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

Many models of diabetes dyslipidemia are available. Animals with chemically-induced diabetes have been used to study insulin-dependent diabetes. Hypercholesterolemia in streptozotocin-induced diabetes in rats results from increased intestinal absorption and synthesis of cholesterol. Lipoproteins from diabetic rats are oxidized and demonstrate cytotoxicity, a feature which can be prevented by insulin or antioxidant treatment. Diabetic rabbits fed a cholesterol-rich diet do not develop atherosclerotic lesions because accumulated VLDL are apo E-depleted, too large and do not enter into the arterial wall. Models for non-insulin-dependent diabetes (NIDDM) are obtained through selective breeding or dietary conditions. The obese Zucker rat (fa/fa) is characterized by hyperphagy, hyperglycaemia, hyperinsulinemia, insulin-resistance, hypertriglyceridemia and hypercholesteolemia. It responds to dietary, hormonal and drug treatments, but does not develop atherosclerosis spontaneously. It is used as a model for obesity, NIDDM and type IV hyperlipidemia. The JCR:LA cp rat bears the corpulent gene and develops similar characteristics to those of the Zucker rat. However, insulin-resistance is more severe in homozygous males (cp/cp), and cardiovascular lesions are observed. Their appearance is reduced by treatments which decrease hyperinsulinemia and insulin resistance but not by lowering lipid levels alone. The sand rats (Psammomys obesus) develop obesity and NIDDM when fed a laboratory diet. When cholesterol and anti-thyroid drug are added to the diet, they develop cardiovascular lesions. This species constitutes a new model for studying atherosclerosis-related diabetes.
 ...
PMID:Dyslipidemia and diabetes: animal models. 762 69

Sterol carrier protein-2 (SCP2) is a 13.2-kilodalton protein that has been implicated in intracellular cholesterol transport, whereas a related sterol carrier protein, sterol carrier protein-X (SCPx; 58 kilodaltons) has been suggested to function also in the beta-oxidation of fatty acids. Although diabetes-related hyperlipidemia and altered cholesterol metabolism have been extensively studied, the intracellular cholesterol transport capacity during hyperglycemic states has not been examined. The fact that beta-oxidation is increased in diabetes whereas hepatic cholesterol metabolism is reduced suggests that differential expression of these sterol carrier proteins may accompany diabetic dyslipidemia. In this study, SCP2 protein levels were reduced by 60% in mildly hypercholesterolemic (cholesterol, > 130 and < 150 mg/dl; P < 0.01) diabetic rats and by 90% in severely hypercholesterolemic (cholesterol, > 150 mg/dl; P < 0.002) diabetic animals. In contrast, hepatic SCPx protein expression increased (3.5-fold) after diabetes induction with streptozotocin (STZ). The decline in SCP2 was inversely related to serum cholesterol levels. Hepatic SCP messenger RNA levels examined by ribonuclease protection assay demonstrated that hepatic SCP messenger RNA was increased 2-fold in diabetic animals. Northern blot analysis indicated that both the 0.8-kilobase SCP2-specific and the 2.1-kilobase SCPx-specific transcripts increased after STZ injection. SCPx protein induction preceded the decline in SCP2 by 4-5 days. Insulin treatment reversed the increase in SCPx and prevented the decline in SCP2. We conclude that SCP2 and SCPx are differentially expressed in the STZ-diabetic rat and suggest that this change in SCP expression should be considered a potential contributing mechanism through which cholesterol metabolism may be altered in diabetes.
 ...
PMID:Differential expression of hepatic sterol carrier proteins in the streptozotocin-treated diabetic rat. 762 71

