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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes mellitus is characterized by microangiopathy and increased angiogenic response in various organs. Basic fibroblast growth factor (bFGF) as well as vascular endothelial growth factor (VEGF) are both angiogenic and are involved in vascular endothelial cell growth. The purpose of this study was to determine serum levels of bFGF and VEGF, in children and adolescents (youngsters) with type 1 diabetes mellitus, and correlate them with parameters reflecting the severity of the disease. Forty diabetic youngsters without clinical evidence of complications were compared with 30 healthy control subjects (mean age +/- SD, 14.3 +/- 3.6 and 13.8 +/- 3.6 y, respectively). Diabetes duration and metabolic control (expressed by glycosylated Hb) were (mean +/- SD) 6.2 +/- 3.8 y and 9.6 +/- 1.8%, respectively. bFGF and VEGF (pg/mL) were measured in serum samples by enzyme immunoassays, and both were not significantly different between the type 1 diabetes mellitus and the control group (p = 0.952 and p = 0.559, respectively). Restricting the analysis to the type 1 diabetes mellitus group, neither the duration nor the metabolic control of the disease showed any correlation with bFGF and VEGF serum levels, whereas a significantly positive correlation was found between the two examined angiogenic factors both in the diabetic (r = 0.3464, p = 0.025) and the control group (r = 0.4619, p = 0.0013). In conclusion, serum levels of bFGF and VEGF were not found to vary significantly in diabetic youngsters in relation to controls and had no correlation with the duration and metabolic control of the disease. Nevertheless, a positive correlation was found between these two angiogenic factors both in the type 1 diabetes mellitus and the control group.
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PMID:Serum levels of basic fibroblast growth factor and vascular endothelial growth factor in children and adolescents with type 1 diabetes mellitus. 985 20

Insulin-dependent diabetes mellitus (IDDM), is characterized by a lack of insulin production from beta cells in the pancreas. One of the metabolic consequences of this insulin deficit is an increased hepatic synthesis of ketone bodies, resulting in a serious medical complication, diabetic ketoacidosis (DKA). DKA, in turn, has been associated with the development of cerebral edema. The severity of this complication ranges from death to a subclinical presentation, but seems to be invariably present to some degree. The etiology of the cerebral edema is unknown, but changes in osmolality, pH, and insulin effects on the blood-brain barrier have all been suggested as possible culprits. Blood-brain barrier impermeability is maintained by the endothelial cells (EC) lining the blood vessels. Thus, it would seem likely that alterations in EC function would be necessary for the development of cerebral edema. However, no studies have examined the effects of ketone bodies on brain endothelial cells. The two major ketone bodies in DKA are acetoacetate (AcAc) and beta-hydroxybutyrate (BOHB). In the present study we examined the effect of these ketone bodies on a major intracellular signalling pathway. The changes in intracellular calcium concentration, and the production of two vasoactive peptides, endothelin-1 (ET-1) and vascular permeability factor (VPF/VEGF) in mouse brain microvascular endothelial cells (MBMEC). The present studies demonstrate the BOHB can increase vascular permeability factor. In contrast, AcAc increases the production of the potent vasoconstrictor, endothelin-1. This data would suggest that brain ECs are potential targets of the metabolic alterations in DKA.
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PMID:Acetoacetate and beta-hydroxybutyrate differentially regulate endothelin-1 and vascular endothelial growth factor in mouse brain microvascular endothelial cells. 1043 73

In the present study, we examined the effect of glucose concentration on the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta (TGF-beta) mRNA using reverse transcriptase-polymerase chain reaction (RT-betaCR) in normal healthy leukocytes in vitro and in leukocytes from patients with type 1 diabetes mellitus. In vitro, the level of TGF-beta mRNA was altered in response to the glucose concentration (maximum at 10 mmol/L), while bFGF mRNA remained relatively constant and VEGF mRNA varied with no clear correlation with the glucose concentration. Leukocytes from type 1 patients showed no difference in bFGF or TGF-beta mRNA levels compared with age-matched healthy controls. However, VEGF mRNA was significantly lower in type 1 patients compared with controls (P < .05). When the patients were subtyped according to the severity of retinopathy, the level of TGF-beta mRNA was elevated selectively in patients with evidence of active new retinal vessels (P < .01) and VEGF121 mRNA was reduced in patients with mild to moderate retinopathy. Thus, leukocyte growth factor mRNAs respond to acute changes in the glucose concentration in vitro, and are differentially expressed in type 1 diabetic patients during the course of the disease.
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PMID:Regulation of transforming growth factor-beta, basic fibroblast growth factor, and vascular endothelial cell growth factor mRNA in peripheral blood leukocytes in patients with diabetic retinopathy. 1048 60

