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Type I Diabetes (type + i_diabetes)
Terms modified by Type I Diabetes Selected AbstractsDistinct patterns of serum immunoreactivity as evidence for multiple brain-directed autoantibodies in juvenile neuronal ceroid lipofuscinosisNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 5 2006M. J. Lim Autoantibodies to glutamic acid decarboxylase (GAD65) have been reported in sera from the Cln3,/, mouse model of juvenile neuronal ceroid lipofuscinosis (JNCL), and in individuals with this fatal paediatric neurodegenerative disorder. To investigate the existence of other circulating autoreactive antibodies, we used sera from patients with JNCL and other forms of neuronal ceroid lipofuscinosis (NCL) as primary antisera to stain rat and human central nervous system sections. JNCL sera displayed characteristic patterns of IgG, but not IgA, IgE or IgM immunoreactivity that was distinct from the other forms of NCL. Immunoreactivity of JNCL sera was not confined to GAD65-positive (GABAergic) neurons, but also stained multiple other cell populations. Preadsorption of JNCL sera with recombinant GAD65 reduced the intensity of the immunoreactivity, but did not significantly change its staining pattern. Moreover, sera from Stiff Person Syndrome and Type I Diabetes, disorders in which GAD65 autoantibodies are present, stained with profiles that were markedly different from JNCL sera. Collectively, these studies provide evidence of the presence of autoreactive antibodies within multiple forms of NCL, and are not exclusively directed towards GAD65. [source] Increased plasma fibrin gel porosity in patients with Type I diabetes during continuous subcutaneous insulin infusionJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2003G. Jörneskog Summary.,Background:,Patients with Type 1 diabetes have a tighter plasma fibrin gel structure, to which impaired glycemic control might contribute. Improved glycemic control can be achieved with continuous subcutaneous insulin infusion (CSII). Objectives:,The aim of the present study was to investigate the effect of CSII on plasma fibrin gel properties and circulating markers of inflammatory activity in patients with Type 1 diabetes. Patients and methods:,Twenty-eight patients were investigated before and after 4,6 months' treatment with CSII. Fibrin gel structure formed in vitro from plasma samples was investigated by liquid permeation of hydrated fibrin gel networks. P-fibrinogen was analyzed by a syneresis method. Comparisons were made between patients with improved (> 0.5%) and unchanged (< 0.5%) glucosylated hemoglobin (HbA1c) during CSII. Results:,Eighteen patients showed improved and 10 patients unchanged HbA1c during CSII. P-fibrinogen, high sensitive C-reactive protein and serum amyloid A-antigen were not significantly changed, while fibrin gel permeability (Ks) and fiber mass,length ratio (µ) increased in both groups (P < 0.02). P-insulin and triglycerides decreased (P < 0.05) in both groups, while reductions of total cholesterol and intercellular adhesion molecule-1 were seen only in patients with improved HbA1c (P < 0.05). Absolute changes in Ks were inversely correlated to changes in plasma fibrinogen (r = 0.50; P < 0.01) and in LDL-cholesterol (r = 0.46; P < 0.05). Conclusions:,Treatment with CSII in patients with Type 1 diabetes is associated with increased plasma fibrin gel porosity. Slight attenuation of the inflammatory activity was also observed. The changes in fibrin gel porosity seem to be mainly mediated by changes in plasma fibrinogen and blood lipids, and are probably secondary to improved insulin sensitivity. [source] Effects of hyperglycaemia on ocular development in rabbit: refraction and biometric changesOPHTHALMIC AND PHYSIOLOGICAL OPTICS, Issue 2 2005Peter Herse Abstract Aim:, To determine the effect of acute and chronic hyperglycaemia on the refraction and development of the rabbit eye. Methods:, Ocular dimensions of five alloxan-induced hyperglycaemic and six control rabbits were measured over 9 weeks using A scan biometry. Refraction was measured using retinoscopy. The animals were 10 weeks of age at the start of the experiment. Results:, The acute onset of hyperglycaemia was associated with a fast and stable 2 D hyperopic shift in refraction. Lens thickness increased during the first 2 weeks of hyperglycaemia, returned to near normal thickness after 3,5 weeks of hyperglycaemia and then decreased in thickness in the last 4 weeks of the study. The hyperopic refraction remained unchanged during