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

Both impaired glucose tolerance (IGT) (as defined by the 1985 World Health Organization criteria) and impaired fasting glucose (IFG) (as defined by the 1997 American Diabetes Association criteria) represent intermediate metabolic states between normal and diabetic glucose homeostasis. Cardiovascular disease may be related to postglucose load rather than fasting glycemia, i.e., IGT rather than IFG. We hypothesized that subjects with IGT may be more insulin resistant and have higher levels of common cardiovascular risk factors than those with isolated IFG. In the Insulin Resistance Atherosclerosis Study (IRAS), we studied S(i) and first-phase insulin secretion (acute insulin response [AIR]), as derived from a frequently sampled intravenous glucose tolerance test, as well as common cardiovascular risk factors in four different glucose tolerance categories (NFG/NGT [n = 654], NFG/IGT [n = 255], IFG/NGT [n = 59], and IFG/IGT [n = 102]) among nondiabetic subjects. Subjects with isolated postchallenge hyperglycemia (NFG/IGT) had lower S(i) (means +/- SE: 2.10 +/- 0.04 vs. 2.59 +/- 0.13 x 10(-4) min(-1). microU(-1). ml(-1); P = 0.005), lower proinsulin levels (34.4 +/- 1.8 vs. 42.0 +/- 4.5 pmol/l; P = 0.03), higher AIR (273.1 +/- 18.1 vs. 215.9 +/- 30.0 pmol/l; P = 0.04), higher C-reactive protein (2.49 +/- 0.3 vs. 1.49 +/- 0.5 mg/l; P = 0.0015), and higher triglyceride levels (137.7 +/- 5.5 vs. 108.4 +/- 8.9 mg/dl; P = 0.0025) than subjects with isolated fasting hyperglycemia (IFG/NGT). The relation of insulin resistance to glucose tolerance category was consistently seen in women and men and across the three ethnic groups of the IRAS (non-Hispanic whites, African Americans, and Hispanics). Nondiabetic individuals with isolated postchallenge hyperglycemia (IGT) are more insulin resistant than individuals with isolated fasting hyperglycemia (IFG). The risk factor pattern (including increased insulin resistance) seen in isolated IGT identifies a subgroup of nondiabetic individuals who are likely to benefit from early intervention.
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PMID:Differences in insulin resistance in nondiabetic subjects with isolated impaired glucose tolerance or isolated impaired fasting glucose. 1516 60

Familial combined hyperlipidemia (FCH) is the most common familial hyperlipidemia with a high risk for early atherosclerosis. The aim of this study was to compare levels of soluble intercellular cell adhesion molecule 1 (s-ICAM-1) and soluble vascular cell adhesion molecule 1 (s-VCAM-1) in asymptomatic members of FCH families with healthy controls and to determine the relation between s-ICAM-1, s-VCAM-1 and risk factors accompanying FCH. We also investigated the association between adhesion molecules and the intima-media thickness (IMT) of the common carotid artery, a recognized morphological marker of early atherosclerosis. 82 members of 29 FCH families were divided into the 2 groups: HL (probands and hyperlipidemic first-degree relatives, n = 47) and NL (normolipidemic first-degree relatives, n = 35). The control groups--HL-C (n = 20) and NL-C (n = 20)--consisted of sex- and age-matched healthy individuals. Hyperlipidemic members had significantly higher concentration of s-ICAM-1 (633.7 +/- 169.6 ng/ml versus 546.2 +/- 155.9 ng/ml, p < 0.05). The elevation of s-VCAM-1 was not significant (880.8 +/- 202.9 ng/ml versus 826.5 +/- 174.6 ng/ml, N.S.). Levels of s-ICAM-1 and of s-VCAM-1 in normolipidemic relatives were not significantly different from the control group (530.8 +/- 113.9 ng/ml versus 530.0 +/- 101.0 ng/ml and 860.2 +/- 265.7 ng/ml versus 822.1 +/- 197.0 ng/ml respectively). There was a significant correlation between s-ICAM-1 and apoB (r = 0.42; p < 0.01) in hyperlipidemic subjects and between s-ICAM-1 and proinsulin (r = 0.54; p < 0.01) in normolipidemic subjects. S-ICAM-1 correlated with IMT (r = 0.32; p < 0.05) in all members of FCH families. The increase of s-ICAM-1 in asymptomatic hyperlipidemic members of FCH families reflects their high cardiovascular risk. The positive association between s-ICAM-1 and IMT could indicate s-ICAM-1 as a potential predictor of atherosclerosis manifestation.
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PMID:Soluble cell adhesion molecules s-VCAM-1 and s-ICAM-1 in subjects with familial combined hyperlipidemia. 1617 Mar 96

