Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The monitoring of diabetic patients by evaluating glycated protein levels is now widely accepted and performed. The microchromatographic version of the high performance liquid chromatography method is the technique most frequently used in clinical practice. The DCA 2000 instrument (Bayer Diagnostics, Milan, Italy), based on an immunochemical technique, has been proposed for the rapid and simple evaluation of HbAlc, using even capillary blood. We evaluated 171 subjects including 22 healthy volunteers, 78 type 2 diabetic patients with different degrees of metabolic control, 11 women affected by gestational diabetes mellitus (GDM), 6 patients with hyperlipemia, 38 patients with chronic renal failure, 13 diabetic patients with chronic renal failure, and 3 patients with hemoglobinopathies. The DCA 2000 model was compared with the Diamat HPLC system. Data from within-run imprecision studies showed excellent precision, for both DCA 2000 and the HPLC system. The correlation between the two different systems, as shown by other statistical evaluations, was good (y = 0.911x + 0.462, r = 0.923). Results from the control group and diabetic patients were used to compare the two methods. Values obtained using the DCA 2000 were significantly lower (p < 0.0001) than those obtained with the HPLC system, in both healthy subjects and diabetic patients. To detect possible interferences, selected samples were analyzed from patients with hyperlipemia, diabetes and chronic renal failure, and hemoglobinopathies. While in the case of hyperlipemia, an acceptable correlation coefficient between the two systems was confirmed (y = 1.047x - 1.236, r = 0.876), in the case of chronic renal failure the correlation turned out to be very low (y = 0.254x + 3.456, r = 0.203). Our results indicate that the DCA 2000 gives accurate and reliable results in the clinical field of interest.
Acta Diabetol 2000 Mar
PMID:Evaluation of diagnostic reliability of DCA 2000 for rapid and simple monitoring of HbA1c. 1092 29

Fluvastatin, the first fully synthetic HMG-CoA reductase inhibitor, has been shown to reduce cholesterol in patients with hyperlipidaemia, to prevent subsequent coronary events in patients with established coronary heart disease, and to alter endothelial function and plaque stability in animal models. Fluvastatin is relatively hydrophilic, compared with the semisynthetic HMG-CoA reductase inhibitors, and, therefore, it is extensively absorbed from the gastrointestinal tract. After absorption, it is nearly completely extracted and metabolised in the liver to 2 hydroxylated metabolites and an N-desisopropyl metabolite, which are excreted in the bile. Approximately 95% of a dose is recovered in the faeces, with 60% of a dose recovered as the 3 metabolites. The 6-hydroxy and N-desisopropyl fluvastatin metabolites are exclusively generated by cytochrome P450 (CYP) 2C9 and do not accumulate in the blood. CYP2C9, CYP3A4, CYP2C8 and CYP2D6 form the 5-hydroxy fluvastatin metabolite. Because of its hydrophilic nature and extensive plasma protein binding, fluvastatin has a small volume of distribution with minimal concentrations in extrahepatic tissues. The pharmacokinetics of fluvastatin are not influenced by renal function, due to its extensive metabolism and biliary excretion; limited data in patients with cirrhosis suggest a 30% reduction in oral clearance. Age and gender do not appear to affect the disposition of fluvastatin. CYP3A4 inhibitors (erythromycin, ketoconazole and itraconazole) have no effect on fluvastatin pharmacokinetics, in contrast to other HMG-CoA reductase inhibitors which are primarily metabolised by CYP3A and are subject to potential drug interactions with CYP3A inhibitors. Coadministration of fluvastatin with gastrointestinal agents such as cholestyramine, and gastric acid regulating agents (H2 receptor antagonists and proton pump inhibitors), significantly alters fluvastatin disposition by decreasing and increasing bioavailability, respectively. The nonspecific CYP inducer rifampicin (rifampin) significantly increases fluvastatin oral clearance. In addition to being a CYP2C9 substrate, fluvastatin demonstrates inhibitory effects on this isoenzyme in vitro and in vivo. In human liver microsomes, fluvastatin significantly inhibits the hydroxylation of 2 CYP2C9 substrates, tolbutamide and diclofenac. The oral clearances of the CYP2C9 substrates diclofenac, tolbutamide, glibenclamide (glyburide) and losartan are reduced by 15 to 25% when coadministered with fluvastatin. These alterations have not been shown to be clinically significant. There are inadequate data evaluating the potential interaction of fluvastatin with warfarin and phenytoin, 2 CYP2C9 substrates with a narrow therapeutic index, and caution is recommended when using fluvastatin with these agents. Fluvastatin does not appear to have a significant effect on other CYP isoenzymes or P-glycoprotein-mediated transport in vivo.
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PMID:Clinical pharmacokinetics of fluvastatin. 1136 92

