Edith Schober | Medizinische Universität Wien (original) (raw)
Papers by Edith Schober
European Radiology, May 1, 2003
The purpose of this study was to compare the diagnostic accu
J Clin Endocrinol Metab 99 391 394, Feb 1, 2014
Hyperinsulinemic hypoglycemia (HH), characterized by unregulated insulin secretion, is an importa... more Hyperinsulinemic hypoglycemia (HH), characterized by unregulated insulin secretion, is an important cause of persistent and severe hypoglycemia. The biochemical picture of HH is hypoketotic hypo-fatty-acidemic hypoglycemia along with elevated serum insulin. Not infrequently, serum insulin might be undetectable in HH despite the presence of evidence of insulin action (suppressed ketogenesis and lipolysis). However, autonomous activity of the downstream insulin signaling pathway without the presence of the ligand (insulin) will give rise to the same clinical and biochemical picture, apart from undetectable serum insulin/C-peptide. AKT2, a serine/threonine protein kinase, is involved downstream to the insulin receptor in mediating the physiological effects of insulin. We describe the second report of an activating AKT2 mutation leading to hypoinsulinemic hypoketotic hypoglycemia. The proband presented with hemihypertrophy and symptomatic hypoglycemia. Investigations confirmed evidence of insulin action, despite absence of detectable serum insulin on multiple occasions. Molecular genetic testing for common causes of HH (ABCC8, KCNJ11, and GLUD1) was negative. Sequencing of AKT2 identified a de novo mosaic c.49G→A (p.E17K) mutation, consistent with the clinical and biochemical phenotype. This is the second report of an activating AKT2 mutation leading to hypoinsulinemic hypoketotic hypo-fatty-acidemic hypoglycemia. In patients presenting a clinical and biochemical picture of HH with undetectable serum insulin, consideration of autonomous activation of the downstream insulin signaling pathway should be made.
Endocrine Regulations, Sep 1, 2003
Discordant data were found in recent growth studies in children with type-1 diabetes mellitus. Th... more Discordant data were found in recent growth studies in children with type-1 diabetes mellitus. This study focuses on growth data and final height in the largest cohort of diabetic children studied so far. 7598 growth data collected in a longitudinal/cross sectional way between 1971 and 1996 in 587 diabetic subjects (317 males, 270 females) were available for analysis of height and BMI, together with 3889 HbA1c measurements. Final height data were correlated with target height in 123 subjects. The individual growth and BMI linear regression curve of each patient was compared to growth standards and correlated with HbA1c. Children of both sexes were taller at the first observation (males, SDS 0.15 +/- 1.10, mean +/- SD, P=0.02, females, SDS 0.74 +/- 1.46, P<0.001) and tended to lose height afterwards (males, P<0.001, females, n.s.). Males reached a final height of 176.5 cm (n=62, target height 176.8, n.s.) and females 167.0 cm (n=61, target height 165.6, n.s.). Children of both sexes had a higher than normal BMI at first observation (males, SDS 0.32 +/- 1.31, P<0.001, females, SDS 0.10 +/- 0.52, P=0.02). Females but not males gained weight over-proportionally afterwards. HbA1c did not predict any of the variables. Diabetic children are taller close to the diabetes onset, which may be due to the synchronization of onset of diabetic symptoms with the mid-childhood growth spurt or the pubertal growth spurt accompanied by elevated growth hormone and/or androgen levels and increased insulin resistance. The subsequent growth deceleration may represent a physiological lag-down growth. This concept is supported by normal adult heights following growth deceleration.
Wiener Klinische Wochenschrift Supplementum, 2009
ABSTRACT
Radiologe, 2000
Zusammenfassung Hintergrund. Der Pharynx repräsentiert, durch seine Funktion als Luft- und Spei... more Zusammenfassung Hintergrund. Der Pharynx repräsentiert, durch seine Funktion als Luft- und Speiseweg einerseits sowie durch seine Topographie in der komplexen Zervikalregion andererseits, ein äußerst differenziertes Organsystem. Bildgebungsverfahren. Neben den, in den letzten Jahren und Jahrzehnten einer rasanten Entwicklung unterworfenen, und in der Kopf-Hals-Radiologie unerlässlichen Schnittbildverfahren, spielen, gerade bei der Bildgebung des Pharynx, konventionelle Röntgenverfahren, welche eine dynamische Beurteilung der Funktion erlauben, weiterhin eine wichtige Rolle in der Diagnostik. Die Methoden der Bildgebung stellen somit heute, ergänzend zur klinischen Untersuchung, unumstritten das 2. Standbein in der Abklärung von Pathologien am Pharynx dar. Resümee. Dieses Zusammenwirken bietet dem Radiologen, entsprechend der Fragestellung nach funktionellen oder strukturellen Pathologien, ein vielfältiges Betätigungsfeld, erfordert gleichzeitig aber das grundlegende Verständnis der normalen Anatomie und Physiologie sowie die Kenntnis der spezifischen Vor- und Nachteile der zur Verfügung stehenden bildgebenden Verfahren.