changes in lens thickness. Nine weeks of hyperglycaemia was associated with a 25% reduction in the growth of both the globe and the lens and a 17% decrease in body mass compared with the controls. Conclusion:, The hyperopic refraction change of acute hyperglycaemia is likely to be because of a change in the refractive index of the cortical fibres of the lens and is the probable source of the fluctuating refraction seen in diabetic patients. Chronic hyperglycaemia reduced the axial development of the eye and is the probable source of the chronic hyperopic refraction seen in children with Type I diabetes. [source] Effects of insulin-mimetic vanadyl-poly(,-glutamic acid) complex on diabetic rat modelJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2010Rongzhang Hu Abstract Poly-,-glutamic acid (,-PGA) prepared by fermentation of microbe was used as drug carrier for vanadium sulfate to obtain vanadyl-poly-,-glutamic acid (VO-,-PGA) complex. The FI-IR spectrum of the complex demonstrated that the expected VO-,-PGA complex is formed by the coordination of VO2+ through the side chain carboxylic groups of the ,-PGA. Studies of the complex in treating type I diabetes were carried out on alloxan induced diabetes rats. The results of treating the rats in 2 weeks and then stopping administration for 10 days showed that VO-,-PGA can effectively lower blood glucose levels of diabetic rats during administration. But after ceasing treatment there were no differences between groups in blood glucose level and water intake. The results of oral glucose tolerance and some serum parameters also demonstrated that VO-,-PGA was more effective than vanadium sulfate in treating diabetic rats. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3041,3047, 2010 [source] Profound changes in the GH,IGF-I system in adolescent girls with IDDM: can IGFBP1 be used to reflect overall glucose regulation?PEDIATRIC DIABETES, Issue 3 2000MU Halldin Disturbances in the relations between insulin, growth hormone (GH) and insulin-like growth factor I (IGF-I) may be a major cause behind deteriorated metabolic control in adolescent girls with type I diabetes. These patients have increased GH secretion and low IGF-I concentrations. The aim of this study was to identify possible endocrine mechanisms behind good and poor glycaemic control in such girls, focusing on the insulin,GH,IGF-I axis. Ten girls with well-controlled insulin-dependent diabetes mellitus (IDDM), hemoglobin A1c (HbA1c) 6.5±0.4% (normal range 3.9,5.2%) and nine healthy controls were investigated and compared with 11 girls with poor glucose regulation, HbA1c 10.9±0.4%, and their corresponding controls. Serum profiles of glucose, insulin, GH and IGF-binding protein 1 (IGFBP1) were analysed in addition to IGF-I and HbA1c. Two interesting observations were made. GH concentrations were equally elevated in the two diabetic groups regardless of metabolic control (mean 24 h GH , girls with poorly controlled diabetes 10.0±1.0 mU/L vs 9.8±1.7 , girls with well-controlled diabetes; p=ns). Likewise, the IGF-I concentrations were reduced to the same extent (233±19 vs 242±23 ,g/L; p=0.75). Secondly, despite similar insulin concentrations (mean 24 h insulin , girls with poorly controlled diabetes 22.9±2.6 and girls with well-controlled diabetes 27.3±2.9 mU/L, respectively; p=0.26), there was a marked difference in IGFBP1 concentrations between the two groups with IDDM (mean IGFBP1 , girls with poorly controlled diabetes 70.5±9.1 ,g/L vs girls with well-controlled diabetes 28.6±3.3; p<0.001). Despite equally elevated GH concentrations that may induce insulin resistance, the markedly lower concentrations of IGFBP1 in the well-controlled group indicate a higher hepatic insulin sensitivity in these girls compared with those with a poor control. Furthermore, in spite of similar total IGF-I concentrations, the lower IGFBP1 concentrations may result in higher IGF-I bioactivity in the well-controlled group. This may be reflected in better growth of the well-controlled group whose height of 168.7±0.9 vs 163.6±1.2 cm was significantly different (p<0.004). IGFBP1 may be a marker of overall insulinization in adolescents with type 1 diabetes, independent of the absolute insulin dose used for therapy. [source] Multicenter Analysis of Novel and Established Variables Associated with Successful Human Islet Isolation OutcomesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2010J. S. Kaddis Islet transplantation is a promising therapy used to achieve glycometabolic control in a select subgroup of