accumulation of cholesterol-rich remnant particles (e.g. high levels of apolipoprotein B)--emerged as the greatest "competitor" of low-density lipoprotein-cholesterol among lipid risk factors for cardiovascular disease. Most recent extensions of the fibrates trials (BIP - Bezafibrate Infarction Prevention study, HHS - Helsinki Heart Study, VAHIT--Veterans Affairs High-density lipoprotein cholesterol Intervention Trial and FIELD--Fenofibrate Intervention and Event Lowering in Diabetes) give further support to the hypothesis that patients with insulin-resistant syndromes such as diabetes and/or metabolic syndrome might be the ones to derive the most benefit from therapy with fibrates. However, different fibrates may have a somewhat different spectrum of effects. Other lipid-modifying strategies included using of niacin, ezetimibe, bile acid sequestrants and cholesteryl ester transfer protein inhibition. In addition, bezafibrate as pan-peroxisome proliferator activated receptor activator has clearly demonstrated beneficial pleiotropic effects related to glucose metabolism and insulin sensitivity. Because fibrates, niacin, ezetimibe and statins each regulate serum lipids by different mechanisms, combination therapy--selected on the basis of their safety and effectiveness - may offer particularly desirable benefits in patients with combined hyperlipidemia as compared with statins monotherapy.
Cardiovasc Diabetol 2006 Sep 26
PMID:Atherogenic dyslipidemia in metabolic syndrome and type 2 diabetes: therapeutic options beyond statins. 1700 98

Obstructive sleep apnoea (OSA) is a cardio-metabolic disorder. Whether metabolic syndrome (MS), insulin resistance (IR) and albuminuria are independently associated with OSA is unclear, but defining the interactions between OSA and various cardiovascular (CV) risk factors independent of obesity facilitates the development of therapeutic strategies to mitigate their increased CV risks. We prospectively recruited 38 subjects with OSA and 41 controls. Anthropometric measurements, glucose, lipids, insulin and blood pressure (BP) were measured after an overnight fast. IR state was defined as homeostasis model assessment (HOMA) value >3.99 and MS diagnosed according to the International Diabetes Federation (IDF) criteria. Subjects with OSA were more obese, more insulin resistant, more hyperglycaemic, had higher Epworth score (measure of day time somnolence) and systolic blood pressure levels. The prevalence of MS was higher in OSA compared with non-OSA subjects (74% vs 24%, p < 0.001). The prevalence of microalbuminuria in both groups was negligible. Logistic regression adjusted for age, BMI and smoking showed that the patient with OSA was 5.9 (95% CI 2.0-17.6) times more likely to have MS than non-OSA patient. Triglyceride (p = 0.031), glucose (0.023) and Epworth score (0.003) values were independently associated with OSA after adjusting for BMI and other covariates whilst IR status was found not to be significant. Using the ROC curve analysis, we found that a waist circumference of >103 cm would predict MS in patients with OSA at 75-78% sensitivity and 61-64% specificity. The agreement between MS and IR state in this cohort is poor. Thus, OSA is associated with MS independent of obesity predominantly due to increased triglyceride, glucose and Epworth score values but not IR or microalbuminuria status. This observation suggests an alternative pathogenic factor mediating the increased cardiovascular risk in patients with OSA and MS, other than that due to IR. The independent link between Epworth score and MS in patients with OSA implicates the role of daytime sleepiness and chronic hypoxia as a potential mediator. Given the discordant between MS and IR state, measurement of waist is useful for predicting mainly MS but not insulin resistance status in patients with OSA. Appropriate pharmacological intervention targeting these independent factors is important in reducing the increased CV risks among patients with OSA.
Cardiovasc Diabetol 2006 Nov 01
PMID:Obstructive sleep apnoea is independently associated with the metabolic syndrome but not insulin resistance state. 1707 84

The aim was to compare the Adult Treatment Panel (ATP) III criteria with the International Diabetes Federation (IDF) definition of metabolic syndrome (MS) in adults with excess adiposity who were considered a high-risk population. A cross-sectional study was carried out in 274 adults with excess adiposity. MS was assessed in all volunteers considering the ATP III criteria and the new IDF definition. Among all individuals, 130 (47%) were similarly classified under the two definitions. Under the ATP III criteria, but not the IDF definition, 2 (1%) participants had MS, and 29 (11%) subjects had MS under the IDF definition but not the ATP III criteria (p=0.009). The ATP III criteria and the IDF definition were useful for identifying MS in adults with excess of adiposity; however, the IDF proposal identified a greater percentage of patients.
Acta Diabetol 2006 Nov
PMID:Prevalence of metabolic syndrome in adults with excess of adiposity: comparison of the Adult Treatment Panel III criteria with the International Diabetes Federation definition. 1714 86

