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)

11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) regenerates cortisol from inactive cortisone in liver and adipose tissue. Inhibition of 11 beta-HSD1 offers a novel potential therapy to lower intracellular cortisol concentrations and thereby enhance insulin sensitivity and hepatic lipid catabolism in type 2 diabetes, obesity, and hyperlipidemia. We evaluated this approach using the nonselective 11 beta-HSD inhibitor, carbenoxolone, in healthy men and lean male patients with type 2 diabetes. Six diet-controlled nonobese diabetic patients with hemoglobin A(1c) less than 8%, and six matched controls participated in a double-blind, cross-over comparison of carbenoxolone (100 mg every 8 h, orally, for 7 d) and placebo. They were admitted overnight for infusions of insulin (as required to maintain arterialized plasma glucose of 5.0 mM) and [13C6]glucose. Glucose kinetics were measured in the fasted state from 0700-0730 h, during a 3-h euglycemic hyperinsulinemic clamp (including somatostatin infusion and replacement of physiological GH and glucagon levels), and during a 2-h euglycemic hyperinsulinemic clamp with a 4-fold increase in glucagon levels. Data are the mean +/- SEM. Carbenoxolone had the expected effects of raising blood pressure and lowering plasma potassium. Carbenoxolone reduced total cholesterol in healthy subjects (5.25 +/- 0.34 vs. 4.78 +/- 0.40 mM; P < 0.01), but had no effect on other serum lipids or on cholesterol in diabetic patients. Carbenoxolone did not affect the rate of glucose disposal or the suppression of free fatty acids during hyperinsulinemia. However, carbenoxolone reduced the glucose production rate during hyperglucagonemia in diabetic patients (1.90 +/- 0.2 vs. 1.53 +/- 0.3 mg/kg x min; P < 0.05). This was attributable to reduced glycogenolysis (1.31 +/- 0.2 vs. 1.01 +/- 0.2 mg/kg x min; P < 0.005) rather than altered gluconeogenesis. These observations reinforce the potential metabolic benefits of inhibiting 11 beta-HSD1 in the liver of patients with type 2 diabetes. Further studies in obesity and hyperlipidemia are now warranted. However, clinically useful therapeutic effects will probably require selective 11 beta-HSD1 inhibitors that lower intraadipose cortisol levels and enhance peripheral glucose uptake.
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PMID:Effects of the 11 beta-hydroxysteroid dehydrogenase inhibitor carbenoxolone on insulin sensitivity in men with type 2 diabetes. 1251 67

The Incstar(R) SPQ II human haptoglobin (Hpt) (Incstar Corporation, Stillwater, MN) immunoturbidimetric assay was validated for the determination of serum and plasma Hpt concentrations in dogs and horses. The anti-human Hpt antiserum supplied with the assay, displayed monospecificity to both dog and horse serum Hpt by immunoelectrophoresis and Western blotting techniques. The automated immunoturbidimetric assay results correlated well with the cyanmethemoglobin binding assay (r=0.953 for canine serum and r=0.941 for equine serum), and had excellent precision at both high and low serum Hpt concentrations (within run and between run coefficients of variation near or less than 5%). The assay was linear in both species by serial dilution of pooled-high serum with pooled-low serum, saline and with Hpt-free serum. Interference from hemolysis (> 25 mg/dl hemoglobin) and lipemia greater than 100 mg/dl caused a false decrease and false increase respectively in Hpt yield with the immunoturbidimetric assay. The anti-Hpt antibody supplied with the assay kit, once diluted with polymer diluent and stored at 4 degrees C, was stable for up to 6 days and gave consistent results.
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PMID:Validation of human haptoglobin immunoturbidimetric assay for detection of haptoglobin in equine and canine serum and plasma. 1266 Sep 62

