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

Chronic complications of diabetes are dominated by disorders of the vascular system. They are a much larger burden on both diabetic patients and overall medical costs than diabetes itself. Large vessel problems are far more frequent than microvascular disorders. Loss of arterial elasticity alters arterial flow patterns and increases microcirculatory peak flow rates. Hyperglycemia may directly disrupt elastin formation. Diabetic leg artery disease may be generated by nerve damage, reversing this interactive contribution sequence. The major anatomic feature of microangiopathy in long-term diabetes is an unevenly distributed thickening of the intima of smaller arterioles. The thickening is primarily due to accumulation of type IV (basement membrane) collagen. Arterioles change local vessel diameter to adjust blood distribution to meet current needs. The thickening compromises the maximum local blood flow that may be achieved by this means. Compromise of maximal arteriolar dilatation does not disrupt exercising muscle but in the kidney, retina, and possibly in nerve, local circumstances can generate serious damage. Each of these system's responses has unique features that mediate its vulnerability, but all these organs show arteriolar hyalinization. The increased arteriolar accumulation of type IV collagen appears to be a response to the tangential force generated by flow over local endothelial cells. An increase in peak arteriolar wall force is mediated by a diabetes-specific doubling of erythrocyte membrane curvature change resistance. Red cell aggregation rate determines the rate of damage. The same nonspecific burden may also predispose to heart disease and stroke. Intensive metabolic control improves red cell deformability and protects against arteriolar damage. Therapies that address the rheologic problem more directly may add to the effectiveness of good diabetes control in the future.
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PMID:Development of vascular complications in diabetes. 954 55

In order to clarify the degradation of elastin under abnormal conditions, we examined the aortic elastolytic activity in rat experimental diabetes mellitus induced by treatment with streptozotocin and in rat experimental aneurysm induced by treatment with an inhibitor of lysyloxidase (beta-aminopropionitrile: BAPN). Measurement of the aortic elastolytic activity used 14C-labeled elastin as the substrate, and the determined value was compared with the aortic lysosomal enzyme (acid phosphatase) activity. In the case of experimental diabetes, the aortic elastolytic activity was not changed, but the aortic acid phosphatase activity was significantly increased compared with the control. In the case of the experimental aneurysm, the aortic elastolytic activity measured after 2 and 3 weeks was increased compared with each control. There was a negative correlation (r=-0.435, n=36) between the elastolytic activity and the cross-linking (desmosine) content in the aorta. The ratio of elastolytic activity to desmosine content was significantly increased compared with the control. Therefore, the degradation of aortic elastin in the experimental aneurysm was caused by elastase, not by lysosomal enzymes. We concluded that an elastase-like enzyme mainly contributed to the degradation of elastin in the experimental aneurysm since the inhibitory pattern of the elastolytic activity in the experimental aneurysm was similar to that of pancreatic elastase.
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PMID:Comparison of elastolytic activity between experimental aneurysm and experimental diabetes mellitus. 970 67

The present investigations arose from our interest in the possibility that some structures which arise secondary to protein glycation might bind transition metals such as iron and copper. In support of this we find that, when glycated, three different proteins--albumin, gelatin (a soluble collagen fragment) and elastin--all gain a substantial affinity for the transition metals iron and copper. The glycated proteins bind at least three times as much iron as do the non-glycated proteins. Similarly, glycated albumin and gelatin also bind 2-3 times as much copper. Furthermore, at least in the case of copper bound to glycated albumin, the bound metal retains redox activity and participates in the catalytic oxidation of ascorbic acid. Should similar "glycochelates" form in vivo in diabetics, reactions mediated by these chelates may be involved in certain complications of diabetes.
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PMID:Transition metals bind to glycated proteins forming redox active "glycochelates": implications for the pathogenesis of certain diabetic complications. 975 39