This study was designed to evaluate whether vascular endothelial growth factor serum concentrations may identify adolescents with onset of type 1 diabetes during childhood at greater risk to develop persistent microalbuminuria and incipient diabetic nephropathy. In January 1989, vascular endothelial growth factor serum levels were measured in 101 normoalbuminuric diabetic children and adolescents (aged 7-14.9 yr; onset of diabetes before age 18 yr; duration of diabetes >7 yr). Participants were clinically examined at baseline and annually thereafter. Vascular endothelial growth factor serum concentrations were measured every year during the 8-yr follow-up period. Over 8 yr, 11 of 101 patients (10.9%) developed persistent microalbuminuria; no patient developed overt nephropathy. The risk of developing microalbuminuria was higher in children with increased vascular endothelial growth factor serum levels (using 160 pg/ml as the arbitrary cut-off point; group 1) compared with those with normal vascular endothelial growth factor serum levels at the beginning of the study (group 2; 19.2 vs. 2.0%; P < 0.01; sensitivity, 90.9%; specificity, 53.3%). The odds ratio for the occurrence of microalbuminuria after adjustment for confounding variables (albumin excretion rate, sex, hemoglobin A(1c), mean blood pressure, cholesterol, and triglycerides) in type 1 diabetic adolescents with elevated vascular endothelial growth factor serum levels was 4.1 (95% confidence interval, 2.0-10.9). These results suggest that vascular endothelial growth factor serum concentrations may be one of the predictors and risk factors for microalbuminuria and incipient diabetic nephropathy in adolescents and young adults with onset of diabetes during childhood. Persistently increased vascular endothelial growth factor serum levels may help to identify normotensive, normoalbuminuric patients with type 1 diabetes who are predisposed to develop persistent microalbuminuria later in life.
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PMID:Increased vascular endothelial growth factor serum concentrations may help to identify patients with onset of type 1 diabetes during childhood at risk for developing persistent microalbuminuria. 1150 26

Aberrant neovascularization plays a crucial role in ocular complications in diabetic patients. Sera from these patients contain high levels of angiostimulatory factors, the most important of which is vascular endothelial growth factor (VEGF). Many authors have described elevation of angiotensin-converting enzyme (ACE) activity in the sera of diabetic patients. It is important to determine the possible relationship between these two phenomena. We studied ACE serum activity and VEGF concentrations in patients with type 1 and type 2 diabetes and retinopathy We also investigated the effect of their sera on cutaneous angiogenesis induced in mice by grafting healthy human mononuclear blood leukocytes. We found a negative correlation between the angiostimulatory effect and ACE level in the sera of patients with type 1 diabetes and no correlation between these two parameters in patients with type 2 diabetes. VEGF concentrations were lower and ACE activity was significantly higher in the sera of patients with type 1 diabetes than in the sera of those with type 2 diabetes.
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PMID:Angiotensin-converting enzyme activity and angiomodulatory effects of sera in patients with diabetic retinopathy. 1182 50

There is increasing evidence implicating genetic factors in the susceptibility to diabetic microvascular complications. Recent studies suggest that increased expression of the cytokine vascular endothelial growth factor (VEGF) may play a role in the pathogenesis of diabetic complications. A number of polymorphisms in the promoter region of the VEGF gene have been identified. The aim was to investigate whether an 18 base pair (bp) deletion (D)/insertion (I) polymorphism at position -2549 in the promoter region of the VEGF gene is associated with the susceptibility to diabetic microvascular complications. Two hundred and thirty-two patients with type 1 diabetes mellitus (T1DM) and 141 normal healthy controls were studied. The D/D genotype was significantly increased in those patients with nephropathy (n=102) compared to those with no complications after 20 years duration of diabetes (uncomplicated, n=66) (40.2% vs. 22.7%, respectively, chi(2)=5.5, P<.05). The combination of polymorphisms of VEGF together with the aldose reductase (ALR2) gene showed that in the nephropaths, 8 of the 83 subjects had the VEGF I allele together with the Z+2 5'ALR2 allele compared with 27 of the 62 uncomplicated patients (chi(2)=26.7, P<.00001). The functional role of the D/I polymorphism was examined by cloning the region into a luciferase reporter assay system and transient transfection into HepG2 cells. The construct containing the 18 bp deletion had a 1.95-fold increase in transcriptional activity compared with its counterpart that had the insert (P<.01). These results suggest that polymorphisms in the promoter region of the VEGF gene together with the ALR2 may be associated with the pathogenesis of diabetic nephropathy.
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PMID:Polymorphisms of the vascular endothelial growth factor and susceptibility to diabetic microvascular complications in patients with type 1 diabetes mellitus. 1250 48