The prevalence of the metabolic syndrome in different elderly European populations has not been well studied. The aim of this study was to measure the prevalence of metabolic syndrome, as well as its individual components, in an elderly Swedish cohort. A random sample of 778 individuals (372 men and 406 women) was selected from a 70-year-old cohort in the H70 study, a gerontological and geriatric population study carried out in Gothenburg, Sweden. The study included medical and treatment history assessments, laboratory procedures and physical examinations to determine the presence of each of the five components of the metabolic syndrome as defined by the National Cholesterol Education Program Adult Treatment Panel III. Of the 508 adults (243 men and 265 women) included in the study, 22.6% had metabolic syndrome. The prevalence was higher in men (26.3%) than in women (19.2%). One third of the total sample had at least one of the five risk factors for metabolic syndrome. High blood pressure (> or =130/85 mmHg or use of antihypertensive/diuretic medication) was the most prevalent risk factor in both men (68.3%) and women (50.2%), while abdominal obesity was the overall second most common risk factor (27.2% of men and 42.7% of women). The prevalence of high fasting plasma glucose (> or =110 mg/dl or use of antidiabetic medication) was 29.0% in men and 19.1% in women. Metabolic syndrome was prevalent in a significant proportion of this elderly Swedish population, highlighting the underdiagnosis of a condition that is important to treat.
Acta Diabetol 2006 Dec
PMID:Prevalence of metabolic syndrome in an elderly Swedish population. 1721 62

The metabolic syndrome (MS) leads to serious health problems like diabetes and has serious economic consequences for multinational companies. Thus, the workplace is an important setting for primary prevention. Aim of this study was to evaluate the prevalence of MS in a mixed working population to provide a basis for interventional strategies. In 2006, 1,594 employees attended a screening program at BASF Ludwigshafen, the number of employees with MS was determined and the distribution of impaired glucose tolerance (IGT), type 2 diabetes and cardiovascular disease (CVD) analyzed. The study-population consisted of 1,075 men and 519 women, aged 17-64. 374 individuals (23.5%) were classified to be affected by MS, of which 86.9% were male (prevalence MS in men 30%, in women 9.7%). Subjects with MS had higher BMI (P < 0.01), blood pressure (P < 0.01), heart rate (P < 0.01), liver enzymes (P < 0.01), uric acid (P < 0.01) and LDL (P < 0.01), while HDL was significantly lower (P < 0.01). (Pre)-Diabetes and CVD were found more frequently in subjects with MS. There were no significant differences between individuals with different types of employment ("white collar vs. blue collar" workers) or smoking status. We found a high prevalence of MS in our working population, thus interventional programmes should be implemented. The workplace-setting can be used to promote long-term prevention strategies in this adult working population.
Acta Diabetol 2008 Mar
PMID:Metabolic syndrome in a large chemical company: prevalence in a screened worksite sample. 1788 49

The incretin system has been shown to stimulate insulin secretion in a glucose dependent manner and currently fosters considerable hope for the treatment of diabetes. Recently, we have shown that the dipeptidylpeptidase-4 (DPP4) gene, which is responsible for incretin inactivation, was overexpressed in omental adipose tissue of obese men with the metabolic syndrome, compared to men not characterized by this condition. Since the cardiovascular disease (CVD) risk profile shows substantial inter-individual variability in obesity, this study aimed at verifying whether DPP4 polymorphisms contribute to explain such a difference. In the first step of this multi-stage study, seven tagging SNPs were genotyped in a sample of 576 obese (BMI>40 kg/m(2)) individuals and tested for their association with blood pressure and lipids, as well as diabetes-related phenotypes. Then, in an additional sample of 572 obese individuals (stage 2), SNPs showing trends (P<0.10) for an association in the first sample were genotyped and reanalyzed. Logistic regressions were used to compute odds ratio for obesity-related metabolic complications. In sample 1, homozygotes for rs17848915 and rs7608798 minor alleles were at lower risk of hyperglycemia/diabetes (P=0.002) and elevated plasma triglyceride levels (P=0.030) respectively, whereas rs1558957 heterozygotes were at higher risk to have high plasma triglyceride (P=0.040), HDL- (P=0.021), LDL- (P=0.001) and total-cholesterol (P=0.003) levels. However, none of these associations was consistently replicated in stage 2. This first comprehensive genetic analysis does not support the notion that DPP4 polymorphisms could modulate the CVD risk profile among obese patients.
Acta Diabetol 2009 Mar
PMID:Comprehensive genetic analysis of the dipeptidyl peptidase-4 gene and cardiovascular disease risk factors in obese individuals. 1868 83

