Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate whether molecular variation in the renin gene contributes to the greater blood pressure of spontaneously hypertensive rats (SHR) versus normotensive Brown Norway (BN) rats, we measured blood pressure in an SHR progenitor strain and an SHR congenic strain that are genetically identical except at the renin gene and an associated segment of chromosome 13 transferred from the BN strain. Backcross breeding and molecular selection at the renin locus were used to create the SHR congenic strain (designated SHR.BN-Ren) that carries the renin gene transferred from the normotensive BN strain. We found that transfer of the renin gene from the BN strain onto the genetic background of the SHR did not decrease blood pressure in rats fed either a normal or high-salt diet. In fact, the systolic blood pressures of the SHR congenic rats tended to be slightly greater than the systolic blood pressures of the SHR progenitor rats. However, the congenic strain exhibited lower serum high-density lipoprotein cholesterol, and greater levels of total cholesterol, very-low-density lipoprotein, and intermediate-density lipoprotein cholesterol during administration of a high-fat, high-cholesterol diet. These findings demonstrate that (1) under the environmental circumstances of the current study, the greater blood pressure of SHR versus BN rats cannot be explained by strain differences in the renin gene and (2) a quantitative trait locus affecting lipid metabolism exists on chromosome 13 within the transferred chromosome segment. The SHR.BN-Ren congenic strain may provide a useful new animal model for studying the interaction between high blood pressure and dyslipidemia in cardiovascular disease.
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PMID:Effect of renin gene transfer on blood pressure in the spontaneously hypertensive rat. 945 31

Insulin resistance is characterized principally by impaired insulin-mediated glucose uptake which provokes a compensatory increase in pancreatic beta-cell secretory activity. For a time this may produce well-controlled plasma glucose levels but as the insulin resistance worsens the augmented insulin production becomes inadequate to keep plasma glucose at euglycemia leading to the development of non-insulin dependent diabetes mellitus (NIDDM), accompanied by hyperinsulinemia and hyperglycemia. A number of metabolic defects are associated with NIDDM including obesity, hypercoagulability, cardiovascular disease risk factors such as hypertension and dyslipidemia and these constitute the insulin resistance syndrome. The identity of the biochemical factor that might link all these defects is not yet known. We have hypothesized that platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, PAF) may be such a link. In this study, we measured plasma acetylhydrolase (EC.1.1.48), which degrades PAF to the inactive metabolise lyso-PAF, as a surrogate for PAF activity in three groups of hypercholesterolemic subjects: lean controls (n = 9), non-diabetic obese (n = 6) and NIDDM subjects (n = 6). The ages and body mass indices of the subjects were 46 +/- 3.1 and 24.2 +/- 2.2 for the lean controls, 52 +/- 2.5 and 28.7 +/- 0.9 for the NIDDM subjects and 60 +/- 2 and 27.6 +/- 2.1 for the obese, non-diabetic subjects (mean +/- S.E.M.). The measurements were made before and after therapy with the cholesterol-lowering drug lovastatin, a 3-hydroxy 3 methylglutaryl (HMG) coenzyme. A reductase inhibitor (40 mg/day) for 3 months. Fasting plasma glucose (FPG) levels were 91 +/- 11, 96 +/- 3 and 146 +/- 11 mg/dl, for the lean, obese and NIDDM subjects, respectively, before therapy began. Lovastatin did not affect FPG in any of the three subject groups. Before treatment, the fasting plasma insulin (FPI) levels were 6.1 +/- 0.92, 10.83 +/- 2.03 and 14.68 +/- 3.64 mU/l for the lean, non-diabetic obese and NIDDM subjects, respectively. After lovastatin therapy only the obese group exhibited a significant change in FPI (15.35 +/- 2.47 mU/l) (P < 0.05). Total cholesterol levels were similar in all three groups both before and after lovastatin therapy but within each group lovastatin therapy significantly reduced the total cholesterol by 32, 29 and 34% in the lean, obese and NIDDM subject groups respectively (P < 0.0001). Lovastatin therapy reduced LDL-cholesterol levels by 40, 32 and 46% in the lean, obese and NIDDM subjects, respectively, but produced no significant effect on HDL or triglyceride levels. Before therapy, the plasma acetylyhydrolase activities were 104 +/- 7, 164 +/- 7 and 179 +/- 7 nmol/ml per min in the lean, obese and NIDDM subjects, respectively. Lovastatin therapy reduced plasma acetylhydrolase levels to 70 +/- 7, 87 +/- 6 and 86 +/- 7 nmol/ml per min in the lean, obese and NIDDM subjects, respectively. Plasma acetylhydrolase activity was predominantly (> 80%) associated with LDL cholesterol both before and after lovastatin treatment. Also, plasma acetylhydrolase activity significantly correlated with fasting plasma insulin levels before lovastatin therapy but not after. Taken together, this study clearly implicates PAF metabolism in three defects associated with the insulin resistance syndrome: hypercholesterolemia, obesity and NIDDM. Additionally, we conclude that chronic hyperinsulinemia may play a significant role in the production of plasma acetylhydrolase.
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PMID:Plasma PAF acetylhydrolase in non-insulin dependent diabetes mellitus and obesity: effect of hyperinsulinemia and lovastatin treatment. 945 36

