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)

To evaluate whether or not activated coagulation is present in the preclinical phases of type 2 diabetes mellitus, we studied 46 non-diabetic first-degree relatives of type 2 diabetic patients and 21 matched controls with no family history of diabetes. We determined the plasma levels of prothrombin fragment 1 + 2, D-dimer, fibrinogen, plasminogen activator inhibitor type 1, tissue plasminogen activator, von Willebrand factor and coagulation factors VII and VIII. Glucose tolerance, beta-cell function and insulin sensitivity were assessed in all subjects by a continuous glucose infusion of 5 mg.kg ideal body weight-1.min-1 for 60 min with model assessment of glucose, insulin and C-peptide values. Plasma levels of prothrombin fragment 1 + 2 (median 1.24 vs 0.68 nmol.l-1; P = 0.0001) and D-dimer (331 vs 254 micrograms.l-1 UEF; P = 0.018) were higher in relatives, without significant differences in the other haemostatic variables. Relatives showed higher fasting (5.5 vs 4.9 mmol.l-1, P = 0.004) and post-infusion (9.3 vs 8.3 mmol.l-1, P = 0.02) serum glucose, no differences in insulin or C-peptide levels, lower beta-cell function (122% vs 147%; P = 0.02) and no significant differences in insulin sensitivity. Fifteen relatives were glucose-intolerant and had lower beta-cell function and insulin sensitivity than glucose-tolerant relatives. Both subsets of relatives exhibited higher levels of prothrombin fragment 1 + 2 and D-dimer than control subjects. Thus, first-degree relatives of type 2 diabetic patients present an activated coagulation, even in the absence of minor degrees of glucose intolerance. These abnormalities can play a role in the pathogenesis of cardiovascular diseases frequently seen at diagnosis of type 2 diabetes.
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PMID:Increased prothrombin fragment 1 + 2 and D-dimer in first-degree relatives of type 2 diabetic patients. Prethrombotic state in relatives of type 2 diabetic patients. 887 Aug 13

Insulin deficiency is a protein catabolic state. In vivo studies have shown that insulin enhances short-side-chain amino acid intracellular uptake, stimulates transcription and translation of RNA, increases the gene expression of albumin and other proteins and inhibits liver protein breakdown enzymes. In IDDM patients most of the whole-body protein turnover studies have shown that insulin deficiency increases protein breakdown and increases amino acid oxidation and that these effects are reversed by insulin treatment. Recent studies have demonstrated that a substantial increase in leucine transamination during insulin deprivation contributes to leucine catabolism in IDDM patients. Protein synthesis in the insulin-deprived state is also increased although to a lesser extent than protein breakdown, and this increased whole-body protein synthesis is reduced with an insulin infusion; thus the effects of insulin are largely mediated through its effects on protein breakdown. The metabolic derangements in diabetes frequently involve disturbances in substrates and hormones other than insulin. The observed effects of insulin deficiency in diabetic patients vary in different body compartments; most of the effects of insulin on protein synthesis appear to occur in non-muscular tissues especially in the splanchnic area. In addition, insulin has a differential effect on hepatic protein synthesis, i.e. inhibits fibrinogen synthesis and promotes albumin synthesis. Insulin's anticatabolic effect in IDDM patients is largely due to its inhibition of protein breakdown. The net protein anabolism due to insulin occurs largely in skeletal muscle. In patients with NIDDM these effects are not noted, presumably because of residual endogenous insulin secretion. In fact, treatments that result in improvement of glucose metabolism in obese NIDDM patients do not affect protein metabolism.
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PMID:Protein metabolism in diabetes mellitus. 902 53

Increased plasma plasminogen activator inhibitor type 1 (PAI-1), coagulation factor VII (FVII) and fibrinogen levels have been recognized as risk factors for cardiovascular disease. Because a substantially high incidence of cardiovascular disease has been reported in diabetic patients with nephropathy compared with those without nephropathy, we measured plasma levels of PAI-1, FVII activity and fibrinogen in non-insulin-dependent diabetic patients (NIDDM) with normoalbuminuria (without nephropathy), microalbuminuria (incipient nephropathy) and macroalbuminuria (overt nephropathy). PAI-1 and FVII levels were significantly increased in NIDDM with overt nephropathy compared with NIDDM without nephropathy. Fibrinogen levels were comparable between the patients with normo-, micro- and macro-albuminuria. Univariate regression analysis indicated that PAI-1 and FVII levels were significantly correlated with the albumin excretion rate (AER) in urine. PAI-1, FVII and fibrinogen levels were significantly correlated with the degree of insulin resistance estimated by the steady state plasma glucose concentration (SSPG) during the continuous infusion of glucose, insulin and octreotide. PAI-1 levels were correlated with plasma triglyceride (TG) levels. Multiple regression analysis revealed that AER was significantly associated with PAI-1 and FVII levels, whereas TG lost significant correlation with PAI-1 when AER, SSPG and plasma TG were entered as independent variables. SSPG retained an independent correlation with fibrinogen, PAI-1 and FVII levels. These results suggest that elevated plasma levels of PAI-1 and FVII in NIDDM patients with nephropathy are directly associated with renal damage, whereas insulin resistance widely regulates hemostatic components in NIDDM patients, irrespective of the presence of nephropathy.
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PMID:Albuminuria is directly associated with increased plasma PAI-1 and factor VII levels in NIDDM patients. 918 10