The prevalence and incidence of chronic heart failure (HF) have now reached epidemic proportions. However, the issue of the prevention of HF has been raised only recently. New US guidelines have introduced a new classification system that includes 4 categories: patients at risk, patients with asymptomatic left ventricular dysfunction, patients with symptomatic HF, and those with refractory HF. Because coronary artery disease is the major cause of HF, its risk factors are also those of HF. Hypertension favors the development of HF through accelerated atherosclerosis and increased left ventricular wall stress and hypertrophy. Left ventricular hypertrophy is also a powerful risk factor for HF, independent of blood pressure. Angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and diuretics are the antihypertensive agents that have been associated with favorable effects in patients with overt HF. Therefore, they may be preferred in the prevention of this syndrome. Diabetes is the most frequent noncardiac comorbidity of HF and is independently associated with an increased risk. Normalization of glycemic and glycosylated hemoglobin levels is a desirable goal of treatment. However, no direct evidence exists in the prevention of HF. A greater control of the other risk factors (eg, hypertension, hyperlipidemia) is, on the other hand, particularly important. Beta-blockers and ACE inhibitors have both been shown to have favorable effects across all spectrums of severity of HF. The ACE inhibitor ramipril has also been shown to prevent the development of HF in patients at risk without left ventricular dysfunction. The role of antiplatelet agents, warfarin, and statins is clear in the prevention of the coronary artery disease. However, it has not been adequately assessed in patients with HF and awaits the results of ongoing trials.
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PMID:Prevention and management of chronic heart failure in patients at risk. 1272 47

Type 1 diabetes mellitus is potentially associated with serious microvascular and macrovascular complications, although these are usually subclinical during the pediatric and adolescent years. There is no "grace" period for the beginnings of such complications. Duration of diabetes, glycemic control, age, and pubertal stage are critical factors contributing toward development of such problems. Other risk factors include family history (genetic predisposition), hyperlipidemia, hypertension, and smoking. The Diabetes Control and Complications Trial (DCCT) proved the importance of glycemic control and emphasized the ability of improved glucose control to prevent or decrease retinopathy, nephropathy, and neuropathy using a multidisciplinary same-philosophy-of-care approach plus targeted glucose and hemoglobin A(1c) values. Other natural history and intervention studies support the findings of the DCCT. Although our current tools are not perfect, they allow us to decrease microangiopathic complications very significantly if we educate our patients and their family members. Metabolic control counts.
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PMID:Complications of pediatric and adolescent type 1 diabetes mellitus. 1276 57

Spinal transection of one of a parabiotic pair of rats is immediately followed by a state indistinguishable in visual and hematologic characteristics from spontaneous "parabiosis intoxication." The transected rat develops erythremia, hyperhemoglobinemia, and an increased hematocrit count; whereas the twin concurrently shows anemia characterized by a decrease in hemoglobin, erythrocyte count, and hematocrit reading, and often also lipemia. These findings are ascribed to whole blood transfusion of one rat by the other followed by adjustments compensatory to the resulting distortion in the respective blood volumes. It is suggested that parabiosis intoxication is a manifestation of this same process and is not due, as has been contended, to an immune response.
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PMID:On the nature of parabiosis intoxication: shock as the precipitating cause. 1328 31

