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)

The relative importance and behaviour of plasma and platelet plasminogen activator inhibitor (PAI-1) in disease has not hitherto been examined. In this study the concentration of PAI-1 in the plasma and platelets of patients with a variety of disorders was examined using a specific ELISA and a functional assay. Mean plasma PAI-1 was elevated in groups of patients with diabetes mellitus, hypertension, alcoholic cirrhosis, angina and myocardial infarction. Plasma PAI-1 was raised in the post-operative phase and the PAI-1 released after surgery was not derived from platelets. In all groups PAI-1 in the platelet pool reflected the platelet count, except in type II diabetes mellitus and chronic renal failure, where a reduced quantity of PAI-1 antigen per platelet was found. In severe chronic renal failure, abnormal platelets and diminished platelet PAI-1 may contribute to the haemorrhagic tendency sometimes seen in this disorder. Plasma PAI-1 represents a larger proportion of total circulating PAI-1 in disease than it does in healthy individuals; PAI-1 per platelet is abnormal only in a minority of disorders. Plasma and platelet pools of PAI-1 vary independently in disease and both merit consideration in evaluating the importance, if any, of PAI-1 in thrombosis or haemorrhage.
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PMID:The platelet and plasma pools of plasminogen activator inhibitor (PAI-1) vary independently in disease. 220 5

The fibrinolytic resistance of platelet-rich arterial thrombi received much attention. Clot lysis method was used to assess the in vitro fibrinolytic properties in diabetes mellitus. Platelet rich (PRP) clots were formed by addition of thrombin, and lysis was induced by tissue-plasminogen-activator. The coagulation and lysis was followed by the light scattering properties. A special pattern of good initial lysis followed by a second clotting phase was observed in more than half of insulin dependent diabetic patients, while a similar pattern of clot-lysis was only occasionally found in non-insulin dependent diabetes mellitus or in the healthy control group. Following the thrombin activation of washed, gel-filtered platelets, the supernatants possessed an inhibitory action on in vitro lysis of PPP-clots. This suppression was remarkably stronger in IDDM, along with the highest PAI-1 activity concentration ratio of the platelet lysates, compared to plasmatic levels. The relation of this special type of PRP clot-lysis resistance to diabetic vascular complications needs further clarifying and investigations.
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PMID:Altered lysis resistance of platelet-rich clots in patients with insulin-dependent diabetes mellitus. 749 4

It is not clear whether elevated levels of the fibrinolytic inhibitor, plasminogen activator inhibitor-1 (PAl-1) in Type 2 diabetes mellitus are the result of obesity or coexistent atherosclerosis. Therefore the relationship between PAl-1 and insulin resistance, determined by the homeostasis model assessment (HOMA) was investigated in a group of 26 insulin-resistant, normotensive newly diagnosed Type 2 diabetic patients with a low probability of atherosclerosis. Compared with a normal control group, closely matched for body mass index (BMI), fibrinolytic activity was depressed in the diabetic patients due to elevated levels of the inhibitor PAl-1, 17.6 (11.1-28) vs 8.4 (4.9-14.1) IU ml-1, p < 0.001. PAl-1 was related to BMI, r = 0.59, p < 0.001 plasma insulin, r = 0.66, p < 0.001; insulin resistance, r = 0.54, p < 0.005 and urinary albumin excretion, r = 0.48, p < 0.01, but not HbA1c or fasting glucose. PAl-1 was not related to blood pressure or plasma triglyceride levels. This study suggests that at the time of diagnosis of Type 2 diabetes mellitus, elevated PAl-1 levels are already linked to other risk factors for vascular disease including hyperinsulinaemia, insulin resistance, and urinary albumin excretion, and this is not the result of obesity or coexistent atherosclerosis.
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PMID:The relationship between plasminogen activator inhibitor-1 and insulin resistance in newly diagnosed type 2 diabetes mellitus. 840 25

Elevated levels of PAI-1 are found in coronary artery disease (CAD) and non-insulin-dependent diabetes (NIDDM). PAI-1 may be involved in the pathogenesis of CAD through suppression of fibrinolysis, alternatively the high levels may result from vascular damage. There is evidence that PAI-1 levels are related to genotype at a PAI-1 promoter polymorphism. Genotype at this 4G/5G polymorphism was determined in 160 NIDDM (90 males and 70 females) patients with (n = 38) or without (n = 122) clinical evidence of CAD. Levels of cholesterol were higher (6.5 vs 5.9 mM, p < 0.01) and PAI-1 tended to be higher (PAI-1 activity 23.0 vs 20.4 U/ml) with CAD. The frequency of the 4G/4G genotype was increased and the 5G/5G genotype decreased, in the group CAD compared to those without (p < 0.05). These results suggest that possession of the 4G/4G PAI-1 promoter genotype is a risk factor for the development of CAD in subjects with NIDDM.
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PMID:Plasminogen activator inhibitor-1 (PAI-1) promoter polymorphism and coronary artery disease in non-insulin-dependent diabetes. 856 Apr 7