Insulin-like growth factor 1 (IGF1) is a polypeptide hormone that has a high degree of structural similarity to human proinsulin. Owing to its ubiquitous nature and its role in promoting cell growth, strategies to inhibit IGF1 actions are being pursued as potential adjunctive measures for treating diseases such as short stature, atherosclerosis and diabetes. In addition, most tumour cell types possess IGF1 receptors and conditions in the tumour microenvironment, such as hypoxia, can lead to enhanced responsiveness to IGF1. Therefore, inhibiting IGF1 action has been proposed as a specific mechanism for potentiating the effects of existing anticancer therapies or for directly inhibiting tumour cell growth.
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PMID:Modifying IGF1 activity: an approach to treat endocrine disorders, atherosclerosis and cancer. 1790 44

We report a large family in which four members showed a plasma lipid profile consistent with the clinical diagnosis of familial combined hyperlipidemia (FCHL). One of these patients was found to have markedly reduced HDL cholesterol (HDL-C) (0.72 mmol/l) and Apo A-I (72 mg/dl) levels, a condition suggestive of the presence of a mutation in one of the HDL-related genes. The analysis of APOA1 gene revealed that this patient was heterozygous for a cytosine insertion in exon 3 (c.49-50 ins C), resulting in a frame-shift and premature stop codon at position 26 of pro-Apo A-I (Q17PFsX10). This novel mutation, which prevents the synthesis of Apo A-I, was also found in four family members, including three siblings and the daughter of the proband. Carriers of Apo A-I mutation had significantly lower HDL-C and Apo A-I than non-carriers family members (0.77+/-0.15 mmol/l vs. 1.15+/-0.20 mmol/l, P<0.005; 71.4+/-9.1mg/dl vs. 134.0+/-14.7 mg/dl, P<0.005, respectively). Two of the APOA1 mutation carriers, who were also heavy smokers, had fibrous plaques in the carotid arteries causing mild stenosis (20%). The intimal-media thickness in the two other adult carriers was within the normal range. The other non-carriers family members with FCHL had either overt vascular disease or carotid atherosclerosis at ultrasound examination. This observation suggests that the low HDL-C/low Apo A-I phenotype may result from a genetic defect directly affecting HDL metabolism, even in the context of a dyslipidemia which, like FCHL, is associated with low plasma HDL-C.
Atherosclerosis 2008 May
PMID:A novel mutation of the apolipoprotein A-I gene in a family with familial combined hyperlipidemia. 1795 Jul 41