We evaluated the possible additive effect of overweight and diabetes in the occurrence of coronary heart disease (CHD) and stroke, and their interaction with other established risk factors. In a cross-sectional study, we evaluated the frequency of CHD and stroke in four groups of subjects: (1) lean non-diabetic subjects (n=250); (2) lean diabetic subjects (n=269); (3) overweight non-diabetic subjects (n=203); and (4) overweight diabetic subjects (n=446). CHD was more frequent among diabetic subjects, and even more among overweight diabetic subjects; stroke was more frequent among diabetic subjects, but equally frequent in overweight and in lean diabetic subjects. At multiple logistic regression analysis, age, arterial hypertension, diabetes were independent risk factors for CHD and for stroke; BMI and hyperlipidemia were risk factors only for CHD. CHD was an independent risk factor for stroke, and stroke was a risk factor for CHD. We conclude that obesity and diabetes are additional risk factors for CHD but not for stroke. The value of established risk factors such as arterial hypertension and hyperlipidemia in determining the appearance of CHD and stroke is maintained in the presence overweight and diabetes. Finally, CHD is frequently associated with stroke, suggesting a common process of atherosclerosis underlying both diseases.
Acta Diabetol 2002 Jun
PMID:Additive effect of overweight and type 2 diabetes in the appearance of coronary heart disease but not of stroke: a cross-sectional study. 1212 Sep 18

Obesity, impaired glucose tolerance, type 2 diabetes, hyperlipidemia, hypertension, and insulin resistance are wellknown components of metabolic syndrome and are associated to increased cardiovascular morbidity. The present study aimed to evaluate the relationships between cardiorespiratory fitness, body fat distribution, and selected coronary heart disease risk factors. A total of 22 untrained subjects affected by one or more features of metabolic syndrome and without clinical history of cardiovascular disease were studied. Nondiabetic subjects underwent an oral glucose tolerance test for glucose and insulin measurement; fasting glucose and insulin were measured in diabetic patients. Complete lipid profile, thyroid hormones, and thyroid-stimulating hormone were measured in all subjects. Basal energy expenditure and cardiorespiratory fitness were measured using a K4 analyzer. Cardiorespiratory fitness ( VO(2max)/kg) was assessed using a treadmill graded exercise test. Peak aerobic capacity ( VO(2max)/kg) was predicted by body fat distribution, insulin sensitivity index, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol ( p<0.001). A significant relationship was found between cardiorespiratory fitness ( VO(2max)/kg) and body mass index (BMI), insulin sensitivity index, and LDL cholesterol ( r=0.60, p<0.05; r=0.66, p<0.01 and r=0.54, p<0.05, respectively). Data demonstrated that aerobic fitness is related to metabolic parameters and to body fat distribution, and suggest that its modification may improve well-known predictors of coronary artery disease.
Acta Diabetol 2003 Oct
PMID:Lipid profile, BMI, body fat distribution, and aerobic fitness in men with metabolic syndrome. 1461 52

The metabolic syndrome is characterized by diabetes mellitus, obesity, hypertension, hyperlipidaemia and polycystic ovary syndrome. The lipid profiles of patient with metabolic syndrome is often characterized by the appearance of hypertrygliceridaemia and small, dense LDL-cholesterol, together with low HDL-cholesterol. Patients with these abnormalities are at an increased risk for premature coronary artery disease. Treatment is a multifactorial process and includes modification of lifestyle factors such as diet and physical activity, weight reduction, correction of dyslipidemia, meticulous blood pressure and glycemic control. The case of a 36-year-old woman who develops metabolic syndrome is discussed.
Acta Diabetol 2003 Dec
PMID:Metabolic syndrome. 1470 75

The effects of gamma-oryzanol, a drug mainly used for the treatment of hyperlipidaemia, on several cytochrome P450 (CYP) specific reactions in human liver microsomes were investigated to predict drug interactions with gamma-oryzanol in vivo from in vitro data. The following eight CYP catalytic reactions were used in this study: CYP1A1/2-mediated 7-ethoxyresorufin O-deethylation, CYP2A6-mediated coumarin 7-hydroxylation, CYP2B6-mediated 7-benzyloxyresorufin O-debenzylation, CYP2C8/9-mediated tolbutamide methylhydroxylation, CYP2C19-mediated S-mephenytoin 4'-hydroxylation, CYP2D6-mediated bufuralol 1'-hydroxylation, CYP2E1-mediated chlorzoxazone 6-hydroxylation, and CYP3A4-mediated testosterone 6beta-hydroxylation. gamma-Oryzanol had little inhibitory effects on CYP activities, indicating that this compound would not be expected to cause clinically significant interactions with other CYP-metabolized drugs at expected therapeutic concentrations.
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PMID:Effect of gamma-oryzanol on cytochrome P450 activities in human liver microsomes. 1525 60

