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)

Obesity is a multifactorial disease with a marked genetic component. The situation is further complicated by the heterogeneity of obesity demonstrated by the topographical distribution of body fat, e.g. upper body (central) and lower body (gluteal) obesity. Furthermore, the distribution of fat shows a stronger heritable tendency compared with total body fat. Central obesity is characterized by hyperinsulinaemia and insulin resistance, a feature in common with non-insulin dependent diabetes mellitus, hypertension and atherosclerosis. In order to study the molecular genetics of central obesity we have examined 56 severely obese (mean body mass index 40), unrelated British Caucasoid young non-diabetic women for associations of restriction fragment length polymorphism of candidate genes with anthropometric measurements and indices of insulin secretion and resistance. The candidate genes examined were insulin receptor, insulin sensitive glucose transporter and insulin. An association of the class 3 allele of the hypervariable region in the 5' flanking region of the insulin gene was found with upper segment obesity (P = 0.005). Furthermore, the class 3 allele was also associated with fasting hyperinsulinaemia (P = 0.01), stimulated insulin secretion (P = 0.01) and insulin resistance as calculated from the homeostatic model of assessment (HOMA; P = 0.008). No such associations were found with the other candidate genes studied. This data suggests that polymorphisms in the 5' flanking region of the insulin gene may affect expression of the gene and thereby modulate insulin production in severely obese female subjects.
 ...
PMID:Central obesity and hyperinsulinaemia in women are associated with polymorphism in the 5' flanking region of the human insulin gene. 135 60

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

Medical writings on cardiovascular disease focus on intravascular pressures. Tissue pressure is assumed to be essentially atmospheric. Yet, under dynamic conditions of sitting, standing, walking, breathing, and the beating of the heart, significant pressures, both above and below atmospheric, do develop outside of important arteries. These dynamic extra-arterial pressures either decrease or increase the pressure gradients across arterial walls, i.e. the transmural pressures are changed. Physical fitness may either prevent the development of negative extra-arterial pressure or increase positive extra-arterial pressure, thereby protecting important arteries from high effective pressures. Deconditioning, old age, abdominal obesity, and other cardiovascular disease risk factors may do just the opposite, in effect, causing 'localized hypertension' in clinically important arteries. This, in turn, may lead to localized acceleration of atherosclerosis. The correlation of predictions made from this hypothesis with clinical findings is so remarkable that it suggests there is a direct cause and effect relationship between transmural arterial pressure and atherosclerosis. The concept of dynamic extra-arterial pressure seems to solve a number of puzzles and paradoxes in cardiovascular disease, it suggests key measurements that may be predictive of disease, and it offers new ideas for treatment and prevention.
 ...
PMID:Physical fitness, dynamic extra-arterial pressures, and the pathogenesis and distribution of atherosclerosis. 178 17

Whereas up to the end of the last century overweight reflected the privilege of the high society and her relative good health, the recent epidemiological studies have assessed the relations between body weight and general or cause specific morbidity and mortality. The major diseases associated with obesity are hypertension, atherosclerosis and diabetes, as well as certain types of cancer. Less well known complications include hepatic steatosis, gallbladder diseases, pulmonary function impairment, endocrine abnormalities, obstetric complications, trauma to the weight bearing joints, gout, cutaneous diseases, proteinuria, increased hemoglobin concentration and possibly immunologic impairments. From these wide epidemiological studies arise the definition of obesity: with an excess of 20% beyond the desirable weight, the complications bound to the overweight become statistically more frequent. Over there a U or J shaped curve illustrates the relation between the overweight and the degree of these various complications. An excess of 45 kg or more represents the critical level which defined "morbid obesity" with its own complications, the most important are sudden unexplained death, ventilatory disorders, circulatory congestion and functional limitations in activities of daily living and of course psychological consequences. When for certain complications, such as diabetes, the relationship with the overweight is evident, discrepancies between certain studies, especially for the cardiovascular diseases, had focused the attention on the regional patterns of fat distribution. Cross-sectional studies have shown abdominal obesity to be strongly associated with risk factors for cardiovascular disease, stroke and death independent of the total degree of obesity.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[The contribution of epidemiology to the definition of obesity and its risk factors]. 266 68

Since there is evidence that fat distribution is a better predictor of cardiovascular disease than the degree of obesity, some risk factors for atherosclerosis have been evaluated in middle age Type II male diabetics and in obese subjects with and without glucose intolerance. In non-insulin-dependent diabetics (NIDD), abdominal obesity reflected by the waist/hip-circumference ratio (WHR) is related to parameters of metabolic control, lipid parameters, insulin status and response, hypertension, and vascular complications. High WHR is associated with: (a) significantly (p less than 0.01) higher HbA1 values than in the group without abdominal fat distribution; (b) a highly significant (p less than 0.001) negative correlation with high-density-lipoprotein cholesterol (HDL-C) and a positive correlation with the total/HDL-C ratio, which remains after correction for the body mass index; (c) higher apolipoprotein B concentrations; and (d) an elevated atherogenic index. Both fasting and postprandial insulin and C-peptide values may be a link between abdominal fat deposits and metabolic disturbances. Obese patients with upper body fat accumulation have significantly lower HDL-C levels, and a higher prevalence of glucose intolerance and diabetes than do patients with lower body fat obesity. Fasting glycemia, insulin, and the insulin area under the curve during an oral glucose load are significantly (p less than 0.005) increased in those with the greatest WHR, which is similar to that in NIDD and central obesity. An excess of abdominally located fat, even without manifest obesity, is associated with metabolic disturbances that indicate increased risk of atherogenesis and of higher morbidity and mortality, which may be due to characteristics of abdominally located adipocytes.
 ...
PMID:Upper body adiposity and the risk for atherosclerosis. 269 50

