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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 the clinical effect of ibudilast, a prostacyclin-mediated vasodilator and antiplatelet agent, on diabetic nephropathy, 8 nonhypertensive patients with type 2 diabetes mellitus (DM; 4 men and 4 women, mean age: 58.9 +/- 11.4 years, duration of diabetes: 16.9 +/- 3.2 years) with microalbuminuria [20-200 mg/g creatinine (Cr)] were administered ibudilast (30 mg/day) for 18 months (ibudilast group). The urinary albumin excretion index (UAE, mg albumin/g Cr) was compared with 8 age-matched type 2 DM with microalbuminuria (control group). During the study, the UAE significantly decreased in the ibudilast group, while it significantly increased in the control group. After 18 months, the UAE (52 +/- 19 mg/g Cr) in the ibudilast group was significantly (p < 0.05) lower than that (99 +/- 46 mg/g Cr) in the control group. These results suggest that ibudilast may inhibit the progression of early diabetic nephropathy in type 2 DM.
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PMID:Inhibitory effect of ibudilast on urinary albumin excretion in type 2 diabetes mellitus with microalbuminuria. 1181 99

Factors were studied that may initiate macroangiopathy or enhance or aggravate its pathogenesis in patients with type 2 diabetes mellitus. A total of 151 diabetics were compared with healthy controls (n=50); all patients and subjects were normotensive and without renal failure. Plasma endothelin-1 and free radical levels were measured. In addition, plasma prostacyclin levels were assessed by assaying its stable, spontaneous, breakdown product 6-keto-prostaglandin-F1a. Diabetics were divided into three groups: those with clinically evident macroangiopathy and those with early or without atherosclerosis (as determined by the carotid intima-media thickness. Plasma endothelin-1 levels were increased in all diabetics with atherosclerosis. Plasma free radical levels were increased in diabetics with macroangiopathy when compared with control subjects. The plasma levels of 6-keto-prostaglandin-F1a were slightly, but significantly, decreased in the diabetics with macroangiopathy when compared with control subjects. The carotid intima-media thickness was significantly greater in diabetics without macroangiopathy when compared with the controls. Furthermore, the intima-media thickness increased significantly in this group of diabetics but not in the controls over a 30-month follow-up period. Several factors may contribute to atherogenesis in diabetics. These include increased plasma endothelin-1 and free radical levels as well as a deficiency of prostacyclin. These factors may become targets for intervention as well as markers of disease progression.
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PMID:Carotid atherosclerosis in type 2 diabetes mellitus: potential role of endothelin-1, lipoperoxides, and prostacyclin. 1202 15

Enhanced platelet function, particularly in response to collagen, is a common occurrence in diabetes that increases the risk of cardiovascular disease. Ginkgo biloba extract is ingested primarily to improve mental focus but it possesses a blood-thinning potential, which has not been well characterized. This study was designed to compare the effect of ingesting G. biloba extract on platelet aggregation in platelet-rich plasma (PRP) and prostanoid urinary excretion in healthy volunteers and subjects with Type 2 diabetes mellitus (T2DM). Before and after ingesting 120 mg of standardized G. biloba extract for 3 months, platelet aggregation was studied in PRP and urinary metabolites of thromboxane B(2) (TXB(2)) and prostacyclin (PGI(2)) were measured. In healthy volunteers (age, 42+/-11 years; BMI, 28.4+/-4.8 kg/m(2); n=28), the ingestion of G. biloba extract significantly increased fasting insulin and C-peptide (10+/-4 vs. 12+/-6 microU/ml, p<0.007 and 1.3+/-0.8 vs. 2.1+/-1.1 ng/ml, p<0.001, respectively) and significantly reduced collagen but not PAF-mediated platelet aggregation, converting 21 of 28 subjects with [COL+/EPI+] platelets to the [COL-/EPI+] phenotype. This was accompanied by a reduction of 11-dehydro-TXB(2) from 12.4+/-6.1 to 10.3+/-6.1 ng/mg Cr (p<0.04) and PGI(2) metabolites (2,3-dinor-6-keto-PGF(1alpha) and 6-keto-PGF(1alpha)) from 2.2+/-0.8 to 1.8+/-0.8 ng/mg Cr (p<0.05). In the T2DM subjects (age, 54+/-8; BMI, 36.6+/-7.9 kg/m(2); n=19), G. biloba ingestion did not affect pancreatic beta-cell function but significantly reduced platelet aggregation, converting 16 of 19 [COL+/EPI+] platelets to the [COL-/EPI+] phenotype. Unlike the healthy volunteers, this was not accompanied by a reduced urinary prostanoid excretion. G. biloba-induced reduction of both classes of prostanoid metabolites in healthy volunteers, but not in T2DM subjects, may suggest a nonselective inhibition of COX-1-mediated TXA(2) in platelets and COX-2-mediated PGI(2) production by the endothelial cells and perhaps platelet-enriched levels of arachidonic acid or COX-1 activity, or both, in T2DM subjects.
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PMID:Effect of the ingestion of Ginkgo biloba extract on platelet aggregation and urinary prostanoid excretion in healthy and Type 2 diabetic subjects. 1259 Sep 52