It has been proposed that the hexosamine pathway acts as a nutrient-sensing pathway, protecting the cell against abundant fuel supply, and that accumulation of hexosamines represents a biochemical mechanism by which hyperglycemia and hyperlipidemia induce insulin resistance. We hypothesized that if an increased flux through the hexosamine pathway caused insulin resistance in humans, the hexosamine levels should be increased in adipose and/or muscle tissue in insulin-resistant subjects, such as patients with type 2 diabetes and obese individuals. In addition, we reasoned that if the hexosamine pathway were a nutrient-sensing pathway, hexosamine levels in adipose and skeletal muscle tissue should be correlated with levels of circulating nutrients, such as glucose and free fatty acids (FFAs) and leptin concentrations. In a human cross-sectional study of 55 patients [20 with type 2 diabetes mellitus (DM) and 21 normal-lean (NL) and 14 normal-obese (NO) subjects] who underwent hip replacement surgery, adipose and muscle tissue biopsies were obtained and analyzed for levels of hexosamines [UDP-N-acetylglucosamine (UDP-GlcNAc) and UDP-N-acetylgalactosamine] and hexoses (UDP-glucose and UDP-galactose). Fasting plasma glucose, glycosylated hemoglobin, serum insulin and homeostasis model assessment calculations, serum lipids, and leptin were measured on the same day. Hexosamines were not elevated in adipose and muscle tissue of patients with type 2 DM compared with NL and NO subjects (UDP-GlcNac DM vs. NL vs. NO, 3.3 +/- 2.3 vs. 2.2 +/- 2.1 vs. 3.0 +/- 2.0 nmol/g tissue in adipose tissue and 8.1 +/- 2.9 vs. 7.8 +/- 2.8 vs. 7.6 +/- 2.8 nmol/g tissue in muscle tissue, respectively). Hexosamines in adipose tissue were positively correlated with circulating levels of FFA (UDP-GlcNAc, r = 0.33, P < 0.05; UDP-N-acetylgalactosamine, r = 0.41, P < 0.01). Adipose tissue UDP-GlcNAc was correlated with leptin levels (r = 0.33; P < 0.05). No such relationship was identified in muscle tissue. In conclusion, these findings argue against a pathophysiological role of the hexosamine pathway in insulin resistance in humans but support the hypothesis that the hexosamine pathway in adipose tissue, not in muscle, is a FFA-sensing pathway and could be involved in the regulation of leptin expression.
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PMID:Role of hexosamines in insulin resistance and nutrient sensing in human adipose and muscle tissue. 1547 17

Atherosclerotic disease accounts for much of the increased mortality and morbidity associated with type 2 diabetes. Epidemiological studies support the potential of improved glycemic control to reduce cardiovascular complications. An association between glycosylated hemoglobin (HbA(1c)) level and the risk for cardiovascular complications has frequently been reported. Most epidemiological data implicate postprandial hyperglycemia in the development of cardiovascular disease, whereas the link between fasting glycemia and diabetic complications is inconclusive. Moreover, in many studies, postprandial glycemia is a better predictor of cardiovascular risk than HbA(1c) level. Postprandial glucose may have a direct toxic effect on the vascular endothelium, mediated by oxidative stress that is independent of other cardiovascular risk factors such as hyperlipidemia. Postprandial hyperglycemia also may exert its effects through its substantial contribution to total glycemic exposure. The present review examines the hypothesis that controlling postprandial glucose level is an important strategy in the prevention of cardiovascular complications associated with diabetes.
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PMID:Postprandial glucose regulation and diabetic complications. 1550 21

The aim of this study was to examine whether motivating patients to gain expertise and closely follow their risk parameters will attenuate the course of microvascular and cardiovascular sequelae of diabetes. A randomized, prospective study was conducted of 165 patients who had type 2 diabetes, hypertension, and hyperlipidemia and were referred for consultation to a diabetes clinic in an academic hospital. Patients were randomly allocated to standard consultation (SC) or to a patient participation (PP) program. Both groups were followed by their primary care physicians. The mean follow-up was 7.7 yr. The SC group attended eight annual consultations. The PP patients initiated on average one additional consultation per year. There were 80 cardiovascular events (eight deaths) in the SC group versus 47 events (five deaths) in the PP group (P = 0.001). The relative risk (RR) over 8 yr for a cardiovascular event in the intervention (PP) versus the control (SC) group was 0.65 (95% confidence interval, 0.89 to 0.41). There were 17 and eight cases of stroke in the SC and PP groups, respectively (P = 0.05). RR for stroke was 0.47 (95% confidence interval, 0.85 to 0.32). In the SC group, 14 patients developed overt nephropathy (four ESRD) versus seven (one ESRD) in the PP group (P = 0.05). Throughout the study period, BP, LDL cholesterol, and hemoglobin A1c were significantly lower in the PP than in the SC patients. Well informed and motivated patients were more successful in obtaining and maintaining good control of their risk factors, resulting in reduced cardiovascular risk and slower progression of microvascular disease.
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PMID:Treatment of high-risk patients with diabetes: motivation and teaching intervention: a randomized, prospective 8-year follow-up study. 1593 28

