Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atherosclerosis is considered to be the major complication of diabetes mellitus. Since diabetic patients have increased blood levels of lipid peroxidation products we investigated whether the susceptibility of blood components to oxidation is altered in this disease. We analysed the parameters characterizing the extent of oxidative change and the antioxidant status of low density lipoprotein (LDL) and high density lipoprotein (HDL) in a group of diabetic patients and in a control population. LDL oxidizability was significantly higher for patients (P = 0.001) than for individuals in the control group. There were no significant differences in the alpha-tocopherol content or levels of performed peroxides in LDL samples isolated from diabetic patients and control individuals which could account for this effect. Similarly, LDL glycation, common in diabetes mellitus, was not responsible, since LDL glycated in vitro was more rather than less resistant to oxidation. Even the presence of unbound glucose at normal or elevated physiological concentrations had a delaying effect on the oxidation of LDL. The increased oxidizability of LDL isolated from diabetic patients could be reduced to control levels by a 6-week standard treatment with Probucol, originally applied to reduce their blood cholesterol.
 ...
PMID:Increased oxidizability of plasma lipoproteins in diabetic patients can be decreased by probucol therapy and is not due to glycation. 155 98

Studies of lipoproteins in this homogenous study population indicate clear and consistent associations between obesity and abnormalities in lipoproteins. These include both increases in VLDL and lower HDL, which were observed in both men and women. A high production of total body cholesterol in obese subjects, probably associated with increased flux of glucose and free fatty acids, leads to a greater production of VLDL. This, in turn, creates a greater flux of metabolic products of VLDL either back to the liver or through LDL. Obesity induces an increase in hepatic lipase, perhaps in women because of lower estrogen levels, which is associated with lower HDL concentrations, and altered HDL composition. Several of these observed changes, such as the greater proportion of VLDL remnants, the greater flux of particles through the LDL compartment, and the altered HDL composition, may be associated with increased atherosclerosis. However, preliminary data do not show a relationship between obesity and death from coronary heart disease in this population. More studies are needed to resolve this apparent conflict.
 ...
PMID:Obesity, lipoproteins, and heart disease. 157 83

Utilising a combination of m-aminophenyl-borate affinity chromatography and an immunoradiometric assay for apolipoprotein B (apo B), we have developed a specific and highly sensitive (6 ng/ml) procedure for the assay of glycated apo B. We studied 52 diabetic patients, 50 non-diabetic control subjects and 12 patients heterozygous for familial hypercholesterolaemia (FH). Both insulin-dependent and non-insulin dependent diabetics were included in our study. Total apo B in the diabetics (108 +/- 5 mg/dl; mean +/- S.E.M) was increased (controls: 95 +/- 4 mg/dl; P less than 0.05). In the FH group the serum apo B concentration (216 +/- 24 mg/dl) was significantly higher (P less than 0.001) than both the other groups studied. Both the serum glycated apo B concentration (9.3 +/- 0.8 mg/dl versus 4.8 +/- 0.7 mg/dl) and the percentage glycated apo B (7.9 +/- 0.4% compared to 3.9 +/- 0.2%) were significantly higher in the diabetics than in non-diabetic controls (P less than 0.001). A positive correlation was found between the percentage of glycated apo B and glycated haemoglobin (r = 0.65; P less than 0.001) and fasting glucose concentration (r = 0.52; P less than 0.001) in diabetics. The percentage of glycated apo B in FH patients was not significantly different from controls, but the serum concentration of glycated apo B, because of the greatly increased total level of apo B was raised (8.2 +/- 1.4 mg/dl) to a similar extent to that of the diabetics.
Atherosclerosis 1992 Apr
PMID:Non-enzymatic glycation of apolipoprotein B in the sera of diabetic and non-diabetic subjects. 159 Aug 28

Coronary heart disease risk factor levels were studied in 184 first-degree relatives (sisters and brothers) of non-insulin-dependent diabetic subjects (124 relatives with normoglycemia, 34 relatives with impaired glucose tolerance [IGT], and 26 relatives with non-insulin-dependent diabetes mellitus [NIDDM]) and in 215 relatives of nondiabetic subjects (194 relatives with normoglycemia and 21 relatives with IGT). Subjects with IGT exhibited the highest insulin responses to an oral glucose load. Systolic blood pressure was significantly higher; serum high density lipoprotein cholesterol level was significantly lower; and total, low density lipoprotein, and very low density lipoprotein triglyceride levels were higher in the relatives with a family history of diabetes who had IGT or NIDDM than in the normoglycemic relatives without a family history of diabetes. These abnormal changes were not seen in normoglycemic relatives or relatives with IGT who had no family history of NIDDM. Thus, in relatives of diabetics, abnormal glucose tolerance seems to induce changes in cardiovascular heart disease risk factor levels that are similar to those observed in NIDDM. Therefore, a family history of diabetes adds substantially to the risk for atherosclerosis, particularly in subjects with IGT.
 ...
PMID:Early abnormalities in coronary heart disease risk factors in relatives of subjects with non-insulin-dependent diabetes. 159 Dec 29