Diabetol Stoffwechs, 2009
Eur J Endocrinology, 1987
Diabetologie Und Stoffwechsel, 2007
JAMA, Jan 21, 2015
Exposing the oral mucosa to antigen may stimulate immune tolerance. It is unknown whether treatme... more Exposing the oral mucosa to antigen may stimulate immune tolerance. It is unknown whether treatment with oral insulin can induce a tolerogenic immune response in children genetically susceptible to type 1 diabetes. To assess the immune responses and adverse events associated with orally administered insulin in autoantibody-negative, genetically at-risk children. The Pre-POINT study, a double-blind, placebo-controlled, dose-escalation, phase 1/2 clinical pilot study performed between 2009 and 2013 in Germany, Austria, the United States, and the United Kingdom and enrolling 25 islet autoantibody-negative children aged 2 to 7 years with a family history of type 1 diabetes and susceptible human leukocyte antigen class II genotypes. Follow-up was completed in August 2013. Children were randomized to receive oral insulin (n = 15) or placebo (n = 10) once daily for 3 to 18 months. Nine children received insulin with dose escalations from 2.5 to 7.5 mg (n = 3), 2.5 to 22.5 mg (n = 3), or 7....
Archives of disease in childhood, 2014
Increased weight gain has been reported prior to disease onset (accelerator hypothesis) and as a ... more Increased weight gain has been reported prior to disease onset (accelerator hypothesis) and as a side effect of intensified insulin therapy in type 1 diabetes (T1D). Paediatric studies are complicated by the age-dependency and gender-dependency of BMI, and also by a trend towards obesity in the general population. The aim of this study was to evaluate factors related to the increase in BMI during the course of diabetes in children and adolescents with T1D in a large multicentre survey. Within the DPV database (Diabetespatienten Verlaufsdokumentation) a standardised, prospective, computer-based documentation programme, data of 53,108 patients with T1D, aged <20 years, were recorded in 248 centres. 12,774 patients (53% male, mean age 13.4±3.9, mean diabetes duration 4.7±3.0 years and mean age at diabetes onset 8.7±4.0 years) were included in this analysis. Population-based German reference data were used to calculate BMI-SDS and define overweight and obesity. 12.5% of T1D patients ...
PLoS medicine, 2014
Severe hypoglycemia is a major complication of insulin treatment in patients with type 1 diabetes... more Severe hypoglycemia is a major complication of insulin treatment in patients with type 1 diabetes, limiting full realization of glycemic control. It has been shown in the past that low levels of hemoglobin A1c (HbA1c), a marker of average plasma glucose, predict a high risk of severe hypoglycemia, but it is uncertain whether this association still exists. Based on advances in diabetes technology and pharmacotherapy, we hypothesized that the inverse association between severe hypoglycemia and HbA1c has decreased in recent years. We analyzed data of 37,539 patients with type 1 diabetes (mean age ± standard deviation 14.4 ± 3.8 y, range 1-20 y) from the DPV (Diabetes Patienten Verlaufsdokumentation) Initiative diabetes cohort prospectively documented between January 1, 1995, and December 31, 2012. The DPV cohort covers an estimated proportion of >80% of all pediatric diabetes patients in Germany and Austria. Associations of severe hypoglycemia, hypoglycemic coma, and HbA1c levels we...