Dyslipidemia is a major factor associated with cardiovascular disease, which is the leading cause of death in hemodialysis patients. Low molecular weight heparin (LMWH) is superior to conventional unfractionated heparin in treating hyperlipidemia in nondiabetic long-term hemodialysis patients and has fewer side-effects. Only a few reports have addressed the influence of LMWH on serum lipids in diabetic patients, although dyslipidemia is common among this population. We investigated the effect of LMWH on serum lipids in 12 nondiabetic and eight diabetic hypercholesterolemic patients receiving long-term hemodialysis. Patients had been receiving hemodialysis with unfractionated heparin for a minimum of 6 months before beginning the study. Continuous LMWH infusion during hemodialysis was administered to all patients for 2 months, followed by unfractionated heparin administration for 2 months. During LMWH treatment, plasma anti-factor Xa activity increased from 0.06 +/- 0.04 IU/mL before dialysis to 0.49 +/- 0.25 IU/mL after 3 hours. Serum total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and apolipoprotein B (Apo B) in both nondiabetic and diabetic patient groups and lipoprotein (a) (Lp(a)) in patients with higher initial values (> or = 15 mg/mL) decreased significantly after LMWH treatment (TC from 6.38 +/- 1.14 to 5.07 +/- 1.09 mmol/L, LDL-C from 3.08 +/- 0.93 to 2.15 +/- 0.88 mmol/L, Apo B from 100 +/- 18 to 78 +/- 18 mg/dL, all p < 0.01; Lp(a) from 41.8 +/- 34.5 to 28.5 +/- 22.8, p < 0.05). They rebounded to pre-LMWH levels after the 2 months on unfractionated heparin (TC 5.72 +/- 1.11 mmol/L, LDL-C 2.97 +/- 1.01 mmol/L, Apo B 98 +/- 20 mg/dL, Lp(a) 38.1 +/- 29.0 mg/dL). We conclude that continuous infusion of LMWH during dialysis reduces serum total cholesterol, low-density lipoprotein-cholesterol, and apolipoprotein B concentrations in both diabetic and nondiabetic hypercholesterolemic hemodialysis patients, and does not increase the risk of bleeding compared with unfractionated heparin.
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PMID:Low molecular weight heparin in diabetic and nondiabetic hypercholesterolemic patients receiving long-term hemodialysis. 948 Oct 65

The high prevalence rate of mortality in diabetic patients is explained by atherothrombotic cardiovascular disease. Hyperinsulinemia and insulin resistance, dyslipidemia, chronic hyperglycemia, decrease of endothelial cells and of monocytes-macrophage cell functions, and hypercoagulability are the main side-effects which are involved in the pathogenesis of diabetic atherothrombotic disease. Its clinical manifestations are coronary heart disease, peripheral vascular insufficiency, cerebral vascular insufficiency and reno-vascular hypertension. The common characteristics are a clinical latent period, the frequency of acute complications and the widespread bilateral distal localisation of vascular insufficiency. The therapeutic strategy in diabetic atherothrombotic disease is becoming better codified, leading to screening and prevention. The evaluation of diabetic vascular risk could reduce the prevalence of thrombotic events.
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PMID:[Management of diabetic vasculopathy]. 950 77

