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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dysfunction of the vascular endothelium is considered an early step in the development of diabetic angiopathy. Hyperglycaemia results in endothelial dysfunction, both through direct effects of glucose and through formation of advanced glycosylation end-products (AGEs). We hypothesized that the effects of glucose and AGEs on endothelial function in insulin-dependent diabetes mellitus (IDDM) are distinct and are reflected by distinct plasma markers of endothelial function. We therefore measured plasma levels of von Willebrand factor (vWF), soluble (s) E-selectin and vascular cell adhesion molecule-1 (sVCAM-1), and evaluated the relationship with HbA1c and urinary excretion of pentosidine, an AGE product, in 56 patients with IDDM. Urinary pentosidine excretion was higher in the diabetic than in a control group (n = 60) of similar age (P < 0.0001) and showed a steeper increase with age (P < 0.02 vs controls). In the diabetic group, sE-selectin was correlated to HbA1c (r = 0.52, P < 0.0001), whereas sVCAM-1 was not (r = 0.11, P = 0.47). In contrast, sVCAM-1 showed a trend towards a correlation with log (pentosidine excretion) (r = 0.27, P = 0.06), whereas sE-selectin did not (r = -0.16, P = 0.27). Log(vWF) was correlated to HbA1c (r = 0.50, P < 0.0001) and tended to correlate with log (pentosidine excretion) (r = 0.25, P = 0.07). Multivariate analyses with both pentosidine and HbA1c as independent variables showed significant associations of sE-selectin with HbA1c, of sVCAM-1 with pentosidine, and of log(vWF) with both HbA1c and pentosidine (all P-values < 0.02). Our results imply that the effects of glucose and AGEs on the endothelium can be reflected by distinct endothelial markers. Plasma sE-selectin may reflect short-term effects of glucose on the endothelium, sVCAM-1 the effects of AGEs, and vWF the combined effect of glucose and AGEs.
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PMID:Distinct associations of HbA1c and the urinary excretion of pentosidine, an advanced glycosylation end-product, with markers of endothelial function in insulin-dependent diabetes mellitus. 968 85

The high incidence of cardiovascular morbidity and mortality in non-insulin-dependent diabetes mellitus with albuminuria cannot be fully explained by the presence of standard cardiovascular risk factors. We assessed some pathogenic factors of diabetic vascular atherosclerotic damage in 72 non-insulin-dependent diabetes mellitus patients controlled by diet alone and 60 healthy controls. Our study aim was to assess the early onset of these alterations and to correlate them with the presence of microalbuminuria. We determined their incidence in two carefully selected groups of diabetic patients without clinical signs of cardiovascular risk and complications, where diet alone achieved glycometabolic balance. Microalbuminuric patients had an alterated oxide-reductive balance and elevated values of plasminogen activator inhibitor, tissue plasminogen activator, von Willebrand factor, endothelin-1 and betathromboglobulin compared with the normoalbuminuric diabetics and controls. Our findings support the hypothesis that a state of endothelial dysfunction characterized by altered oxide-reductive balance, modified hemostasis and changes in the endothelial barrier properties occurs much earlier in non-insulin-dependent diabetic patient especially in diabetics with microalbuminuria. In addition, alterations in the oxide-reductive balance, and hemostasis occur early and may be an underlying cause of microangiopathic complications in microalbuminuric diabetics.
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PMID:Early endothelial alterations in non-insulin-dependent diabetes mellitus. 968 51

Recent developments in cell biology have identified new areas of direct relevance to the pathogenesis of Type 1 (insulin-dependent) diabetes mellitus and its complications. Endothelial damage is well recognized in diabetes--endothelial cell markers von Willebrand factor, soluble E-selectin, and soluble thrombomodulin are providing further evidence of the relationship between activation and damage to the vasculature and clinical disease in this condition. Cell surface bound adhesion molecules may also have a role in the development of atherosclerosis in patients with diabetes but the importance of the soluble forms of these molecules, such as intercellular adhesion molecule-1, is unclear. Evidence of platelet dysfunction has long been acknowledged in diabetes and new data are discussed. It is likely that a greater appreciation of the intimate interactions between endothelial integrity, adhesion molecules and platelets in Type 1 diabetes mellitus will provide a greater understanding of the risk of cardiovascular disease and stroke in patients with this disorder.
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PMID:Endothelial integrity, soluble adhesion molecules and platelet markers in type 1 diabetes mellitus. 1022 99

