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

Partially inconsistent data exist on mutual relations between nontraditional atherosclerotic risk factors, including the magnitude of insulin resistance (IR), as well as on their relevance for atherogenesis in the metabolic syndrome. Subjects exhibiting combined impaired fasting glucose and impaired glucose tolerance (IFG/IGT) are exposed to an exceptionally high risk for atherogenesis and development of type 2 diabetes mellitus. Because of islet Beta-cell dysfunction, the usefulness of commonly used indices of IR is limited in IFG/IGT. Our aim was to assess the relationship between extent of angiographic coronary artery disease (CAD) and nontraditional atherosclerotic risk factors (including IR by a clamp-based golden standard method) in IFG/IGT. Fifty-three subjects (32 men, 21 women; mean age, 55 +/- 11 years) with stable angina, preserved left ventricular systolic function, and IFG/IGT were divided into 3 groups: group A (no coronary stenoses >50%, n = 22), group B (1-vessel CAD, n = 15), and group C (2/3-vessel CAD, n = 16). Insulin sensitivity was quantified by a hyperinsulinemic euglycemic clamp technique and expressed as M. M value, plasma homocysteine (Hcy) level, and asymmetric dimethyl-L-arginine (ADMA)/L-arginine ratio were independent determinants of CAD extent as shown by forward stepwise discriminant function analysis. Compared with group A (M = 32.7 +/- 9.3 micromol/kg fat-free mass [FFM] per minute; Hcy, 8.1 +/- 1.4 micromol/L), lower M and higher Hcy levels were found in group B (M = 16.9 +/- 8.2 micromol/kg FFM per minute, P < .001; Hcy, 11.2 +/- 2.9 micromol/L, P = .003) and C (M = 16.4 +/- 7.8 micromol/kg FFM per minute, P < .001; Hcy, 12.8 +/- 3.9 micromol/L, P < .001). The ADMA/L-arginine ratio was increased in group C (0.0078 +/- 0.0011) compared with group A (0.0063 +/- 0.0013, P = .03) and B (0.0058 +/- 0.0012, P = .01). Multivariate correlates (P < .05) of plasma Hcy concentrations were M (beta = -.34 +/- .12, P = .008), creatinine clearance (beta = -.23 +/- .10, P = .03) and fasting insulin (beta = .25 +/- .12, P = .04). This indicates an additive contribution of IR, plasma Hcy, and elevated ADMA/L-arginine ratio to the extent of angiographic CAD in combined IFG/IGT.
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PMID:Nontraditional atherosclerotic risk factors and extent of coronary atherosclerosis in patients with combined impaired fasting glucose and impaired glucose tolerance. 1716 Dec 29

Epidemiological data suggest an association between kidney stones and some features of metabolic syndrome such as an overweight condition, arterial hypertension or glucose intolerance. However, mechanisms remain to be elucidated. This study aimed to evaluate insulin resistance, as assessed by homeostasis model assessment (HOMA-IR), and urine composition analysis in patients affected by calcium nephrolithiasis. A cohort of 61 (38 male, 29-57 years of age) non-diabetic calcium stone formers was studied. Data about body mass index, arterial blood pressure, serum biochemistry including parathyroid hormone and calcitriol were recorded in all the patients; fasting glucose and insulin were determined to calculate HOMA-IR value and accordingly the patients were grouped into tertiles. Urine pH and urinary excretion of calcium, citrate, phosphate, oxalate, uric acid, urea and creatinine were measured on 24h urine samples. Patients of the highest HOMA-IR tertile showed lower urine citrate levels than patients of the lowest HOMA-IR tertile (475+/-243 vs. 630+/-187 mg/24h, p<0.05), whereas no difference was detected as far as urinary oxalate, calcium, uric acid, phosphate, and urine pH and urine volume output were concerned. HOMA-IR values were positively related to uric acid serum levels (r=0.31, p<0.05) and negatively to urinary citrate excretion (r=-0.26, p<0.05). Hypocitraturic patients showed higher levels of HOMA-IR than normocitraturic ones (3.03+/-0.92 vs. 2.25+/-1.19, p<0.05). This study shows that a higher level of insulin resistance is associated with lower urinary citrate excretion, and that hypocitraturic patients show a greater insulin resistance than normocitraturic calcium stone formers. This may be related to changes in citrate, Na(+)-K(+) and H(+) renal tubule transports, which have been described in insulin resistance. In conclusion, insulin resistance may contribute to an increased risk of calcium stone formation by lowering urinary citrate excretion. This finding suggests the need for a careful metabolic assessment in patients known to form calcium stones in order to ensure stone recurrence prevention and cardiovascular protection.
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PMID:Insulin resistance and low urinary citrate excretion in calcium stone formers. 1718 67