Cardiovascular disease is the leading cause of death in Louisiana and in the United States. Louisiana women have the second highest mortality rate for cardiovascular disease in the country. The major risk factors in both men and women include cigarette smoking, hypertension, dyslipidemia, diabetes mellitus, obesity, sedentary lifestyle, and poor nutrition. A body of evidence is accumulating to support the existence of nontraditional risk factors such as elevated homocysteine levels and antioxidants. Gender-specific risks and interventions also exist in the form of oral contraceptives and hormone replacement therapy respectively. Raloxifene and other selective estrogen receptive modulators may alter the regimens of hormone replacement therapy in the future. This article reviews cardiac risk factors focusing on gender differences, the arguments for and against hormone replacement therapy as it relates to coronary disease, and some practical aspects of hormone replacement therapy that physicians encounter when considering hormone replacement therapy in the postmenopausal woman.
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PMID:Coronary heart disease risk factors in women: focus on gender differences. 951 Jun 11

Both insulin resistance and abdominal fat patterning are related to aging, and have been related to cardiovascular disease (CVD) risk factors such as dyslipidemia and hypertension. However, previous studies have not used direct methods to quantify the independent strength of the association of each of these two putative primary factors with metabolic outcomes. We quantified overall obesity by the body mass index (BMI) and used a previously validated magnetic resonance imaging (MRI) method to quantify abdominal fat in 63 healthy nondiabetic individuals aged 22 to 83 years. We also measured the glucose and insulin response to an oral glucose tolerance test and the insulin sensitivity ([SI] by modified minimal model analysis). Body fat patterning was evaluated by the waist to hip ratio (WHR) and by MRI, which allowed direct measurement of subcutaneous (SCF) and intraabdominal (IAF) fat depots at the umbilicus in these subjects. These independent parameters were related to risk factors for CVD (blood pressure, lipids, and lipoproteins) and to plasma concentrations of free fatty acids (FFAs). Measures of overall obesity (BMI), total fat [TF], and/or SCF measured at the abdomen by MRI), glucose/insulin metabolism and SI, and central fat patterning (WHR or IAF measured by MRI) were correlated with mean arterial pressure (MAP), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) levels in univariate analysis and after controlling for age and gender. An index of central fat patterning (WHR) added to the informativeness of the insulin area under the curve (IAUC) in explaining 24% of the variability in plasma TG concentration, but measures of overall obesity were not independently related. Both the BMI and TF contributed to the IAUC in explaining 32% to 34% of the variability in MAP, but central fat patterning was not independently related. No index of overall obesity, fat patterning, glucose/insulin metabolism, and/or SI, was independently related to the plasma concentration of HDL-C after controlling for any one of the other two. Direct measurement of glucose/insulin metabolism and SI, as well as fat patterning, provides information on their relative associations with CVD risk factors. The measures of glucose/insulin metabolism and SI were more consistently related to dyslipidemia and hypertension than were the overall obesity and fat patterning in this healthy population.
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PMID:Insulin resistance and fat patterning with aging: relationship to metabolic risk factors for cardiovascular disease. 955 May 36

Non-insulin-dependent diabetes mellitus (NIDDM) affects approximately 12 million people in the United States. NIDDM is frequently found to coexist with other conditions, such as obesity, dyslipidemia, atherosclerotic vascular disease, and hypertension, which contribute to morbidity and mortality. Although the major clinical objective in the management of NIDDM is to control hyperglycemia, the long-term objective is to prevent microvascular and macrovascular complications. Cardiovascular disease is the major cause of death in NIDDM patients. Although hyperglycemia may be adequately controlled, risk factors for coronary heart disease may remain unchanged. Treatment with metformin controls hyperglycemia and may have positive effects on cardiovascular risk factors. When used alone or in combination with sulfonylureas, metformin tends to stabilize or decrease weight, maintains or reduces insulin levels, has beneficial effects on plasma lipid profiles, and may also have beneficial effects on blood pressure and the fibrinolytic system.
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PMID:Metformin: effects on cardiovascular risk factors in patients with non-insulin-dependent diabetes mellitus. 955 89