Diabetes can cause the development of pulmonary complications due to collagen and elastin changes, as well as microangiopathy. This study demonstrates the relationship between pulmonary complications and other chronic complications in diabetes. Twenty-seven patients with diabetes, aged 21 to 62 years, who had had the disease from 3 to 32 years, were included in this study. The protein excretion rate (PER) and the diffusion capacity of the lung for carbon monoxide (DLCO) were included as parameters of the severity of complications. PER was determined by the Biuret method. DLCO was measured by the single-breath method and was corrected by the measurement of alveolar volume (VA). The values of DLCO as corrected by VA (DLCO/VA) were included in the statistical evaluation of the results. The variables of age, duration of diabetes, and complication parameters were included in a multiple regression model with forward, stepwise selection to assess their value in predicting DLCO/VA. The variables were found to be significant predictors of DLCO/VA (R2 = 0.46, adjusted R2 = 0.32, p < 0.022). However, proteinuria was the only significant independent predictor of DLCO/VA. This finding indicates that both renal and pulmonary complications of diabetes share a similar microangiopathic background.
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PMID:Reduction of diffusion capacity for carbon monoxide in diabetic patients. 979 73

People with diabetes are prone to develop peripheral vascular and nerve abnormalities which, in extreme cases, can lead to limb amputations. Although numerous theories have been advanced for these complications, no firm explanation is yet available. Recently, evidence has appeared suggesting that these vascular and nerve abnormalities may involve transition metals; administration of chelators such as desferrioxamine has been shown to prevent or actually reverse slowed peripheral nerve conduction and neuronal blood flow, as well as impaired endothelium-dependent arterial relaxation. Here, we argue that (i) the heavily glycated proteins known to accumulate in people with diabetes gain an increased affinity for transition metals such as iron and copper, (ii) as a result, proteins such as elastin and collagen within the arterial wall-which are known to be particularly heavily glycosylated in diabetes-may accumulate bound metal, especially copper, (iii) the bound metal causes the catalytic destruction of endothelium derived relaxing factor (nitric oxide or a derivative thereof), thereby engendering a state of chronic vasoconstriction. The resulting impairment of blood flow to peripheral nerves restricts the delivery of oxygen and nutrients and, in extremis, nerve death eventuates. If this hypothesis is proved correct, there are important implications for the development of novel pharmaceuticals for the treatment of diabetic peripheral neuropathy.
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PMID:Glycochelates and the etiology of diabetic peripheral neuropathy. 1071 47

In order to further investigate the radical scavenging and anti-arteriosclerotic activities of vitamin K2 and estradiol, the comparative effects of vitamin K2 and estradiol on aortic calcium (Ca) and inorganic phosphorus (P) levels in the aorta and the elastin fraction (fr.) were investigated in male rats after experimental arteriosclerosis with diabetes mellitus was induced by vitamin D2 and radical producing substance, streptozotocin (STZ). Pharmacological dose of vitamin K2 (100 mg/kg b.w.) and medical dose of estradiol (83 micrograms/kg b.w.) suppressed the increased serum glucose, and vitamin K2 and estradiol increased the decrease in serum insulin. Moreover, vitamin K2 and estradiol inhibited the increase of Ca and P in the aorta and the elastin fr. Vitamin K2 and estradiol decreased the increase in serum lipid peroxide (LPO). It is suggested that both the pharmacological dose of vitamin K2 and medical dose of estradiol suppressed the development of arteriosclerosis associated with diabetes mellitus, owing to radical scavenging activity of vitamin K2 and estradiol.
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PMID:Comparative effects of vitamin K2 and estradiol on experimental arteriosclerosis with diabetes mellitus. 1121 55

Levels of elastin-derived peptides (EDP) were determined by enzyme-linked immunosorbent assay (ELISA) in sera of 28 children with Type 1 (insulin-dependent) diabetes mellitus (mean age 11.6+/-2.8 years, diabetes duration 5.1+/-2.5 years). None of the children had clinical or laboratory evidence of vascular complications. The children were followed over a period of 6 years, and 24 healthy children of similar age and sex served as a control group. During the investigative period, 10 diabetic patients had increased EDP levels, with 9 having been diabetic for more than 5 years and 1 patient less than 5 years. Seven of these patients developed diabetic microvascular complications. In this group, EDP were independently associated with age (r=.39, P=.047), retinopathy (r=.48, P=.034), and antibodies to advanced glycation endproducts (AGE) (r=.52, P=.018). The data of this pilot study are not strong enough to appear that EDP are a useful predictor of subsequent development of microvascular complications. This may be due to the small number of subjects, short duration of the study, manner in which EDP or the endpoints were measured, or frequency of which EDP measurements were made. Further prospective and longer studies of larger populations are needed to identify the role of EDP as an early marker for the development of diabetic microvascular complications.
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PMID:Relationship between elastin-derived peptides and the development of microvascular complications: a longitudinal study in children with Type 1 (insulin-dependent) diabetes mellitus. 1170 10

