Mikromanipulation und Einzelzellenanalysen an kutanen B-Zell-Lymphomen

In der vorliegenden Arbeit werden die Immunglobulinsequenzen von primär kutanen B-Zell-Lymphomen untersucht und die Methoden der Mikromanipulation und Einzelzell-PCR erstmalig in der dermatologischen Forschung angewendet. Mutationsanalysen der Immunglobulingene von B-Lymphozyten können Auskunft darüber geben, in welchem Stadium ihrer Entwicklung sich die B-Zellen zum Zeitpunkt ihrer Untersuchung befinden, wodurch Rückschlüsse auf die Herkunft der Lymphomzellen möglich sind. Wir untersuchten insgesamt 106 B-Lymphozyten von zwei Patienten mit primär kutanem B-Zell-Lymphom, die in beiden Fällen aus mindestens zwei verschiedenen Biopsien gewonnen wurden. Die Sequenzanalyse konnte sowohl für das primär kutane Keimzentrumszell-Lymphom als auch für das großzellige B-Zell-Lymphom der unteren Extremität die Tumorzellen als reife, mutierte germinal center-B-Zellen oder deren Abkömmlinge identifizieren, was die histologische Beurteilung dieser Zellen als von Keimzentrumszellen abstammend unterstützt. Zumindest für das Keimzentrumszell-Lymphom des Patienten UK konnte nachgewiesen werden, daß die Zellen nach ihrer Transformation zu Tumorzellen noch zur Hypermutation befähigt waren. Eindeutige Indizien für eine antigenabhängige Verteilung der Mutationen gibt es - die derzeitigen Analyseverfahren (R/S-Ratio) nutzend - nicht, was aber die Rolle eines Antigens bei der Entstehung oder gar Progression des Tumorklons nicht ausschließt, wie in der Diskussion ausführlich erläutert wird. Anhand der vorliegenden Sequenzen konstruierte single chains (über einen linker gekoppelte variable Fragmente der H- und L-Kette) oder besser vollständige antigenbindende Fragmente (H- und L-variables Fragment plus den C1-Domänen) werden in Bindungsstudien die Frage der Spezifität und Affinität der Tumorantikörper beantworten helfen. Molekularbiologische Unterschiede zwischen beiden untersuchten Tumorentitäten bestehen zum einen in der deutlich höheren Mutationsfrequenz sowie dem Fehlen von intraklonaler Diversität bzw. andauernder Mutation des VH-Gens der Patientin IL mit dem großzelligen B-Zell-Lymphom der unteren Extremität. Es ist selbstverständlich notwendig, mehrere Fälle zu untersuchen, um einen molekularbiologischen Unterschied zwischen den Keimzentrumszell-Lymphomen und den großzelligen Lymphomen der unteren Extremität zu konstatieren und somit einen Beitrag für die Klassifikation primär kutaner B-Zell-Lymphome zu leisten

Expected Basal Insulin Requirement during CSII therapy by Age Group, Sex and BMI, based on 25,718 Young People with Type 1 Diabetes in the DPV Registry.

Background Since the introduction of insulin pumps into the therapy of paediatric subjects, different approaches have been taken to find optimal basal rates. Previously, the DPV registry provided circadian basal rate patterns for different age groups. As the number of pump users has increased recently and short-acting insulin analogues are now predominant, we performed a new analysis with a larger data pool. Methods We included all recent basal profiles from T1D patients between 1 and 25 years from the DPV 2021 data pool. We excluded night-time-only pump users, human regular insulin users, and daily basal rates 1.0 U/kgBW/d. Results In the analysis of profiles from 25,718 young persons with T1D, differences in the daily pattern of basal rates were found between age groups. In addition, we saw significant (p<0.001) differences in total daily basal dose between genders in all age groups except adults. In addition, the shape of the expected basal-rate pattern differed by BMI, HbA1c and use of continuous glucose monitoring. Discussion This analysis demonstrates multiple factors influencing basal patterns and insulin requirement, including age group, gender, overweight, HbA1c, bolus frequency and sensor use. As circadian basal rates are still mandatory for initiating insulin pump therapy with or without automation, a multimodal approach is necessary to estimate optimal basal rates

Type 1 diabetes and epilepsy in childhood and adolescence: Do glutamic acid decarboxylase autoantibodies play a role? Data from the German/Austrian/Swiss/Luxembourgian DPV Registry

AimsWe aimed to analyze the relationship between epilepsy and glutamic acid decarboxylase autoantibodies (GADA) in patients with type 1 diabetes mellitus (T1DM) and the impact of GADA on demographic, clinical, and metabolic data in T1DM patients with epilepsy.MethodsWe searched for patients with T1DM ≤20 years and GADA measurements, and within this group for patients with epilepsy. We formed groups: T1DM + Epilepsy + GADA positive; T1DM + Epilepsy + GADA negative; T1DM + GADA positive; T1DM + GADA negative. We used logistic regression to analyze the relationship between epilepsy and GADA with odds ratio adjusted for sex, duration of diabetes (DOD), and age at diabetes onset (ADO). We used logistic regression with odds ratio adjusted for DOD and ADO onset using epilepsy as a dependent variable and GADA, HbA1c, ketoacidosis, severe hypoglycemia (SH), sex, celiac disease, and autoimmune thyroiditis as independent variables. We conducted regression analyses adjusted for sex, DOD, and ADO to analyze differences in clinical/metabolic parameters between the groups.ResultsEpilepsy was not more frequent in GADA-positive patients (GPP). Logistic regression including all patients with GADA measurements showed that hypoglycemia with coma (HC) correlated with epilepsy when compared to no SH. We found no differences in clinical and metabolic data between GPP and GADA-negative patients (GNP) with epilepsy. SH occurred more often in GPP with epilepsy in comparison to GPP without epilepsy. GNP with epilepsy had a higher rate of HC than GPP without epilepsy.ConclusionWe found no relationship between epilepsy and GADA. A relationship between T1DM and epilepsy might be explainable by SH

