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)

Type 2 diabetes mellitus is frequently accompanied by hypercoagulability and hypofibrinolysis. Both are related to increased cardiovascular risk, but possibly with endothelial injury as well. Studies with nondiabetic persons indicate that unopposed oestrogen replacement therapy (oERT) decreases cardiovascular risk, possibly mediated in part by effects on coagulation and fibrinolysis. In a double-blind, randomised placebo-controlled trial, we assessed the effect of oral 17 beta-oestradiol daily during 6 weeks on indicators of coagulation and of fibrinolysis in postmenopausal women with type 2 diabetes mellitus. We observed significant increases of Factor VII (FVII) and von Willebrand factor (vWF) after oERT and no change in the already high fibrinogen. Prothrombin fragment 1 + 2 (F1 + 2) increased after oERT, whereas thrombin-antithrombin (TAT) complexes was unchanged, but increments of F1 + 2 and TAT correlated. Soluble fibrin (SF) levels remained stable. In fibrinolysis, a clear reduction in plasminogen activator inhibitor 1 (PAI-1) was observed, but no significant change in tissue-type plasminogen activator antigen (t-PA-Ag) or activity was found, although fibrinolytic activity assessed as t-PA activity (t-PA-Act) tended to increase after oERT. Indicators of fibrinolytic activity (plasmin-antiplasmin complexes and fibrin degradation products) however did not change. oERT increased C-reactive protein (CRP) but none of the coagulation or fibrinolysis changes significantly associated with the CRP changes. It is concluded that oERT increases the coagulation potency as well as the fibrinolytic potency raising the question of the net effect in their balance. Increase in F1 + 2 suggests that in diabetic women oERT effectively increases the chronic, continuous activation of coagulation, which appears to be compensated for or not effective in the blood compartment as judged from the unchanged levels of SF. Suspected increased fibrin formation in the vascular wall is at least not followed by increases in fibrinogen degradation products (TDP), which suggests the possibility of accumulation and increased cardiovascular risk. The results indicate that specific attention should be paid to fibrin turnover in studying other categories of women and the effects of the addition of progesterone.
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PMID:The effect of 17 beta-oestradiol on variables of coagulation and fibrinolysis in postmenopausal women with type 2 diabetes mellitus. 1261 82

Linkage analysis has identified a susceptibility locus for type 2 diabetes mellitus (T2DM) on chromosome 1q21-q23 in several populations. Results from recent prospective studies indicate that increased levels of C-reactive protein (CRP), a marker of immune system activation, are predictive of diabetes, independent of adiposity. Because CRP is located on 1q21, we considered it a potential positional candidate gene for T2DM. We therefore evaluated CRP and the nearby serum amyloid P-component, APCS, which is structurally similar to CRP, as candidate diabetes susceptibility genes. Approximately 10.9kb of the CRP-APCS locus was screened for polymorphisms using denaturing high performance liquid chromatography and direct sequencing. We identified 27 informative polymorphisms, including 26 single nucleotide polymorphisms (SNPs) and 1 insertion/deletion, which were divided into 7 linkage disequilibrium clusters. We genotyped representative SNPs in approximately 1300 Pima samples and found a single variant in the CRP promoter (SNP 133552) that was associated with T2DM (P=0.014), as well as a common haplotype (CGCG) that was associated with both T2DM (P=0.029) and corrected insulin response, a surrogate measure of insulin secretion in non-diabetic subjects (P=0.050). Linkage analyses that adjusted for the effect of these polymorphisms indicated that they do not in themselves account for the observed linkage with T2DM on chromosome 1q. However, these findings suggest that variation within the CRP locus may play a role in diabetes susceptibility in Pima Indians.
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PMID:A C-reactive protein promoter polymorphism is associated with type 2 diabetes mellitus in Pima Indians. 1261 85

Experimental and epidemiologic studies support the role of inflammation in the development of type 2 diabetes and atherosclerosis. Serum levels of inflammatory markers, in particular highly sensitive C-reactive protein, have been found to be strong predictors of increased risk for type 2 diabetes and cardiovascular disease independent of traditional risk factors. A beneficial effect of thiazolidinediones, angiotensin-converting enzyme inhibitors, and statins in the prevention of type 2 diabetes and cardiovascular events has recently been reported, and potential anti-inflammatory mechanisms of action for these compounds have been described. Prospective, randomized clinical trials are currently underway to confirm these initial findings and define indications for treatment of patients at risk.
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PMID:Role of inflammatory pathways in the development and cardiovascular complications of type 2 diabetes. 1264 64

