Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among hemorheologic parameters, plasma viscosity is one of the most studied in epidemiology, so that it has emerged as an independent risk factor. In diabetes, plasma viscosity is frequently elevated. For this reason we tried to define characteristics of non-insulin dependent diabetics with high plasma viscosity (>1.45 mPa.s) and whether they were more insulin resistant and/or exhibited other hemorheologic disturbances. 12 subjects (age 56.1+/-11.7; BMI 28.6+/-4.8) were thus found to have a value of plasma viscosity >1.45 mPa.s. They were compared to 20 age and BMI-matched NIDDMs. Patients have similar insulin sensitivity, HbA1c, and fibrinogen. RBC aggregation, rigidity and hematocrit were not significantly different. Whole blood viscosity at high shear rate was slightly higher (p=0.05). When corrected for hematocrit whole blood viscosity is no longer different. However, hematocrit was not lower in subjects with hpl >1.45. By contrast blood pressure was markedly higher (systolic: 177.5+/-2.5 mmHg vs 140+/-8 mmHg, p<10(-8); diastolic 110+/-14 vs 83+/-9 mmHg, p<10(-9); mean 132+/-18 mmHg vs 102+/-7 mmHg p<10(-9)). Therefore, in NIDDM, higher plasma viscosity, regardless insulin resistance and adiposity, is strongly related to blood pressure.
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PMID:Type 2 diabetics with higher plasma viscosity exhibit a higher blood pressure. 1525 68

Diabetes is associated with an increased risk of developing cardiovascular disease, which is not fully accounted for by the accumulation of classic cardiovascular risk factors in patients. Recent evidence has demonstrated fibrinogen to be a powerful independent risk marker for cardiovascular disease in the general population, and it is also likely to contribute toward the increased atherosclerotic risk in diabetes. The etiology of hyperfibrinogenemia in diabetes is likely to be multifactorial, and at present the mechanisms involved have not been clarified. However, insulin, insulin resistance and inflammation are likely to be involved, especially in type 2 diabetes. The influence of diabetes in determining an individual's atherothrombotic risk is likely to extend beyond that of elevated fibrinogen levels, and may also act via changes in the structure and function of the fibrin clot that forms. Further research is needed to determine the mechanisms underlying these changes, which may lead to development of future interventions to reduce the excessive vascular risk associated with this disease.
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PMID:Fibrinogen and fibrin clot structure in diabetes. 1534 Jul 32

Metabolic syndrome is a cluster of cardiovascular risk factors. Pathogenesis of metabolic syndrome implies 3 potential etiological mechanisms: obesity and adipose tissue disorders, insulin resistance, and a constellation of independent factors. Clinical recognition of the metabolic syndrome is based on finding several well-recognized signs in clinical practice: abdominal obesity, elevated triglycerides, reduced HDL cholesterol, raised blood pressure, and elevated plasma glucose. In addition, other components commonly aggregate with the major components: elevated apolipoprotein B, small LDL particles, insulin resistance and hyperinsulinemia, impaired glucose tolerance (IGT), elevated C-reactive protein (CRP), and variation in coagulation factors (plasminogen activator inhibitor [PAI]-I and fibrinogen). Cardiovascular disease (CVD) is the primary clinical outcome of metabolic syndrome. Additionally, risk for type 2 diabetes is higher. Diabetes is itself a major risk factor for CVD. ATP III criteria for diagnosis of metabolic syndrome provide a practical tool to identify patients at increased risk for CVD. World Health Organization (WHO) and American Association of Clinical Endocrinologists (AACE) criteria require further oral glucose testing if IFG and diabetes are absent. IGT on OGTT denotes greater risk for diabetes than does metabolic syndrome without elevated fasting glucose.
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PMID:Metabolic syndrome--new insights into a growing entity. 1552 16

Plasminogen activator inhibitor-1 (PAI-1) levels were found to be associated with obesity, indicating that adipocytes might influence PAI-1 plasma levels. In addition, the 4G/5G promoter polymorphism of the PAI-1 gene possibly modulates PAI-1 gene transcription and, as a consequence, PAI-1 plasma levels. Metabolic parameters, diabetes complications, PAI-1 plasma levels, and PAI-1 promoter genotypes were determined and were tested for correlation in 547 Caucasian patients with type 2 diabetes. Genotyping was performed by using allele-specific PCR, and PAI-1 plasma levels were measured in 547 well-characterized subjects with type 2 diabetes. The allelic frequencies of the polymorphism (0.56 for the 4G-genotype, 0.44 for the 5G-genotype) were not different from those observed in nondiabetic controls. The PAI-1 concentration was positively associated with MI, but not with the 4G/5G polymorphism. Statistical analysis of metabolic parameters, diabetic complications, and the 4G/5G polymorphism revealed that serum fibrinogen levels were significantly higher in the 4G/4G subgroup compared with the 4G/5G and 5G/5G subgroups. The correlation between serum fibrinogen and 4G allele remained significant, even when additional variables, such as gender, age, BMI, duration of diabetes, and HbA1c, were controlled. In patients with type 2 diabetes mellitus, the PAI-1 4G/5G promoter polymorphism does not predict PAI-1 plasma levels and is not associated with common metabolic parameters besides fibrinogen levels.
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PMID:Allelic frequency of the PAI-1 4G/5G promoter polymorphism in patients with type 2 diabetes mellitus and lack of association with PAI-1 plasma levels. 1555 60