Insulin sensitivity varies greatly within the general population; factors contributing to this variability include genetic pre-disposition, obesity, unfavorable body fat distribution, and lack of physical activity. Impaired insulin sensitivity may lead to impaired glucose tolerance and, even in individuals with modest insulin deficiency, to the development of type 2 diabetes mellitus. Of equal concern in patients with impaired insulin sensitivity is the development of the insulin resistance syndrome, in which hypertension, dyslipidemia, and impaired glucose tolerance form a cluster of risk factors for cardiovascular disease. Treatment of insulin resistance includes metformin and the thiazolidinedione troglitazone. Both drugs have been shown to be effective in the treatment of insulin resistance, one of the central abnormalities in type 2 diabetes mellitus. The purpose of this study was to review the current understanding of insulin resistance and its implications for the treatment of type 2 diabetes mellitus. To do this, a MEDLINE search of the clinical literature was conducted and the content analyzed.
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PMID:Insulin resistance: current concepts. 958 14

Microalbuminuria is a strong predictor of cardiovascular disease. The aim of this study was to investigate whether microalbuminuria is part of a cluster of risk factors, the insulin resistance syndrome (IRS), or whether it is only associated with, and presumably a complication of, hypertension and non-insulin-dependent diabetes mellitus (NIDDM). An age-, sex- and glucose tolerance-stratified random sample from a 50-75 year old general population (n = 622) was investigated. The urinary albumin-to-creatinine ratio was measured in an early morning spot urine sample. Microalbuminuria was defined as an albumin-to-creatinine ratio greater than 2.0 mg/ mmol. We considered, as IRS-related variables, fasting hyperinsulinaemia, insulin resistance (IR; calculated from the formula of the homeostasis model assessment), dyslipidaemia, glucose intolerance, hypertension and waist-to-hip ratio (WHR). Dyslipidaemia was defined as levels of HDL-cholesterol in the lowest and/or levels of triglyceride in the highest tertile. Fasting insulin levels, IR and WHR were divided into tertiles; the highest tertiles were compared to the lowest tertiles. Age-, sex- and glucose tolerance-adjusted analyses showed microalbuminuria to be significantly associated with hypertension, NIDDM and WHR. In multiple logistic regression analyses, microalbuminuria showed independent associations with hypertension, NIDDM and WHR, with odds ratios (ORs [95% confidence interval]) of 3.33 (1.86-5.96), 2.26 (1.14-4.48) and 2.49 (1.09-5.70), respectively. No associations were found with impaired glucose tolerance, hyperinsulinaemia, IR or dyslipidaemia. Multiple logistic regression analyses in diabetic and non-diabetic subjects separately showed that microalbuminuria was independently associated only with hypertension (ORs 4.31 and 2.69). In this Caucasian population, microalbuminuria was associated with hypertension, NIDDM and WHR and not with other variables of the IRS. It is therefore likely that microalbuminuria is a complication of hypertension and NIDDM, and not an integral part of the IRS.
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PMID:Microalbuminuria is strongly associated with NIDDM and hypertension, but not with the insulin resistance syndrome: the Hoorn Study. 966 52

Hyperglycemia and dyslipidemia are two biochemical markers of diabetes mellitus. Increased incidence of cardiovascular disease and impaired fibrinolytic activity have been found in diabetic subjects. Previous studies have demonstrated that low density lipoproteins (LDLs) stimulate the production of plasminogen activator inhibitor-1 (PAI-1) and reduce the generation of tissue plasminogen activator (tPA) in vascular endothelial cells (ECs). The present study investigated the effect of glycated LDL on the production of PAI-1 and tPA in cultured human umbilical vein ECs (HUVECs). Glycation increased the abundance of glucitollysine and conjugated dienes in LDL and amplified the overproduction of PAI-1 and the reduction in tPA generation from HUVECs induced by LDL. The steady-state levels of PAI-1 mRNA in glycated LDL-treated ECs were significantly higher than those in native LDL-treated cells. Actinomycin D blocked the increase in PAI-1 generation induced by glycated LDL. Glycated LDL did not significantly reduce the levels of tPA mRNA but attenuated de novo synthesis of tPA in ECs. Treatment with 25 mmol/L aminoguanidine, an antioxidant and inhibitor of the formation of advanced glycation end products, during glycation normalized glycated LDL-induced generation of PAI-1 and tPA in ECs. The results of the present study indicate that glycation enhances the production of PAI-1 and attenuates tPA synthesis in ECs induced by LDL, which may contribute to the increased incidence of cardiovascular complications in diabetes. Formation of advanced glycation end products or peroxidation may be involved in glycated LDL-induced alterations in the generation of fibrinolytic regulators from ECs.
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PMID:Influence of glycation on LDL-induced generation of fibrinolytic regulators in vascular endothelial cells. 967 75


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