The endothelium has several diverse functions in maintaining vascular integrity in terms of structure and function. Two key vasodilators, nitric oxide (NO) and prostacyclin, maintain the vascular pathway, inhibit platelet aggregation, and are antithrombotic. More recently, they have been shown to be anti-inflammatory, and thus are potentially antiatherogenic. It has recently been noted that insulin stimulates NO release by the endothelium. Insulin is a vasodilator, has antiplatelet activity, and is anti-inflammatory. Similar anti-inflammatory effects of thiazolidinediones (TZDs), troglitazone and rosiglitazone, suggest that they too may have potential antiatherogenic effects. These effects of insulin and TZDs are important because the two major states of insulin resistance, obesity and type 2 diabetes, are associated with a marked increase in atherosclerosis coronary heart disease, and stroke. These recent observations have extremely momentous implications for the understanding of the pathogenesis of atherosclerosis in insulin-resistant states and for a rational approach to their comprehensive treatment, including the prevention of atherosclerosis and its complications.
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PMID:Endothelium, inflammation, and diabetes. 1264 90

This review focuses on the link between diabetes mellitus and oxidative stress and, in particular, on the role that moderate wine consumption may play in preventing diabetic complications and the onset of diabetes. With this aim, a search of PubMed was carried out for literature published up to March 2003. In diabetes mellitus, oxidative stress results both from exposure to hyperglycaemia through glycoxidation and sorbitol system activation, and from functional limitation of the hexose monophosphate shunt, leading to a decrease in glutathione synthesis. Oxidative stress alters the plasma lipoprotein profile (particularly low-density lipoproteins), the coagulative parameters (with an increased thrombotic risk), the endothelium (with a decrease in prostacyclin synthesis and an increase of thromboxane production) and the cell membranes (which undergo peroxidation). In diabetic patients, an altered oxidative pattern is present not only in the fasting state but also especially after food intake. In particular, food intake induces a decrease in the total radical-trapping antioxidant parameter (TRAP) and an elevation of hydroperoxides and thiobarbituric acid reactive substances (TBARS). Previously several clinical trials tried to improve the diabetic oxidative status using alpha-tocopherol, ascorbic acid and beta-carotene supplementation. Some authors found, in normal subjects, a reduction of hydroperoxides postprandially when the meal included red wine. Other authors showed that the oxidative pattern present in type 2 diabetic patients was mitigated by red wine. These actions may reduce cardiovascular risk. Moreover, an inverse relationship was observed between alcohol consumption and the incidence of type 2 diabetes; this relationship was valid for a light to moderate intake and it seemed to depend on drinking regularly and to be independent of the type of alcoholic beverage. In conclusion, moderate and regular wine consumption could ameliorate the diabetic oxidative status. This lifestyle measure might contribute to preventing diabetic complications and the onset of diabetes.
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PMID:Diabetes mellitus: oxidative stress and wine. 1460 79

The normal endothelium performs the function of vasodilation, platelet inhibition, and the suppression of inflammation through the secretion of nitric oxide (NO) and prostacyclin (PGI2). Endothelial damage through diabetes, hypercholesterolemia, and other atherosclerotic risk factors results in the reduction of NO and PGI2 synthesis and secretion; and these changes turn the blood vessel into a proconstrictor, proaggregatory, and proinflammatory state. Because atherosclerosis is a chronic inflammation of the arterial wall, abnormal endothelial function would predispose the artery to atherogenesis and to a prothrombotic state. Recent studies have demonstrated that insulin exerts an anti-inflammatory effect in addition to inhibiting platelet aggregation and the expression of other prothrombotic factors. These facts challenge the conventional view that insulin is the mediator of atherogenesis in insulin-resistant states of obesity and type 2 diabetes, which are characterized by hyperinsulinemia. Furthermore, insulin has been shown to be anti-inflammatory, antioxidant, and profibrinolytic and cardioprotective in patients with acute myocardial infarction. Insulin is required as an anti-inflammatory hormone with potential antiatherosclerotic effects.
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PMID:Advances in diabetes for the millennium: diabetes and the endothelium. 1564 11

Coupling factor 6 (CF6) is a novel endogenous inhibitor of prostacyclin. Plasma CF6 and 6-keto-PGF(1a) were measured by radioimmunoassay in 70 consecutively recruited patients with type 2 diabetes and in 56 healthy controls. A significantly increased plasma CF6 level was found in diabetics compared with controls. The CF6 level was inversely correlated with plasma 6-keto-PGF(1a) level and positively correlated with blood glucose and lipids. These results suggest that CF6 might be an obvious marker of impaired endothelium and might contribute to vascular damage in diabetes.
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PMID:Plasma level of mitochondrial coupling factor 6 increases in patients with type 2 diabetes mellitus. 1689 12