Interleukin-12 (IL-12) has been identified as a pro-inflammatory cytokine which is thought to contribute to the development of atherosclerosis. However, to date, the various associations between factors related to the course of type 2 diabetes, like metabolic compensation, beta cell secretory dysfunction, insulin resistance and IL-12 serum levels, remain unclear. Our study involved 41 patients with type 2 diabetes, 19 patients with coronary artery disease (CAD), and 19 healthy controls. We measured serum levels of fasting glucose, HbA(1)c, 1,5-anhydro-d-glucitol, and lipids. In addition, serum levels of C-peptide, insulin, proinsulin and IL-12 were assayed. HOMA(IR) score was calculated. The serum concentrations of IL-12 were higher in diabetics than in either patients with CAD or healthy controls, and were correlated with BMI, C-peptide, insulin, HOMA(IR), proinsulin and HDL serum levels. Multiple regression analysis revealed that the IL-12 serum level in type 2 diabetics primarily is dependent upon fasting proinsulin concentration. Our results demonstrate that elevated IL-12 serum levels in type 2 diabetics treated with sulphonylureas are induced especially by peripheral insulin resistance and beta cells dysfunction, as expressed by fasting serum proinsulin levels. This finding gives us hope that treatment to decrease peripheral insulin resistance and to avoid excessive proinsulin secretion might be successful in the prevention of IL-12-induced atherosclerosis.
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PMID:IL-12 serum levels in patients with type 2 diabetes treated with sulphonylureas. 1839 31

Recently more and more evidences have emerged about the oncogenic effect of type 2 diabetes and metabolic syndrome. Among these evidences epidemiological data are in first line. There is a causal relationship according to gender, ethnicity and geographic situation between different tumors and type 2 diabetes/metabolic syndrome as well. Supposed pathomechanisms are obesity, cytokines, secreted excessively in adipose tissue, permanent and postprandial hyperglycemia, hyperinsulinism and insulin resistance, other growth factors, like proinsulin, insulin like growth factor-1, reactive oxygen species, angiogenesis, inflammation, and the multiple effects of inflammatory cytokines. It proved to be evident that both peroxisome-proliferator-activated receptors and the regulatory ubiquitin proteasome system have significant role in insulin sensitivity and in co-ordinating cell proliferation and angiogenesis. These mechanisms in metabolic syndrome are risk factors towards atherosclerosis and cancer diseases as well. This newly emerged knowledge may open new pathways in treating and preventing the above-mentioned pathologic processes.
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PMID:[The metabolic syndrome and type-2 diabetes mellitus as conditions predisposing for malignant tumors]. 1907 51

The proinsulin connecting peptide, C-peptide, is a cleavage product of insulin synthesis that is co-secreted with insulin by pancreatic beta-cells following glucose stimulation. Recombinant insulin, used in the treatment of diabetes, lacks C-peptide and preclinical and clinical studies suggest that lack of C-peptide may exacerbate diabetes-associated complications. In accordance with this, several studies suggest that C-peptide has beneficial effects in a number of diabetes-associated complications. C-peptide has been shown to prevent diabetic neuropathy by improving endoneural blood flow, preventing neuronal apoptosis and by preventing axonal swelling. In the vascular system, C-peptide has been shown to prevent vascular dysfunction in diabetic rats, and to possess anti-proliferative effects on vascular smooth muscle cells, which may prevent atherosclerosis. However, C-peptide depositions have been found in arteriosclerotic lesions of patients with hyperinsulinemic diabetes and C-peptide has been shown to induce pro-inflammatory mediators, such as nuclear factor kappa B, inducible nitric oxide synthase, and cyclooxygenase-2, indicating that C-peptide treatment could be associated with side-effects that may accelerate the development of diabetes-associated complications. This review provides a brief summary of recent research in the field and discusses potential beneficial and detrimental effects of C-peptide supplementation.
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PMID:Proinsulin C-peptide: friend or foe in the development of diabetes-associated complications? 1933 42

