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  • 1
    Electronic Resource
    Electronic Resource
    Sexual dimorphism in transmission of expression of islet autoantibodies to offspring (1995)
    Springer
    Diabetologia 38 (1995), S. 1353-1357 
    Details
    ISSN: 1432-0428
    Keywords: Islet autoantibodies ; offspring ; autoimmunity ; transmission
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To help elucidate the mode of inheritance of insulin-dependent diabetes mellitus (IDDM), we measured GAD (glutamic acid decarboxylase) autoantibodies (GAD65Ab), insulin autoantibodies (IAA), and cytoplasmic islet cell autoantibodies (ICA) in 292 sequentially screened non-diabetic offspring of patients with IDDM. The prevalence of these islet autoantibodies was higher in offspring of diabetic fathers than in offspring of diabetic mothers. The prevalences of GAD65Ab, IAA, and ICA in the offspring of diabetic fathers were 11.5%, 10.8%, and 8.1% vs 2.1%, 1.4%, and 2.8%, respectively in the offspring of diabetic mothers (p〈0.002, p〈0.001, and p=0.06 NS). Amongst autoantibody-positive relatives the IAA and ICA levels were significantly higher in offspring of diabetic fathers than of diabetic mothers (p〈0.002 and p〈0.01, respectively). The frequencies of these autoantibodies were equal in male and female offspring. We conclude that IDDM mothers transmitted islet autoimmunity less frequently to their offspring than IDDM fathers. Given the markedly lower frequency of autoantibodies in offspring of mothers, larger sample sizes will be required to determine whether islet autoantibodies are influenced by age of IDDM onset of mothers, maternal age of pregnancy, and presence of diabetes in these mothers prior to conception.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00401769
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  • 2
    Electronic Resource
    Electronic Resource
    Sexual dimorphism in transmission of expression of islet autoantibodies to offspring (1995)
    Springer
    Diabetologia 38 (1995), S. 1353-1357 
    Details
    ISSN: 1432-0428
    Keywords: Key words Islet autoantibodies ; offspring ; autoimmunity ; transmission.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To help elucidate the mode of inheritance of insulin-dependent diabetes mellitus (IDDM), we measured GAD (glutamic acid decarboxylase) autoantibodies (GAD65Ab), insulin autoantibodies (IAA), and cytoplasmic islet cell autoantibodies (ICA) in 292 sequentially screened non-diabetic offspring of patients with IDDM. The prevalence of these islet autoantibodies was higher in offspring of diabetic fathers than in offspring of diabetic mothers. The prevalences of GAD65Ab, IAA, and ICA in the offspring of diabetic fathers were 11.5 %, 10.8 %, and 8.1 % vs 2.1 %, 1.4 %, and 2.8 %, respectively in the offspring of diabetic mothers (p 〈 0.002, p 〈 0.001, and p = 0.06 NS). Amongst autoantibodypositive relatives the IAA and ICA levels were significantly higher in offspring of diabetic fathers than of diabetic mothers (p 〈 0.002 and p 〈 0.01, respectively). The frequencies of these autoantibodies were equal in male and female offspring. We conclude that IDDM mothers transmitted islet autoimmunity less frequently to their offspring than IDDM fathers. Given the markedly lower frequency of autoantibodies in offspring of mothers, larger sample sizes will be required to determine whether islet autoantibodies are influenced by age of IDDM onset of mothers, maternal age of pregnancy, and presence of diabetes in these mothers prior to conception. [Diabetologia (1995) 38: 1353–1357]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050434
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  • 3
    Electronic Resource
    Electronic Resource
    Large incidence variation of Type I diabetes in central-southern Italy 1990–1995: lower risk in rural areas (1999)
    Springer