The aim of this project was to study the risk of developing hypertension over a 6-year follow-up in normotensive men with baseline hyperuricemia (serum uric acid >7.0 mg/dL) but without diabetes/glucose intolerance or metabolic syndrome. We analyzed the data on men without metabolic syndrome or hypertension at baseline from the Multiple Risk Factor Intervention Trial. These men (n=3073; age: 35 to 57 years) were followed for an average of 6 years by annual examinations. Follow-up blood pressure among those with baseline was consistently higher than among those with normal serum uric acid concentration. We used Cox regression models for adjustment for the effects of serum creatinine, body mass index, age, blood pressure, proteinuria, serum cholesterol and triglycerides, alcohol and tobacco use, risk factor interventions, and use of diuretics. In these models, normotensive men with baseline hyperuricemia had an 80% excess risk for incident hypertension (hazard ratio: 1.81; 95% CI: 1.59 to 2.07) compared with those who did not. Each unit increase in serum uric acid was associated with a 9% increase in the risk for incident hypertension (hazard ratio: 1.09; 95% CI: 1.02 to 1.17). We conclude that the hyperuricemia-hypertension risk relationship is present among normotensive middle-aged men without diabetes/glucose intolerance or metabolic syndrome.
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PMID:Hyperuricemia and incidence of hypertension among men without metabolic syndrome. 1719 Aug 77

Chronic kidney disease coexists with metabolic syndrome and this relationship may be apparent before overt manifestations of cardiovascular disease. To investigate early stages of the natural history of associations between renal function and metabolic syndrome, we phenotyped 1572 young (mean age=18.4 years), apparently healthy men for metabolic risk factors and estimated their creatinine clearance based on the Cockcroft-Gault equation. High metabolic risk (clustering of at least three metabolic risk factors) was revealed in 8.7% (137) of the subjects and was associated with a 6.9-fold increase in the odds of glomerular hyperfiltration (95% confidence interval (CI): 3.9-11.5) when compared to reference (from none to two metabolic risk factors). Overweight, elevated blood pressure, and low high-density lipoprotein (HDL) cholesterol increased the multivariate-adjusted odds ratio of glomerular hyperfiltration to 6.6 (95% CI: 3.8-11.6), 1.8 (95% CI: 1.0-3.0), and 2.5 (95% CI: 1.5-4.3), respectively. Systolic and diastolic blood pressures clustered together with leptin in the factor analysis and this blood pressure-adiposity component correlated with estimated creatinine clearance (r=0.329, P<0.0001) and explained on its own 10.2% of the variance in the estimated renal function. Our data reveal the silent epidemics of metabolic risk among young, apparently healthy men. Furthermore, the results indicate that high metabolic risk is associated with glomerular hyperfiltration before overt manifestations of cardiovascular disease.
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PMID:Glomerular hyperfiltration: a new marker of metabolic risk. 1763 26

Microalbuminuria (MA) is defined as a persistent elevation of albumin in the urine of >30 to <300 mg/d (>20 to <200 microg/min). Use of the morning spot urine test for albumin-to-creatinine measurement (mg/g) is recommended as the preferred screening strategy for all patients with diabetes and with the metabolic syndrome and hypertension. MA should be assessed annually in all patients and every 6 months within the first year of treatment to monitor the impact of antihypertensive therapy. It is an established risk marker for the presence of cardiovascular disease and predicts progression of nephropathy when it increases to frank microalbuminuria>300 mg/d. Data support the concept that the presence of MA is the kidney's warning that there is a problem with the vasculature. The presence of MA is a marker of endothelial dysfunction and a predictor of increased cardiovascular risk. MA can be reduced, and progression to overt proteinuria prevented, by aggressive blood pressure reduction, especially with a regimen based on medications that block the renin-angiotensin-aldosterone system, and control of diabetes. The National Kidney Foundation recommends that blood pressure levels be maintained at or below 130/80 mm Hg in anyone with diabetes or kidney disease.
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PMID:Microalbuminuria: what is it? Why is it important? What should be done about it? An update. 1734 95

