Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 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

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.
Diabetes Res 1994
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

Degenerative aortic stenosis represents the most common form of aortic stenosis. The aim of this study was to evaluate the relationship between symptoms, valvular disease severity and prognosis. We studied the evolution of valvular aortic stenosis in 65 patients (39 males and 26 females, mean age 77.78 +/- 6.2 years) for a period of 7 years. All patients were submitted to accurate anamnestic examination, ECG, color Doppler echocardiography. Sixteen patients (26%) underwent cardiac catheterization. Associated diseases were: hypertension (45%), diabetes (40%), dyslipidemia (29%), chronic obstructive lung disease (6%). In 64% patients, the diagnosis of aortic stenosis was made after symptoms onset, and in 36% was occasional. Mean age at symptoms onset was 70 +/- 17 years: dispnoea was present in 81%, chest pain in 32%, and syncope in 8%. At the beginning of the follow-up, echocardiography showed, aortic stenosis to be mild in 21.73%, moderate in 60.8% and severe in 17.4%. At the end of the follow-up, mild stenosis was present in 9.5%, moderate in 38.7%, and severe in 51.8%. At entry, 56.6% had pure aortic stenosis, 34.78% had steno-insufficiency and 8.7 had an associated mitral valve insufficiency. At the end of the follow-up pure aortic stenosis was present in 17%, steno-insufficiency in 40%, and associated mitral valve insufficiency in 4.3%. Surgery was performed in 21% of the patients (77% valve replacement and 23% valve replacement and aortocoronary bypass). The mortality, at the end of the follow-up, was 31%. Causes of death were: heart failure (61%), arrhythmias (23%), and surgical complications (16%).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Characteristics and clinical course of degenerative aortic stenosis in the elderly]. 767 Dec 73

The early lesions of atherosclerosis in youth are strongly related to antemortem levels of total and low-density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, and triglyceride to ponderal index and to blood pressure. The major apolipoproteins of LDL and high-density lipoprotein (HDL), apoB and apoA1 respectively, and levels of Lp(a) lipoprotein are often abnormal in children born in a family with premature coronary artery disease (CAD). Other risk factors for CAD include obesity, high blood pressure, cigarette smoking, diabetes mellitus, positive family history of CAD, and physical inactivity. Children from families with premature CAD, dyslipidemia, or hypertension, and/or two other risk factors should have a lipoprotein profile determined. Treatment begins with a diet low in total fat, saturated fat, and cholesterol, combined with treatment of overnutrition and obesity, if necessary, and regular habits of aerobic physical activity. Children with inherited disorders of LDL metabolism may require the addition of lipid-lowering therapy. The early detection and treatment of youth at risk for premature CAD offer the greatest promise to decrease morbidity and mortality.
 ...
PMID:Detection and treatment of elevated blood lipids and other risk factors for coronary artery disease in youth. 769 75

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.
Diabetes 1995 Apr
PMID:Diabetes and cardiovascular disease. The "common soil" hypothesis. 769 2

A survey was made on a sample of Italian practitioners to evaluate the diagnostic and therapeutic approach to arterial hypertension. A questionnaire was distributed containing thirteen questions, that was personally completed and restituted by 919 physicians. The first datum that was evidenced was that the hypertensive patient observed by the practitioner is, in the great majority of cases, in old age. The percentage of patients with concomitant diseases (dyslipidemia, diabetes, obesity, cardiac failure) is very high. The blood pressure measurement is correct, especially by expert physicians. By contrast, the younger physicians tend to prescribe further diagnostic instrumental measures. The antihypertensive therapy is prescribed very accurately. According to the sample studied, the first line drugs that are more often recommended are the ACE-inhibitors, especially by younger physicians. From this survey a prualently positive judgment by the physicians emerged in relation to the available drugs for the anti-hypertensive therapy, as consequence of the observation of satisfactory therapeutic efficacy and tolerability by the patients.
 ...
PMID:[The diagnostic-therapeutic approach to hypertension. A study of 1000 Italian physicians]. 770 40

Insulin resistance and reactive hyperinsulinemia occur not only in patients with obesity, impaired glucose tolerance or non-insulin-dependent (Type 2) diabetes mellitus, but also in many non-obese, non-diabetic individuals with essentiell hypertension and their normotensive, lean young offsprings. The common coexistance of a genetic predisposition for hypertension with insulin resistance helps to explain the frequent occurrence of hypertension as well as dyslipidemia, obesity and diabetes Type 2 in a given individual. In the pathogenesis of hypertension, inappropriate vasoconstriction and/or a structural vasculopathy appears to be an important and ultimate causative event. Several pressor mechanisms are discussed and a distinct sodium retention appears to be almost obligatory associated with diabetes mellitus, while essential and particularly obesity-associated hypertension involves predominantly a tendency for sympathetic activation. Acute hyperinsulinemia on one hand causes arterial vasodilation and on the other hand enhances renal sodium reabsorption and sympathetic activity. Chronically, hyperinsulinemia may promote cardiovascular muscle cell proliferation and atherogenesis. Insulin resistance affecting certain transmembrane cation transporters might lead to an elevation of intracellular cytosolic calcium levels thereby inducing inappropriate vasoconstriction. Nevertheless, whether insulin resistance and hyperinsulinemia contribute to the pathogenesis of hypertension per se is still unproven. Considering antihypertensive drugs, thiazide diuretics given in medium or high dosage as well as beta-blockers appear to promote insulin resistance, reactive hyperinsulinemia and dyslipidemia. Almost all calcium antagonists and the conventional sympthatolytics are metabolically neutral, while ACE-inhibitors and alpha 1-blockers tend to improve insulin resistance. In Type 2 diabetic patients, ACE-inhibitors exert in addition to their antihypertensive a potentially useful anti-diabetic effect. Nevertheless, the prognostic relevance of the metabolic side effects of antihypertensive drugs awaits further clarification.
 ...
PMID:[Insulin resistance and arterial hypertension]. 771 73

Insulin resistance with consecutive hyperinsulinemia is associated with dyslipidemia in individuals with metabolic syndrome or "syndrome x". This dyslipidemia is characterized by a hypertriglyceridemia and reduced levels of HDL-(high density lipoprotein)cholesterol in plasma. Table 1 summarizes the alterations of lipoproteins in insulin resistance. In severe forms of insulin resistance LDL-(low density lipoprotein)cholesterol can be elevated as well. The hypertriglyceridemia is caused by an elevated synthesis and secretion of VLDL (very low density lipoprotein) in the liver and by reduced metabolism, mediated e.g. by lipoprotein lipase. The alterations of VLDL-metabolism are associated with a reduced concentration of HDL-cholesterol. In addition the composition of lipoprotein particles can be altered, which might interfere with their normal metabolism. Furthermore addition direct effects of insulin on cellular cholesterol metabolism have been described. These alterations in lipid metabolism which are due to an insulin resistance and hyperinsulinemia might be related to the increased coronary risk which has been observed in patients with metabolic syndrome. Therefore the diagnostic approach in patients with hypertriglyceridemia should consider the possibility of an underlying glucose intolerance or Type 2 diabetes. Therapeutic aims and strategies are discussed. In accordance to guidelines of the American Heart Association the goals of lipid-lowering therapy take into account the prevalence of various cardiovascular risk factors in an individual patient (Table 2). Principle actions of lipid-lowering drugs on plasma lipids are outlined in Table 3. Table 4 summarizes the effect of antihypertensive drugs on plasma lipids and lipoproteins, which should be considered in the treatment of patients with dyslipidemia.
 ...
PMID:[Disorders of lipid metabolism in insulin resistance]. 771 75


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