    Diabetologia 42 (1999), S. 789-792 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin-dependent diabetes mellitus ; Type I diabetes ; epidemiology ; incidence ; childhood ; urban ; rural.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. To evaluate the relation between the incidence of childhood Type I (insulin-dependent) diabetes mellitus and the degree of urbanization in the central-southern part of Italy. Methods. The incidence was determined in two areas: area A encompasses 3 regions of central-eastern Italy (Marche, Abruzzo, Umbria), whereas area B encompasses one southern region (Campania). During 1990–1995, 706 children aged 14 or under with insulin-dependent diabetes mellitus of recent onset were registered. The completeness of the case ascertainment in the registries analysed separately for each region was high, ranging from 96.3 % to 99 %. Results. The age-standardized incidence was higher in area A (9.6 per 100 000 person per year; 95 % confidence interval: 8.5–10.8) than in area B (5.4 per 100 000 person per year; 95 % confidence interval: 4.9–6.0). In both areas the standardized incidence ratios increased with the degree of urbanization (chi-squared for trend: area A = 140, p 〈 0.0001; area B = 79, p 〈 0.0001). The highest standardized incidence ratios were in the most urban communities. Conclusion/interpretation. This study showed a statistically significant difference in incidence of childhood insulin-dependent diabetes mellitus among different areas of the continental peninsula of Italy. People living in the rural communities appear to have a lower risk. [Diabetologia (1999) 42: 789–792]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051228
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  • 4
    Electronic Resource
    Electronic Resource
    Presence of pancreatic glucagon in the portal plasma of human neonates. Differences in the insulin and glucagon responses to glucose between normal infants and infants from diabetic mothers (1972)
    Springer
    Diabetologia 8 (1972), S. 296-300 
    Details
    ISSN: 1432-0428
    Keywords: hypoglycemia ; glucagon ; neonate ; intravenous glucose ; hyperinsulinism ; diabetes ; pancreatic α-cell ; diabetic mother ; portal plasma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Les auteurs ont étudié des nouveau-nés humains pendant les premières heures de la vie. La glycémie, les taux d'insuline et de glucagon dans le plasma portal ont été dosés à intervalles réguliers jusqu'à la 24ème heure après la naissance, de même què au cours d'une surcharge glucosée intraveineuse pratiquée à la 24ème heure. — Un matériel présentant les caractéristiques immunologiques du glucagon pancréatique a été mis en évidence dans le plasma portal des nouveau-nés normaux et de mère diabétique. La surcharge glucosée intraveineuse ne réduit pas le taux de glucagon plasmatique chez le nouveau-né normal ni chez l'enfant de mère diabétique. — Dans la phase tardive de la surcharge glucosée intraveineuse, les valeurs de la glucagonémie portale sont plus élevées chez l'enfant normal que chez le nouveau-né de mère diabétique. L'insulinémie portale est plus élevée chez le nouveau-né de mère diabétique à la 24ème heure de la vie et à la phase initiale de la surcharge glucosée. — L'hypothèse est proposée que la différence de comportement du glueagon pourrait résulter de l'hyperinsulinisme relatif de l'enfant de mère diabétique, l'insuline favorisant la pénétration de glucose dans la cellule α et permettant, par ce mécanisme, une suppression plus efficace de la sécrétion de glucagon.
    Abstract: Zusammenfassung Menschliche Neugeborene wurden während der ersten Lebensstunden untersucht. Blut-glucose, portales Plasmainsulin und Glucagon wurden sowohl in regulären Abständen bis zu 24 Std nach der Geburt als auch während einer intravenösen Glucosebelastung in der 24. Std untersucht. — Eine Substanz mit den immunologischen Charakteristika von Pancreasglucagon wurde im portalen Plasma sowohl von normalen Kindern als auch von Kindern diabetischer Mütter gefunden. Die intravenöse Glucosebelastung hat weder bei den normalen Neugeborenen noch bei den Kindern diabetischer Mütter das Plasmaglucagon unterdrückt. Im Vergleich zu den Kindern diabetischer Mütter wurden bei den normalen Neugeborenen in der späten Phase der intravenösen Glucosebelastung höhere Plasmaglucagonwerte beobachtet. Portales Plasmainsulin war bei den Kindern diabetischer Mütter sowohl nach 24 Std als auch während der ersten Phase des intravenösen Glucosetoleranztests erhöht gefunden worden. — Es wird die Hypothese vorgeschlagen, daß das Verhalten der Unterschiede in der Glucagonsekretion möglicherweise eine Folge des relativen Hyperinsulinismus der Kinder diabetischer Mütter sei, welcher der Glucose den Eintritt in die Zelle durch Insulin erleichtert und so eine effektvollere Glucagonverminderung erlaubt.