The term 'microalbuminuria' has been introduced to describe a measurable increase in urine albumin excretion, which is still within normal total urine protein excretion levels. Many data suggest that microalbuminuria is of value as an index of vascular damage, especially in hypertension and diabetes, and there is increasing information on its associations with traditional cardiovascular risk factors and its prognostic value. The association between microalbuminuria and peripheral markers of endothelial damage or dysfunction, such as von Willebrand factor, suggests the possibility that microalbuminuria may be a simple, cheap and easy index of endothelial abnormalities in cardiovascular disease. Nevertheless, further information on the value of microalbuminuria in other atherosclerotic vascular complications, such as ischaemic heart disease, stroke and peripheral artery disease is still needed.
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PMID:Microalbuminuria and cardiovascular risk. 970 56

This study determined whether retinal degeneration during diabetes includes retinal neural cell apoptosis. Image analysis of retinal sections from streptozotocin (STZ) diabetic rats after 7.5 months of STZ diabetes identified 22% and 14% reductions in the thickness of the inner plexiform and inner nuclear layers, respectively (P < 0. 001). The number of surviving ganglion cells was also reduced by 10% compared to controls (P < 0.001). In situ end labeling of DNA terminal dUTP nick end labeling (TUNEL) identified a 10-fold increase in the frequency of retinal apoptosis in whole-mounted rat retinas after 1, 3, 6, and 12 months of diabetes (P < 0.001, P < 0. 001, P < 0.01, and P < 0.01, respectively). Most TUNEL-positive cells were not associated with blood vessels and did not colocalize with the endothelial cell-specific antigen, von Willebrand factor. Insulin implants significantly reduced the number of TUNEL-positive cells (P < 0.05). The number of TUNEL-positive cells was also increased in retinas from humans with diabetes. These data indicate that retinal neural cell death occurs early in diabetes. This is the first quantitative report of an increase in neural cell apoptosis in the retina during diabetes, and indicates that neurodegeneration is an important component of diabetic retinopathy.
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PMID:Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin. 971 Apr 47

Endothelial injury has been implicated in the enhanced vascular disease associated with diabetes mellitus. In diabetic humans elevated plasma von Willebrand factor (vWF) levels have been interpreted as an indication of endothelial damage. Using the BB rat as a model of inherited insulin dependent-diabetes mellitus, plasma vWF and aortic endothelial ultrastructural alterations were examined during the first 7 months of diabetes. Total plasma vWF levels were determined by ELISA and vWF multimeric composition by electrophoresis. vWF was identified immunohistochemically. Following the onset of hyperglycemia, there were progressive alterations in aortic endothelial morphology, which were consistent with injury, and aortic intimal thickening was significantly greater in rats diabetic for 7 months compared to age-matched controls. Significant increases in the Weibel Palade (WP) body content of the endothelial cells were observed after 1 week and 2 months of diabetes, but not at later times. Endothelial alterations associated with the possible release of vWF appeared to involve fusion of WP bodies with other vacuoles rather than direct fusion with the cell membrane. Plasma vWF levels in diabetic rats were varied, but were not significantly different from those of control animals and did not correlate with either glucose or insulin levels. The multimeric composition of plasma vWF was also similar at all times in both diabetic and non-diabetic animals. From these observations, plasma vWF levels do not provide an indicator of the endothelial perturbations which occurs in diabetic rats.
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PMID:Changes in the aortic endothelium and plasma von Willebrand factor levels during the onset and progression of insulin-dependent diabetes in BB rats. 971 35

