Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    ISSN: 1432-5233
    Keywords: Insulin-dependent diabetes ; Islet cell antibodies ; Complement-fixing ICA ; C-peptide ; Geographical variation ; Seasonal variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Finland and Sweden have the highest incidence of insulin-dependent diabetes in children in the world, about 3–4 times that of countries in the Mediterranean area, with the exception of Sardinia. We have collected information from several European clinics and from Pittsburgh, USA, in order to find out whether this difference in incidence is associated with corresponding differences of the disease pattern. Patients in Finland or Sweden (‘North’) and Pittsburgh were younger (〈10 years old) at diagnosis compared with those in the other clinics in Europe (P〈0.05 versusP〈0.02). In the North, boys were in excess (58%) in contrast to France (40%) and Pittsburgh (46%). Patients in the North had a shorter duration of symptoms (〈8 days;P〈0.001) and higher blood glucose (〉20 mmol/l;P〈0.05) than those attending the other European clinics. Irrespective of age, there were more ICA-positive patients in the North (94%) than in Berlin-Vienna (67%;P〈0.01) or in France (70%;P〈0.01). There was a tendency for non-diabetic parents and siblings in the North to have lower C-peptide values (〈0.26 pmol/ml) at the time of diagnosis of the proband and to be ICA-positive more often than relatives in the other European clinics. The seasonal variation of diagnosis, showed no obvious geographical differences, with recorded diagnosis always lowest during the summer. We conclude that certain factors seem to cause not only a high incidence of diabetes in children in Finland and Sweden but perhaps also a more aggressive early disease process.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; haplotypes ; heterogeneity ; HLA-DR2 segregation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Segregation of HLA-DR2 among affected and unaffected offspring was studied in 66 HLA-genotyped families with Type 1 diabetes in whom at least one parent carried DR2. The frequency of DR2-positive parents (21%) was not different from that of control families (29%). Among the diabetic probands, the gene frequency of DR2 was significantly decreased compared with control subjects (0.05 versus 0.17, p 〈 0.001) as were DR5 (0.07 versus 0.17, p〈 0.01) and DR7 (0.06 versus 0.13, p〈0.003). Twenty probands carried DR2, in 11 of whom (55%) it was found in combination with either DR3 or DR4. The nine cases who carried another DR allele included one who was DR2 homozygous. Transmission of DR2 was reduced in affected offspring, and random in unaffected siblings, compared with the expected ratio. However, when the DR2 transmission was analysed separately for parents bearing DR2 with DR3, DR4 or another DR allele, it appeared that DR2 transmission to affected offspring was random when the parents carried neither DR3 or DR4, the transmission deficit being due to over-transmission of DR3 and DR4. The haplotype analysis showed that the haplotype A3, Cw7, B7, BfS, DR2, found in 19% of “non-diabetic” DR2 haplotypes was practically absent among “diabetic” DR2-haplotypes (4%). In conclusion, population and segregation analysis could not demonstrate a specific protective effect of DR2.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; children ; HLA-types ; heterogeneity symptoms at onset ; partial remission ; genetic susceptibility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The presence of HLA-DR 3 was analysed in 745 patients with Type 1 (insulin-dependent) diabetes with age at diagnosis between 1–19 years. HLA-DR 3 and/or 4 was found in 678/745 (91%) of the patients. Presence of DR 2 with neither DR 3 nor 4 was demonstrated in 15 patients. Patients with HLA-DR 3 without DR 4 presented with Type 1 diabetes more evenly over the year; they also presented without incidence peaks at 7 years or 10–11 years, as seen especially in DR 3/4 patients. The DR 3 patients more often had mild disease with less ketonuria at diagnosis, less often ketoacidotic symptoms and more often a subsequent partial remission. The apparently more severe disease among diabetic girls may, at least to some extent, be explained by their higher prevalence of HLA-DR4. The differences found were similar in North America and Europe. The results suggest that Type 1 diabetes is a genetically heterogenous disease and that HLA-typing may be a useful marker of this heterogeneity.