    Notes: Summary Human neonates have been studied during the first hours of life. Blood glucose, portal plasma insulin and glucagon have been determined both at regular intervals up to 24 h after birth and during an intravenous glucose load performed at the 24th h. A material presenting the immunological characteristics of pancreatic glucagon has been found in the portal plasma of both normal infants and infants from diabetic mothers (IDM). The intravenous glucose load did not suppress plasma glucagon in the normal neonates nor in the IDM. Higher portal plasma glucagon values were observed in the late phase of the intravenous glucose load in normal neonates compared to IDM. Portal plasma insulin has been found higher in IDM both at the 24th h of life and during the early phase of the intravenous glucose tolerance test. The hypothesis is put forward that the behaviour difference in glucagon secretion might be a consequence of the relative nyperinsulinism of IDM with insulin facilitating the entry of glucose into the α cell thus permitting a more effective glucagon suppression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01225575
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  • 5
    Electronic Resource
    Electronic Resource
    Diagnostic sensitivity of immunodominant epitopes of glutamic acid decarboxylase (GAD65) autoantibodies in childhood IDDM (1996)
    Springer
    Diabetologia 39 (1996), S. 1091-1098 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin-dependent diabetes mellitus ; autoimmunity ; autoantibodies ; radioimmunoassay ; recombinant protein.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The prevalence and titre of epitope-specific autoantibodies to glutamic acid decarboxylase (GAD65) in 155 insulin-dependent diabetic (IDDM) and 9 GAD65 antibody (Ab)-positive healthy children were determined using four GAD65/67 chimaeric molecules which discriminate among the N-terminal (N), middle (M) and C-terminal (C) epitopes of GAD65. Radioligand binding assays for IgG Ab used immunoprecipitation of in vitro translated 35S-GAD. We found autoantibodies to GAD65 in 116 of 155 (75 %), to GAD67 in 19 of 155 (12 %) (p 〈 0.0001) and to the GAD65-N-67 chimaera in 25 of 155 (16 %) (p 〈 0.0001) IDDM sera. GAD67Ab were found almost exclusively (17 of 19, 89 %) in GAD65Ab-positive sera and the levels of GAD67Ab correlated with those of GAD65Ab (r 2 = 0.5913; p = 0.009). GAD65Ab directed to GAD65-M were found in 104 of 155 (67 %), to GAD65-C in 104 of 155 (67 %) and to GAD65-M + C in 116 of 155 (75 %) of IDDM sera, and indicated reactivity to at least two distinct epitopes. Among the nine GAD65Ab-positive healthy children, two (22 %) were also positive with GAD67, nine (100 %) with GAD65-M + C, seven (78 %) with GAD65-M, eight (89 %) with GAD65-C and two (22 %) with GAD65-N-67. Titres of GAD65Ab (p = 0.007), GAD65-C-Ab (p = 0.002) and GAD65-C + M-Ab (p = 0.003), but not of GAD65-M-Ab (p = 0.101) were significantly higher in IDDM than in healthy children. We conclude that GAD65Ab in IDDM and healthy children are directed to middle and C-terminal epitopes, and propose that levels of antibodies specifically directed to the carboxy-terminal end of GAD65 may distinguish IDDM from healthy children. [Diabetologia (1996) 39: 1091–1098]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400659
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  • 6
    Electronic Resource
    Electronic Resource
    Diagnostic sensitivity of immunodominant epitopes of glutamic acid decarboxylase (GAD65) autoantibodies in childhood IDDM (1996)
    Springer
    Diabetologia 39 (1996), S. 1091-1098 
    Details
    ISSN: 1432-0428