individuals with type I diabetes. However, features that characterize human islet isolation success prior to transplantation are not standardized and lack validation. We conducted a retrospective analysis of 806 isolation records from 14 pancreas-processing laboratories, considering variables from relevant studies in the last 15 years. The outcome was defined as postpurification islet equivalent count, dichotomized into yields ,315 000 or ,220 000. Univariate analysis showed that donor cause of death and use of hormonal medications negatively influenced outcome. Conversely, pancreata from heavier donors and those containing elevated levels of surface fat positively influence outcome, as did heavier pancreata and donors with normal amylase levels. Multivariable logistic regression analysis identified the positive impact on outcome of surgically intact pancreata and donors with normal liver function, and confirmed that younger donors, increased body mass index, shorter cold ischemia times, no administration of fluid/electrolyte medications, absence of organ edema, use of University of Wisconsin preservation solution and a fatty pancreas improves outcome. In conclusion, this multicenter analysis highlights the importance of carefully reviewing all donor, pancreas and processing parameters prior to isolation and transplantation. [source] Anticarbohydrate Antibody Repertoires in Patients Transplanted with Fetal Pig Islets Revealed by Glycan ArraysAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009O. Blixt Ten patients with type I diabetes were transplanted with porcine fetal islet-like cell clusters (ICC) between 1990 and 1993. A significant rise in the anti-,-Gal antibody titers was seen posttransplant, but also non-,-Gal-specific antibodies were detected in some patients. We have reanalyzed the carbohydrate specificity of antibodies in the sera from seven of these patients taken before transplantation, 1, 6 and 12 months posttransplantation using a glycan array with 200 structurally defined glycans. The main findings were: (i) prepig ICC transplantation patients had antibodies reactive with terminal ,-GalNAc (e.g. the Forssman antigen, but not the blood group A determinant in blood group A patients), ,-Gal (except blood group B determinants in B individuals), ,3-linked Gal especially Gal,1,3GlcNAc even if terminally sulfated or sialylated, ,-GlcNAc except if ,1,3-linked and oligomannosyl compounds; (ii) the titers of all carbohydrate-specific antibodies detected before transplantation rose after transplantation; (iii) the kinetics of the antibody responses differed between patients; (iv) in some patients antibodies reacting with Gal,1,3Lex and several structures terminated with Neu5Gc appeared after transplantation. In conclusion, anti-,-Gal antibodies are the predominant anticarbohydrate antibodies detected after porcine ICC transplantation, with some patients also developing Neu5Gc-specific antibodies. Their clinical significance needs to be established. [source] Modified Two-Layer Preservation Method (M-Kyoto/PFC) Improves Islet Yields in Islet IsolationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2006H. Noguchi Islet allotransplantation can achieve insulin independence in patients with type I diabetes. Recent reports show that the two-layer method (TLM), which employs oxygenated perfluorochemical (PFC) and UW solution, is superior to simple cold storage in UW for pancreas preservation in islet transplantation. However, UW solution has several disadvantages, including the inhibition of Liberase activity. In this study, we investigated the features of a new solution, designated M-Kyoto solution. M-Kyoto solution contains trehalose and ulinastatin as distinct components. Trehalose has a cytoprotective effect against stress, and ulinastatin inhibits trypsin. In porcine islet isolation, islet yield was significantly higher in the M-Kyoto/PFC group compared with the UW/PFC group. There was no significant difference in ATP content in the pancreas between the two groups, suggesting that different islet yields are not due to their differences as energy sources. Compared with UW solution, M-Kyoto solution significantly inhibited trypsin activity in the digestion step; moreover, M-Kyoto solution inhibited collagenase digestion less than UW solution. In conclusion, the advantages of M-Kyoto solution are trypsin inhibition and less collagenase inhibition. Based on these data, we now use M-Kyoto solution for clinical islet transplantation from nonheart-beating donor pancreata. [source] | ||||||||||