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes mellitus ; prediction ; risk for siblings ; HLA-DR3,4 ; C4BQO ; islet cell antibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To determine whether genetic markers can improve the predictive value of islet cell antibodies for development of Type 1 (insulin-dependent) diabetes mellitus, 536 siblings aged 2–29 years were consecutively enrolled in a 8-year prospective survey. The risk of developing diabetes was estimated, using life-table methods, by years of follow-up and age, according to genetic factors (shared HLA-haplotypes, DR antigens, C4 allotypes) and islet cell antibody status. Fifteen siblings (2.8%) developed Type 1 diabetes during the study period (risk 4.4% after 8 years, 4% by age 22 years). DR3,4 heterozygosity identified higher risk (16% after 8 years, 12% by age 22 years, p 〈10−5) than HLA-identity (10% and 7%, respectively, p 〈0.01); risks for DR3 or DR4 positive and for haplo-identical siblings were low (4%, 3% and 4.4%, respectively, NS). C4BQO also conferred significant risk (11% vs 3% in non-C4BQO siblings, p〈0.01). The predictive value of genetic markers alone was poor (12% for DR3,4, 7% for HLA-identity, 9% for C4BQO) compared with that of islet cell antibody levels greater than 4 Juvenile Diabetes Foundation units (41%, risk 56% after 8 years, p 〈10−7). HLA markers significantly contributed to risk prediction in combination with islet cell antibodies: islet cell antibody-positive DR3,4+ subjects had the highest risk (70% after 8 years, predictive value 58%, p 〈10−7) compared with islet cell antibody-positive DR3,4− (37% and 20%, respectively) and islet cell antibody-negative DR3,4+ (5% and 3.6%, respectively). Furthermore, islet cell antibody-positive DR3,4+ siblings progressed to diabetes at a younger age (risk 84% by age 22 years vs 20% in islet cell antibody-positive DR3,4− siblings, p 〈0.005). Siblings with moderate islet cell antibody levels who carry the DR3,4 antigens have been identified as a subgroup with increased risk and more rapid progression to Type 1 diabetes.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    ISSN: 1432-0428
    Keywords: Keywords Diabetes mellitus ; MODY ; glucokinase mutations ; insulin secretion ; genetics.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Mutations in glucokinase are associated with defects in insulin secretion and hepatic glycogen synthesis resulting in mild chronic hyperglycaemia, impaired glucose tolerance or diabetes mellitus. We screened members of 35 families with features of maturity-onset diabetes of the young for mutations in the glucokinase gene and found 16 different mutations. They included 14 new mutations in the glucokinase gene: 9 missense mutations (A53S, G80A, H137R, T168P, M210T, C213R, V226M, S336L and V367M); 2 nonsense mutations (E248X and S360X); a deletion of one nucleotide resulting in a frameshift (V401del1); a substitution of a conserved nucleotide at a splice acceptor site (L122-1G → T); and a 10 base pair deletion that removed the GT of the splice donor site and the following eight nucleotides (K161 + 2del10). In addition, we found two previously identified mutations: R186X and G261R. Study of 260 subjects with glucokinase-deficient hyperglycaemia from 42 families with 36 different GCK mutations made it possible to define the clinical profile of this subtype of non-insulin-dependent diabetes mellitus (NIDDM). Hyperglycaemia due to glucokinase deficiency is often mild (fewer than 50 % of subjects have overt diabetes) and is evident during the early years of life. Despite the long duration of hyperglycaemia, glucokinase-deficient subjects have a low prevalence of micro- and macro-vascular complications of diabetes. Obesity, arterial hypertension and dyslipidaemia are also uncommon in this form of NIDDM. [Diabetologia (1997) 40: 217–224]
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    ISSN: 1432-0428
    Keywords: Insulin-deficient diabetes ; onset of diabetes ; insulinaemia ; diabetic child and adolescent
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Chez 45 jeunes diabétiques au début de l'évolution de leur maladie et non encore soumis á l'insulinothérapie nous avons dosé l'insuline plasmatique au cours d'une ou plusieurs épreuves d'hyperglycémie provoquée par voie buccale. — Les résultats montrent: dans tous les cas et dès le début une insuffisance partielle ou complète de la sécrétion insulinique; une assez bonne correspondance entre la réponse insulinique et l'état clinique et biologique des malades. Dans les cas d'acidose grave, l'insulinémie est nulle. La réponse insulinique est nulle ou très abaissée dans les formes accompagnées de cétonurie. Chez les diabétiques non cétosiques, nous avons trouvé en général une réponse insulinique décelable mais inférieure à celle des sujets normaux en dépit d'une hyperglycémie très importante. Dans ces cas, nous avons distingué deux modalités principales de la sécrétion d'insuline sous surcharge 1. une élévation lente et tardive 2. une élévation progressive suivie d'un effondrement secondaire malgré une montée considérable de la glycémie.