    Keywords: Insulin-dependent diabetes mellitus ; autoimmunity ; autoantibodies ; radioimmunoassay ; recombinant protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The prevalence and titre of epitope-specific autoantibodies to glutamic acid decarboxylase (GAD65) in 155 insulin-dependent diabetic (IDDM) and 9 GAD65 antibody (Ab)-positive healthy children were determined using four GAD65/67 chimaeric molecules which discriminate among the N-terminal (N), middle (M) and C-terminal (C) epitopes of GAD65. Radioligand binding assays for IgG Ab used immunoprecipitation of in vitro translated 35S-GAD. We found autoantibodies to GAD65 in 116 of 155 (75%), to GAD67 in 19 of 155 (12%) (p〈0.0001) and to the GAD65-N-67 chimaera in 25 of 155 (16%) (p〈0.0001) IDDM sera. GAD67Ab were found almost exclusively (17 of 19, 89%) in GAD65Ab-positive sera and the levels of GAD67Ab correlated with those of GAD65Ab (r 2=0.5913; p=0.009). GAD65Ab directed to GAD65-M were found in 104 of 155 (67%), to GAD65-C in 104 of 155 (67%) and to GAD65-M + C in 116 of 155 (75%) of IDDM sera, and indicated reactivity to at least two distinct epitopes. Among the nine GAD65Ab-positive healthy children, two (22%) were also positive with GAD67, nine (100%) with GAD65-M + C, seven (78%) with GAD65-M, eight (89%) with GAD65-C and two (22%) with GAD65-N-67. Titres of GAD65Ab (p=0.007), GAD65-C-Ab (p=0.002) and GAD65C + M-Ab (p=0.003), but not of GAD65-M-Ab (p=0.101) were significantly higher in IDDM than in healthy children. We conclude that GAD65Ab in IDDM and healthy children are directed to middle and C-terminal epitopes, and propose that levels of antibodies specifically directed to the carboxy-terminal end of GAD65 may distinguish IDDM from healthy children.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400659
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  • 7
    Electronic Resource
    Electronic Resource
    HLA class II is associated with the frequency of glutamic acid decarboxylase Mr 65 000 autoantibodies in Japanese patients with insulin-dependent diabetes mellitus (1996)
    Springer
    Acta diabetologica 33 (1996), S. 108-113 
    Details
    ISSN: 1432-5233
    Keywords: Key words  Autoantigen ; Autoimmunity ; Insulin-dependent diabetes mellitus ; Human leukocyte antigen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Autoantibodies to glutamic acid decarboxylase (GAD65Ab) are common in both caucasian and Japanese patients with insulin-dependent diabetes mellitus (type 1), while the type 1-associated HLA haplotypes differ. In the present study, we analyzed GAD65Ab in relation to HLA-DQ and -DR alleles in Japanese type 1 patients. GAD65Ab were found in 58% short-duration (less than 5 years) type 1, 23% long-duration type 1, 56% slowly progressive type 1, 3% type 2 patients, and 1.7% healthy individuals. In 75 HLA-typed type 1 patients, the GAD65Ab frequency was higher in short-duration patients with DRB1*08 allele (100%, Pc〈0.05). GAD65Ab frequencies in DQB1*0302, DQB1*0303, and DRB1*09-positive, long-duration type 1 patients were lower than those in short-duration type 1 patients (14%, 19%, and 20%, Pc〈0.02 compared with short-duration type 1, 90%, 75%, and 71%, respectively), while the frequency varied less in DQB1*04 individuals (44% and 30% in short- and long-duration type 1 patients, respectively). These findings were also observed among patients with DRB1*04, i.e., the haplotype DRB1*0405-DQB1*0401 showed less variation in frequency of GAD65Ab (44% and 35% in short- and long-duration type 1 patients, respectively), while DRB1*04xx-DQB1*0302 showed lower frequency in long-duration type 1 than short-duration (13% and 100%, respectively). Thus, HLA class II is associated with frequency GAD65Ab, and this association might be affected by disease duration in Japanese type 1 patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00569419