Platelets and fibrinogen might be involved in the pathogenesis of thrombus formation and MI. The Bgl II gene polymorphism of the alpha2beta1 integrin, which is a platelet collagen receptor, and the -455G/A polymorphism in the beta fibrinogen gene have been suggested as genetic risk factors for MI. The aim of this study was to look for a relationship between the -455G/A polymorphism in the beta fibrinogen gene and the development of MI in Caucasians with type 2 diabetes. One hundred and forty-two subjects with type 2 diabetes and MI were compared to 234 diabetic subjects with no history of coronary artery disease. There were no significant differences in the frequency of the Bgl II gene polymorphism or of the -455G/A polymorphism in the beta fibrinogen gene in the patients with MI compared to the patients without MI: Bgl II (+/+) genotype was found in 19.7% of patients with MI and 15.4% of controls and -455GG genotype was found in 58.4% of patients with MI and 57.7% of controls. The present study demonstrates that neither the Bgl II gene polymorphism nor -455G/A polymorphism in the beta fibrinogen gene is a genetic marker for MI in Slovene population (Caucasians) with type 2 diabetes.
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PMID:The -455G/A polymorphism of the beta fibrinogen gene and the Bgl II polymorphism of the alpha2beta1 integrin gene and myocardial infarction in patients with type 2 diabetes. 1570 16

The aim of this study was to determine the respective contribution of abdominal visceral adipose tissue (AT) accumulation and insulin resistance (IR) to the determination of a comprehensive cardiovascular metabolic risk profile in 108 postmenopausal women not receiving hormone therapy. Insulin sensitivity (M/I) was determined by a hyperinsulinemic-euglycemic clamp, and visceral AT area was measured by computed tomography. Median values of visceral AT (133.9 cm(2)) and insulin sensitivity (0.010189 mg . kg(-1) . min(-1) . pmol(-1)) were used to form four subgroups: 1) low visceral AT-low IR (n = 35), 2) low visceral AT-high IR (n = 19), 3) high visceral AT-low IR (n = 19), and 4) high visceral AT-high IR (n = 35). Women with isolated IR (low visceral AT and high IR) were characterized by significantly higher fasting and 2-h glycemia and higher fibrinogen, triglyceride, and VLDL-apolipoprotein (apo)B concentrations than women with low visceral AT and low IR (P < 0.05). The plasma lipid-lipoprotein profile and inflammatory markers were not significantly different between women with high visceral AT and low IR and women with low visceral AT and low IR. Women with high visceral AT and high IR had higher fasting and 2-h glycemia, triglyceride, and VLDL-apoB levels; lower apoAI and HDL(2) cholesterol levels; as well as higher C-reactive protein and interleukin-6 concentrations than women with low visceral AT and low IR (P < 0.05). In addition, 15 of the 35 women (42.9%) in the high visceral AT and high IR group were newly diagnosed with type 2 diabetes, whereas no women were diagnosed with type 2 diabetes in the group of women with low visceral AT and low IR. These results show that although the presence of high IR in its isolated form is associated with some metabolic alterations, it is the combination of both high visceral AT and high IR that is the most detrimental for the metabolic health in postmenopausal women.
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PMID:Contribution of abdominal visceral obesity and insulin resistance to the cardiovascular risk profile of postmenopausal women. 1573 55

Intercellular adhesion molecule-1 (ICAM-1) is involved in inflammation and development of atherosclerotic change of vascular endothelium. The aim of the present study is to investigate whether K469E polymorphism of the ICAM-1 gene is associated with various clinical factors including plasma fibrinogen in patients with type 2 diabetes. ICAM-1 gene polymorphism was examined using polymerase chain reaction and restriction enzyme analysis in 360 type 2 diabetic patients. Plasma fibrinogen levels and other clinical variables were measured as well as circulating soluble ICAM-1 (sICAM-1) levels by enzyme-linked immunosorbent assay. The distribution of ICAM-1 genotypes, EE, EK, and KK, was not significantly different between type 2 diabetes and 152 healthy control subjects. Among 3 groups according to ICAM-1 genotypes in type 2 diabetes, no difference was found in adiposity, glycemic control, lipid profile, insulin sensitivity evaluated by homeostasis model assessment, or sICAM-1. Regarding fibrinogen, the patients with E allele showed significantly lower plasma fibrinogen levels in a dose-dependent manner (P = .033). Spearman rank correlation analyses revealed that ICAM-1 genotype showed significant correlation with plasma fibrinogen level (P < .001). In multiple regression analysis, ICAM-1 genotype was independent contribution factor of plasma fibrinogen level as well as high-density lipoprotein-cholesterol and urinary albumin excretion (R2 = 0.148, P < .001). In conclusion, K469E polymorphism of the ICAM-1 gene had impact on plasma fibrinogen level independently of other clinical factors in 360 type 2 diabetic patients, suggesting that fibrinogen is a candidate which links the ICAM-1 gene polymorphism to atherosclerosis.
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PMID:The K469E polymorphism of the intercellular adhesion molecule-1 gene is associated with plasma fibrinogen level in type 2 diabetes. 1573 17