Researchers have found that oral contraceptives (OCs) change carbohydrate and lipoprotein metabolism and these changes are like those linked with increased risk of cardiovascular (CV) disease, especially myocardial infarction and stroke. Since CV disease is the major cause of death in US women, it is important that OCs not induce changes in carbohydrate and lipoprotein metabolism. A new progestin, norgestimate, has an advantage over other progestins in that it tends not to induce male traits. This is beneficial because androgenicity is related to atherosclerosis which increases the risk of myocardial infarction. Further studies show that the new combined OC (250 mcg norgestimate/35 mcg ethinyl estradiol) does not influence serum glucose tolerance levels. It also does not affect the physiologic regulating system of prostacyclin, the inhibitor of platelet aggregation, by high density lipoprotein (HDL). In addition, it increases prostacyclin metabolites and HDL which may indeed decrease the risk of occlusive thrombotic vascular diseases. Moreover a study in Germany demonstrates that it causes no changes in fibrinopeptide A,m the anticoagulation factors antithrombin III and protein C, or coagulation promoting factors fibrinogen, factor VII, and the components of VIII. In women, it is absorbed well and metabolized extensively before the body eliminates it. Moreover this new combined OC has an overall Pearl index of 0.25. Studies to data indicate that norgestimate/ethinyl estradiol may be more advantageous than other OC formulations. Yet only long term epidemiologic studies can determine if it can indeed decrease the risk of CV diseases linked with older OCs.
 ...
PMID:Norgestimate: a clinical overview of a new progestin. 160 87

Non-insulin-dependent diabetes (NIDDM) has long been recognized as being associated with a cluster of disorders including obesity, hypertension, dyslipidemia, and atherosclerotic heart disease. It was only recently, however, that Reaven, DeFronzo, and Ferrannini with techniques to quantitate insulin resistance suggested that this represents a common factor in this group of disorders and that hyperinsulinemia resulting from insulin resistance could be the cause of the hypertension, dyslipidemia, and atherosclerosis. The names syndrome X or the insulin-resistance syndrome have been used to identify this pathological entity, and considerable investigations have been done and are in progress to establish whether or not these coexisting disorders represent an as yet unexplained association of cardiovascular risk factors or if, indeed, insulin resistance and hyperinsulinism represent the primary cause for most of the other disorders. To paraphrase a philosophical comment, if syndrome X did not exist, we probably would have had to invent it. In addition to the intellectual satisfaction of being able to "lump" these diverse ills under a single etiology, the main value of grouping these disorders as a syndrome is to continually remind physicians that the therapeutic goals are not only to correct hyperglycemia in NIDDM but also to manage the elevated blood pressure and dyslipidemia that cause cerebrovascular and cardiac morbidity as well as mortality in these patients. Having a syndrome X reduces the fragmentation of medical care among subspecialties and decreases the likelihood of prescribing drugs that correct hypertension but raise lipids or drugs that lower lipids but raise blood glucose. Finally, it encourages the selection of drugs that reduce hyperglycemia without increasing insulin secretion and to the development of new drugs for this purpose. Unfortunately, the concept of insulin resistance with hyperinsulinism being a cause of the other associated disorders is still unproved but continues to be open to experimental investigation. The remainder of this article reviewed the use of sulfonylureas in the management of NIDDM, discussed new molecular and cellular mechanisms by which they promote insulin secretion, and reviewed the controversy as to whether an extrapancreatic action contributes to their glucose-lowering effects in NIDDM. A closing section listed some other oral drugs that can lower blood glucose without stimulating the pancreatic beta cell. Their insulin-sparing hypoglycemic effect makes them potentially useful in NIDDM therapy, particularly if the fundamental premise of syndrome X is substantiated, which implicates hyperinsulinemia as contributing to the morbidity and mortality from atherosclerotic vascular disease.
 ...
PMID:Type II diabetes and syndrome X. Pathogenesis and glycemic management. 161 69

Accelerated atherosclerosis is a major complication of long-term diabetes mellitus, and this is partly due to associated abnormalities of lipoprotein metabolism. Hypertriglyceridemia is usually due to poorly controlled diabetes and responds to improved glucose control. Hypercholesterolemia is usually not related to poor diabetic control and should be treated with a cholesterol lowering diet and drugs according to the National Cholesterol Education Program guidelines. Low HDL-C is common in NIDDM and does not fully return to normal with improved diabetic control. Dyslipidemia in diabetics should be aggressively identified and treated to decrease cardiovascular risk.
 ...
PMID:Management of hyperlipidemia in diabetes mellitus. 161 72