Pediatric diabetes, 2012
To determine whether screening for islet autoantibodies in children prevents ketoacidosis and oth... more To determine whether screening for islet autoantibodies in children prevents ketoacidosis and other metabolic complications at diabetes onset and improves the clinical course after diagnosis. The German BABYDIAB and the Munich Family Study follow children with a first-degree family history of type 1 diabetes for the development of islet autoantibodies and type 1 diabetes. The Diabetes Prospective Documentation (DPV) Initiative registers and collects information on pediatric patients with type 1 diabetes throughout Germany. Here, clinical characteristics at diabetes onset [ketoacidosis, mean hemoglobin A1c (HbA1c), and length of hospitalization] and the 5-yr clinical course (HbA1c and insulin dose) of screened and followed islet autoantibody-positive children (n = 101) and 49 883 non-screened children within the DPV registry were compared. At diabetes onset, children who were followed after screening and were positive for islet autoantibodies had lower HbA1c (8.6 vs. 11%, p < 0.00...
Diabetologia, 2014
The study aimed to compare participant characteristics, treatment modalities and clinical outcome... more The study aimed to compare participant characteristics, treatment modalities and clinical outcomes in registry participants less than 6 years old. Participant characteristics, treatment modalities and clinical outcomes (HbA1c, severe hypoglycaemia [SH] and diabetic ketoacidosis [DKA]) as well as frequencies of attaining HbA1c goals in line with the International Society for Pediatric and Adolescent Diabetes (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;7.5% [&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;58 mmol/mol]) and ADA (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;8.5% [&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;69 mmol/mol]) were compared. Insulin pump use was more frequent (74% vs 50%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and HbA1c levels lower in the Prospective Diabetes Follow-up Registry (DPV) than in the T1D Exchange (T1DX) (mean 7.4% vs 8.2%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). A lower HbA1c level was seen in the DPV compared with the T1DX for both pump users (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and injection users (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). More children from DPV were meeting the recommended HbA1c goals, compared with children from T1DX (HbA1c &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;7.5%: 56% vs 22%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001; HbA1c &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;8.5%: 90% vs 66%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The adjusted odds of having an HbA1c level &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;7.5% or &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;8.5% were 4.2 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and 3.6 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) higher for the DPV than the T1DX,…
Wiener klinische Wochenschrift, Jan 21, 2014
Despite a marked improvement in the overall prognosis of patients with type 1 diabetes mellitus (... more Despite a marked improvement in the overall prognosis of patients with type 1 diabetes mellitus (T1DM), cardiovascular morbidity/mortality is still increased. Since cellular and microvascular aberrations have been demonstrated already in children with T1DM, albeit a good glycemic control (CO), we hypothesized that early macrovascular changes can be detected by common carotid artery intima-media thickness (CCA-IMT). We included 73 children/adolescents with T1DM (34 boys, 39 girls; mean age, 14.8 ± 2 years) and 243 sex- and age-matched healthy CO. In T1DM mean HbA1c was 7.9 ± 1.1 rel.%, and duration of disease 7.5 ± 3.1 years. High-resolution ultrasonography was used to assess CCA-IMT, defined as the mean of 24 measurements of the near and far wall on both right and left CCA. CCA-IMT was not different in the total of children and adolescents with T1DM compared with CO (0.302 ± 0.057 vs. 0.301 ± 0.054 mm; p = 0.88). Analysis according to gender, however, revealed higher CCA-IMT values ...
Wiener klinische Wochenschrift, 2012
Hyperglycemia significantly contributes to micro- and macrovascular complications in patients wit... more Hyperglycemia significantly contributes to micro- and macrovascular complications in patients with diabetes mellitus. While lifestyle interventions remain cornerstones of disease prevention and treatment, most patients with type 2 diabetes will eventually require pharmacotherapy for glycemic control. The definition of individual targets in regard of optimal therapeutic efficacy and high therapeutic safety is of great importance. In this guideline we present the best and most current evidence-based clinical practice data for healthcare professionals.
Wiener klinische Wochenschrift, 2012
In contrast to adults Diabetes mellitus type 1 (DMT1) is the most frequent form of diabetes melli... more In contrast to adults Diabetes mellitus type 1 (DMT1) is the most frequent form of diabetes mellitus during childhood and adolescence (&amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 95 %). After diagnosis, the management of these DMT1-patients should take place in specialized paediatric centres, not in a primary care setting. The lifelong substitution of insulin is the cornerstone of therapy, the form of insulin-therapy should be adapted according to the age of the patient (conventional, intensified or pump therapy). Diabetes education is also an essential part in the management of diabetes patients and their families. The ISPAD (International Society for Paediatric and Adolescent Diabetes) recommends an HbA1c &amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 7.5 rel.%(IFCC &amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 58 mmol/mol) as good metabolic control, although it might be difficult to achieve this goal during different phases of life (e.g. toddlers or puberty). The aim of diabetes education and management is avoidance of acute and late diabetes related complications, as well as achievement of normal growth and psychosocial development and wellbeing.