In order to assess the relationship between obesity and serum lipids, a homogenous group of adult men and premenopausal women is assessed for body mass index, body fat distribution reflected by the waist/hip ratio (WHR), serum lipid parameters and apolipoproteins. Body fat distribution is distinguished in an abdominal and gluteal-femoral type using a cut-off point of 1.00 for the ratio of waist-to-hips girth for men. In women the cut-off value is considered as 0.80 but was also evaluated when considered as 0.85. In the next step tertiles for WHR are created to show a graded relationship between WHR and lipoprotein fraction. The results indicate that WHR is an important determinant for most atherosclerosis-related lipids and apoproteins: in both men (P less than 0.05) and women (P less than 0.005) WHR is significantly correlated with apolipoprotein B. Using multiple regression analysis, in women WHR seems to be the most important dependent variable, where body mass index is not significantly contributing to the explained variance. In men, however, besides WHR age is the most significant variable, although age distribution is similar in men and women. Using tertiles of WHR, we show a clear graded relationship with most lipids and lipoproteins; this gives additionally an argument to confirm that in women WHR = 0.80 is the most accurate cut-off value for abdominal obesity. This study demonstrates that both obese men and women with an abdominal fat mass distribution show a lipid and apoprotein profile that is less favorable than that seen in gluteal-femoral obese subjects insofar as the risk of coronary artery disease is concerned.
 ...
PMID:Apolipoprotein concentrations in obese subjects with upper and lower body fat mass distribution. 276 78

Due to the recent knowledge that the distribution of fat deposits would be a better predictor of cardiovascular disease than the degree of obesity, some risk factors for atherosclerosis were evaluated in middle age type II male diabetics and in obese subjects with and without glucose intolerance. In non-insulin dependent diabetes, abdominal adiposity reflected by the waist/hip-circumference (WHR) was related to parameters of metabolic control, lipid parameters, blood rheology, insulin status, hypertension and known vascular complications in three different groups. In the groups with abdominal obesity, the mean annual HbA1 is significantly (p less than 0.01) higher than the group without an abdominal fat mass distribution. Atherogenic index is significantly increased in the group with the highest WHR. HDL-cholesterol levels are significantly decreased in both groups with upper body fat distribution. A highly significant (p less than 0.001) correlation was present between WHR and HDL-cholesterol and WHR and total/HDL-cholesterol ratio; this significant correlation remains after correction for body mass index. Whole blood and plasma viscosity and fibrinogen levels are significantly (p less than 0.05) increased in diabetics with upper body fat accumulation and could be compared to patients with proven coronary ischemic heart disease. The frequency of peripheral vascular disease, coronary ischemic heart disease and hypertension is most prominent in diabetics with an abdominal fat mass distribution. Systolic blood pressure even seems to be increased in non-obese diabetics with the highest WHR. A correlation could be found between WHR and both systolic and diastolic blood pressure. When corrected for body mass index the same significant correlation between WHR and blood pressure remained. Both fasting and postprandial insulin and C-peptide values may be the link between abdominal fat deposits and all metabolic disturbances. These results confirm the negative effect of an excess of abdominally located fat cells, even without manifest obesity, on diabetes metabolic control, lipid fractions, hypertension, insulin behaviour, blood rheology and cardiovascular complications. In obese patients with upper body fat accumulation a higher prevalence of glucose intolerance and diabetes is present, in contrast to their counterparts with lower body fat deposit. Both fasting glycemia, insulin and insulin area are significantly (p less than 0.005) increased in the group with the greatest WHR.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Body fat mass distribution. Influence on metabolic and atherosclerotic parameters in non-insulin dependent diabetics and obese subjects with and without impaired glucose tolerance. Influence of weight reduction. 280 Jun 85

Because recent knowledge indicates that the distribution of fat deposits in men may be a better predictor of cardiovascular disease than the degree of obesity alone, some risk factors for atherosclerosis were evaluated in 51 middle-aged men with non-insulin-dependent diabetes mellitus. Abdominal adiposity (waist/hip ratio, WHR) was related to parameters of metabolic control, lipid parameters, and known vascular complications in three different groups. In groups with abdominal obesity, mean annual hemoglobin A1 was significantly (P less than .01) higher than in patients without an abdominal fat distribution. Atherogenic index was significantly increased in the group with the highest WHR and high-density lipoprotein cholesterol (HDL-chol) levels were significantly decreased in both groups with upper-body fat distribution. The frequency of peripheral vascular disease, coronary ischemic heart disease, and hypertension was most prominent in diabetic subjects with an abdominal fat mass distribution. A highly significant (P less than .001) correlation was present between WHR and HDL-chol and WHR and the total-cholesterol/HDL-chol ratio; this significant correlation remains after correction for body mass index. A similar correlation could be found between WHR and systolic and diastolic blood pressures. These results demonstrate an association of excess abdominal fat, even without manifest obesity, with worse diabetes metabolic control, cardiovascular complications, and blood lipid levels actually considered to play an important role in atherogenesis.
 ...
PMID:Relationship of body fat distribution pattern to atherogenic risk factors in NIDDM. Preliminary results. 338 30

Numerous studies show increasing evidences that a low post-prandial triglyceride metabolic capacity is likely to favour cardio-vascular disease, particularly coronary and cerebro-vascular atherosclerosis. Because of high fasting triglycerides, low HDL and high LDL3 lipid profile, abdominal obesity and insulin-resistance, Type 2 diabetic patients are candidates to altered post-prandial lipemia. However many practical and methodological difficulties remain concerning the nature, lipid quantity and composition of the lipid load, the choice of accurate markers of liver derived lipoproteins, pointing out the urgent need for a standardization procedure.
 ...
PMID:[Post-prandial lipemia in diabetes. How? Why?]. 762 70

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


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