    Abstract: Zusammenfassung Bei 45 jugendlichen, noch nicht mit Insulin behandelten Diabetikern zu Beginn ihrer Erkrankung wurde der Insulinspiegel im Verlaufe eines oder mehrerer Glucosetoleranztests bestimmt. — Die Ergebnisse zeigen in allen Fällen und von Anfang an eine partielle oder vollständige Insuffizienz der Insulinsekretion; einen Zusammenhang zwischen dem poststimulatorischen Insulinspiegel und dem klinischen und biologischchemischen Bild. In den Fällen schwerer Acidose konnte kein Insulin nachgewiesen werden. In den mit Ketonurie einhergehenden Fällen war der Insulinanstieg null oder sehr niedrig. Bei den nicht ketotischen Patienten war im allgemeinen eine Insulinsekretion vorhanden, die jedoch trotz des Vorliegens einer starken Hyperglykämie nicht die bei gesunden Kontrollpersonen gefundenen Werte erreichte. In diesen Fällen haben wir im wesentlichen zwei Formen der Insulinfreisetzung beobachtet: 1. einen langsam und verspätet ansteigenden Insulinspiegel, 2. einen anfänglichen Anstieg gefolgt von einem sekundären Abfall trotz eines weiterhin ansteigenden Blutzuckers.
    Notes: Summary Plasma-insulin levels during oral glucose-tolerance tests have been measured in 45 young diabetics at the beginning of their disease, and who were not yet under insulin therapy. — The results were: a partial or total deficiency of insulin secretion in all cases; a relationship between the poststimulatory insulin levels and the clinical and biochemical status of the patients. In cases of severe acidosis no insulin was detected. Insulin response was absent or very low in cases accompanied by ketonuria. In the non-ketotic diabetics we generally found an insulin response, but it was less than that of healthy controls in spite of marked hyperglycaemia. In these cases we distinguished two principal modes of insulin release: 1. slow and late increase, 2. initial increase followed by secondary collapse in spite of considerably high glucose levels.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    ISSN: 1432-0428
    Keywords: Insulin dependent diabetes ; HLA complex ; DR ; Bf ; DRw3/4 heterozygosity.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary HLA genotypes were ascertained in 53 French Caucasian families, comprising 68 juvenile onset insulin-dependent diabetic siblings. Among the 49 alleles detected at different loci in the HLA complex (A, C, B, Bf, DR) 4 appeared to occur at a significantly higher frequency among the 53 index cases than in a control series of 116 healthy individuals: HLA-B18 (p〈10-3), DRw3, DRw4 and BfF1 (p〈10-6). The excess of HLA identical affected siblings confirms genotype disequilibrium and supports the hypothesis of an HLA-linked gene(s) conferring susceptibility. There was no increase of homozygosity for HLA DRw3 and DRw4 whereas there was a marked excess heterozygosity for HLA DRw3/DRw4 in diabetic patients (32% versus 0% in the control series, p〈0.001). These data provide evidence for the existence of two cooperating genes, linked to each of the HLA DR alleles.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    ISSN: 1432-0428
    Keywords: HLA ; complement ; Type 1 diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The complement proteins, Bf, C2, C4A and C4B, are closely linked to HLA. In 74 propositi and their families, and 97 controls genotyped for HLA-A, -B, -C, -DR, -Bf, a high incidence of the C4BQ0 variant was detected in the patient group (33% versus 12%, p〈 0.00001); C4BQ0 was more frequent in propositi than in non-affected siblings (40 out of 74 versus 36 out of 92, p〈0.05). When comparing the distribution of the phenotype C4BQ0 in Type 1 diabetic patients and normal control subjects, the difference was significant in patients bearing DR3 or DR4 (56% and 25%, respectively, p〈 0.003). The main linkage disequilibria were observed among the 74 propositi: B18, BfF1, C4, A3, BQ0, DR3; B12, BfS, C4, A3, BQ0, DR4. The existence of a silent allele at the C4 B locus is known to be associated with a defective immune response.