Pediatric Research, 2002
In persistent hyperinsulinemic hypoglycemia of infancy, ketone body concentrations are abnormally... more In persistent hyperinsulinemic hypoglycemia of infancy, ketone body concentrations are abnormally low at times of hypoglycemia, depriving the brain of its most important alternative fuel. The neuroprotective effect of endogenous ketone bodies is evidenced by animal and human studies, but knowledge about exogenous supply is limited. Assuming that exogenous ketone body compounds as a dietetic food might replace this alternative energy source for the brain, we have monitored the fate of orally supplemented DL sodium beta-hydroxybutyrate (beta-OHB) in two 6-mo-old infants with persistent hyperinsulinemic hypoglycemia for 5 and 7 mo, while on frequent tube-feedings and treatment with octreotide. Near total (95%) pancreatectomy had been ineffective in one patient and was refused in the other. In blood, concentrations of beta-OHB increased to levels comparable to a 16- to 24-h fast while on DL sodium beta-OHB 880 to 1000 mg/kg per day. In cerebrospinal fluid, concentrations of beta-OHB increased to levels comparable to a 24- to 40-h fast, after single dosages of 4 and 8 g, respectively. High ratios of beta-OHB to acetoacetate indicated exogenous origin of beta-OHB. An increase of intracerebral concentrations of beta-OHB could be demonstrated by repetitive single-voxel proton magnetic resonance spectroscopy by a clear doublet at 1.25 ppm. Oral DL sodium beta-OHB was tolerated without side effects. This first report on oral supplementation of DL sodium beta-OHB in two patients with persistent hyperinsulinemic hypoglycemia demonstrates effective uptake across the blood-brain barrier and could provide the basis for further evaluation of the neuroprotective effect of beta-OHB in conditions with hypoketotic hypoglycemia.
European Radiology, May 1, 2003
The purpose of this study was to compare the diagnostic accu
J Clin Endocrinol Metab 99 391 394, Feb 1, 2014
Hyperinsulinemic hypoglycemia (HH), characterized by unregulated insulin secretion, is an importa... more Hyperinsulinemic hypoglycemia (HH), characterized by unregulated insulin secretion, is an important cause of persistent and severe hypoglycemia. The biochemical picture of HH is hypoketotic hypo-fatty-acidemic hypoglycemia along with elevated serum insulin. Not infrequently, serum insulin might be undetectable in HH despite the presence of evidence of insulin action (suppressed ketogenesis and lipolysis). However, autonomous activity of the downstream insulin signaling pathway without the presence of the ligand (insulin) will give rise to the same clinical and biochemical picture, apart from undetectable serum insulin/C-peptide. AKT2, a serine/threonine protein kinase, is involved downstream to the insulin receptor in mediating the physiological effects of insulin. We describe the second report of an activating AKT2 mutation leading to hypoinsulinemic hypoketotic hypoglycemia. The proband presented with hemihypertrophy and symptomatic hypoglycemia. Investigations confirmed evidence of insulin action, despite absence of detectable serum insulin on multiple occasions. Molecular genetic testing for common causes of HH (ABCC8, KCNJ11, and GLUD1) was negative. Sequencing of AKT2 identified a de novo mosaic c.49G→A (p.E17K) mutation, consistent with the clinical and biochemical phenotype. This is the second report of an activating AKT2 mutation leading to hypoinsulinemic hypoketotic hypo-fatty-acidemic hypoglycemia. In patients presenting a clinical and biochemical picture of HH with undetectable serum insulin, consideration of autonomous activation of the downstream insulin signaling pathway should be made.
