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)

A relationship between plasma fibrinogen levels and insulinemia, as well as the different parameters of the insulin resistance syndrome has been described. The aim of the present paper was to investigate whether plasma fibrinogen concentrations were linked to plasma insulin levels or to the degree of insulin resistance. For this purpose, 62 nondiabetic, nonhypertensive patients, 30 men and 32 women, with body mass indexes (BMIs) and ages ranging from 18.6 to 50.2 kg/m(2) and from 19 to 60 years, respectively, were studied. Insulin sensitivity was quantified by the minimal model procedure over a 180-min intravenous glucose tolerance test with iterative sampling. Plasma insulin was determined by radioimmunoassay without cross-reactivity to human proinsulin, and fibrinogen by the method of Clauss. Insulin sensitivity ranged from 0.009 to 23.2 min(-1)/(microU/ml)x10(-4), covering the whole range of insulin sensitivities. Fibrinogen ranged from 1.70 to 5.07 g/l. There was a significant negative correlation between fibrinogen and insulin sensitivity (r=-0.76,P<0.0001) and a positive correlation between fibrinogen and basal insulin (r=0.56,P<0.0001). After adjustment for BMI, body fat mass and waist-to-hip ratio, these two relationships remained significant. In addition, a multiple regression analysis was performed to assess the independent effect of the following related variables: fibrinogen, insulin sensitivity, insulinemia and BMI. Only insulin sensitivity appeared to account for the ability to predict fibrinogen values. Thus, we hypothesized it was likely that the state of insulin resistance rather than hyperinsulinemia per se was related to hyperfibrinogenemia. We proposed an interpretation of these data in connection with some factors like free fatty acids or tumor necrosis factor-alpha, which have been implicated in the pathogenesis of insulin resistance. Nevertheless, prospective and intervention studies are needed to assess whether there is a simple association or a causal relationship between insulin resistance and hyperfibrinogenemia.
Atherosclerosis 2000 Jun
PMID:Relationships between fibrinogen and insulin resistance. 1085 28

The aim of this study was to examine the association between intact insulin, insulin propeptides, and femoral artery intima-media thickness. The design was a cross-sectional study and the study group (n = 391) consisted of randomly recruited clinically healthy 58-year-old Swedish men. The intima-media thickness of the common femoral artery was measured with ultrasound. Fasting plasma insulin; intact insulin; proinsulin; 32,33 split-proinsulin; and C-peptide concentrations were assessed. The results showed that the common femoral artery intima-media thickness correlated significantly and univariately with waist-hip ratio, systolic blood pressure, serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, ApoB, low-density lipoprotein peak particle size, and cigarette years. Furthermore, of intact insulin and insulin propeptides, only intact insulin and C-peptide were univariately associated with common femoral artery intima-media thickness (r= 0.14, p < 0.01; r= 0.18, p < 0.01; respectively). In a multiple regression analysis, common femoral artery intima-media thickness was independently associated with systolic blood pressure (beta-coefficient = 0.004, p = 0.002), ApoB (beta-coefficient = 0.338, p < 0.001 ) and cigarette years (beta-coefficient = 0.0004, p < 0.001), (R2= 25%, p<O0.00). In conclusion, smoking, systolic blood pressure, and ApoB but not insulin or insulin propeptides were independently associated with femoral atherosclerosis.
 ...
PMID:Intact insulin, insulin propeptides, and intima-media thickness in the femoral artery in 58-year-old clinical healthy men--the Atherosclerosis and Insulin Resistance Study. 1133 May 5

Previous studies have indicated that beta-cell dysfunction predicts the development of diabetes, although it is unknown whether the use of combinations of insulin secretory measures further improves prediction. The Insulin Resistance Atherosclerosis Study is a prospective, multicenter, epidemiological study of the relationship between insulin sensitivity and the risk of diabetes and cardiovascular disease. At baseline, fasting concentrations of insulin, intact proinsulin (PI), and split PI were measured, and acute insulin response (AIR) was determined during a frequently sampled intravenous glucose tolerance test (FSIGTT). Subjects who were nondiabetic at baseline (n = 903) were reexamined after 5 years of follow-up; 148 had developed diabetes. In separate logistic regression models adjusted for age, sex, clinic, and ethnicity, 1 SD differences in measures of beta-cell dysfunction were associated with diabetes incidence (AIR: odds ratio [OR] 0.37, 95% CI 0.27-0.52; intact PI: OR 1.90, 95% CI 1.57-2.30; split PI: OR 1.94, 95% CI 1.63-2.31). After additional adjustment for BMI, impaired glucose tolerance, and insulin sensitivity, these measures continued to be significantly associated with risk of diabetes (all P < 0.0001). Furthermore, in models that included both PI and AIR, each was an independent predictor, and individuals who had combined low AIR and high PI experienced the highest diabetes risk. In conclusion, both low AIR and high PI independently predicted diabetes in a well-characterized multiethnic population. Although fasting PI is simpler to assess, determining AIR from an FSIGTT may further improve prediction. If pharmacological agents to prevent diabetes are proved to be efficacious in ongoing clinical trials, then it may be beneficial to perform FSIGTTs to identify better (for intensive intervention) prediabetic subjects who would ultimately require lifelong pharmacological therapy.
 ...
PMID:Increased proinsulin levels and decreased acute insulin response independently predict the incidence of type 2 diabetes in the insulin resistance atherosclerosis study. 1191 54