Diabetes mellitus is an important risk factor for cardiovascular morbidity and mortality. The metabolic abnormalities caused by diabetes mellitus induce vascular endothelial dysfunction that predisposes patients with diabetes mellitus to atherosclerosis. Two mega clinical trials showed that intensive glycemic control does not have favorable effects on reducing macrovascular events although it demonstrated significant reductions in microvascular complications. It is becoming worthwhile to clarify the beneficial effects of tight controls on blood pressure, serum lipids, and postprandial hyperglycemia to prevent atherosclerosis in patients with type 2 diabetes mellitus. Here, we focus on vascular endothelium as a target of the prostaglandin I2 analog beraprost sodium and the peroxisome proliferators-activated receptor alpha activator fenofibrate for the prevention and treatment of atherosclerosis in patients with type 2 diabetes mellitus. Beraprost sodium lowered circulating vascular cell adhesion molecule- 1 (VCAM-1) concentration and prevented the progression of carotid atherosclerosis in type 2 diabetic patients, probably through inhibiting VCAM-1 expression in vascular endothelium. Fenofibrate up-regulated endothelial nitric oxide synthase expression, which may explain its effects to improve endothelium-dependent vasodilatation and to prevent the progression of coronary atherosclerosis. The approaches to target the molecules expressed in vascular endothelium will become important for preventing the atherosclerosis in type 2 diabetes mellitus.
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PMID:Vascular endothelium as a target of beraprost sodium and fenofibrate for antiatherosclerotic therapy in type 2 diabetes mellitus. 1731 6

The normal endothelium produces a number of vasodilator substances such as nitric oxide (NO) and prostacyclin (PGI2) that regulate vasomotor tone, reduce platelet aggregation, and inhibit the recruitment and activity of inflammatory cells. The functions of vascular endothelial cells are disturbed in diabetic patients. The major cause for mortality and a great percent of morbidity in patients with diabetes mellitus is atherosclerosis. Insulin has recently been shown to stimulate NO release and the expression of NO synthase by the endothelium. Insulin is thus a vasodilator, has anti-platelet activity, and now has been shown to be anti-inflammatory and thus, potentially anti-atherogenic. Similar anti-inflammatory effects of thiazolidenediones (TZDs), troglitazone, and rosiglitazone suggest that they too may have potential anti-atherogenic effects. These effects of insulin and TZDs are of importance since the two major states of insulin resistance, obesity and type 2 diabetes, are associated with a marked increase in atherosclerosis, coronary heart disease, and stroke. These recent observations have extremely important implications for the understanding of the pathogenesis of atherosclerosis in insulin-resistant states and for a rational approach to their comprehensive treatment, including the prevention of atherosclerosis and its complications. This review challenges the previously proposed hypothesis that hyperinsulinemia represents a common pathophysiological pathway of diabetic complications and advances our hypothesis that insulin, through its effect on the endothelium, leucocytes, and platelets, has anti-inflammatory and thus potentially anti-atherogenic properties. Furthermore, through its anti-inflammatory effects, its use improves clinical outcomes in at least two clinical states characterized by profound inflammation-acute myocardial infarction and sepsis.
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PMID:Endothelium, inflammation, and diabetes. 1837 Jun 22

The purpose of this study was to determine whether cyclooxygenase expression in arteries is affected by diabetes. Streptozotocin-injected rats and Goto-Kakizaki rats were used as animal models for type 1 and type 2 diabetes, respectively. Cyclooxygenase-2 expression was induced by lipopolysaccharide. Lipopolysaccharide-induced cyclooxygenase-2 expression was significantly lower in aortas isolated from streptozotocin-injected rats and Goto-Kakizaki rats than in aortas of control rats, while expression level of cyclooxygenase-1 was not affected by lipopolysaccharide and was not different in aortas of the three groups of rats. The level of 6-keto-prostaglandin F(1alpha) that accumulated in the presence of lipopolysaccharide as well as the basal accumulation level in the absence of lipopolysaccharide was significantly lower in aortas of streptozotocin-injected rats and Goto-Kakizaki rats than in aortas of control rats. The net increase in 6-keto-prostaglandin F(1alpha) level in response to stimulation with lipopolysaccharide, which was calculated by subtracting the basal accumulation level from the total accumulation level, was also significantly lower in aortas of streptozotocin-injected rats and Goto-Kakizaki rats than in aortas of control rats. There were no significant differences in the accumulated 6-keto-prostaglandin F(1alpha) levels in the absence or presence of lipopolysaccharide and the levels of basal and lipopolysaccharide-induced cyclooxygenase-2 expression in control or Goto-Kakizaki rat aortas under the conditions of different glucose concentrations in the medium. These results suggest that lipopolysaccharide-induced cyclooxygenase-2 expression and subsequent prostacyclin production are decreased in aortas isolated from both type 1 and type 2 diabetes rats.
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PMID:Depression of cyclooxygenase-2 induction in aortas of rats with type 1 and type 2 diabetes mellitus. 1870 4


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