Endocrine Regulations, Sep 1, 2003
Discordant data were found in recent growth studies in children with type-1 diabetes mellitus. Th... more Discordant data were found in recent growth studies in children with type-1 diabetes mellitus. This study focuses on growth data and final height in the largest cohort of diabetic children studied so far. 7598 growth data collected in a longitudinal/cross sectional way between 1971 and 1996 in 587 diabetic subjects (317 males, 270 females) were available for analysis of height and BMI, together with 3889 HbA1c measurements. Final height data were correlated with target height in 123 subjects. The individual growth and BMI linear regression curve of each patient was compared to growth standards and correlated with HbA1c. Children of both sexes were taller at the first observation (males, SDS 0.15 +/- 1.10, mean +/- SD, P=0.02, females, SDS 0.74 +/- 1.46, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) and tended to lose height afterwards (males, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001, females, n.s.). Males reached a final height of 176.5 cm (n=62, target height 176.8, n.s.) and females 167.0 cm (n=61, target height 165.6, n.s.). Children of both sexes had a higher than normal BMI at first observation (males, SDS 0.32 +/- 1.31, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001, females, SDS 0.10 +/- 0.52, P=0.02). Females but not males gained weight over-proportionally afterwards. HbA1c did not predict any of the variables. Diabetic children are taller close to the diabetes onset, which may be due to the synchronization of onset of diabetic symptoms with the mid-childhood growth spurt or the pubertal growth spurt accompanied by elevated growth hormone and/or androgen levels and increased insulin resistance. The subsequent growth deceleration may represent a physiological lag-down growth. This concept is supported by normal adult heights following growth deceleration.
Wiener Klinische Wochenschrift Supplementum, 2009
ABSTRACT
Radiologe, 2000
Zusammenfassung Hintergrund. Der Pharynx repräsentiert, durch seine Funktion als Luft- und Spei... more Zusammenfassung Hintergrund. Der Pharynx repräsentiert, durch seine Funktion als Luft- und Speiseweg einerseits sowie durch seine Topographie in der komplexen Zervikalregion andererseits, ein äußerst differenziertes Organsystem. Bildgebungsverfahren. Neben den, in den letzten Jahren und Jahrzehnten einer rasanten Entwicklung unterworfenen, und in der Kopf-Hals-Radiologie unerlässlichen Schnittbildverfahren, spielen, gerade bei der Bildgebung des Pharynx, konventionelle Röntgenverfahren, welche eine dynamische Beurteilung der Funktion erlauben, weiterhin eine wichtige Rolle in der Diagnostik. Die Methoden der Bildgebung stellen somit heute, ergänzend zur klinischen Untersuchung, unumstritten das 2. Standbein in der Abklärung von Pathologien am Pharynx dar. Resümee. Dieses Zusammenwirken bietet dem Radiologen, entsprechend der Fragestellung nach funktionellen oder strukturellen Pathologien, ein vielfältiges Betätigungsfeld, erfordert gleichzeitig aber das grundlegende Verständnis der normalen Anatomie und Physiologie sowie die Kenntnis der spezifischen Vor- und Nachteile der zur Verfügung stehenden bildgebenden Verfahren.
Diabetol Stoffwechs, 2009
Eur J Endocrinology, 1987
Diabetologie Und Stoffwechsel, 2007
JAMA, Jan 21, 2015
Exposing the oral mucosa to antigen may stimulate immune tolerance. It is unknown whether treatme... more Exposing the oral mucosa to antigen may stimulate immune tolerance. It is unknown whether treatment with oral insulin can induce a tolerogenic immune response in children genetically susceptible to type 1 diabetes. To assess the immune responses and adverse events associated with orally administered insulin in autoantibody-negative, genetically at-risk children. The Pre-POINT study, a double-blind, placebo-controlled, dose-escalation, phase 1/2 clinical pilot study performed between 2009 and 2013 in Germany, Austria, the United States, and the United Kingdom and enrolling 25 islet autoantibody-negative children aged 2 to 7 years with a family history of type 1 diabetes and susceptible human leukocyte antigen class II genotypes. Follow-up was completed in August 2013. Children were randomized to receive oral insulin (n = 15) or placebo (n = 10) once daily for 3 to 18 months. Nine children received insulin with dose escalations from 2.5 to 7.5 mg (n = 3), 2.5 to 22.5 mg (n = 3), or 7....