The thiazolidinediones (TZDs) are a new class of oral antidiabetic agents used in the treatment of type 2 diabetes mellitus. TZDs are selective and potent agonists of peroxisome proliferator-activated receptor-gamma, which is expressed in target tissues for insulin action and in a variety of cells that play an important role in atherosclerosis. TZDs primarily improve glycemic control by reducing insulin resistance in target tissues. Evidence also suggests that the TZDs may have a direct, beneficial effect on beta-cell function. In patients with impaired glucose tolerance (prediabetics), treatment with a TZD improves insulin secretory responses and proinsulin concentrations. These beta-cell-specific effects may result in prolongation of beta-cell function and the enduring glycemic control necessary to prevent microvascular complications. Durable glycemic control has not been clearly demonstrated with other antihyperglycemic agents. The TZDs may prevent or delay the macrovascular complications associated with type 2 diabetes. TZDs improve the characteristic dyslipidemia of type 2 diabetes, promote decreases in blood pressure, and enhance fibrinolysis. In addition, they exert direct effects on the vasculature, including the ability to decrease the intimal medial thickness and inhibit transendothelial migration of monocytes. These demonstrated antiatherogenic effects may reduce the cardiovascular complications commonly associated with type 2 diabetes. TZDs also reduce microalbuminuria to a greater extent than other agents. Use of a TZD early in the course of therapy may reduce the risk of development of many of the long-term microvascular and macrovascular complications associated with type 2 diabetes.
 ...
PMID:Effects of thiazolidinediones for early treatment of type 2 diabetes mellitus. 1240 10

The accumulation of Nxi-(carboxymethyl)lysine (CML), a product of glycoxidation and lipoxidation reactions, on tissue proteins is related to the formation and acceleration of diabetic and nondiabetic atherosclerotic lesions. Yet, little is known about the levels of circulating serum CML-containing protein in nondiabetic patients with clinical symptoms of advanced atherosclerosis. We measured the levels of immunoreactive CML in sera from non-diabetic patients with accelerated symptoms of coronary heart disease, from diabetic patients with no late complications, and from healthy individuals. Serum CML was significantly higher in non-diabetic patients with coronary heart disease than in healthy control subjects and was comparable to serum CML in patients with type 2 diabetes mellitus without late complications and coronary heart disease. In nondiabetic patients with coronary heart disease, a significant inverse correlation was found between serum levels of CML and proinsulin C-peptide, a marker of pancreatic beta cells activity that affects microvascular function. Serum levels of CML and high density lipoprotein (HDL) were positively correlated in this group. We conclude that glycoxidation and lipoxidation are associated with serum HDL levels and the secretive capacity of pancreatic beta cells in nondiabetic patients with coronary heart disease.
 ...
PMID:Serum N-epsilon-(carboxymethyl)lysine is elevated in nondiabetic coronary heart disease patients. 1267 29

Adiponectin, one of the most abundant gene transcript proteins in human fat cells, has been shown to improve insulin action and is also suggested to exert antiatherogenic effects. We measured circulating adiponectin levels and risk factors for atherosclerosis in 45 healthy first-degree relatives of type 2 diabetic subjects (FDR) as well as 40 healthy control subjects (CON) without a known family history of diabetes. Insulin sensitivity (S(i)) was studied with the minimal model, and measurements of adiponectin, metabolic variables, inflammatory markers, and endothelial injury markers, as well as lipoprotein concentrations, were performed. FDR were insulin resistant (3.3 +/- 2.4 vs. 4.5 +/- 2.6 x 10(-4) x min(-1) per microU/ml [mean +/- SD], P < 0.01), and their circulating plasma adiponectin levels (6.6 +/- 1.8 vs. 8.1 +/- 3.0 microg/ml, P < 0.03) were decreased. After adjustments for age in FDR, adiponectin levels were negatively correlated with fasting proinsulin (r -0.64, P < 0.001), plasminogen activator inhibitor (PAI)-1 activity (r -0.56, P < 0.001), fasting insulin (r -0.55, P < 0.001), and acute insulin response (r -0.40, P < 0.05); they were positively related to HDL cholesterol (r 0.48, P < 0.01) and S(i) (r 0.41, P < 0.01). Furthermore, when adjusted for age, waist, and S(i), adiponectin was associated with HDL cholesterol and proinsulin, which explained 51% of the variation in adiponectin in multiple regression analyses in that group. In conclusion, circulating plasma adiponectin levels were decreased in nonobese but insulin-resistant FDR and, in addition, related to several facets of the insulin resistance syndrome (IRS). Thus, hypoadiponectinemia may be an important component of the association between cardiovascular disease and IRS.
 ...
PMID:Circulating adiponectin levels are reduced in nonobese but insulin-resistant first-degree relatives of type 2 diabetic patients. 1271 50