To investigate the interaction of metabolic and genetic factors in relation to PAI-1, genotype was determined at a 4G/5G polymorphism in the PAI-1 gene promoter and a Hind III RFLP of the PAI-1 gene in 189 Caucasian NIDDM patients. PAI-1 levels were equivalent in each genotype group and PAI-1 activity correlated with fasting insulin (r=0.45), triglyceride (r=0.39) body mass index (r=0.44), cholesterol (r=0.17) and glucose (r=0.15). The regression slope (B) of PAI-1 activity on triglycerides was steeper in the 4G/4G group than the other two groups: 4G/4G B = 0.91, r = 0.62; 4G/5G B = 0.36, r=0.27; 5G/5G B=0.31, r=0.29 (difference between slopes p=0.02) and the association between PAI-1 activity and glucose remained only in the 4G/4G group (r=0.35). These results confirm the association of PAI-1 levels with the features of insulin resistance and indicate that the association between PAI-1 levels and both triglyceride and glucose is influenced by genotype in the region of PAI-1 gene promoter.
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PMID:Environmental and genetic factors in relation to elevated circulating levels of plasminogen activator inhibitor-1 in Caucasian patients with non-insulin-dependent diabetes mellitus. 857 8

Elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1) have been shown to be a risk factor for the development of vascular complications in obese and hyperinsulinemic non-insulin-dependent diabetes (NIDDM) patients. To clarify whether PAI-1 also plays an essential role in the development of such complications in NIDDM patients without obesity or hyperinsulinemia, PAI-1 was analyzed in relation to blood pressure, fasting plasma levels of glucose (FPG), hemoglobin A1C (HbA1c), immunoreactive insulin (F-IRI), C-peptide (CPR), total cholesterol (TC), triglyceride (TGL), and HDL-cholesterol (HDL-C) in 77 NIDDM patients and 10 healthy control subjects. The NIDDM patients were not obese (body mass index [BMI]:<26 kg/m2) or hyperinsulinemic, and BMI in the controls was between 19 and 24 kg/m2. In addition, parameters of insulin secretion reserve, including sigmaIRI, insulinogenic index, and CPR at 5 min after glucagon loading, were evaluated simultaneously. Plasma levels of PAI-1 were higher in the NIDDM group (9.3+/-0.9 ng/ml) than in the controls (4.3+/-0.7 ng/ml;P<0.01). Levels of FPG and HbA1c were also elevated in the NIDDM group (P<0.05 for each), but F-IRI did not differ between the two groups. However, multiple regression analysis revealed no significant correlation in the NIDDM between PAI-1 and F-IRI or the parameters of insulin secretion reserve. Regardless of the presence or absence of vascular complications, PAI-1 did not vary significantly in the NIDDM. These findings suggest that the effects of PAI-1 on the development of diabetic complications in NIDDM patients may not proceed in the same way in those with versus those without obesity or hyperinsulinemia, because no correlation was found between PAI-1 and insulin secretion reserve, while plasma levels of PAI-1 were higher in the NIDDM group than in the controls.
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PMID:Plasminogen activator inhibitor-1 in nonobese subjects with non-insulin-dependent diabetes mellitus. 863 10

Diabetes mellitus is associated with disturbances in hemostasis that could contribute to the development of diabetic vascular disease. We investigated the changes in parameters of blood coagulation and the fibrinolytic system and in plasma levels of lipoprotein(a)(Lp(a)) in 124 patients with type II diabetes mellitus and 44 healthy control subjects matched for age and body mass index (BMI) to determine whether hemostatic disturbances may lead to increased cardiovascular mortality. Median levels of fibrinogen (P < 0.0001), thrombin-antithrombin III complex (TAT) (P < 0.005), and plasminogen activator inhibitor-1 (PAI-1) activity (P < 0.05) in plasma were significantly elevated in diabetic patients compared with controls. The median concentration of Lp(a) was significantly higher in diabetic patients than in normal controls (18.2 vs. 12.6 mg/dl. P < 0.0005). Lp(a) levels tended to be elevated in patients with a prolonged history of diabetes. There was no evidence that Lp(a) levels were affected by metabolic control or by type of treatment. Twenty-two diabetics with coronary heart disease (CHD) had significantly higher levels of fibrinogen (P < 0.05), TAT (P < 0.05), and Lp(a) (24.7 vs. 13.7 mg/dl, P < 0.01) than the 51 patients without diabetic angiopathy. Our data indicate that impaired hemostatic balance in diabetes may cause hypercoagulability and may thus contribute to the increased cardiovascular mortality in diabetes.
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PMID:Hypercoagulability and high lipoprotein(a) levels in patients with type II diabetes mellitus. 864 73

