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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 11 (1975), S. 313-320 
    ISSN: 1432-0428
    Keywords: Insulin secretion ; perinatal period ; rat ; in vivo ; invitro ; perifusion ; isolated islets ; glucose ; glibenclamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary During the perinatal period of the rat the effect of glucose and glibenclamide (HB 419) on the secretion of insulin was studied in vivo and in vitro. In the in vitro experiments isolated islets of 21 day old fetal and 5 day old newborn rats were perifused with 16.7 mM glucose or 16.7 mM glucose plus 1 μ/ml glibenclamide, while in the in vivo experiments glucose, 0.5 g/kg of body weight, or glibenclamide, 0.5 mg/kg of body weight were tested. Glucose elicited a small first phase of insulin release in 21 day old fetal islets, while glucose plus glibenclamide evoked a biphasic pattern. The injection of glibenclamide to the mother lowered the blood sugar in the fetus and increased the fetal serum insulin concentration. In one day old newborn rats glibenclamide stimulated the secretion of insulin after an i.p. injection. Glucose was without effect. Both substances increased the serum insulin concentration in five day old newborn animals. Dynamic studies at that age revealed a monophasic response to glucose and a biphasic pattern to glucose plus glibenclamide.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Key words Height ; weight ; obesity ; siblings ; genetic factors ; bone age.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Normal growth and development, as well as the prevention of overweight, are major goals in the treatment of paediatric patients with insulin-dependent diabetes mellitus (IDDM). We therefore evaluated longitudinally the anthropometric measurements of height and weight, as well as bone age, in an unselected group of 389 patients with IDDM treated at one institution. In order to identify genetic influences on these parameters, height and weight were determined in 186 unaffected siblings and 177 pairs of parents. At diagnosis, patients were slightly taller than average (median z score: + 0.37). During the subsequent course of diabetes, age-adjusted heights decreased progressively for the first 9 years, catching up again after more than 10 years of diabetes. Bone ages were progressively retarded with increasing duration of diabetes. In 76 patients of 18 years or older, median z-score for height was + 0.30, not different from their unaffected siblings (median z-score: + 0.22). The correlation with mid-parental height was identical for diabetic and non-diabetic siblings (r = 0.43). In contrast, children with diabetes were significantly heavier (z-score for weight: + 0.74 compared to + 0.34 in unaffected siblings; p 〈 0.002). Obesity developed primarily during and after puberty. We conclude that: 1) during the course of diabetes, longitudinal growth is temporarily reduced and maturation is delayed in children with diabetes compared to unaffected siblings. However, this effect of diabetes is transient and small compared to genetic influences on height in an individual child. 2) As a group, children with IDDM become significantly overweight, which is likely to increase the cardiovascular risk during adulthood [Diabetologia (1994) 37: 925–929].
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Viral antibodies ; Beta-cell function ; population study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Viral antibodies were tested in a cohort of 44 isletcell antibody-positive individuals age 7–19 years, and 44 of their islet cell antibody-negative age and sex-matched classmates selected from a population study of 4208 pupils who had been screened for islet cell antibodies. Anti-coxsackie B1-5 IgM responses were detected in 14 of 44 (32%) of the islet cell antibody-positive subjects and in 7 of 44 (16%) control subjects. This difference did not reach the level of statistical significance. None of the islet cell antibody-positive subjects had specific IgM antibodies to mumps, rubella, or cytomegalovirus. There was also no increase in the prevalence or the mean titres of anti-mumps-IgG or IgA and anti-cytomegalovirus-IgG in islet cell antibody-positive subjects compared to control subjects. These results do not suggest any association between islet cell antibodies, and possibly insulitis, with recent mumps, rubella or cytomegalo virus infection. Further studies are required to clarify the relationship between islet cell antibodies and coxsackie B virus infections.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Height ; weight ; obesity ; siblings ; genetic factors ; bone age
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Normal growth and development, as well as the prevention of overweight, are major goals in the treatment of paediatric patients with insulin-dependent diabetes mellitus (IDDM). We therefore evaluated longitudinally the anthropometric measurements of height and weight, as well as bone age, in an unselected group of 389 patients with IDDM treated at one institution. In order to identify genetic influences on these parameters, height and weight were determined in 186 unaffected siblings and 177 pairs of parents. At diagnosis, patients were slightly taller than average (median z score: +0.37). During the subsequent course of diabetes, age-adjusted heights decreased progressively for the first 9 years, catching up again after more than 10 years of diabetes. Bone ages were progressively retarded with increasing duration of diabetes. In 76 patients of 18 years or older, median z-score for height was +0.30, not different from their unaffected siblings (median z-score: +0.22). The correlation with midparental height was identical for diabetic and nondiabetic siblings (r=0.43). In contrast, children with diabetes were significantly heavier (z-score for weight: +0.74 compared to +0.34 in unaffected siblings; p〈0.002). Obesity developed primarily during and after puberty. We conclude that: 1) during the course of diabetes, longitudinal growth is temporarily reduced and maturation is delayed in children with diabetes compared to unaffected siblings. However, this effect of diabetes is transient and small compared to genetic influences on height in an individual child. 2) As a group, children with IDDM become significantly overweight, which is likely to increase the cardiovascular risk during adulthood.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 32 (1989), S. 198-202 