Rosiglitazone, a potent member of the thiazolidinedione class of oral antidiabetic agents, reduces hyperglycaemia by improving insulin sensitivity--an important underlying factor in the development of both type 2 diabetes and its related cardiovascular complications. Rosiglitazone has now been available in clinical practice for more than three years, so there is a large body of evidence supporting its efficacy and safety as an antihyperglycaemic agent in patients with type 2 diabetes. Given the significant burden imposed on patients and healthcare resources by diabetes-related cardiovascular disease (CVD), there is growing interest in the thiazolidinediones in terms of their potential to ameliorate CVD risk factors as a result of their insulin-sensitising action and thus improve cardiovascular outcomes in individuals with type 2 diabetes. As reviewed below, rosiglitazone has a beneficial impact on a number of factors associated with insulin resistance and CVD, including microalbuminuria, hypertension, dyslipidaemia, visceral fat, elevated plasminogen activator inhibitor-1 levels and increased concentrations of C-reactive protein. These thiazolidinedione compounds are not problem-free and the long-term implications of some of rosiglitazone side-effects such as weight gain, changes in LDL-cholesterol concentration and fluid retention remain to be resolved. Large-scale clinical outcome studies should give a clearer picture for rosiglitazone and related thiazolidinediones in relation to the extent of their impact on diabetes disease progression and incident cardiovascular events.
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PMID:Rosiglitazone: potential beneficial impact on cardiovascular disease. 1266 97

Soluble CD14 (sCD14), detectable at high concentrations constitutively present in the circulation, plays a key role in the neutralization of lipopolysaccharide, one of the most potent biologic response modifiers currently recognized and involved in the regulation of the inflammatory cascade. We tested whether circulating sCD14 was linked to inflammatory parameters and to insulin resistance in apparently healthy subjects. Serum sCD14 concentration did not significantly correlate with body mass index (BMI), waist to hip ratio, systolic or diastolic blood pressure, serum glucose, fasting insulin, fasting insulin resistance index [homeostasis model assessment (HOMA)], or serum uric acid among 123 subjects. The association between sCD14 and fasting insulin (r = -0.19, P = 0.08) and between sCD14 and HOMA (r = -0.21, P = 0.06) tended toward statistical significance among men. Unexpectedly, sCD14 correlated positively with fasting triglycerides (TG) in all the subjects (r = 0.22, P = 0.014), and this association was most significant in men (r = 0.34, P = 0.002). After controlling for TG, the relationships between sCD14 levels and fasting insulin (r = -0.25, P = 0.029), HOMA (r = -0.28, P = 0.014), and uric acid (r = -0.30, P = 0.006) were significant in men. Among nonsmoking men (n = 44), sCD14 significantly correlated with waist diameter (r = -0.30, P = 0.03), diastolic blood pressure (r = -0.34, P = 0.022), and HOMA (r = -0.30, P = 0.03). In a multiple linear regression analysis, BMI (P < 0.00001), TG (P = 0.003), and sCD14 (P = 0.04) (but not age, sex, waist, or smoking status) independently contributed to 26% of HOMA variance. A polymorphism of the CD14 gene, a C-to-T transition at bp -159 from the major transcription start site, seems to play a significant role in regulating serum sCD14 levels. In a subsample of 33 healthy subjects, carriers of the T allele were similar (in age, sex, BMI, fat mass, waist to hip ratio, blood pressure, and fasting glucose and insulin levels) to C/C homozygotes. In the former, integrated area under the curve for serum glucose concentrations after an oral glucose tolerance test was significantly lower (P = 0.02), and insulin sensitivity (SI) index (minimal model analysis) significantly higher (P = 0.036), than in C/C homozygotes. Among 32 type 2 diabetic subjects, carriers of the T allele also showed a significantly higher SI index (P = 0.03) and had significantly lower C-reactive protein (P = 0.03) and lower circulating soluble intercellular adhesion molecule-1 concentrations (P = 0.01) than did C/C homozygotes. To our knowledge, this is the first study to suggest an effect of a genetic polymorphism on both SI (healthy subjects and type 2 diabetic patients) and endothelial dysfunction (sICAM-1 levels) in type 2 diabetes mellitus.
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PMID:CD14 monocyte receptor, involved in the inflammatory cascade, and insulin sensitivity. 1267 73

A 50-year-old woman with a 15-year history of type 2 diabetes mellitus was admitted to our hospital due to high fever and a skin lesion with severe pain, swelling and a sensation of heat in the right thigh. Laboratory examination showed elevated C-reactive protein (CRP), thrombocytopenia, nephrotic syndrome and renal dysfunction. Her blood glucose level had been well controlled. Streptococcus agalactiae was detected in both the skin lesion and blood culture, and pathological examination revealed neutrophil infiltration in the fascia and muscle layer. The patient was diagnosed with necrotizing fasciitis, septic shock and disseminated intravascular coagulation. A combination therapy of antibiotics and surgical debridement resulted in the improvement of symptoms as supported by laboratory findings, and the skin lesion also showed improvement. Although group A streptococcus is well known to be implicated in the pathogenesis of necrotizing fasciitis, only S. agalactiae, belonging to group B streptococcus, was isolated from the tissue and blood cultures in this case. Although this organism is not virulent and rarely causes a necrotizing fasciitis, both the superficial fascial layer and underlying muscle were affected in this case. There have been only a few reports of necrotizing fasciitis due to S. agalactiae in patients with diabetes mellitus. Although the blood glucose level was well controlled in our patient, this disease might be caused by other factors, including diminished sense of touch and pain, abnormality of microcirculation and hypogammaglobulinemia due to nephrotic syndrome.
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PMID:Successful treatment of necrotizing fasciitis associated with diabetic nephropathy. 1275 84