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes ; HLA-types ; heterogeneity ; age at onset ; sex ; genetic susceptibility ; extended haplotypes ; C4 ; Bf complement components — DRβ ; DQβ ; DNA polymorphism ; restriction fragment length polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Heterogeneity between two haplotypes in linkage disequilibrium with DR3: B8, C4AQOB1,BfS,DR3 and B18,C4A3BQO,BfF1,DR3, with regard to age at onset of Type 1 (insulin-dependent) diabetes mellitus, was investigated in 325 unrelated French patients (146 males and 179 females, age at onset 1 month to 29 years) who were genotyped for HLA-A, B, C, DR and Bf and 225 of whom were typed for the C4A, B complement components. A subgroup of 82 patients and 75 control subjects were tested for DRβ and DQβ DNA restriction fragment length polymorphism. The distribution according to age at onset and the mean ages at onset were compared between patients bearing B8, DR3 (n=58), B18,DR3 (n=62) or other DR3 haplotypes (Bx, DR3, n=70), the haplotype segments C4AQOB1.DR3 (n=41) or C4A3BQO,DR3 (n = 52) and the C4 null alleles C4AQO (N=48) or C4BQO (n=112) alone. The B8,DR3 haplotype, its smaller segment C4AQOB1,DR3 or C4AQO alone were associated with age at onset after 6 years (p〈0.01, 〈0.08 and 〈0.02 respectively); on the other hand, the B18,DR3 haplotype, its segment C4A3BQO,DR3 or C4BQO alone were significantly more frequent in patients aged less than 6 years at onset (p〈0.02, 〈0.01 and 〈0.01 respectively). Accordingly, the mean age of onset was significantly lower in the latter compared with the former patiens (p〈0.02, 〈0.02 and 〈0.01 respectively). No age-related variation was observed in BX,DR3 patients and their mean age of onset was intermediate. The observed age distributions were sex dependent: that of C4AQO was mainly observed in males, that of C4BQO in females. Restriction fragment length polymorphism analysis in 37 patients and 32 control subjects positive for DR3 showed distinct patterns which correlated with DR3 and/or DQW2 borne by the B8 (n=11) and the B18 (n=18) haplotypes, respectively. BX,DR3 subjects exhibited either one or the other of these patterns. In the patients, the B18 associated fragments were found in most cases; whereas the B8 associated pattern was more frequent in the control subjects. These results provide evidence that a heterogeneous genetic background associated with two subsets of DR3 and/or silent alleles of the fourth component of complement could account for differences in the clinical expression of Type 1 diabetes.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes mellitus ; HLA DR3, 4 ; shared haplotypes ; segregation ; multiple affected siblings ; risk for siblings ; maternal effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The susceptibility determinants of Type 1 (insulin-dependent) diabetes mellitus are known to be associated with both HLA-DR3 and DR4. In our study we wished to determine if the parental origin of these antigens could influence susceptibility to the disease. We analysed the inheritance of DR3 and DR4 haplotypes from the father or mother (DR3p, DR4p, DR3m and DR4m, respectively), in the index cases and in the affected and non-affected siblings of 246 diabetic simplex and 41 multiplex families without affected parents. An independent series of 80 multiplex families (GAW 5) was also studied. Among the DR3,4 positive index cases and affected siblings, the paternal and maternal DR3 and DR4 antigens were not distributed randomly: 62% and 72%, respectively, had received DR4 from their father and DR3 from their mother (DR4p/DR3m), while only 38% and 28%, respectively, had received a paternal DR3 together with a maternal DR4 (DR3p/DR4m). This differed significantly from the 50% expected ratio (p〈0.01) and was not observed in unaffected siblings. No excess of maternal DR3 in the absence of DR4 and no excess of paternal DR4 in the absence of DR3 were observed. The finding suggests that some maternal DR3 related event (presumably during pregnancy) might play an enhancing role in the pathogenesis of Type 1 diabetes. It also implies that siblings with both DR4p and DR3m have a significantly higher risk for disease than those with DR3p and DR4m.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...