    ISSN: 1432-0428
    Keywords: Skeletal growth ; somatomedin ; insulin ; growth hormone ; rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of insulin on skeletal growth was examined by (1) systemic injection, (2) local administration into the tibia growth plate and (3) in vitro by use of chondrocytes in culture. (1) Male rats, body weight 60–75 g, were hypophysectomised. One week after the operation, the animals were divided into three groups. Group A received intraperitoneally saline, group B insulin (5–30 U·kg−1·day−1) and group C human growth hormone (250 μg/kg/day) for the following 10 days. In addition, on day 10 the rats were injected with 10 μCi 35-S-sulfate intraperitoneally. Twenty-four h later in the non-fasting state plasma glucose, insulin, somatomedin activity (porcine assay), body weight, nose-rump length, width of the tibia growth plate, and the 35-S-sulfate incorporation into rib cartilage were determined. Compared to saline, growth hormone and insulin treatment significantly enhanced body weights, nose-rumb lengths, the widths of the proximal tibia growth plates and the incorporation of sulfate into rib cartilage. For the three skeletal growth parameters, growth hormone was more effective than insulin, while body weights did not differ after insulin or growth hormone treatment. So matomedin activity (U/ml) was low in group A (0.39±0.04, n=9, Mean±SEM) and group B (0.34±0.08, n=8) and high in the growth hormone treated group C (0.90±0.09, n=7; p〈0.002). (2) To test the possibility that insulin might directly augment skeletal growth, insulin (80 mU) was injected into the proximal tibia growth plate of one leg and saline into the cartilage zone of the other leg. Insulin treatment significantly increased the width of the cartilage zones. Insulin: 211±22 μm, saline 200±22 μm, (Mean±SD, n=6, p〈0.05). (3) Addition of human biosynthetic insulin and growth hormone to the culture medium increased colony formation of chondrocytes in a bell-shaped fashion. A plateau in colony formation was reached with 3.1–6.25 ng/ml insulin and 25–50 ng/ml growth hormone, but with larger dosages of both hormones, the effect was diminished. The results suggest that insulin might stimulate postnatal skeletal growth by a direct effect on the target cells.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Keywords Body mass index ; puberty ; metabolic control ; insulin dose ; intensified insulin therapy.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Overweight in insulin-dependent diabetes mellitus (IDDM) has been repeatedly reported, especially in girls during adolescence. Potential pathophysiologic factors include tight metabolic control, insulin dose, treatment regimen, puberty and genetics. A standardized data-base from all IDDM patients treated at our institution was evaluated. IDDM patients with hypothyroidism or celiac's disease as well as all records from the first year of diabetes were excluded, resulting in a total of 427 patients (2454 patient-years) available for analysis. BMI and SD-score for BMI based on the Zurich longitudinal growth study were evaluated. Standardized BMI was higher in pubertal children ( + 1.07 ± 0.06) compared to prepubertal children ( + 0.68 ± 0.07; p 〈 0.002). This increase was present both for boys and girls. Increasing overweight during puberty was found irrespective of the age at diagnosis of diabetes (prepubertal or pubertal). The daily dose of insulin and the long-term metabolic control had only a minor impact on the development of overweight. In contrast, in pubertal children, SDS-BMI was significantly higher in patients on intensified insulin regimens (3 or 4 daily injections) compared to patients with 2 injections (p 〈 0.05). These data demonstrate that both boys as well as girls with IDDM develop overweight during puberty. Multiple injection therapy, not daily dose of insulin or the level of metabolic control achieved, was the main predictor of weight gain. This finding may be explained by increased caloric intake due to the flexibility allowed by intensified treatment. [Diabetologia (1998) 41: 542–547]
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 53 (1975), S. 1057-1060 
    ISSN: 1432-1440
    Keywords: Chemotaxis ; Diabetes ; Granulocyten ; intracelluläre Abtötung ; NBT-Index ; Phagocytose ; Chemotaxis ; Diabetes ; Granulocytes ; intracellular killing ; NBT-index ; Phagocytosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Granulocyte function of 10 diabetic children has been investigated. At the time of testing the diabetes was in poor control. Five children were retested one week later after adjustment of diet and insulin dose. In contrast to some reports we did not find a phagocytic defect in the ingestion of particles, but the capacity of intracellular killing of Staphylococcus aureus was impaired. Chemotaxis was also reduced whereas the NBT-index and intracellular killing of Candida albicans were normal. Better control of the diabetes led to an improvement of bactericidal killing capacity.