An important factor in the development of vascular wall alterations is degradation of the elastic fiber major protein-elastin. Elastin peptides derived from this degradation are present in the circulating blood and they are a stimulus for increased production of anti-elastin antibodies (AEAb). The aim of the present study was to examine the possible association between serum elastin AEAb and the development of diabetic vascular complications. Levels of AEAb (IgG, IgM and IgA) were determined by ELISA in sera of 28 children with Type 1 (insulin-dependent) diabetes mellitus (mean age 11.6+/-2.8 years, diabetes duration 5.1+/-2.5 years). None of the children had clinical or laboratory evidence of vascular complications. The children were followed over a period of 7 years, and 24 healthy children of similar age and sex served as a control group. During the study, four diabetics developed retinopathy, six microalbuminuria and two both retinopathy and microalbuminuria. Anti-elastin IgG showed correlation with diabetes duration (r=.48, P=.0007), HbA1c (r=.28, P=.05), triglycerides (r=.28, P=.05) and antibodies to advanced glycation endproducts (AGE) (r=.41, P=.005). Anti-elastin IgM correlated with HbA1c (r=.26, P=.038) and IgA with retinopathy (r=.32, P=.017). Our results suggest an association between the level of anti-elastin IgA antibodies and the development of diabetic retinopathy.
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PMID:An association of anti-elastin IgA antibodies with development of retinopathy in diabetic children. 1170 14

We experienced a case of 62-year-old woman who was admitted for the evaluation of her trembling hands. She was diagnosed as Williams syndrome (WS) by fluorescent in situ hybridization (FISH) analysis. She was short in stature, had a characteristic face and moderate mental retardation, whereas she was talkative and gregarious. She also presented impaired visuospatial cognition, cerebellar ataxia and tremor like involuntary movement of the hands. No remarkable abnormality is noted in MRI of the brain. MRA study of the brain revealed the arteriosclerotic vascular change, such as elongation of basilar artery and dilatation of bilateral carotid arteries. Heterozygous microdeletion of chromosome 7q11.23 of this patient is typical for WS, the delction including elastin (ELN) and LIMK 1 gene. Although she was complicated by diabetes mellitus and hyperlipidemia, she had no cardiovascular abnormalities like supravalvular aortic stenosis (SVAS), and survived to her age in good condition. The tremor-like involuntary movement disappeared after her discharge and its mechanism remains to be elucidated.
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PMID:[Clinical features of a senior patient with Williams syndrome]. 1196 43

The effects of risk modifiers such as diabetes, obesity and hypertension on vascular healing after stent deployment are largely unknown, because of a lack of an appropriate animal model to study. Since many inbred strains of rats expressing these phenotypes are available, we validated a carotid artery model of in-stent restenosis in the rat. A detailed histomorphometric analysis was performed on 2-cell Multi-Link(TM) stents (1.5 x 5 mm) deployed in the common carotid artery of male Wistar rats. Early focal thrombus formation around stent struts with adherent leukocytes was evident by day 3. The number of ED-1-positive macrophages was maximal by day 7 and declined markedly thereafter. Neointimal cell proliferation peaked by day 7 (19.3 +/- 6.9) and progressively decreased to <2% by day 60. By day 14, neointimal area was significantly increased (0.39 +/- 0.03 vs. 0.18 +/- 0.05 mm(2) at day 7, p = 0.003) characterized by an enhanced number of alpha-actin-positive smooth muscle cells surrounded by extracellular matrix rich in versican and hyaluronan. At day 28, neointimal area was maximal accompanied by an appreciable decrease in the staining intensity for hyaluronan and versican. By day 60, neointimal area decreased significantly (0.28 +/- 0.04 vs. 0.45 +/- 0.07 mm(2) at day 28, p = 0.04) independent of a change in cell density. This regression phase was accompanied by a marked increase in elastin fibrils and collagen type I. In summary, vascular healing following carotid artery stenting in the rat parallels that of larger animals; however, it is accelerated relative to humans.
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PMID:A novel rat model of carotid artery stenting for the understanding of restenosis in metabolic diseases. 1229 4


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