Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Increased plasma fibrinogen levels have been identified as a risk indicator for myocardial infarction, stroke, and thrombosis. Both environmental and genetic factors make an important contribution to plasma fibrinogen levels in humans. In the present study we evaluated, in patients with serum cholesterol levels between 4 and 8 mmol/L, the relation of plasma levels and polymorphisms of fibrinogen with coronary artery disease (CAD), cross-sectionally at baseline and after a 2-year follow-up period in which they received either a placebo or pravastatin. Higher plasma fibrinogen levels (3.9 g/L) were observed at baseline in patients with the -455AA genotype than in patients with the -455GA (3.2 g/L) and -455GG (3.1 g/L) genotypes of the -455G/A fibrinogen beta gene polymorphism (P<.05). Plasma levels of fibrinogen were not related to the baseline angiographic variables (mean segment diameter [MSD] and minimum obstruction diameter [MOD]), nor to the quantitative changes in these angiographic variables. However, in the placebo group, patients with the -455AA genotype had more progression of CAD, expressed by a significantly greater decrease of the MSD and MOD, after the 2-year follow-up period than patients with the other genotypes. The -455G/A polymorphism was related to the progression of CAD, and pravastatin therapy seemed to offset this deleterious effect. We hypothesized that the -455A allele may promote a stronger acute-phase response in fibrinogen and that the resulting higher fibrinogen levels may form the pathogenetic basis for the stronger progression of coronary atherosclerosis. Experiments to verify this hypothesis are being proposed and advocated, in view of the possibility of identifying a genetic marker that can recognize a subgroup of patients with an increased risk who may benefit from early treatment with lipid-lowering or anticoagulant drugs.
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PMID:-455G/A polymorphism of the beta-fibrinogen gene is associated with the progression of coronary atherosclerosis in symptomatic men: proposed role for an acute-phase reaction pattern of fibrinogen. REGRESS group. 948 92

Type 2 diabetes mellitus, one of the most prevalent and disruptive diseases in our older population, occurs in approximately 10% of persons over age 65. Its cause is usually a combination of deficient insulin production and resistance to insulin. In approximately one-half of those with diabetes, symptoms occur slowly over time and escape diagnosis. Complications include cardiovascular disease with myocardial infarction and stroke, nephropathy, retinopathy, peripheral neuropathy, and sexual dysfunction. Risk factors include age, family history, obesity, and sedentary lifestyle. Screening and early diagnosis are important secondary means of prevention, but physicians should also think about primary prevention based on family history, diet, and physical activity.
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PMID:Type 2 diabetes: causes, complications, and new screening recommendations. I. 951 74

Most people with diabetes die from thrombotic complications superimposed to degenerative arterial vascular lesions, mostly myocardial infarction. Diabetes is a risk factor per se for such complications, but often clusters with dyslipoproteinemia, hypertension and obesity. In NIDDM (Type-II) patients this is referred to as "metabolic syndrome" and often operates on a genetically programmed susceptibility which accelerates the pathogenesis of coronary artery disease in front of a much wider diabetes specific cardiopathy. From a pathophysiological point of view none of these associated risk factors explains the pathogenetic series of events leading to the precipitation of an occlusive thrombus at sites of complicated coronary plaques. In patients with diabetes the coagulation system is switched towards a prethrombotic state, involving increased plasmatic coagulation, diminished fibrinolysis, decreased endothelial thromboresistance and predominantly platelet hyperreactivity ("diabetic thrombocytopathy"). Some of these factors are associated with an increased coronary risk (e.g. fibrinogen, PAI-1, platelets), but are also directly linked to the pathogenesis of "atherothrombosis". Altered cardiac remodelling together with adhesion and coagulation mechanisms appears suitable to explain decreased functional performance of infarcted organs, decreased success of acute (reduced fibrinolytic response, reperfusion injury) and longterm intervention strategies (PTCA, CABG) in diabetes. Glucose adjustment alone will not adequately neutralize these complex mechanisms. Particularly in diabetes a multidimensional interventional repertoire is required including antihypertensive, antidyslipoproteinemic and antithrombotic drugs, customized according to the individual patients needs as assessed by early diagnostic measures ("early secondary prevention").
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PMID:Heart disease in diabetes mellitus: a challenge for early diagnosis and intervention. 951 54