Transplantation of pancreatic islets is proposed as a treatment for type 1 diabetes, but insufficient blood supply can cause the loss of viable grafted islets. In the present study, we investigated the influence of vascular endothelial growth factor (VEGF) on the angiogenesis of omentum during encapsulated islet allotransplantation and consequently on islet survival. Fifty rat islets, cultured for 24 h, were encapsulated in the presence or absence of human VEGF and implanted in the peritoneal cavity of rats (n = 6). After 7, 14 and 28 days of implantation, encapsulation devices with surrounding omentum were removed. Histological analysis of this tissue was performed. Cellular adhesion at the membrane surface was characterized by a phagocytosis test. The morphological aspect of the islets was analyzed and their functionality was evaluated by measuring insulin secretion. At each step of the study, there was a two-fold increase in the number of vessels in the presence of VEGF. In addition, VEGF increased the vessel diameter and the surface area of the angiogenic pedicle. Moreover, the presence of VEGF significantly decreased the distance between the devices and vessels (16.2 +/- 5.6 vs. 51.6 +/- 10.1 microm, p < 0.001). Membrane surface analysis showed a decrease in macrophage adhesion in the presence of VEGF. Furthermore, islet structure and functionality was preserved in the presence of VEGF. Stimulation of angiogenesis of omentum induced by VEGF is associated with preservation of islet viability. Local delivery of VEGF proved to be a relevant approach to ameliorate the outcome of islet transplantation.
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PMID:Induction of angiogenesis in omentum with vascular endothelial growth factor: influence on the viability of encapsulated rat pancreatic islets during transplantation. 1289 Oct 5

At present, diabetic kidney disease affects about 15-25 % of patients with type 1 diabetes (T1D) and 30-40 % of patients with type 2 diabetes (T2D). Several decades of extensive research have elucidated various pathways to be implicated in the development of diabetic kidney disease. These include metabolic factors beyond blood glucose (e.g. advanced glycation endproducts (AGEs)), haemodynamic factors (e.g. the renin angiotensin system (RAS)), intracellular signaling molecule proteins (e.g. protein kinase C (PKC)) and growth factors/cytokines (e.g. growth hormone (GH), insulin-like growth factors (IGFs), transforming growth factor beta (TGF-beta) and vascular endothelial growth factor (VEGF)). This review focuses on the role of three of these growth factors, i.e. GH, IGFs and VEGF. A brief discussion of each system is followed by description of its expression in the normal kidney. Then, for each system, in vitro, experimental and clinical evidence addressing the role of the system in diabetic kidney disease is presented. The interplay of each system to other potential pathways will also be addressed. Finally, well-known and potential therapeutic strategies targeting the GH/IGF and VEGF systems in a specific or indirect way will discussed.
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PMID:The involvement of growth hormone (GH), insulin-like growth factors (IGFs) and vascular endothelial growth factor (VEGF) in diabetic kidney disease. 1554 23

Diabetes alters microvascular structure and function and is a major risk factor for cardiovascular diseases. In diabetic skeletal muscle, impaired angiogenesis and reduced VEGF-A expression have been observed, whereas in healthy muscle exercise is known to have opposite effects. We studied the effects of type 1 diabetes and combined exercise training on angiogenic mRNA expression and capillarization in mouse skeletal muscle. Microarray and real-time PCR analyses showed that diabetes altered the expression of several genes involved in angiogenesis. For example, levels of proangiogenic VEGF-A, VEGF-B, neuropilin-1, VEGFR-1, and VEGFR-2 were reduced and the levels of antiangiogenic thrombospondin-1 and retinoblastoma like-2 were increased. Exercise training alleviated some of these changes, but could not completely restore them. VEGF-A protein content was also reduced in diabetic muscles. In line with the reduced levels of VEGF-A and other angiogenic factors, and increased levels of angiogenesis inhibitors, capillary-to-muscle fiber ratio was lower in diabetic mice compared to healthy controls. Exercise training could not restore capillarization in diabetic mice. In conclusion, these data illustrate that type 1 diabetes is associated with reduced skeletal muscle capillarization and the dysregulation of complex angiogenesis pathways.
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PMID:Effects of experimental type 1 diabetes and exercise training on angiogenic gene expression and capillarization in skeletal muscle. 1681 23

We compared the levels of transforming growth factor beta1 (TGF-beta1), vascular endothelial growth factor (VEGF) and other biochemical parameters in patients with type 1 diabetes mellitus with and without incipient diabetic nephropathy (iDN) and compared them with healthy control subjects. We also measured the effect of 3 and 6 months of ramipril treatment in diabetes patients with iDN. Compared with healthy controls, TGF-beta1 levels were increased in both groups of diabetes patients, whereas VEGF was only elevated in patients with iDN. Ramipril did not have a significant effect on TGF-beta1 or VEGF levels. We observed a significant decrease in microalbuminuria and cystatin C following ramipril treatment. Increased VEGF levels in patients with iDN suggest a role for this cytokine in the pathogenesis of diabetic nephropathy. Cystatin C would make a suitable marker for the screening and assessment of iDN, and for the evaluation of the therapeutic efficacy of drugs.
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PMID:The effect of ramipril therapy on cytokines and parameters of incipient diabetic nephropathy in patients with type 1 diabetes mellitus. 1759 66


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