The Konelab 20XT (Thermo Electron Oy, Finland) is a clinical chemistry analyzer for colorimetric, immunoturbidimetric and ion-selective electrode measurements. The aim of our work was to evaluate the analytical performances of the Konelab 20XT according to the European Clinical Chemistry Laboratory Standards Guidelines. A total of 30 analytes including substrates, enzymes, electrolytes and specific proteins were tested. Investigation results showed low imprecision (within-run coefficient of variation was below 3.5% and between-day coefficient of variation was less than 2.5% for most analytes at all three levels studied) and acceptable accuracy of the analyzer. No significant sample- or reagent-related carry-over was found. It was demonstrated that the analytical system operates within the claimed linearity ranges. The results compared well with those obtained by instruments routinely used in our laboratory (Olympus AU2700, Behring Nephelometer II). In general, the data on interference by hemoglobin, hyperbilirubinemia and turbidity are in accordance with known facts. However, slight hemolysis was found to interfere with the alkaline phosphatase (ALP) assay and mild lipemia affected the glucose assay. The Konelab 20XT is an easy-to-use analyzer that is suitable for routine and emergency analyses in small laboratories.
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PMID:Evaluation of the Konelab 20XT clinical chemistry analyzer. 1600 62

Cardiovacular disease is the main cause of morbidity and mortality in hemodialysis (HD) patients. However, there are no reliable data neither on the prevalence of cardiovacular disease nor its risk factors in Spain. The Morbidity and mortality Anemia Renal study (MAR) is a two-year multicenter, open-label, prospective cohorts study. Its main objective is to assess the general morbidity and mortality, particularly of a cardiovascular cause, and its relationship with the degree of anemia. Secondary objectives are: a/ the description of current clinical practices in anemia, dialysis, vascular access, and CV risk factor management; and b/ the description of hospitalization and mortality causes. This paper describes the prevalence of cardiovascular disease and risk factors of the HD population in Spain. A total of 1.710 patients were included (60% male, aged 64.4 years, 16.2 months on HD). The mean co-morbidity Charlson index was 6.5 +/- 2.3. Cardiovascular disease was the most prevalent comorbidity, 16.7% had a coronary disease, and 13.9% had different degrees of heart failure, while 11.6% had arrhythmia, 1.7% stroke and 5.5% peripheral artery disease. The prevalence of hypertension was 75.8%, 74.4% of patients received antihypertensive drugs, and still 40% of patients had an inadequate blood pressure control. The investigators considered as dyslipidemic 34.1% of patients, and prescribed treatment to 69.5% of them, while the remaining 30.5% (10.4% of the total) had hyperlipidemia with no drug therapy. Eleven percent was active smoker, and 26.6% former smoker. There was 47.4% of patients with a corporal mass index above 25. Secondary hyperparathyroidism with PTH above of 300 pg/ml was present in 22.2% of patients. Despite the EBPG and K-DOQI recommendations, only 68.8% of prevalent hemodialysis patients attained a hemoglobin (Hb) above 11 g/dl, 89.4% ferritin levels above 100 ng/ml, 66.5 degrees/a a transferrin saturation index (TSI) above 20%, and 61.1% met all three objectives. In summary, this first cross-sectional analysis has allowed us to know in detail the standard practice in multiple aspects of management of HD population in Spain. It has also established clear differences in the prevalence of cardiovascular disease and risk factors from the US registries. Last but not least we have identified therapeutic opportunities to improve the course and prognosis of our patients.
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PMID:[Cardiovascular risk in hemodialysis in Spain: prevalence, management and target results (MAR study)]. 1605 11


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