Upper-body obesity (UBO) in white women is associated with increased fatty acid turnover and resistance to the effects of insulin on systemic glucose metabolism. The present study determined whether the abilities of insulin to stimulate glucose transport and suppress lipolysis are impaired in adipocytes from white UBO (W-UBO) women. Because the clinical risks associated with UBO are attenuated in black women, the effects of race on adipocyte insulin sensitivity were assessed. Forty-two healthy, equally obese women were selected for study on the basis of race (black or white) and body fat distribution (UBO or lower-body obesity [LBO]). In white women, both abdominal and gluteal fat cells from the UBO versus LBO group were less responsive to the stimulatory effects of insulin on glucose uptake and less sensitive to the antilipolytic effects of insulin and the adenosine analog, phenylisopropyladenosine (PIA). In contrast, in black women, fat cells from UBO and LBO groups were equally sensitive to the stimulatory effects of insulin on glucose transport and the suppressive effects of insulin and PIA on lipolysis. These in vitro data correlate well with previous clinical findings that UBO in white women but not in black women is associated with insulin resistance and dyslipidemia. Thus, resistance to the antilipolytic effects of insulin and adenosine at the level of adipose tissue may increase systemic lipolysis and play a role in the development or maintenance of peripheral insulin resistance associated with UBO in white women, but not in black women.
 ...
PMID:Insulin resistance in adipocytes of obese women: effects of body fat distribution and race. 763 56

Dyslipidaemia in insulin resistance comprises elevated plasma triglycerides, decreased HDL, a preponderance of small, dense LDL and increased postprandial lipaemia. In terms of cause and effect, small, dense LDL, alimentary hyperlipidaemia and changes in HDL are consequences of elevated triglycerides. These abnormalities can become frequent if triglycerides exceed a threshold value of approximately 1.5 mmol/l. Therefore, it is mandatory to maintain plasma triglycerides as low as possible in noninsulin-dependent diabetic and insulin-resistant individuals to prevent the potentially atherogenic and metabolic consequences of hypertriglyceridaemia.
 ...
PMID:Insulin resistance and lipoprotein metabolism. 764 4

The study was undertaken to evaluate the development and association of parameters related to the metabolic syndrome during celiprolol treatment. Hyperinsulinemic euglycemic clamp and independent oral glucose tolerance tests (OGTT) were performed on 25 nondiabetic patients with controlled hypertension and dyslipidemia. The tests were carried out during the patients' previous antihypertensive monotherapy (beta- or Ca-blocker, or an ACE inhibitor), and after 6 and 12 months of celiprolol treatment. About one third of patients were randomized to a control group in which treatment was kept unchanged. Insulin sensitivity index (ISI), measured by the euglycemic clamp test, increased 35% in the celiprolol group at 6 months and remained at that level at 12 months, independent of the previous treatment (p = 0.03, compared to the change in the control group). During a 2 hour OGTT, incremental glucose area under the curve (AUC) decreased from 4.5 to 1.9 hr x mmol/l during 6 months of celiprolol treatment, and decreased further to 1.5 hr x mmol/l at 12 months (p < 0.001). Insulin AUC decreased from 113 to 72 hr x mU/l, and decreased further to 68 hr x mU/l (p < 0.01). All insulin parameters in OGTT were highly significant (p < 0.0001) and inversely associated with ISI. Insulin AUC had the best linear correlation with ISI (r = -0.682, p < 0.0001). Glucose parameters in OGTT correlated only weakly and inversely with insulin sensitivity. From the fasting serum lipids, triglycerides showed an inverse (p < 0.001) and HDL a weak (p < 0.05) positive association with ISI. Four out of 20 metabolic, clinical, and demographic parameters proved to be independently significant predictors for ISI in multiple regression analysis. These were insulin AUC, fasting insulin levels, triglyceride values, and age. The coefficient of determination in this four-parameter linear model was 69%. In this preliminary, observer-masked trial with a limited control group, celiprolol improved the impaired insulin sensitivity and glucose tolerance of dyslipidemic hypertensive patients. A fairly predictive model can be formulated to evaluate the peripheral insulin sensitivity of hypertensive patients with suspected metabolic syndrome using OGTT with serum insulin determinations.
 ...
PMID:Association between serum lipids, glucose tolerance, and insulin sensitivity during 12 months of celiprolol treatment. 766 96