The aim of this study was to assess the prevalence of long-term complications in a large sample of French NIDDM patients. Therefore, 427 NIDDM patients 35-74 years old were recruited in ten centers. Standardized clinical criteria and central reading for retinal and electrocardiographic changes were used to assess the presence of complications. The prevalence rates of complications were 29.7% and 3.3% for background and proliferative retinopathy; 21.8%, 6.1%, and 2.8% for microalbuminuria, proteinuria, and renal insufficiency; 19.9 and 11.7% for asymptomatic and symptomatic pheripheral neuropathy; 8.2% for orthostatic hypotension; 10.1% and 8.4% for angina pectoris and myocardial infarction; and 13.1% and 6.3% for mild and moderate to severe peripheral vascular disease, respectively. In conclusion, prevalence rates in this study were lower than in most studies from other countries.
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PMID:Low prevalence of long-term complications in non-insulin-dependent diabetes mellitus in France: a multicenter study. CODIAB-INSERM-ZENECA Pharma Study Group. 955 86

We set out to determine the genotype distributions of the PI(A) polymorphism of platelet glycoprotein IIIa, the HPA-3 polymorphism of platelet glycoprotein IIb, and the variable number tandem repeat (VNTR) polymorphism of platelet glycoprotein Ib in subjects with Type 2 diabetes mellitus (Type 2 DM) with (n = 125) and without (n = 90) a clinical history of macrovascular disease. In 215 white European subjects with Type 2 DM, presence of coronary artery disease was determined as a clinical history of angina, myocardial infarction (MI), coronary angioplasty or coronary artery by-pass grafting. Presence of peripheral vascular disease was defined as a clinical history of intermittent claudication with confirmatory vascular ultrasound or angiography, intermittent claudication with undetectable foot pulses and no history of arthralgia or surgery for leg ischaemia, confirmed by reference to medical case notes. Polymorphisms were detected by polymerase chain reaction amplification of DNA. There was no difference in the genotype distributions of subjects with and without macrovascular disease. In subjects with a first MI before the age of 60 years (n = 26), there was a 38% incidence of PI(A2) compared to 29% in subjects free from clinically evident macrovascular disease, but this difference did not reach statistical significance. This study does not support the hypothesis that polymorphisms of platelet glycoproteins, in particular the PI(A) polymorphism of platelet glycoprotein IIIa, play an important role in the pathogenesis of macrovascular disease in subjects with Type 2 DM.
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PMID:Polymorphisms of platelet glycoproteins in relation to macrovascular disease in type 2 diabetes mellitus. 958 97

A cross-sectional survey with the aim to study the prevalence of diabetes and long-term complications was carried out in a health care district in Sweden with 125,500 inhabitants. Information was extracted from the medical records. 4127 people with diabetes were identified of whom 87% were classified as NIDDM (non-insulin-dependent diabetes mellitus), 12% as IDDM (insulin-dependent diabetes mellitus) and 0.7% as secondary or unclassified diabetes. The prevalence of diagnosed diabetes was 3.3%. A total of 83% received their regular routine care at primary health care centres, 31% were treated with diet only, 36% had oral hypoglycaemic agents, 31% had insulin and 2% had combination therapy. The mean HbA1c was 7.2% (ref. range 4.0-5.3%). Of the adults (> 18 years) 27% had retinopathy, 13% had nephropathy and 27% had loss of pallaesthesia. 50% had hypertension, 21% angina pectoris, 11% had had myocardial infarction, 11% stroke, 21% had signs of peripheral arterial disease, 2% had been amputated and 21% were smokers. The conclusion is that in a population of patients with diabetes with acceptable metabolic control, complications are still a great problem.
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PMID:Diabetes and it's complications in a Swedish county. 959 86

Proteinuria is a well known risk factor for cardiovascular morbidity. There has been no report on cardiovascular morbidity in Indian NIDDM patients with proteinuria. Hence this study has been undertaken to estimate the prevalence of cardiovascular diseases (CVD) in South Indian NIDDM with proteinuria. We studied two groups of NIDDM patients with diabetes for > or = 5 years: group PR with persistent proteinuria of > 500 mg/day (n = 297) and group NPR with normoalbuminuria (albuminuria < or = 30 micrograms/mg creatinine)(n = 296), who reported for review during the study period. They were matched for age, duration of diabetes and BMI. The prevalence of cardiovascular diseases, namely myocardial infarction, the presence of ischaemic heart disease and the history of coronary bypass surgery were compared in the two groups. The prevalence of hypertension was higher among the PR than the NPR patients (56.5 vs 24.7%, chi 2 = 61.3, P < 0.01). CVD were detected in 39.2% (n = 116) of the PR and 13.2% (n = 39) of the NPR groups. (chi 2 = 54.85, P < 0.001). The risk was thus three-fold higher in the PR group. Univariate analysis showed that in the proteinuric group, the prevalence of complications was higher in association with hypertension (45.8% vs 30.2%, chi 2 = 6.82, P = 0.009). Multiple logistic regression analysis showed that the factors associated with CVD were proteinuria (odds ratio 5.03), age (OR 1.08) and BMI (OR 1.07) while sex, age at onset of diabetes, duration of diabetes, hypertension, smoking, HbA1, serum creatinine, cholesterol and triglycerides did not show independent contribution. The study, highlights the high risk conferred by macroproteinuria in Indian NIDDM patients. This risk is found to be independent of the presence of associated hypertension.
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PMID:Cardio vascular morbidity in proteinuric south Indian NIDDM patients. 967 70