Cataract in children and adolescents with type 1 diabetes. Insights from the German/Austrian DPV registry

Objective To study diabetic cataract in type 1 diabetes in a large pediatric cohort. Methods The 92,633 patients aged 0.5-21 years from German/Austrian multicenter diabetes registry (DPV) were analyzed. The 235 patients (0.25%) with diabetic cataract were found, 200 could be categorized: 67 with early cataract (3 months before diabetes onset - 12 months afterwards), 133 with late cataract (>12 months after diabetes onset). Regression models adjusted for age and gender were used to compare clinical parameters at diabetes onset. Regression models for patients with late cataract were implemented for the total documentation period and additionally adjusted for diabetes duration. Results Rate of cataract development shows a peak at diabetes onset and declines with longer diabetes duration. Patients with cataract showed strong female preponderance. Patients developing early cataract were older at diabetes onset (12.8 years [11.8/13.9] vs. 8.9 [8.9/9.0]; p < 0.001) and showed higher HbA1c than patients without cataract (9.0% [8.55/9.38] vs. 7.6% [7.60/7.61]; p < 0.001). They had lower height-SDS, (-0.22 [-0.48/0.04] vs. 0.25 [0.24/0.26]; p < 0.001), lower weight-SDS (-0.31 [-0.55/-0.08] vs. 0.21 [0.20/0.21]; p < 0.001) and lower BMI-SDS (-0.25 [-0.49/-0.02] vs. 0.12 [0.12/0.13); p = 0.002). Patients with late cataract showed higher HbA1c at diabetes onset (8.35% [8.08/8.62] vs. 8.04% [8.03/8.05]; p = 0.023) and higher mean HbA1c during total documentation period (8.00% [7.62/8.34] vs. 7.62% [7.61/7.63]; p = 0.048). Conclusions Our data confirm known demographic and clinical characteristics of patients developing early cataract. Hyperglycemia-induced osmotic damage to lens fibers at diabetes onset might be the main pathomechanism. Long term glycemic control is associated with cataract development

Diabetes and gender incongruence: frequent mental health issues but comparable metabolic control – a DPV registry study

ContextThe condition when a person’s gender identity does not match the sex assigned at birth is called gender incongruence (GI). Numbers of GI people seeking medical care increased tremendously over the last decade. Diabetes mellitus is a severe and lifelong disease. GI combined with diabetes may potentiate into a burdensome package for affected people.ObjectiveThe study aimed to characterize people with GI and diabetes from an extensive standardized registry, the Prospective Diabetes Follow-up Registry (DPV), and to identify potential metabolic and psychological burdens.MethodsWe compared demographic and clinical registry data of persons with type 1 or type 2 diabetes and GI to those without GI and used propensity score matching (1:4) with age, diabetes duration and treatment year as covariates.Results75 persons with GI, 49 with type 1 and 26 with type 2 diabetes were identified. HbA1c values were similar in matched persons with type 1 or 2 diabetes and GI compared to those without GI. Lipid profiles showed no difference, neither in type 1 nor in type 2 diabetes. Diastolic blood pressure was higher in the type 1 and GI group than in those without, whereas systolic blood pressure showed comparable results in all groups. Depression and anxiety were significantly higher in GI people (type 1 and 2). Non-suicidal self-injurious behaviour was more common in type 1 and GI, as was suicidality in type 2 with GI.ConclusionMental health issues are frequent in people with diabetes and GI and need to be specially addressed in this population

Metabolic Safety of Growth Hormone in Type 1 Diabetes and Idiopathic Growth Hormone Deficiency

Objective To evaluate metabolic consequences of growth hormone (GH) treatment in children with type 1 diabetes. Study design This study is an analysis of metabolic changes in 37 patients with childhood-onset GH deficiency and type 1 diabetes, documented in the Diabetes Patienten Verlaufsdocumentationsystem database. Main outcome measures were changes in hemoglobin A1c and daily insulin requirements during GH therapy in children with GH deficiency and type 1 diabetes compared with a large cohort of adolescents with type 1 diabetes. Results Thirty-seven patients with type 1 diabetes and a diagnosis of idiopathic GH deficiency after onset of diabetes were compared with 48 856 patients with type 1 diabetes. After adjustment for age, sex, duration of diabetes, and migration background, a significant difference in mean daily insulin requirement was seen between the 2 groups (1.0 IU/kg/day in subjects with GH deficiency and type 1 diabetes vs 0.85 IU/kg/day in controls; P .05). Conclusion An increased daily insulin requirement should be considered in patients with type 1 diabetes treated with GH. With adequate adaptation of insulin dosage, metabolic control is not impaired during GH treatment