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  • 8
    Electronic Resource
    Electronic Resource
    HLA class II is associated with the frequency of glutamic acid decarboxylase M r 65 000 autoantibodies in Japanese patients with insulin-dependent diabetes mellitus (1996)
    Springer
    Acta diabetologica 33 (1996), S. 108-113 
    Details
    ISSN: 1432-5233
    Keywords: Autoantigen ; Autoimmunity ; Insulin-dependent diabetes mellitus ; Human leukocyte antigen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Autoantibodies to glutamic acid decarboxylase (GAD65Ab) are common in both caucasian and Japanese patients with insulin-dependent diabetes mellitus (type 1), while the type 1-associated HLA haplotypes differ. In the present study, we analyzed GAD65Ab in relation to HLA-DQ and-DR alleles in Japanese type 1 patients. GAD65Ab were found in 58% short-duration (less than 5 years) type 1,23% long-duration type 1,56% slowly progressive type 1,3% type 2 patients, and 1.7% healthy individuals. In 75 HLA-typed type 1 patients, the GAD65Ab frequency was higher in short-duration patients with DRB1*08 allele (100%,Pc〈0.05). GAD65Ab frequencies in DQB1*0302, DQB1*0303, and DRB1*09-positive, long-duration type 1 patients were lower than those in short-duration type 1 patients (14%, 19%, and 20%,Pc〈0.02 compared with short-duration type 1, 90%, 75%, and 71%, respectively), while the frequency varied less in DQB1*04 individuals (44% and 30% in short- and long-duration type 1 patients, respecitively). These findings were also observed among patients with DRB1*04, i.e., the haplotype DRB1*0405-DQB1*0401 showed less variation in frequency of GAD65Ab (44% and 35% in short- and long-duration type 1 patients, respectively), while DRB1*04xx-DQB1*0302 showed lower frequency in long-duration type 1 than short-duration (13% and 100%, respectively). Thus, HLA class II is associated with frequency GAD65Ab, and this association might be affected by disease duration in Japanese type 1 patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00569419
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  • 9
    Electronic Resource
    Electronic Resource
    Xenotransplantation of microencapsulated pancreatic islets contained in a vascular prosthesis: preliminary results (1991)
    Springer
    Transplant international 4 (1991), S. 200-204 
    Details
    ISSN: 1432-2277
    Keywords: Xenotransplantation, islet ; Islet transplantation ; Pancreatic islet, xenotransplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Porcine and human pancreatic islets were microencapsulated in an alginate-polylysine biomembrane and put in a chamber of a new vascular prosthesis composed of an inner tubing of Dacron mesh and an outer tubing of expanded polytetrafluorethylene material. The vascular prosthesis was anastomized between the iliac artery and the contralateral vein of diabetic dogs. The recipients did not receive any immunosuppressive therapy. Function of porcine and human islets was monitored by measuring serum glucose levels and human C-peptide concentrations. After transplantation, serum glucose levels were maintained at values lower than 200 mg/dl, and C-peptide concentrations were between 0.8 and 3.2 ng/ml. Injected insulin requirements decreased by 50%–60%. Four to 8 weeks after transplantation, histologic examination showed well-preserved and functioning islets in the majority of intact microcapsules. Fibrin and inflammatory cells were not observed in the chamber. These data suggest long-term survival and function of microencapsulated pancreatic islets in the vascular prosthesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00649103
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