Archives of disease in childhood, 2014
Increased weight gain has been reported prior to disease onset (accelerator hypothesis) and as a ... more Increased weight gain has been reported prior to disease onset (accelerator hypothesis) and as a side effect of intensified insulin therapy in type 1 diabetes (T1D). Paediatric studies are complicated by the age-dependency and gender-dependency of BMI, and also by a trend towards obesity in the general population. The aim of this study was to evaluate factors related to the increase in BMI during the course of diabetes in children and adolescents with T1D in a large multicentre survey. Within the DPV database (Diabetespatienten Verlaufsdokumentation) a standardised, prospective, computer-based documentation programme, data of 53,108 patients with T1D, aged <20 years, were recorded in 248 centres. 12,774 patients (53% male, mean age 13.4±3.9, mean diabetes duration 4.7±3.0 years and mean age at diabetes onset 8.7±4.0 years) were included in this analysis. Population-based German reference data were used to calculate BMI-SDS and define overweight and obesity. 12.5% of T1D patients ...
PLoS medicine, 2014
Severe hypoglycemia is a major complication of insulin treatment in patients with type 1 diabetes... more Severe hypoglycemia is a major complication of insulin treatment in patients with type 1 diabetes, limiting full realization of glycemic control. It has been shown in the past that low levels of hemoglobin A1c (HbA1c), a marker of average plasma glucose, predict a high risk of severe hypoglycemia, but it is uncertain whether this association still exists. Based on advances in diabetes technology and pharmacotherapy, we hypothesized that the inverse association between severe hypoglycemia and HbA1c has decreased in recent years. We analyzed data of 37,539 patients with type 1 diabetes (mean age ± standard deviation 14.4 ± 3.8 y, range 1-20 y) from the DPV (Diabetes Patienten Verlaufsdokumentation) Initiative diabetes cohort prospectively documented between January 1, 1995, and December 31, 2012. The DPV cohort covers an estimated proportion of >80% of all pediatric diabetes patients in Germany and Austria. Associations of severe hypoglycemia, hypoglycemic coma, and HbA1c levels we...
Pediatric diabetes, 2012
To determine whether screening for islet autoantibodies in children prevents ketoacidosis and oth... more To determine whether screening for islet autoantibodies in children prevents ketoacidosis and other metabolic complications at diabetes onset and improves the clinical course after diagnosis. The German BABYDIAB and the Munich Family Study follow children with a first-degree family history of type 1 diabetes for the development of islet autoantibodies and type 1 diabetes. The Diabetes Prospective Documentation (DPV) Initiative registers and collects information on pediatric patients with type 1 diabetes throughout Germany. Here, clinical characteristics at diabetes onset [ketoacidosis, mean hemoglobin A1c (HbA1c), and length of hospitalization] and the 5-yr clinical course (HbA1c and insulin dose) of screened and followed islet autoantibody-positive children (n = 101) and 49 883 non-screened children within the DPV registry were compared. At diabetes onset, children who were followed after screening and were positive for islet autoantibodies had lower HbA1c (8.6 vs. 11%, p < 0.00...
Diabetologia, 2014
The study aimed to compare participant characteristics, treatment modalities and clinical outcome... more The study aimed to compare participant characteristics, treatment modalities and clinical outcomes in registry participants less than 6 years old. Participant characteristics, treatment modalities and clinical outcomes (HbA1c, severe hypoglycaemia [SH] and diabetic ketoacidosis [DKA]) as well as frequencies of attaining HbA1c goals in line with the International Society for Pediatric and Adolescent Diabetes (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;7.5% [&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;58 mmol/mol]) and ADA (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;8.5% [&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;69 mmol/mol]) were compared. Insulin pump use was more frequent (74% vs 50%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and HbA1c levels lower in the Prospective Diabetes Follow-up Registry (DPV) than in the T1D Exchange (T1DX) (mean 7.4% vs 8.2%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). A lower HbA1c level was seen in the DPV compared with the T1DX for both pump users (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and injection users (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). More children from DPV were meeting the recommended HbA1c goals, compared with children from T1DX (HbA1c &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;7.5%: 56% vs 22%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001; HbA1c &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;8.5%: 90% vs 66%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The adjusted odds of having an HbA1c level &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;7.5% or &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;8.5% were 4.2 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and 3.6 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) higher for the DPV than the T1DX,…
Wiener klinische Wochenschrift, Jan 21, 2014
Despite a marked improvement in the overall prognosis of patients with type 1 diabetes mellitus (... more Despite a marked improvement in the overall prognosis of patients with type 1 diabetes mellitus (T1DM), cardiovascular morbidity/mortality is still increased. Since cellular and microvascular aberrations have been demonstrated already in children with T1DM, albeit a good glycemic control (CO), we hypothesized that early macrovascular changes can be detected by common carotid artery intima-media thickness (CCA-IMT). We included 73 children/adolescents with T1DM (34 boys, 39 girls; mean age, 14.8 ± 2 years) and 243 sex- and age-matched healthy CO. In T1DM mean HbA1c was 7.9 ± 1.1 rel.%, and duration of disease 7.5 ± 3.1 years. High-resolution ultrasonography was used to assess CCA-IMT, defined as the mean of 24 measurements of the near and far wall on both right and left CCA. CCA-IMT was not different in the total of children and adolescents with T1DM compared with CO (0.302 ± 0.057 vs. 0.301 ± 0.054 mm; p = 0.88). Analysis according to gender, however, revealed higher CCA-IMT values ...