In order to study the plasminogen activator inhibitor activity (PAI-1) in subjects at different risk of non-insulin-dependent diabetes and ischaemic heart disease we examined 89 subjects with diet controlled NIDDM (49 Caucasian, 40 Asian), 29 with impaired glucose tolerance (IGT) (13 Caucasian, 16 Asian), and 149 with normal glucose tolerance (67 Caucasian, 82 Asian). Diabetes was diagnosed by WHO criteria and highly specific, monoclonal antibody-based assays were used to measure insulin, intact proinsulin, and des 31,32 proinsulin. Subjects with NIDDM were significantly more obese, had more central distribution of obesity, higher fasting plasma specific insulin concentrations (NIDDM median 74 pmol l-1 vs IGT 41 pmol l-1, p < 0.01 and vs normals 34 pmol l-1, p < 0.001) and higher PAI-1 activity than normals and those with IGT (NIDDM 23.0 +/- 6.9 vs IGT 16.8 +/- 5.0, p < 0.001 and vs normals 17.1 +/- 6.9 AU ml-1, p < 0.001). However, PAI-1 activity was not significantly different between Asian and Caucasian normals (17.5 +/- 7.3 vs 16.5 +/- 6.4 AU ml-1, p = ns) and diabetic (22.8 +/- 7.3 vs 23.1 +/- 6.6 AU ml-1, p = ns) subjects. In addition to relationships with obesity and plasma triglyceride, PAI-1 activity, after controlling for age, sex, body mass index, and waist-hip ratio, was related to fasting insulin (partial r = 0.22, p < 0.001), intact proinsulin (partial r = 0.36, p < 0.001), and des 31,32 proinsulin concentrations (partial r = 0.33, p < 0.001) as measured by highly specific assays. The association of PAI-1 with diabetes was weakened but remained statistically significant (p = 0.042) after controlling for age, sex, ethnicity, obesity, plasma triglyceride, and all insulin-like molecules. We conclude that, although PAI-1 activity is raised in subjects with diet-treated NIDDM, it is normal in subjects with IGT and non-diabetic Asians, populations at high risk of NIDDM and ischaemic heart disease. Raised PAI-1 activity may play an important role in the pathogenesis of macrovascular disease in subjects with NIDDM, but is unlikely to explain excess risk of ischaemic heart disease in Asians and those with impaired glucose tolerance.
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PMID:Plasminogen activator inhibitor (PAI-1) activity is elevated in Asian and Caucasian subjects with non-insulin-dependent (type 2) diabetes but not in those with impaired glucose tolerance (IGT) or non-diabetic Asians. 874 14

We have investigated the effects of metformin treatment on concentrations of proinsulin-like molecules in subjects with Type 2 (non-insulin-dependent) diabetes mellitus. Metformin was given for 12 weeks in an increasing dose up to 850 mg three times daily in a double-blind placebo-controlled cross-over design to 27 subjects (age 53.0 +/- 9.9 years; 19 male, 8 female). Concentrations of insulin and proinsulin-like molecules were measured by highly specific enzymoimmunometric assays. The end of metformin treatment was compared with end of placebo treatment. Metformin lowered fasting plasma glucose concentrations (at 12 weeks, metformin: 8.0 +/- 2.5 vs placebo: 12.0 +/- 2.3 mmol l-1, p r2 0.001;). Concentrations of intact (median change -2.9 (range -28.4 to +2.5 pmol l-1), p = 0.02) and des 31,32 proinsulin (median change -1.6 (range -14.1 to +5.4 pmol l-1), p = 0.07) and percentage of proinsulin-like molecules were reduced by metformin treatment (median change -6% (range -16% to +6%), p = 0.02). Changes in the ratio of proinsulin-like molecules were significantly related with those in fasting plasma glucose (r1 = 0.69, p < 0.001). Changes in concentrations of intact and des 31,32 proinsulin on metformin were not related to changes in body mass index or fasting glucose concentration or changes in concentrations of total triglyceride, cholesterol, and plasminogen activator inhibitor-1. Therefore, metformin treatment in subjects with Type 2 diabetes mellitus significantly reduced concentrations of proinsulin-like molecules over a 12-week period. However, these changes were not related to changes in cardiovascular risk factors seen during metformin treatment. We conclude that short-term effects of metformin treatment on proinsulin-like molecules are similar to those previously observed with dietary treatment in subjects with Type 2 diabetes but opposite to those of sulphonylurea treatment. The effect of long-term treatment with metformin on proinsulin-like molecules needs to be assessed.
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PMID:Effect of metformin on intact proinsulin and des 31,32 proinsulin concentrations in subjects with non-insulin-dependent (type 2) diabetes mellitus. 886 52

Non-insulin dependent diabetes mellitus carries a markedly elevated risk of cardiovascular disease. For that reason the efficacy of any treatment modality for this disease should be assessed in terms of the known cardiovascular risk factors, as for example serum lipids. Sulfonylurea do not affect serum lipid levels to any significant extent. These drugs promote beta-cell secretion by dosing potassium ion channels. These channels are also present in vascular smooth muscle cells. Some, though not all, sulfonylureas are able to inhibit the vascular dilatory response to potassium ion openers, thereby adversely affecting the cardioprotective vascular response to ischaemia. Sulfonylureas, in contrast to insulin, seem able to inhibit the fibrinolytic system, possibly via the stimulating effect of proinsulin on the endothelial PAI-1 expression. These observations need further confirmation. Of clinical importance is the frequent occurrence of hypoglycaemia for which several risk factors are recognized.
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PMID:Role of sulfonylureas in non-insulin-dependent diabetes mellitus: Part II--"The cons". 891 91


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