Although platelet-derived growth factor (PDGF) is thought to be a major mediator of atherosclerotic disease, the pathophysiology of diabetic vasculopathy, including atherosclerosis, is unclear. By means of an enzyme immunoassay that used a monoclonal antibody against human PDGF-B chain, PDGF-like immunoreactivity was determined in serum, platelet-poor plasma, and platelet lysate of 28 patients with non-insulin-dependent diabetes mellitus and 11 control subjects. Growth-promoting activity was also measured by tritiated thymidine incorporation into DNA of cultured human fibroblasts. The PDGF-like immunoreactivity in serum was correlated (r = 0.42; p less than 0.01) with that in platelet lysate prepared from a fixed volume of blood. Furthermore, a correlation (r = 0.70; p less than 0.001) was found between the PDGF-like immunoreactivity and the growth-promoting activity in platelet lysate but not in serum. There was no significant difference between patients with diabetes and control subjects with respect to the PDGF-like immunoreactivity in serum or in platelet lysate (38.2 +/- 2.2 vs 42.8 +/- 3.1 ng/ml or 49.1 +/- 2.4 vs 56.2 +/- 3.4 ng/mg protein; mean +/- SEM). In contrast, the serum growth-promoting activity was lower (p less than 0.05) in patients with diabetes than in control subjects (88.1% +/- 7.1% vs 117.4% +/- 6.9%) and there was a negative correlation (r = -0.39; p less than 0.05) between the serum growth-promoting activity and the fasting plasma glucose level. The growth-promoting activity in platelet lysate of patients with diabetes did not differ from that of the control subjects (59.9% +/- 11.6% vs 65.9% +/- 11.2%).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Platelet-derived growth factor and growth-promoting activity in the serum samples and platelets of patients with non-insulin-dependent diabetes mellitus. 161 32

Silent myocardial ischemia (SI), an asymptomatic manifestation of coronary artery disease (CAD), was identified in 10% of apparently healthy nonsmoking, nondiabetic older (60 +/- 7 years, mean +/- SD) men with normal plasma cholesterol levels. We hypothesized that in the absence of other major risk factors for CAD, the men with SI would have reduced plasma levels of high density lipoprotein (HDL) and HDL2 subspecies due to an upper-body fat distribution (waist-to-hip ratio [WHR]), hyperinsulinemia, and abnormal postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities. Compared with 47 normal control subjects of similar age, obesity, and maximal aerobic capacity, the 18 men with SI had higher plasma triglyceride (TG) (162 +/- 71 versus 102 +/- 39 mg/dl, p less than 0.001) and lower HDL-C (33 +/- 6 versus 37 +/- 7 mg/dl, p less than 0.02) levels with no difference in low density lipoprotein cholesterol level. The HDL2b and HDL2a subspecies measured by gradient gel electrophoresis were also lower in the men with SI (p less than 0.01). The plasma glucose and insulin responses during an oral glucose tolerance test were the same in both groups. Postheparin plasma HL activity was significantly higher in 12 men with SI than in 41 control subjects (34 +/- 8 versus 27 +/- 10 mumol/ml.hr-1, p less than 0.03) and was correlated with log insulin area (r = 0.36, p less than 0.05) and WHR (r = 0.32, p less than 0.05) in the control subjects but not in the men with SI. In the control group, the percent HDL2b subspecies was correlated inversely with postheparin plasma HL activity (r = -0.46, p less than 0.01, n = 41) as well as WHR (r = -0.49, p less than 0.001, n = 47) and log insulin area (r = -0.37, p less than 0.05, n = 47) but not in the men with SI. Postheparin LPL activity was the same in both groups of men and did not correlate with HDL, WHR, insulin, or plasma TG levels. As the control subjects and men with SI had comparable degrees of abdominal obesity and hyperinsulinemia, these results suggest that the reduced HDL-C levels in men with SI may be related to elevations in HL activity. Thus, abdominal obesity, hyperinsulinemia, elevated TG levels, and low HDL-C and HDL2 subspecies levels may predispose these older men to atherosclerosis.
 ...
PMID:Reduced HDL2 cholesterol subspecies and elevated postheparin hepatic lipase activity in older men with abdominal obesity and asymptomatic myocardial ischemia. 161 6

1. The effects of D-fenfluramine were studied in the JCR:LA-corpulent rat that is grossly obese, hyperphagic, hyperlipidaemic, hyperinsulinaemic and atherosclerosis-prone. 2. Daily doses of 1, 2.5 and 5 mg kg-1 of D-fenfluramine produced sustained decreases in body weight and food intake over a period of 30 days in 6 month old female rats fed ad libitum. This was accompanied by decreases in the circulating concentrations of glucose, triacylglycerol, free cholesterol and insulin. 3. Food restriction imposed by meal feeding also decreased circulating glucose, triacylglycerols, cholesterol and insulin and diminished the effect of D-fenfluramine on these parameters in male and female rats. 4. Addition of D-fenfluramine to drinking water to give a dose of about 0.25 mg kg-1 daily produced a sustained decrease in body weight and food intake of male and female rats over a nine week period. 5. The results show that the JCR:LA-corpulent rat is very sensitive to the pharmacological effects of D-fenfluramine. These rats should provide an appropriate animal model for determining the mechanisms of action of this anti-obesity agent and whether apparently beneficial changes in metabolism translate into long-term protection against premature atherosclerosis.
 ...
PMID:Sustained decreases in weight and serum insulin, glucose, triacylglycerol and cholesterol in JCR:LA-corpulent rats treated with D-fenfluramine. 162 54


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