Changed endothelial function and dyslipidemia are features of insulin-dependent diabetes mellitus complicated with clinical nephropathy. The time relationship between the appearance of these abnormalities is however not well known. We have therefore studied the coincidence of microalbuminuria, endothelial dysfunction and dyslipidemia during a 10 year prospective study of 209 insulin-dependent diabetic patients with normal urinary albumin excretion. Twenty-three patients developed progressing microalbuminuria defined as a median urinary albumin excretion > 30 mg/24-h in two consecutive years and a progression rate in albuminuria higher than 5% per year. Thirty patients who remained normoalbuminuric throughout the observation period were randomly selected to obtain a control group with comparable degree of glycaemic control. The mean level of von Willebrand factor before onset of microalbuminuria tended to be higher in patients developing microalbuminuria than in the control group (NS), but there was no increase in von Willebrand factor in the patients who developed microalbuminuria. Total cholesterol did not change, but a significant decrease in high density lipoprotein cholesterol was observed in patients who developed microalbuminuria. In conclusion, the study demonstrated coincidence of microalbuminuria and decreasing high density lipoprotein cholesterol, but no coincidence between onset of microalbuminuria and endothelial dysfunction assessed by von Willebrand factor.
 ...
PMID:Endothelial function and serum lipids in the course of developing microalbuminuria in insulin-dependent diabetes mellitus. 766 35

To characterize the lipid and lipoprotein abnormalities in patients with diabetes mellitus and evaluate the risks and benefits of marketed pharmacologic therapies, a MEDLINE search of the National Library of Medicine data base was performed of studies published from January 1966 to March 1994. Clinical trials assessing effects on lipids and lipoproteins, and adverse effects of marketed lipid-lowering agents were extracted. Reviews and other relevant articles were included if they provided information regarding lipid and lipoprotein metabolism or guidelines on the treatment of dyslipidemias in patients with diabetes mellitus. An extensive review of clofibrate was not included. The most common dyslipidemia in patients with poorly controlled insulin-dependent diabetes mellitus (IDDM) is combined elevated triglyceride and cholesterol levels, with reduced high-density lipoprotein (HDL) cholesterol (mixed hyperlipidemia). Hypertriglyceridemia combined with a reduced HDL cholesterol is the most common dyslipidemia in patients with noninsulin-dependent diabetes mellitus, but essentially any pattern of dyslipidemia may be present. Small and dense low-density lipoprotein (LDL), glycosylation of lipoproteins, and increased oxidized lipoproteins may be present in patients with diabetes mellitus; all contribute to accelerated atherosclerotic cardiovascular disease. Insulin therapy generally corrects quantitative lipid abnormalities in patients with IDDM, so drug treatment is seldom indicated. Diet, exercise, and insulin or oral sulfonylureas will improve hypertriglyceridemia and low HDL concentrations, but do not always return them to normal. Drug therapy is indicated when nonpharmacologic measures are inadequate. It is administered based on the effects of each agent on lipids and lipoproteins, patient age, adverse effect profile, patient tolerability, and drug-disease and drug-drug interactions. A fibric acid derivative is the drug of choice for marked hypertriglyceridemia in patients with diabetes mellitus. Niacin can worsen glycemic control, but it may be required in severe hypertriglyceridemia, hypercholesterolemia, or mixed hyperlipidemia. Bile-acid binding resins may accentuate hypertriglyceridemia but may be useful in selected patients with marked hypercholesterolemia and normal triglycerides. Hydroxymethylglutaryl coenzyme A reduced inhibitors are preferred in patients with elevated LDL cholesterol and mild hypertriglyceridemia. Patients with marked lipid abnormalities or mixed hyperlipidemias may require carefully dosed combinations of lipid-lowering drugs.
 ...
PMID:Dyslipidemias in patients with diabetes mellitus: classification and risks and benefits of therapy. 766 66