Millions of Americans are at risk for cardiovascular morbidity and mortality related to disorders of glucose intolerance--particularly type 2 diabetes and prediabetic conditions, including the insulin resistance, or "cardiovascular dysmetabolic," syndrome. The latter is apparently more intricately associated with macrovascular disease--myocardial infarction, stroke, and peripheral vascular disease. In some situations the risk of cardiovascular disease might be reduced by the prevention of diabetes and also by prevention or treatment of the cardiovascular dysmetabolic syndrome. Studies have shown that intensive glycemic control can delay the development of microvascular complications in type 1, and possibly type 2, diabetes. Several longitudinal observational studies have demonstrated a relationship between glycemic control and the development of cardiovascular disease. Prospective clinical intervention trials to address this issue are underway. Insulin may have a role in atherogenesis, both directly and by promoting development of such risk factors as hypertension and dyslipidemia. Genetic factors and mechanisms promoting or discouraging development of glucose intolerance are also under investigation. Lifestyle changes--dietary and exercise modification, weight loss, and smoking cessation--have been shown to have a positive effect on cardiovascular disease risk. Clinical trials suggest that oral antidiabetic agents--particularly the new noninsulin secretagogues (including troglitazone and metformin, which act on the liver and on skeletal muscle)--may be useful in delaying or preventing development of type 2 diabetes and the cardiovascular dysmetabolic syndrome, as well as in their treatment, when present. Both agents, acting primarily by different mechanisms of action, have also demonstrated potential beneficial effects on serum lipid profiles and other cardiovascular risk factors and may be useful in patients with cardiovascular dysmetabolic syndrome who do not yet meet the criteria for diabetes.
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PMID:Type 2 diabetes care: the role of insulin-sensitizing agents and practical implications for cardiovascular disease prevention. 970 64

Management of major risk factors (smoking, hypercholesterolaemia, hypertension), in the context of secondary prevention, has an impact on recurrence and life expectancy. However, there is a delay between the publication of therapeutic trials and their diffusion within the medical community. The objective of this study was to evaluate the prevalence and management of the main risk factors in a sample of 500 men, with a mean age of 55.1 +/- 7.5 years, presenting with stable coronary artery disease. 11% of subjects had a family history of premature myocardial infarction. Smoking was frequent: 21% of smokers, 60% of ex-smokers. Hypercholesterolaemia (LDL-C > 3.4 mmole/l or treatment) was present in 82% of subjects. Only 45% of treated subjects had an LDL-C < 3.4 mmole/l. Hypertension (systolic blood pressure > or = 140 mmHg or diastolic blood pressure > or = 90 mmHg or treatment) was present in 61% of subjects. Only 33% of treated subjects were controlled. Non-insulin-dependent diabetes mellitus (blood glucose > or = 7.7 mmole/l or treatment) was present in 21% of subjects. Only 43% of treated subjects were controlled. Calculation of the distribution of major risk factors (smoking, pathological obesity, hypercholesterolaemia, hypertension, diabetes) showed that 90% of coronary patients presented at least two risk factors. Overall, the prevalence and management of risk factors in patients with stable coronary artery disease is far from optimal.
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PMID:[Prevalence and management of major risk factors in 500 men with stable coronary disease]. 980 37

In a controlled, randomized, 6-year trial the safety and efficacy of picotamide, a dual-action antithromboxane agent, were assessed in 50 patients with type 2 diabetes mellitus at increased risk of thrombotic vascular events. The patients were randomized to two groups of equal size and received 900 mg picotamide daily or placebo. After phase I (double-blind; years 1 - 2), patients receiving placebo were treated, if necessary, with antiplatelet drugs (aspirin, ticlopidine) while members of the other group continued to receive 600 mg picotamide daily. In the course of the study 21 vascular events occurred: 16 in the group receiving placebo (fatal myocardial infarction, n = 7; non-fatal stroke, n = 3) and five in the group receiving drug (fatal myocardial infarction, n = 2) (P < 0.005; Fisher's exact test). One patient (placebo group) died of malignant disease. During the initial double-blind phase a total of nine vascular events was observed (six and three in the groups receiving placebo and drug, respectively). Picotamide treatment was well tolerated and no major side-effects were observed during the study periods.
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PMID:Long-term safety and efficacy of picotamide, a dual-action antithromboxane agent, in diabetic patients with carotid atherosclerosis: a 6-year follow-up study. 981 86


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