The relationship between the ultrasonographically determined presence and severity of peripheral arterial disease (PAD) and cardiovascular risk factors was studied in 30 post-menopausal, nonsmoking women with type 2 diabetes mellitus. PAD was established on the basis of decreased ankle/arm index (AAI) of < 0.9 in 15 patients. The control group included 15 type 2 diabetic women with AAI > 1.0. There were no differences with respect to diabetes control and systolic blood pressure between the patients with PAD and controls. The patients with PAD had significantly higher mean fibrinogen concentrations (4.75 +/- 0.35 vs 3.53 +/- 0.36 g/L, P < 0.01) and urinary albumin excretion (UAE) values (893 +/- 501 vs 57 +/- 24 mg/day, P < 0.05) than the subjects in the control group. There was no significant difference between the study groups with respect to any lipid variables. Significant partial correlations adjusted for age were observed between AAI (which expressed the severity of PAD) and log UAE (r = -0.55, P < 0.01), creatinine (r = -0.48, P < 0.01) and fibrinogen (r = -0.45, P < 0.01). In the multiple stepwise regression analysis with AAI as a dependent variable, only fibrinogen (P = 0.033) and log UAE (P = 0.029) were included into the best model. In conclusion, in nonsmoking women with type 2 diabetes mellitus, fibrinogen and albuminuria were the only risk factors associated with both the presence and severity of peripheral arterial disease.
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PMID:Fibrinogen and albuminuria are related to the presence and severity of peripheral arterial disease in women with type 2 diabetes mellitus. 926 41

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

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 prevention of coronary artery disease is based on the control of several factors associated with a disease or clinical condition and suspected to play a pathogenetic role, defined as 'risk factors'. Smoking is a powerful risk factor for coronary artery disease, with risk of events increasing in relation to the number of cigarettes smoked daily. Smoking cessation is associated within 3-4 years, with a significant reduction in cardiovascular risk. Hyperlipidaemia is a powerful predictor of coronary disease with a strong, independent, continuous and graded positive association between cholesterol levels and risk of coronary events. Several large studies have shown the benefit of cholesterol reduction, and there is clear evidence of the efficacy of statins in the reduction of events in primary and secondary prevention. Hypertension is a significant, strong and independent risk factor for coronary artery disease morbidity and mortality and the reduction of events and mortality by antihypertensive treatment is well documented. Obesity is associated with an increase in all-cause mortality and cardiovascular mortality, with a particularly high risk for subjects with central obesity. Central obesity is also part of the so-called 'metabolic X syndrome' including insulin resistance, which appears to be associated with a particularly high risk of coronary artery disease. Type 1 and type 2 diabetes mellitus are associated with an increased risk of cardiovascular disease, especially in women. Several studies have shown that good metabolic control and multifactorial risk factor reduction significantly lower the coronary risk in these patients. Recent evidence is accumulating that some clotting factors (fibrinogen, factor VII, von Willebrand factor) and fibrinolytic factors (t-PA and PAI-1) are associated with an increased risk of coronary artery disease. The European Concerted Action on Thrombosis (ECAT) showed that the levels of fibrinogen, von Willebrand factor antigen, and t-PA antigen are independent predictors of subsequent coronary syndromes in patients with angina pectoris, and that low fibrinogen is associated with a low risk of events despite high cholesterol levels. Post-menopausal status is associated with increased risk of coronary artery disease, particularly when menopause is premature (before the age of 45) or abrupt (surgical). There is strong, thought not yet completely definite evidence that post-menopausal hormone replacement therapy may significantly reduce the risk of events and improve survival. Hyperhomocysteinaemia is an emerging risk factor independently associated with an increased risk of coronary artery disease, cerebral vascular disease, and peripheral vascular disease. The administration of vitamin B6, B12 or folate seems to be useful and is currently under further evaluation. Recently, attention has been focused on the correlation between coronary artery disease and genetic factors, such as ACE gene polymorphism or the gene polymorphism for the IIIa-moiety of the platelet fibrinogen receptor IIb-IIIa. In primary prevention, control of the major risk factors mainly in patients with clustered factors will substantially reduce the risk of ischaemic events. Secondary prevention of CHD is based on: aggressive behavioural advice, blood pressure reduction in hypertensives, good metabolic control of diabetes, and cholesterol reduction. Aspirin, beta-blockers, ACE inhibitors, and oral anticoagulants, may be useful in selected patients.
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PMID:Classical risk factors and emerging elements in the risk profile for coronary artery disease. 951 44