Obesity, now an epidemic in the USA, northern Europe, and Italy, is associated with several co-morbidities that shorten life expectancy, in particular type 2 diabetes mellitus (T2DM), arterial hypertension, and hyperlipidemia. The impact of obesity on mortality is evident in all ages, and is especially strong in young persons. Obesity, especially visceral obesity, associated with a sedentary lifestyle, is among the strongest risk factors for T2DM, and a diagnosis of T2DM seems to increase linearly as a function of duration of obesity. The pathogenesis of T2DM is based on a dual defect, i.e. increased insulin resistance coupled with defective insulin release. The main abnormality in obesity is increased insulin resistance, while insulin release, even though defective compared with body needs, is usually abundant. The incidence of obesity among children aged 6-16 years is now even greater than that among adults: in Italy, figures up to 30% have been reported. As in adults, obesity is a cause, among children, of arterial hypertension, left ventricular hypertrophy, hyperlipidemia, non-alcoholic-steato hepatitis, sleep apnea syndrome (SAS), and orthopedic, psychological, and social problems. Together with an increase in body weight, there is an increase of visceral fat. Obesity in children has also led to a tremendous increase in the prevalence of impaired glucose tolerance (IGT); the percentages span from 25% in a multiethnic cohort in the USA, to 4% in Italian Caucasians. Management of obesity and of T2DM in children has to face the issue of poor compliance; there is consensus that dietary treatment of obese T2DM children is a failure, so that drugs are required; the only drug evaluated in a formal trial is metformin, that behaves in terms of efficacy and of minor side effects as in adults. In conclusion, obesity in children is not pure obesity, but is accompanied by co-morbidities that cluster to form the "metabolic syndrome" just like in the adults. If this epidemics continues and is not properly challenged, in the next decades we will face an epidemic of early cardiovascular morbidity and mortality.
Acta Diabetol 2004 Sep
PMID:Type 2 diabetes mellitus is becoming the most common type of diabetes in school children. 1566 74

The role of resistin in human biology remains uncertain. We measured serum resistin levels in Japanese patients with (n=111) and without (n=98) type 2 diabetes mellitus and investigated the significance of this hormone in the pathophysiology of diabetes. The levels of serum adiponectin and leptin were also measured. Resistin levels were increased significantly in patients with type 2 diabetes compared with non-diabetic subjects (24.7+/-2.6 vs. 15.0+/-1.2 ng/ml, p=0.0013). However, there was no correlation in either patient group between serum resistin levels and markers of insulin resistance, obesity or hyperlipidaemia. These results were in direct contrast to the data of leptin or adiponectin, both of which were closely related to these clinical markers of diabetes. Multivariate regression analysis on the combined data of the two groups demonstrated that the presence of diabetes and HDL cholesterol levels were significant predictors of serum resistin levels (diabetes: beta=0.159, p=0.035; HDL: beta=-0.172, p=0.039). No correlation was observed between C-reactive protein and resistin adjusted for BMI. Taken together, these findings demonstrate that serum resistin levels are increased in patients with type 2 diabetes, but this increase is not linked to markers of insulin resistance or adiposity. Further studies are necessary to elucidate the significance of serum resistin concentration in human pathophysiology.
Acta Diabetol 2005 Jun
PMID:Increased serum resistin levels in patients with type 2 diabetes are not linked with markers of insulin resistance and adiposity. 1594 45

Combined palsies of cranial nerves, especially of the oculomotor nerves, are distinctly uncommon, even in patients with diabetes mellitus. We present a patient with type 2 diabetes mellitus, arterial hypertension and hyperlipidaemia, who had simultaneous oculomotor and trochlear nerve palsies. An MRI scan showed multiple brainstem ischaemic infarcts. The patient was treated with intensified insulin regimen and clopidogrel. Symptoms gradually improved, and at 9 months there was no further improvement.
Acta Diabetol 2006 May
PMID:Simultaneous, painless, homolateral oculomotor and trochlear nerve palsies in a patient with type 2 diabetes mellitus. Neuropathy or brainstem infarction? 1671 Jun 45

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


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