    Notes: Zusammenfassung Bei 10 Kindern mit Diabetes wurde die Funktion der Granulocyten getestet. Zum Zeitpunkt der Untersuchung waren die Patienten schlecht eingestellt. Fünf Kinder wurden nach Korrektur der Insulindosis und der Diät eine Woche später erneut getestet. Im Gegensatz zu Berichten aus der Literatur fanden wir keine verringerte Ingestion von Partikeln. Dagegen war die intracelluläre Abtötung von Staphylococcus aureus gestört. Die chemotaktische Aktivität war ebenfalls verringert, während der NBT-Index und die intracelluläre Abtötung von Candida albicans normal waren. Optimale Einstellung des Diabetes führte zu einer Verbesserung der Abtötungsfähigkeit gegenüber Bakterien.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 54 (1976), S. 717-725 
    ISSN: 1432-1440
    Keywords: Diabetes mellitus ; Pankreashormone ; Insulinantikörper ; Glukosetoleranztest ; Glibenclamide ; Diabetes mellitus ; Pancreatic Hormones ; Insulin Antibodies ; Glucose tolerance test ; Glibenclamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Human C-peptide is determined by radioimmunoassay. On gel filtration of serum from a healthy subject and from a patient with islet cell carcinoma, C-peptide (MW 3025) appears ahead of insulin (MW 5808) and shows much higher molar concentrations than the hormone. Human proinsulin cross-reacts with our antiserum to synthetic human C-peptide. On direct determination of immunomeasurable C-peptide (IMCP) in fasting serum of 25 healthy subjects we find an average of 1.8 (±0.4) ng/ml, corresponding to 60.4 × 10−11 Mol/l. The molar concentration is about five-fold as compared to IMI (immunomeasurable insulin). IMCP and IMI patterns are not identical on stimulation of beta-cell secretion in healthy subjects by i.v. glucose or glucose-glibenclamide. This is probably due to differences in peripheral metabolism of both compounds. We conclude from our results that C-peptide determined in peripheral venous serum is a better indicator of beta-cell secretion than is insulin. Among 26 insulin-treated juvenile diabetics 15 show not measurable and 11 subnormal IMCP levels in fasting serum. No rise in IMCP is found 1–2 h following breakfast. Four juvenile patients receiving no insulin in a phase of total diabetes remission have normal or raised fasting IMCP concentrations. Only 2 out of 24 adult diabetics (16 treated with insulin and 8 with tablets) show non-measurable fasting IMCP concentrations, in another 4 patients values are below and in the remaining 18 cases above 1 ng/ml serum. Stimulation of beta-cell secretion through glucoseglibenclamide is more or less impaired in all adult diabetics compared to the healthy subjects.