The objective of this study was to estimate the prevalence of poor glycaemic control and cardiovascular risk factors in an Italian population-based cohort of subjects with Type 2 diabetes mellitus (DM). Out of a cohort of 1967 subjects (estimated completeness of ascertainment 80%), 1574 (80%) were investigated, and adherence to targets for control of the European NIDDM Policy Group assessed. Prevalence of poor glycemic control (HbA1c > = 8) was 47.7%. Obesity was present in 23.4% of the cohort, hypertension in 83.4%, hypertriglyceridaemia (>2.26 mM) in 19.3%, hypercholesterolaemia (>6.46 mM) in 25.5%, and low HDL-cholesterol (<0.90 mM in men and <1.03 mM in women) in 13.7%. Only 153 (9.7%) subjects were free from other disorders. Subjects were treated as follows: 26.2% exclusively by general practitioners; 13.3%, 69.9%, 10.9%, and 5.9% with diet, oral hypoglycaemic drugs, insulin, and both, respectively. Multiple linear regression analysis showed associations between HbA1c and fibrinogen (p < 0.001), total cholesterol (p = 0.006), and triglycerides (p = 0.04), independent of age, sex, duration of diabetes, and antidiabetic treatment. Neither BMI nor blood pressure were associated with HbA1c. In conclusion, this Italian population-based cohort of subjects with Type 2 DM showed a high prevalence of poor glycaemic control, high consumption of oral hypoglycaemic drugs, and an independent association between glycaemic control and cardiovascular risk factors (fibrinogen, total cholesterol, and triglycerides). The presence of obesity or hypertension was not significantly associated with glycaemic control.
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PMID:Glycaemic control and cardiovascular risk factors in type 2 diabetes: a population-based study. 958 95

To clarify the relationship between platelet function and diabetic complications, we investigated spontaneous platelet aggregation (SPA) and agonist-induced platelet aggregation by a particle counting method using light scattering (LS) and by a conventional light transmission method (LT) in 23 age- and sex-matched control subjects and 74 patients with type II diabetes mellitus. We also observed platelets using the FIC-2 (TOA Medical Electronics, Kobe, Japan) flow cytometer and imaging device. Observation by the FIC-2 device showed microaggregates of platelets in samples with increased SPA-LS. SPA-LS was significantly elevated in patients with type II diabetes mellitus as a whole compared with control subjects. SPA-LS also showed significant differences between control subjects and three diabetic patient subgroups with a varying severity of retinopathy, nephropathy, or neuropathy, and the mean values increased along with the increasing severity of complications. On the other hand, although SPA-LT also showed significant differences between these groups, the absolute values were all less than 10%, which we believe does not warrant quantitative analysis. Adenosine-5'-diphosphate (ADP)-induced platelet aggregation failed to show significant differences between controls and subjects with a varying severity of retinopathy by either LS or LT, which indicates that SPA is more sensitive than agonist-induced platelet aggregation in relation to diabetic complications. We observed significant correlations between SPA-LS and the patients' age, hemoglobin A1c (HbA1c) level, plasma fibrinogen level, or 6-keto-PGF1alpha (6KF) to 11-dehydro-thromboxane B2 (TXB2) ratio. Our study demonstrated a close relationship between platelet hyperaggregability and diabetic complications, and a longitudinal prospective study of SPA-LS in diabetic patients is warranted to clarify cause-and-effect relationships.
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PMID:A cross-sectional evaluation of spontaneous platelet aggregation in relation to complications in patients with type II diabetes mellitus. 962 70

The aim of this study was to determine the effect of the lipid modifying agent gemfibrozil on lipid and coagulation risk factors in patients with Type 2 diabetes mellitus (Type 2 DM). Twenty-six subjects with Type 2 DM and dyslipidaemia were treated for 24 weeks with either gemfibrozil 600 mg orally twice daily or placebo in a double-blind randomized trial. Lipid profiles, fibrinogen, Factor VII, and plasminogen activator inhibitor-1 (PAI-1) were measured by routine laboratory methods. Low density lipoprotein (LDL) size was determined by gradient gel electrophoresis and the resistance of LDL to copper-induced oxidation was assessed by measuring absorbance at 234 nm. Gemfibrozil significantly reduced total cholesterol (-0.9 (-0.48, -1.32) mmol l(-1); p < 0.05) and triglycerides (-2.7 (-1.55, -1.35) mmol l(-1); p < 0.001) vs placebo. The fall in triglyceride was reflected by a fall in VLDL cholesterol levels in the gemfibrozil treated group vs placebo (-1.31 mmol l(-1); p < 0.001). LDL-cholesterol level did not change but LDL particle size increased by 0.5 nm (0.01, 0.93); P < 0.02. The increase in particle size was inversely correlated with the change of triglyceride level (r = -0.79, p < 0.0001) but did not result in any reduction of susceptibility to copper-induced oxidation. There were no significant changes in the coagulation parameters studied. Because of its ability to correct the lipid abnormalities associated with Type 2 DM particularly hypertriglyceridaemia, gemfibrozil provides a useful therapeutic option in the management of diabetic dyslipidaemia but it does not alter in vitro oxidizability of LDL.
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PMID:Gemfibrozil treatment increases low-density lipoprotein particle size in Type 2 diabetes mellitus but does not alter in vitro oxidizability. 979 89


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