Microalbuminuria in diabetic patients is associated with ischemic heart disease and insulin resistance. We previously found a 9% prevalence of microalbuminuria in a nondiabetic population that we have reassessed, investigating associations of microalbuminuria with hypertension, dyslipidemia, hyperinsulinemia, and sodium-lithium countertransport. Of 125 subjects reexamined, 42 had been microalbuminuric 3 years previously. Twelve of these (29%) were microalbuminuric on at least one sample at follow-up, and 30 (76%) were normoalbuminuric on two. Of the 79 previously normoalbuminuric subjects, 12 (15%) became microalbuminuric on one sample, while 67 (85%) remained normoalbuminuric. Subjects who were microalbuminuric at both screening and recall were older (mean +/- SD, 65.9 +/- 11 versus 59.1 +/- 10.2 years, P = .04), with a higher waist-to-hip ratio (0.93 +/- 0.09 versus 0.86 +/- 0.08, P = .008) and at recall, on univariate analysis, had higher specific insulin (44.2 [range, 16.9 to 157.0] versus 28.4 [7.4 to 129.0] pmol/L, P = .005), intact proinsulin (5.1 [1.5 to 11.0] versus 3.0 [0.8 to 14.6] pmol/L, P = .003), and des-31,32-proinsulin (5.0 [0.5 to 9.8] versus 1.0 [0.5 to 12.2] pmol/L, P = .004) concentrations. There was also a significant difference in des-31,32-proinsulin concentration, after adjustment for covariates (P = .013), between subjects classified either as microalbuminuric or as normoalbuminuric at screening. There was no difference in body mass index; fasting blood glucose; systolic or diastolic blood pressure; total, HDL, or LDL cholesterol; triglycerides; plasminogen activator inhibitor-1; or sodium-lithium countertransport activity between consistently normoalbuminuric and persistently microalbuminuric subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Longitudinal study of associations of microalbuminuria with the insulin resistance syndrome and sodium-lithium countertransport in nondiabetic subjects. 767 Sep 46

The management of essential hypertension can no longer be directed toward an isolated reduction in arterial pressure. Optimal reduction in the risk factors associated with hypertension and cardiovascular disease hopefully will reduce coronary heart disease, angina, fatal and nonfatal myocardial infarction, left ventricular hypertrophy, congestive heart failure, and sudden death. Hypertension is a genetic and acquired syndrome that consists of dyslipidemia, insulin resistance and carbohydrate intolerance, central obesity, renal abnormalities, structural abnormalities of smooth muscle, and ion transport abnormalities (membranopathy). The selection of pharmacologic agents should improve the components of the hypertensive syndrome by utilizing the "subsets of hypertension approach" to treatment.
 ...
PMID:The management of hypertension and associated risk factors for the prevention of long-term cardiac complications. 769 47

Unlike classical microvascular complications, large-vessel atherosclerosis can precede the development of diabetes, suggesting that rather than atherosclerosis being a complication of diabetes, both conditions have common genetic and environmental antecedents, i.e., they spring from a "common soil." It is now known that adverse environmental conditions, perhaps related to less-than-optimal nutrition, in fetal and early life are associated with an enhanced risk of both diabetes and cardiovascular disease many decades later. These same adverse environmental conditions are also associated with the development in adult life of abdominal obesity and the insulin-resistance syndrome (IRS). The IRS consists of glucose intolerance, hyperinsulinemia, dyslipidemia (high triglyceride and low high-density lipoprotein [HDL] cholesterol levels), and hypertension. Although the mechanism underlying this cluster is controversial, the statistical association is well established. All of the elements of the IRS have been documented as risk factors for type II diabetes. Some, but not all, of these elements are also cardiovascular disease risk factors, in particular, hypertension and low HDL cholesterol. Other factors associated with the IRS that may enhance cardiovascular disease risk are plasminogen activator inhibitor 1 and small, dense low-density lipoprotein particles. Whether insulin itself is a risk factor remains controversial, but recent epidemiological evidence has been mostly negative. This question has marked clinical relevance because if the IRS enhances cardiovascular disease risk by virtue of its concomitant factors and not the hyperinsulinemia per se, this would tend to alleviate concerns that intensive insulin management of type II diabetic subjects could enhance the risk of large-vessel atherosclerosis. Clinical trials are urgently needed to settle this point.
 ...
PMID:Diabetes and cardiovascular disease. The "common soil" hypothesis. 769 2


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