    Notes: Zusammenfassung Humanes C-Peptid wird radioimmunologisch bestimmt. Bei der Gelfiltration von Serum einer gesunden Probandin und einer Patientin mit Inselzellcarcinom erscheint C-Peptid (MG 3025) vor Insulin (MG 5808). Die molaren Konzentrationen für C-Peptid sind viel höher als für Insulin. Humanes Proinsulin reagiert mit unserem Antiserum gegen synthetisches humanes C-Peptid kreuz. Bei direkter Messung im Serum zeigen 25 Gesunde einen Nüchternspiegel für immunologisch meßbares C-Peptid (IMCP) von 1,8 (±0,4) ng/ml, entsprechend 60,4 × 10−11 Mol/l. Die molare Konzentration für immunologisch meßbares Insulin (IMI) beträgt ungefähr ein Fünftel dieses Wertes. Nach Stimulation der Beta-Zell-Sekretion mit i.v. Glukose oder Glukose-Glibenclamid finden sich bei Gesunden unterschiedliche Verl:aufe für IMCP und IMI. Wahrscheinlich erklärt sich dieser Befund mit einem unterschiedlichen peripheren Metabolismus beider Substanzen. Aus unseren Ergebnissen schließen wir, daß bei Messungen im peripheren venösen Serum C-Peptid ein besserer Indikator der Beta-Zell-Sekretion ist als Insulin. Von 26 insulinpflichtigen juvenilen Diabetikern zeigen 15 nicht meßbare und 11 subnormale IMCP Spiegel im Nüchternserum. 1–2 h nach dem Frühstück findet sich kein Anstieg für IMCP. Bei 4 juvenilen Diabetikern, die während einer totalen Remissionsphase ohne Insulin auskommen, liegen die IMCP Nüchternkonzentrationen im Normbereich für Gesunde oder darüber. Nur bei 2 von 24 erwachsenen Diabetikern (16 Fälle mit Insulin behandelt, 8 mit Tabletten) sind die IMCP Nüchternkonzentrationen nicht meßbar, bei 4 weiteren Patienten liegen sie unter, in den restlichen 18 Fällen dagegen über 1 ng/ml Serum. Die Stimulierbarkeit der Beta-Zell-Sekretion durch Glukose-Glibenclamid ist bei allen erwachsenen Diabetikern im Vergleich mit Gesunden mehr oder weniger eingeschränkt.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 142 (1984), S. 260-265 
    ISSN: 1432-1076
    Keywords: Height prediction ; Height reduction ; Excessively tall girls ; High-dose oestrogen treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Twenty-one girls with familial tall stature were reevaluated at 18 years of age. Fourteen of them had been treated with high-dose oestrogens (I), while seven girls had not been treated (II). The untreated group is comparable but not a strict control group. Recordings on initiation of the study were: Chronologic age: 12.0±1.4 (I) versus 13.5±1.5 years (II; x), Bone age: (1) Greulich-Pyle: 11.8±1.4 (I) versus 13.1±1.1 years (II), (2) Tanner-Whitehouse II: 12.7±1.0 (I) versus 13.6±1.1 years (II). Mean height predictions according to (1) Bayley-Pinneau, (2) Roche-Wainer-Thissen and Tanner (3) with, and (4) without allowance for midparent height ranged from 179.4–184 (I) to 175.7–179.5 cm (II). In the treated group there was an average reduction of predicted height of between 2.3 and 6.5 cm, depending on which of the four methods was used. In the untreated group the average differences between calculated and observed mature height varied from 0.2–3.4 cm. The difference in the reduction of predicted height between the treated and untreated groups was significant (P〈0.05) only with the Bayley-Pinneau method and not with the others. In the treated group highly significant correlations were found between height reduction and the initial chronologic age, bone age and duration of therapy.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 145 (1986), S. 148-150 
    ISSN: 1432-1076
    Keywords: Precocious puberty ; Hypothalamic hamartoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A girl with precocious puberty due to a hypothalamic hamartoma is presented. At the age of 0.41 years vaginal bleeding was documented and signs of puberty were noted: PHIII, BII according to Tanner. The bone age was 1.3 years, and height velocity rose from the 50th to 90th percentile. Plasma concentrations of LH (5.85 mU/ml), FSH (3.29 mU/ml), growth hormone (30 ng/ml), and oestradiol (90 pg/ml) were elevated. The results of a neurological examination including an EEC recording as well as a skull roentgenogram, were unremarkable. The visual evoked potentials were grossly abnormal. A native and contrast CT scan visualized a tumour close to the suprasellar cisterna reaching the chiasma opticum. At the age of 1.2 years the tumours was removed. Histologically the tissue was identified as a hamartoma. Immediately after the operation vaginal bleeding ceased, pubertal development regressed, bone age did not advance any further, the visual evoked potentials normalized and the contrast CT did not show any tumour mass. The levels of LH, FSH, growth hormone and oestradiol 4 months post operation were decreased as follow: LH: 1.14 mU/ml, FSH: 0.70 mU/ml, GH: 15.1 ng/ml, oestradiol: 10 pg/ml. However, there was an increase of FSH (3 mU/ml) 1 year after the operation. No secondary sexual characters reappeared.
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