The structural alterations of endothelium and smooth muscle cells of the hind limb and heart veins and arteries were investigated in Golden Syrian hamsters subjected to streptozotocin induced diabetes. Animals were examined at 5, 10, and 15 weeks after induction of diabetes. At each time point body weight and plasma glucose concentrations were recorded. Anesthetised animals were washed out of blood, fixed in situ, and the femoral vein and artery, saphenous vein and artery, and heart veins and coronaries were dissected out, and processed for electron microscopical examination. Anionic sites of the endothelial plasmalemma were visualized by in situ perfusion of cationized ferritin. The endothelial localization of von Willebrand factor was carried out by immunocytochemistry. The results showed that induction of experimental diabetes generated morphological changes of the endothelium and smooth muscle cells of both hind limb and heart vessels. The common alterations developed in endothelial cells of venous and arterial origin consisted in: 1) the development of a secretory phenotype, enriched in biosynthetic and degradative organelles; 2) the abundance of cytoskeletal elements, especially intermediary filaments; 3) the increase in number of fused plasmalemmal vesicles and transendothelial channels, and 4) the hyperplasia of the basal lamina. In contradistinction to the arterial endothelium, the peculiarities of the venous endothelium in the diabetic hamsters examined were: 1) the uniform distribution of the anionic sites exposed on the luminal plasma-lemma (as in normal animals), and 2) the increased number of copies of Weibel-Palade bodies (up to 13 copies per endothelial cell in the hind limb). Von Willebrand factor was immunodetected in Weibel-Palade bodies, Golgi cisternae and some vesicles of normal and diabetic hamsters. With time, and especially pronounced at 15 weeks of diabetes, the smooth muscle cells of veins and arteries examined exhibited a characteristic secretory phenotype, and were surrounded by a reticulated basal lamina and a hyperplasic extracellular matrix (especially pronounced in arteries). These data indicate that diabetes affects both heart and hind limb veins and arteries, producing structural changes of the endothelium and smooth muscle cells which may account, at least in part, for the specific vascular complications.
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PMID:Diabetes-induced structural changes of venous and arterial endothelium and smooth muscle cells. 985 Oct 55

Elevated plasma von Willebrand factor (vWf) levels are found in diabetes and other vasculopathies, and predict cardiovascular mortality. vWf is stored and released from endothelial cell secretory granules, along with equimolar amounts of its propeptide (vWf:AgII). In the present study, we examined plasma propeptide levels as a marker of endothelial secretion in vivo, using an ELISA based on monoclonal antibodies. vWf but not propeptide levels are influenced by blood groups, explaining in part the smaller variation in plasma propeptide levels among normal individuals. In both controls and insulin-dependent diabetic patients, we found a close correlation between propeptide and immunoreactive vWf levels (r2=0.54, p <0.0001). vWf and propeptide were elevated in patient subgroups with microalbuminuria or overt diabetic nephropathy, whereas only the propeptide was significantly elevated in the normoalbuminuric subgroup. This observation suggests that in conjunction with vWf, propeptide measurements may improve the identification of endothelial activation, which occurs frequently even without increased urinary albumin excretion. In 12 NIDDM patients, a 3-week diet enriched in monounsaturated fat (MUFA) resulted in parallel decreases in vWf (-22%, p <0.05) and propeptide (-17%, p <0.05) levels, indicating that the experimental diet affected endothelial secretion rather than vWf catabolism. A carbohydrate-enriched control diet did not significantly influence either marker. Our results suggest that concomitant determinations of plasma vWf and propeptide are useful tools to assess endothelial activation in vivo, and reinforce our previous conclusion that a diet rich in MUFA can improve endothelial function in NIDDM.
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PMID:von Willebrand factor (vWf) as a plasma marker of endothelial activation in diabetes: improved reliability with parallel determination of the vWf propeptide (vWf:AgII). 986 74