Because of their wide range of actions on glucose homeostasis, lipid metabolism and vascular inflammation, peroxisome proliferator-activated receptors (PPARs) are promising targets for the development of new drugs for the treatment of metabolic disorders such as diabetes, dyslipidemia and atherosclerosis. In clinical practice, PPARalpha agonists, such as the already available fibrates, improve dyslipidemia, while PPARgamma agonists, such as thiazolidinediones, improve insulin resistance and diabetes. The complementary action of simultaneous activation of each PPAR in patients suffering from metabolic syndrome and type 2 diabetes has led to new pharmacological strategies focused on the development of agonists targeting more than one receptor such as the dual PPARalpha/gamma agonists. However, despite the proven benefits of targeting PPARs, safety concerns have recently led to late stage development failures of various PPAR agonists including novel specific PPARgamma agonists and dual PPARalpha/gamma agonists. These safety concerns include potential carcinogenicity in rodents, signs of myopathy and rhabdomyolysis, increase in plasma creatinine and homocysteine, weight gain, fluid retention, peripheral edema and potential increased risk of cardiac failure. Although the discontinued compounds shared common side effects, the reason for discontinuation was always compound specific and the toxicological or adverse effects which have motivated the discontinuation could be either due to the activation of PPARgamma, PPARalpha or both (class effect) or due to a PPAR unrelated effect. Thus, the risk evaluation of each adverse effect should be viewed on a case by case basis considering both the PPAR profile of the drug, its absorption/distribution profile, the nature of the side effect and the putative PPAR-related mechanism of action. This review mainly focuses on the preclinical and clinical adverse events of PPAR agonists that could be of concern when considering the development of new PPAR agonists. The selective modulation of PPAR activities is a promising approach to develop new drugs with preserved efficacy but diminished adverse effects.
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PMID:Safety issues and prospects for future generations of PPAR modulators. 1742 30

Progressive renal vascular sclerosis is a key feature of chronic kidney disease (CKD). Adiponectin, an adipokine with potent anti-inflammatory and antiatherosclerotic properties, is associated with insulin resistance, type II diabetes and cardiovascular disease. In this study, we evaluated the predictive value of adiponectin for the progression of CKD in patients enrolled in the Mild to Moderate Kidney Disease Study. The primary end point was defined as a doubling of the baseline serum creatinine and/or terminal renal failure in 177 patients who completed a prospective follow-up of 7 years. Patients who reached a progression endpoint (n=65) were significantly older, had higher baseline serum creatinine, proteinuria and adiponectin concentrations and more components of the metabolic syndrome. A gender-stratified Cox model revealed adiponectin in men as a significant predictor of progression after adjustment for age, glomerular filtration rate, and proteinuria. Male patients with adiponectin levels above their ROC analysis-derived optimal cutoff of 4 microg/ml had a significantly faster progression than patients below this point. This prospective long-term study in patients with CKD indicates high adiponectin as a novel independent predictor of disease progression in men but not in women. Our observation may be relevant for other conditions of progressive vascular sclerosis and diabetic nephropathy.
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PMID:Gender-specific association of adiponectin as a predictor of progression of chronic kidney disease: the Mild to Moderate Kidney Disease Study. 1755 49

To compare the risk factor demographics and the prevalence of chronic kidney disease (CKD), we analyzed two databases from the 1993 (N=143,948) and 2003 (N=154,019) mass screenings in Okinawa, Japan (Okinawa General Health Maintenance Association registry). We estimated the glomerular filtration rate (GFR) using serum creatinine (SCr) levels. SCr was measured by the modified Jaffe method in 1993 and by enzyme assay in 2003; the relation between the two methods was: SCr (Jaffe) = 0.194 + 1.079 x SCr (enzyme). CKD prevalence was compared using the estimated GFR calculated by the abbreviated Modification of Diet in Renal Disease (MDRD) equation. SCr was measured in 66.2% (1993) and 69.8% (2003) of the total screenees. Proteinuria was present in 3.4% (1993) and 4.3% (2003) of the total screened population, respectively. The prevalence of CKD (GFR<60 ml/min/1.73 m(2)) was similar between the two databases, being 15.7% in 1993 and 15.1% in 2003. However, the demographics of the CKD risk factors changed during the study period. The mean level of systolic blood pressure decreased, whereas the prevalence of obesity and the mean levels of serum cholesterol and fasting plasma glucose increased. In 2003, the estimated prevalence of metabolic syndrome in the general population of Japan calculated using the modified National Cholesterol Education Program (NCEP) criteria was 19.1%. The prevalence of CKD was significantly associated with that of metabolic syndrome: the age- and sex-adjusted odds ratio was 1.332 (95% confidence interval [CI], 1.277-1.389; p<0.0001). In conclusion, the demographics of the participants of the general screenings in Okinawa, Japan differed between the 1993 and 2003 screenings, but the prevalence of CKD seemed to be similar, or at least did not increase substantially, between the two databases.
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PMID:Changes in the demographics and prevalence of chronic kidney disease in Okinawa, Japan (1993 to 2003). 1746 Mar 72