Thiazolidinediones (TZDs) directly improve insulin resistance and appear to preserve beta-cell function. Research has demonstrated beneficial changes in several cardiovascular risk factors, including decreased levels of proinsulin, free fatty acids, diastolic blood pressure, and microalbuminuria, as well as improvement in lipid parameters. TZDs decrease plasminogen activator inhibitor type 1, inhibit vascular smooth muscle cell proliferation, reduce carotid artery intimal-medial thickness, and improve endothelial function. These actions directly improve the vasculature and should decrease cardiovascular risk. Atherosclerosis is an inflammatory process, and TZDs reduce inflammatory markers, such as C-reactive protein, monocyte chemoattractant-1, and p47phox. The data suggest that TZDs may reduce the risk of cardiovascular disease when used in patients with type 2 diabetes.
 ...
PMID:Cardiovascular disease and benefits of thiazolidinediones. 1278 31

High PAI-1 levels post acute myocardial infarction (AMI) are associated with a poor outcome. Concentrations of insulin-like molecules, proinflammatory cytokines and an insertion (5G)/deletion (4G) polymorphism in the promoter of the PAI-1 gene, all influence circulating PAI-1 levels. We studied the determinants of PAI-1 in 123 patients immediately following and at 6 months after AMI. Within 24 h of AMI, PAI-1 levels were related to those of proinsulin-like molecules but not to levels of cytokines (interleukin-1beta, interleukin-6 or tumour necrosis factor-alpha), to genotype, or to interactions between genotype and cytokine concentration. PAI-1 levels 6 months after AMI were related to concentrations of interleukin-1beta but not to genotype. We have found no evidence that subjects with the 4G/4G polymorphism have higher PAI-1 levels on admission or 6 months after AMI. In these patients, levels of PAI-1 are related to concentrations of proinsulin-like molecules and of proinflammatory cytokines.
Atherosclerosis 2003 Jun
PMID:Plasminogen activator inhibitor-1 (PAI-1) activity post myocardial infarction: the role of acute phase reactants, insulin-like molecules and promoter (4G/5G) polymorphism in the PAI-1 gene. 1280 13

The epidemic increase in type 2 diabetes can be prevented only if markers of risk can be identified and used for early intervention. We examined the clinical phenotype of individuals characterized by normal or low IRS-1 protein expression in fat cells as well as the potential molecular mechanisms related to the adipose tissue. Twenty-five non-obese individuals with low or normal IRS-1 expression in subcutaneous abdominal fat cells were extensively characterized and the results compared with 71 carefully matched subjects with or without a known genetic predisposition for type 2 diabetes. In contrast to the commonly used risk marker, known heredity for diabetes, low cellular IRS-1 identified individuals who were markedly insulin resistant, had high proinsulin and insulin levels, and exhibited evidence of early atherosclerosis measured as increased intima media thickness in the carotid artery bulb. Circulating levels of adiponectin were also significantly reduced. Gene analyses of fat cells in a parallel study showed attenuated expression of several genes related to fat cell differentiation (adiponectin, aP2, PPARgamma, and lipoprotein lipase) in the group of individuals characterized by a low IRS-1 expression and insulin resistance. A low IRS-1 expression in fat cells is a marker of insulin resistance and risk for type 2 diabetes and is associated with evidence of early vascular complications. Impaired adipocyte differentiation, including low gene expression and circulating levels of adiponectin, can provide a link between the cellular marker and the in vivo phenotype.
 ...
PMID:A novel cellular marker of insulin resistance and early atherosclerosis in humans is related to impaired fat cell differentiation and low adiponectin. 1289 Jun 97

Although it is difficult to distinguish between the relative effects of insulin resistance and hyperinsulinemia, insulin resistance is clearly associated with significantly increased cardiovascular and cerebrovascular risk. This effect is consistent across the spectrum of worsening glycemic control, from the onset of impaired glucose tolerance to the development of clinical diabetes. It is more difficult to discriminate between the roles of elevated circulating insulin and proinsulin levels; the association between insulin levels and cardiovascular risk is weak. The thiazolidinediones (TZDs) significantly improve insulin sensitivity and exert numerous effects on the vascular bed, including improved endothelial function, decreased vascular inflammation, decreased plasma free fatty acid levels, improved dyslipidemic profiles, and inhibition of vascular smooth muscle proliferation. These findings provide increasing evidence to suggest that the TZDs may have a beneficial effect on atherosclerosis and may reduce the incidence and severity of adverse cardiovascular outcomes. These effects remain to be substantiated by the results of large outcomes studies to evaluate the impact of glycemic control and reversal of insulin resistance on cardiovascular events.
 ...
PMID:The roles of insulin resistance, hyperinsulinemia, and thiazolidinediones in cardiovascular disease. 1467 60


<< Previous 1 2 3 4 5 Next >>