Type 2 diabetes mellitus and atherosclerosis are complex and progressive conditions that share several common antecedents. Recent data suggest that inflammation may play a central role in the origins and complications of cardiovascular disease and, possibly, type 2 diabetes mellitus. C-reactive protein and plasminogen activator inhibitor-1 are circulating markers of low-grade inflammation, thrombosis, and vascular injury. Together with homocysteine, they have been associated with the underlying inflammatory processes and are considered to be "nontraditional" risk factors of atherosclerosis. The role of their measurement in clinical practice remains unclear. In this article, we review the available evidence demonstrating a link between inflammation, cardiovascular disease, and diabetes. We discuss how therapeutic agents used for both cardiovascular disease and diabetes modulate the inflammatory responses and possibly attenuate the complications of these two chronic disorders that cause significant morbidity and mortality.
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PMID:Inflammation and emerging risk factors in diabetes mellitus and atherosclerosis. 1276 74

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.
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PMID:Cardiovascular disease and benefits of thiazolidinediones. 1278 31

Over the past ten years it has become clear that cardiovascular disease (CVD) and atherosclerosis have a 'microinflammatory' component and are often associated with low levels of inflammatory markers that are in the upper part of the 'normal' range. In particular, diseases that predispose to CVD, such as the metabolic syndrome and type 2 diabetes, appear to have a very strong inflammatory component. While the inflammatory process is very complicated, single measures, such as C-reactive protein (CRP) or fibrinogen, have clear benefits as they summarise many different parts of the inflammatory process and are easy to apply. However, it is important to remember that the process of inflammation includes coagulation, fibrinolysis, complement activation, antioxidation, immune response and hormonal regulation through the hypothalamic-pituitary-adrenal axis. Furthermore, genetic variation, differences in exposure to environmental influences and the mass of inflammation-producing tissue (e.g. adipose tissue) can all influence responses. Thus, the relationship between atherosclerosis, the metabolic syndrome and inflammation is extraordinarily complex. Inflammatory markers such as CRP exhibit strong CVD-risk prediction that is consistent across sexes and a number of different populations. They reflect risk not only for 'vulnerable plaque' and myocardial infarction (MI) but also for other cardiovascular diseases. In fact, inflammation is associated with several, if not all, of the chronic diseases of old age, and it is now clear that there are important links between inflammation and general metabolism. For instance, visceral adiposity exerts a major influence on inflammation status. Medications that affect atherosclerosis appear to do so at least in part by influencing inflammation (for instance, the emerging pleiotropic effects of statins), and this has far-reaching ramifications for chronic diseases of old age and their treatment.
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PMID:Inflammation, the metabolic syndrome and cardiovascular risk. 1279 93

To examine the association of low-grade systemic inflammation with diabetes, as well as its heterogeneity across subgroups, we designed a case-cohort study representing the approximately 9-year experience of 10,275 Atherosclerosis Risk in Communities Study participants. Analytes were measured on stored plasma of 581 incident cases of diabetes and 572 noncases. Statistically significant hazard ratios of developing diabetes for those in the fourth (versus first) quartile of inflammation markers, adjusted for age, sex, ethnicity, study center, parental history of diabetes, and hypertension, ranged from 1.9 to 2.8 for sialic acid, orosomucoid, interleukin-6, and C-reactive protein. After additional adjustment for BMI, waist-to-hip ratio, and fasting glucose and insulin, only the interleukin-6 association remained statistically significant (HR = 1.6, 1.01-2.7). Exclusion of GAD antibody-positive individuals changed associations minimally. An overall inflammation score based on these four markers plus white cell count and fibrinogen predicted diabetes in whites but not African Americans (interaction P = 0.005) and in nonsmokers but not smokers (interaction P = 0.13). The fully adjusted hazard ratio comparing white nonsmokers with score extremes was 3.7 (P for linear trend = 0.008). In conclusion, a low-grade inflammation predicts incident type 2 diabetes. The association is absent in smokers and African-Americans.
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PMID:Low-grade systemic inflammation and the development of type 2 diabetes: the atherosclerosis risk in communities study. 1282 49


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