To clarify the relationship between circulating thrombomodulin (TM) and endothelial cell damage in diabetes mellitus, plasma levels of TM were quantitated by an enzyme linked immunoabsorbant assay (ELISA) in 164 type 2 diabetes mellitus and 72 normal control subjects, and these levels were compared with those of von Willebrand factor antigen (vWf: Ag), thrombin antithrombin III complexes (TAT), plasmin-alpha2-plasmin inhibitor complexes (PIC), fibrinogen, D-dimer, urinary albumin excretion rate (AER), intima-media thickness (IMT) and plaque score of the common carotid artery assessed with high resolution B-mode ultrasonography. Plasma levels of TM, vWf: Ag, TAT, PIC, AER, IMT and plaque score were significantly increased in the diabetic patients compared to the normal control subjects. Plasma TM levels showed significant correlation with vWf: Ag (r=0.350, p<0.0001), TAT (r = 0.334, p < 0.0001), PIC (r = 0.450, p < 0.0001), AER (r = 0.334, p < 0.0001), IMT (r = 0.181, P<0.01), plaque score (r=0.385, p<0.0001). Among four groups of diabetic patients, divided based on their severity of diabetic retinopathy, there were no significant differences in age, sex, systolic and diastolic blood pressure levels, HbA,1c, or plasma lipid levels, although the plasma levels of TM, vWf: Ag, TAT, PIC, AER, IMT and the plaque score in the patients with proliferative retinopathy were significantly higher than those of the healthy controls and patients with simple retinopathy. Among the 43 normoalbuminuric patients without intima-media thickness or thickened plaque (AER<30 mg/g Creatinine, IMT<1.0 mm, plaque score = 0), plasma levels of TM, vWf: Ag, TAT, PIC were significantly higher in those patients with retinopathy than in those without retinopathy. Multivariate analysis showed TM, TAT and PIC levels to be independent predictors of diabetic retinopathy. In conclusion, circulating TM reflects endothelial cell damage in patients with diabetic retinopathy, and hypercoagulability might play an important role in endothelial cell damage.
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PMID:Circulating thrombomodulin and hematological alterations in type 2 diabetic patients with retinopathy. 1007 54

Moderately increased plasma concentrations of C-reactive protein are associated with an increased risk of cardiovascular disease. C-reactive protein, its relation to a low degree of inflammatory activation and its association with activation of the endothelium have not been systematically investigated in Type I (insulin-dependent) diabetes mellitus. C-reactive protein concentrations were measured in 40 non-smoking patients with Type I diabetes without symptoms of macrovascular disease and in healthy control subjects, and in a second group of Type I diabetic patients (n = 60) with normo- (n = 20), micro- (n = 20) or macroalbuminuria (n = 20). Differences in glycosylation of alpha1-acid glycoprotein were assayed by crossed affinity immunoelectrophoresis. Activation of the endothelium was measured with plasma concentrations of endothelial cell markers. The median plasma concentration of C-reactive protein was higher in Type I diabetic patients compared with healthy control subjects [1.20 (0.06-21.64) vs. 0.51 (0.04-9.44) mg/l; p<0.02]. The Type I diabetic subjects had a significantly increased relative amount of fucosylated alpha1-acid glycoprotein (79+/-12% vs. 69+/-14% in the healthy control subjects; p<0.005), indicating a chronic hepatic inflammatory response. In the Type I diabetic group, log(C-reactive protein) correlated significantly with von Willebrand factor (r = 0.439, p<0.005) and vascular cell adhesion molecule-1 (r = 0.384, p<0.02), but not with sE-selectin (r = 0.008, p = 0.96). In the second group of Type I diabetic patients, increased urinary albumin excretion was associated with a significant increase of von Willebrand factor (p<0.0005) and C-reactive protein (p = 0.003), which were strongly correlated (r = 0.53, p<0.0005). Plasma concentrations of C-reactive protein were higher in Type I diabetic patients without (clinical) macroangiopathy than in control subjects, probably due to a chronic hepatic inflammatory response. The correlation of C-reactive protein with markers of endothelial dysfunction suggests a relation between activation of the endothelium and chronic inflammation.
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PMID:Plasma concentration of C-reactive protein is increased in type I diabetic patients without clinical macroangiopathy and correlates with markers of endothelial dysfunction: evidence for chronic inflammation. 1009 89


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