Wiener klinische Wochenschrift, 2012
Hyperglycemia significantly contributes to micro- and macrovascular complications in patients wit... more Hyperglycemia significantly contributes to micro- and macrovascular complications in patients with diabetes mellitus. While lifestyle interventions remain cornerstones of disease prevention and treatment, most patients with type 2 diabetes will eventually require pharmacotherapy for glycemic control. The definition of individual targets in regard of optimal therapeutic efficacy and high therapeutic safety is of great importance. In this guideline we present the best and most current evidence-based clinical practice data for healthcare professionals.
Wiener klinische Wochenschrift, 2012
In contrast to adults Diabetes mellitus type 1 (DMT1) is the most frequent form of diabetes melli... more In contrast to adults Diabetes mellitus type 1 (DMT1) is the most frequent form of diabetes mellitus during childhood and adolescence (&amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 95 %). After diagnosis, the management of these DMT1-patients should take place in specialized paediatric centres, not in a primary care setting. The lifelong substitution of insulin is the cornerstone of therapy, the form of insulin-therapy should be adapted according to the age of the patient (conventional, intensified or pump therapy). Diabetes education is also an essential part in the management of diabetes patients and their families. The ISPAD (International Society for Paediatric and Adolescent Diabetes) recommends an HbA1c &amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 7.5 rel.%(IFCC &amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 58 mmol/mol) as good metabolic control, although it might be difficult to achieve this goal during different phases of life (e.g. toddlers or puberty). The aim of diabetes education and management is avoidance of acute and late diabetes related complications, as well as achievement of normal growth and psychosocial development and wellbeing.
Pediatric Research, 2002
In persistent hyperinsulinemic hypoglycemia of infancy, ketone body concentrations are abnormally... more In persistent hyperinsulinemic hypoglycemia of infancy, ketone body concentrations are abnormally low at times of hypoglycemia, depriving the brain of its most important alternative fuel. The neuroprotective effect of endogenous ketone bodies is evidenced by animal and human studies, but knowledge about exogenous supply is limited. Assuming that exogenous ketone body compounds as a dietetic food might replace this alternative energy source for the brain, we have monitored the fate of orally supplemented DL sodium beta-hydroxybutyrate (beta-OHB) in two 6-mo-old infants with persistent hyperinsulinemic hypoglycemia for 5 and 7 mo, while on frequent tube-feedings and treatment with octreotide. Near total (95%) pancreatectomy had been ineffective in one patient and was refused in the other. In blood, concentrations of beta-OHB increased to levels comparable to a 16- to 24-h fast while on DL sodium beta-OHB 880 to 1000 mg/kg per day. In cerebrospinal fluid, concentrations of beta-OHB increased to levels comparable to a 24- to 40-h fast, after single dosages of 4 and 8 g, respectively. High ratios of beta-OHB to acetoacetate indicated exogenous origin of beta-OHB. An increase of intracerebral concentrations of beta-OHB could be demonstrated by repetitive single-voxel proton magnetic resonance spectroscopy by a clear doublet at 1.25 ppm. Oral DL sodium beta-OHB was tolerated without side effects. This first report on oral supplementation of DL sodium beta-OHB in two patients with persistent hyperinsulinemic hypoglycemia demonstrates effective uptake across the blood-brain barrier and could provide the basis for further evaluation of the neuroprotective effect of beta-OHB in conditions with hypoketotic hypoglycemia.