The relation of metabolic syndrome (MetS) with cardiovascular outcome may be less evident when preclinical cardiovascular disease is present. We explored, in a post hoc analysis, whether MetS predicts cardiovascular events in hypertensive patients with electrocardiographic left ventricular hypertrophy (ECG-LVH) in the Losartan Intervention For Endpoint (LIFE) reduction in hypertension study. MetS was defined by >or=2 risk factors plus hypertension: body mass index >or=30 kg/m(2), high-density lipoprotein (HDL)-cholesterol <1.0/1.3 mmol/l (<40/50 mg/dl) (men/women), glucose >or=6.1 mmol/l (>or=110 mg/dl) fasting or >or=7.8 mmol/l (>or=140 mg/dl) nonfasting or diabetes. Cardiovascular death and the primary composite end point (CEP) of cardiovascular death, stroke and myocardial infarction were examined. In MetS (1,591 (19.3%) of 8,243 eligible patients), low HDL-cholesterol (72%), obesity (77%) and impaired glucose (73%) were similarly prevalent, with higher blood pressure, serum creatinine and Cornell product, but lower Sokolow-Lyon voltage (all P<0.001). After adjusting for baseline covariates, hazard ratios for CEPs and cardiovascular death (4.8+/-1.1 years follow-up) were 1.47 (95% confidence interval (CI), 1.27-1.71)- and 1.73 (95% CI, 1.38-2.17)-fold higher with MetS (both P<0.0001), and were only marginally reduced when further adjusted for diabetes, obesity, low HDL-cholesterol, non-HDL-cholesterol, pulse pressure and in-treatment systolic blood pressure and heart rate. Thus, MetS is associated with increased cardiovascular events in hypertensive patients with ECG-LVH, independently of single cardiovascular risk factors.
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PMID:Clusters of metabolic risk factors predict cardiovascular events in hypertension with target-organ damage: the LIFE study. 1747 91

Elevated serum uric acid is commonly seen in association with obesity, glucose intolerance, hypertension and dyslipidemia. There is currently no satisfactory explanation for the relation of uric acid and the metabolic syndrome (MetSyn). This study aimed to evaluate the relations of change in serum uric acid with changes in components of the MetSyn in young adults. We studied 1,249 male and 1,362 female black and white subjects aged 17-35 years (baseline) from the Coronary Artery Risk Development in Young Adults (CARDIA) Study, which attended a 10-year follow-up. Metabolic factors assessed at both time periods included BMI, waist circumference, blood pressure, fasting glucose, insulin, and lipids. Confounders examined (baseline and change variables) were serum creatinine, alcohol, smoking, physical activity, and oral contraceptives. Mean uric acid increased the most in black males (+0.5 mg/dl), followed by white males (+0.3 mg/dl) and black females (+0.2 mg/dl) (all P < 0.01), with the least change among white females (+0.1 mg/dl) (ns). Although change in all of the metabolic factors was associated with change in uric acid in the anticipated directions, in multivariable analyses only BMI and triglycerides had a significant independent association with uric acid in all race-sex-groups. Among confounders, only change in serum creatinine showed a strong independent association with uric acid. In conclusion, besides weight gain and renal excretion, increasing uric acid concentrations in young adults are strongly related to corresponding changes in triglycerides. The correlation of uric acid and triglycerides was found within the normal range and could not be explained by obesity.
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PMID:Ten-year change in serum uric acid and its relation to changes in other metabolic risk factors in young black and white adults: the CARDIA study. 1748 24


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