Patients with insulin resistance and early type 2 diabetes exhibit an increased propensity to develop a diffuse and extensive pattern of arteriosclerosis. Diabetic subjects show a remarkable increase in vascular complications, including myocardial infarction and strokes. The accelerated atherosclerosis in these patients is likely to be multifactorial. In this review, we focus on the advanced glycation end product (AGE)-receptor for AGE (RAGE) axis and the role of C-peptide as a mediator of lesion development. AGEs are proteins or lipids that become glycated after exposure to sugars. By engaging the RAGEs, AGEs induce the expression of proinflammatory mediators in various vascular cell types and are involved in a variety of microvascular and macrovascular complications. In animal models, interruption of the AGE-RAGE interaction reduces lesion size and plaque development and RAGE deficiency in a RAGE(-/-)/apolipoprotein E(-/-) double knockout mouse attenuates the development of atherosclerosis in diabetes. On the other side, patients with type 2 diabetes show increased levels of C-peptide and over the last years various groups examined the effect of C-peptide in vascular cells as well as its potential role in lesion development. Recent data suggest that the proinsulin cleavage product C-peptide could play a causal role in atherogenesis by promoting monocyte and CD4-positive lymphocyte recruitment in early arteriosclerotic lesions and by inducing the proliferation of vascular smooth muscle cells. The following review will summarize these two pathophysiological aspects and discuss on the one hand the potential role of the activated AGE-RAGE axis in diabetes-accelerated atherogenesis and on the other hand the role of C-peptide as a mediator in lesion development in patients with type 2 diabetes.
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PMID:Advanced glycation end products and C-peptide-modulators in diabetic vasculopathy and atherogenesis. 1934 38

The polyol isomalt (Palatinit) is a very low glycaemic sugar replacer. The effect of food supplemented with isomalt instead of higher glycaemic ingredients like sucrose and/or starch hydrolysates on metabolic control in patients with type 2 diabetes was examined in this open study. Thirty-three patients with type 2 diabetes received a diet with foods containing 30 g/d isomalt instead of higher-glycaemic carbohydrates for 12 weeks. Metformin and/or thiazolidindiones were the only concomitant oral antidiabetics allowed during the study. Otherwise, the participants maintained their usual diet during the test phase, but were instructed to refrain from additional sweetened foods. Before start, after 6 weeks and 12 weeks (completion of the study), blood samples were taken and analysed for clinical routine parameters, metabolic, and risk markers. Thirty-one patients completed the study. The test diet was well accepted and tolerated. After 12 weeks, significant reductions were observed for: glycosylated haemoglobin, fructosamine, fasting blood glucose, insulin, proinsulin, C-peptide, insulin resistance (HOMA-IR), and oxidised LDL (an atherosclerosis risk factor). In addition, significant lower nonesterified fatty acid concentrations were found in female participants. Routine blood measurements and blood lipids remained unchanged. The substitution of glycaemic ingredients by isomalt and the consequent on reduction of the glycaemic load within otherwise unchanged diet was accompanied by significant improvement in the metabolic control of diabetes. The present study is in agreement with findings of previous reported studies in human subjects demonstrating beneficial effects of low glycaemic diets on glucose metabolism in patients with diabetes mellitus type 2.
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PMID:Improved metabolic control after 12-week dietary intervention with low glycaemic isomalt in patients with type 2 diabetes mellitus. 1970 77

Patients with insulin resistance and early type 2 diabetes exhibit an increased sensitivity to develop a diffuse and extensive pattern of arteriosclerosis leading to a remarkable increase in vascular complications, including myocardial infarction and stroke. The accelerated atherosclerosis in these patients is likely to be multifactorial. In this review, we introduce the new hypothesis that C-peptide could play a role as a mediator of lesion development. Patients with type 2 diabetes show increased levels of the proinsulin cleavage product C-peptide, and in the past few years, various groups have examined the effect of C-peptide in vascular cells as well as its potential role in lesion development. Recent data suggest that C-peptide deposits in the vessel wall could promote the recruitment of monocytes and CD4-positive lymphocytes in early arteriosclerotic lesions. Furthermore, C-peptide induces proliferation of vascular smooth muscle cells, a critical step in atherogenesis and restenosis formation. The present review summarizes this new pathophysiological aspect and discusses the potential relevance for lesion development.
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PMID:C-Peptide in the vessel wall. 2003 7


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