Negative affective states such as depression are associated with premature mortality and increased risk of coronary heart disease, type 2 diabetes, and disability. It has been suggested that positive affective states are protective, but the pathways through which such effects might be mediated are poorly understood. Here we show that positive affect in middle-aged men and women is associated with reduced neuroendocrine, inflammatory, and cardiovascular activity. Positive affect was assessed by aggregating momentary experience samples of happiness over a working day and was inversely related to cortisol output over the day, independently of age, gender, socioeconomic position, body mass, and smoking. Similar patterns were observed on a leisure day. Happiness was also inversely related to heart rate assessed by using ambulatory monitoring methods over the day. Participants underwent mental stress testing in the laboratory, where plasma fibrinogen stress responses were smaller in happier individuals. These effects were independent of psychological distress, supporting the notion that positive well-being is directly related to health-relevant biological processes.
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PMID:Positive affect and health-related neuroendocrine, cardiovascular, and inflammatory processes. 1584 Jul 27

Plasma fibrinogen level represents a strong cardiovascular risk factor and is regulated by an interplay of genetic and environmental factors. Hyperfibrinogenemia frequently occurs in cluster with dyslipidemia within the frame of insulin resistance syndrome (IRS) and type 2 diabetes mellitus. Genetic variants with a pleiotropic effect have been proposed to cause IRS features including hyperfibrinogenemia. We studied the influence of polymorphisms in lipoprotein lipase (LPL) gene, beta-fibrinogen gene (FIBB) and environmental factors on plasma fibrinogen levels in type 2 diabetes patients. 131 type 2 diabetes patients (mean age 62+/-10 years, 33% male) were genotyped for polymorphisms in LPL gene (intron 6 PvuII, intron 8 HindIII) and FIBB gene (-148C/T, -455G/A) by PCR-RFLP method. Fibrinogen was measured by thrombin coagulation method, albuminuria by immunoturbidimetric assay. Polymorphism LPL PvuII showed a gene-dose effect on fibrinogen levels, with the highest fibrinogen in P-P- homozygotes (p = 0.05, analysis of variance). P-carriers (P-P- and P+P- combined) had significantly higher fibrinogen levels compared with P+P+ homozygotes (3.74+/-1.40 g/l vs 3.06+/-1.20 g/l, p=0.03). Other studied polymorphisms were not significantly related to fibrinogen levels. Age- and sex-adjusted fibrinogenemia correlated significantly with albuminuria (r = 0.48, p=0.001), serum uric acid (r = 0.42, p=0.006) and serum creatinine (r = 0.32, p=0.04). Multiple stepwise linear regression identified interaction term of LPL PvuII and albuminuria as an independent predictor of fibrinogen level, explaining 18% of fibrinogen variance. Albuminuria thus appears to be the best predictor of fibrinogen plasma levels in type 2 diabetic patients. Relationship between albuminuria and fibrinogenemia may be modified by the genotype LPL PvuII, which also shows a weak association with plasma fibrinogen level in type 2 diabetes patients.
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PMID:Relationship among urinary albumin excretion rate, lipoprotein lipase PvuII polymorphism and plasma fibrinogen in type 2 diabetic patients. 1585 59

Insulin resistance is found in around 80-90% of subjects with older onset (type 2) diabetes and in approximately 25% of the general population. Insulin resistance prior to the development of frank type 2 diabetes and type 2 diabetes itself is associated with a significant increase in the risk of atherothrombotic disease, which is due in part to a disruption in the balance of factors regulating coagulation and fibrinolysis. Both insulin resistance and type 2 diabetes are associated with the development of endothelial dysfunction, and enhanced platelet aggregation and activation. Whilst the plasma levels of many clotting factors including fibrinogen, FVII, FVIII, FXII, FXIII b-subunit are elevated, the fibrinolytic system is relatively inhibited as a consequence of an increase in plasminogen activator inhibitor type-1 (PAI-1) levels. These changes favour the development of a hypercoagulable pro-thrombotic state, which may in turn enhance cardiovascular risk by increasing the likelihood of developing an occlusive thrombus within a coronary/cerebral artery, and/or contributing to the development of atherosclerotic lesions. This article reviews the current published evidence of the pro-thrombotic changes that occur in association with type 2 diabetes and insulin resistance, and the putative underlying mechanisms which lead to these changes.
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PMID:Type 2 diabetes: an atherothrombotic syndrome. 1589 51


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