Ophthalmoplegia, despite being a rare entity in diabetes mellitus, is associated with great anxiety for the patients and often appears to be a serious problem from a diagnostic and therapeutic point of view. There have been few studies primarily concerned with the relative frequencies and clinical characteristics of oculomotor neuropathies in diabetic subjects. Those published have emanated largely from neurological and/or ophthalmological referral centres rather than metabolic departments. Objective of this study was to determine the incidence, the clinical characteristics and risk factors for developing ophthalmoplegia among persons with diabetes mellitus. We have performed a retrospective study of all diabetic patients with ophthalmoplegia who were seen in the Metabolic Division at "S. Biagio" Hospital, Marsala, over the 10 year period from 1998 to 2007. A detailed history and blood laboratory profile were obtained for each patient. During the period of the survey a total of 6,765 diabetic subjects were hospitalised and ophthalmoplegia was identified in 27 patients (0.40%). Isolated III nerve palsies accounted for the majority of patients (59.3%), with VI nerve palsies (29.6%) occurring more frequently than multiple palsies (11.1%). These patients had a marked comorbidity and were found to have a poorly controlled diabetes. The patients with VI nerve palsies showed a tendency toward a higher coexistence of diabetic retinopathy and cardiovascular risk factors than those with III cranial nerve palsies. Ophthalmoplegia is a serious and not common problem among patients with diabetes mellitus; the oculomotor nerve was most frequently affected in our case-report. The fact that the coexistence of diabetic complications and cardiovascular risk factors was slightly higher in patients with VI nerve palsy is compatible with the hypothesis that this ischemic event might be more closely related to diabetes and metabolic syndrome in its pathogenesis.
Acta Diabetol 2009 Mar
PMID:Ophthalmoplegia in diabetes mellitus: a retrospective study. 1875 85

Subjects who develop diabetes have an increased cardiovascular risk even before the appearance of diabetes. The aim of this study was to investigate the glycaemic variability measured by continuous glucose monitoring (CGM CV%) in nondiabetic subjects with metabolic syndrome (MS) and to explore if glycaemic variability was associated with circulating levels of interleukin-6 (IL-6), a proinflammatory cytokine, or with an anti-inflammatory factor like adiponectin. Three groups of obese subjects with (MS+: 6m, 8f; BMI 33.1+/-1.4 mean+/-SEM) or without metabolic syndrome (MS-: 2m, 4f; BMI 29.2+/-2.2) and with MS associated with type 2 diabetes (MS/T2D: 3m, 5f; BMI 32.9+/-1.4) were investigated. The glycaemic variability was measured in all subjects in terms of CV% of the glycaemic values obtained every 3 min during the course of a 48 h CGM performed using a subcutaneous glucose sensor. The average CGM CV% increased from MS- group (21.1%) to the MS+ group (23.9%) and to the MS+/T2D group (27.4%) but it was not correlated to the CGM mean glycaemia (r=0.20; P=ns). In some instances, CGM CV% was found higher in MS+ subjects than in some MS+ T2D ones. Stepwise multiple correlation analysis showed that IL-6 predicted CGM CV% (R(2)=0.35, beta=0.13; P<0.05) independently from BMI, waist circumference, adiponectin and insulin concentrations. In conclusion, the CGM CV% may contribute to better describe the individual metabolic state and to understand the pathogenesis of endothelial dysfunction in non diabetic subjects with MS.
Acta Diabetol 2009 Mar
PMID:Glycaemic variability and inflammation in subjects with metabolic syndrome. 1881 62


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>