Poorly controlled pediatric type 1 diabetes mellitus is a risk factor for metabolic dysfunction associated steatotic liver disease (MASLD): An observational study.

OBJECTIVES: Recent studies have suggested a link between type 1 diabetes mellitus (T1D) and metabolic dysfunction associated steatotic liver disease (MASLD) in children and adolescent, but longitudinal evidence is lacking. This study aimed to investigate the potential association between poorly controlled T1D and elevated alanine aminotransferase (ALT), serving as a proxy for MASLD in children and adolescents over time. METHODS: The study included 32,325 children aged 2-17 years with T1D from Germany, Austria, and Switzerland who had undergone at least one assessment of liver enzyme levels recorded in the Diabetes-Patienten- Verlaufsdokumentation registry. Multivariable logistic and Cox regression models were calculated to show possible associations between T1D and elevated ALT values (>26 U/L in males, >22 U/L in females) as a proxy for MASLD. RESULTS: Children with poorly controlled T1D (HbA1c > 11%) exhibited increased odds of elevated ALT values, after adjustment for age, sex, diabetes duration and overweight (odds ratio [OR] 2.54; 95% confidence interval [CI], 2.10-3.10; p < 0.01). This finding is substantiated by a longitudinal analysis, which reveals that inadequately controlled T1D was associated with a higher hazard ratio (HR) of elevated ALT values compared to children with controlled T1D over an observation period extending up to 5.5 (HR: 1.54; 95% CI, 1.19-2.01; p < 0.01). CONCLUSION: In conclusion, the current study strongly links poorly controlled T1D in children and adolescents to MASLD irrespective of overweight. This association is not only present cross-sectionally but also increases over time. The study underscores the critical role of effective diabetes management in reducing the risk of MASLD in this population.

Glycogen storage disease type I patients with hyperlipidemia have no signs of early vascular dysfunction and premature atherosclerosis.

BACKGROUND AND AIMS: Glycogen storage disease type I (GSD I) is associated with hyperlipidemia, a known risk factor for premature atherosclerosis. Few studies have addressed endothelial dysfunction in patients with GSD I, and these studies yielded controversial results. METHODS AND RESULTS: We investigated vascular dysfunction in a cohort of 32 patients with GSD I (26 GSD Ia, 6 GSD Ib, mean age 20.7 (4.8-47.5) years) compared to 32 age-, gender-, and BMI-matched healthy controls using non-invasive techniques such as quantification of carotid intima media thickness, retinal vessel analysis and 24 h-blood pressure measurements. In addition, early biomarkers of inflammatory and oxidative endothelial stress were assessed in blood. Although GSD I patients had a clearly proatherogenic lipid profile, increased oxidative stress, higher levels of high sensitivity C-reactive protein and increased lipoprotein associated phospholipase A2 activity, functional and structural parameters including carotid intima media thickness and retinal vessel diameters did not indicate premature atherosclerosis in this patient cohort. Blood pressure values and pulse wave velocity were comparable in patients and healthy controls, while central blood pressure and augmentation index were higher in GSD patients. CONCLUSION: Our data suggest that GSD I is not associated with early vascular dysfunction up to the age of at least 20 years. Further studies are needed to elucidate the possibly protective mechanisms that prevent early atherosclerosis is GSD I. Longer follow-up studies are required to assess the long-term risk of vascular disease with increased oxidative stress being present in GSD I patients.

Regularized Ordinal Regression and the ordinalNet R Package.

Regularization techniques such as the lasso (Tibshirani 1996) and elastic net (Zou and Hastie 2005) can be used to improve regression model coefficient estimation and prediction accuracy, as well as to perform variable selection. Ordinal regression models are widely used in applications where the use of regularization could be beneficial; however, these models are not included in many popular software packages for regularized regression. We propose a coordinate descent algorithm to fit a broad class of ordinal regression models with an elastic net penalty. Furthermore, we demonstrate that each model in this class generalizes to a more flexible form, that can be used to model either ordered or unordered categorical response data. We call this the elementwise link multinomial-ordinal (ELMO) class, and it includes widely used models such as multinomial logistic regression (which also has an ordinal form) and ordinal logistic regression (which also has an unordered multinomial form). We introduce an elastic net penalty class that applies to either model form, and additionally, this penalty can be used to shrink a non-ordinal model toward its ordinal counterpart. Finally, we introduce the R package ordinalNet, which implements the algorithm for this model class.

[Satellite data for recording health-relevant environmental conditions: examples and interdisciplinary potential]. / Satellitendaten zur Erfassung gesundheitsrelevanter Umweltbedingungen: Beispiele und interdisziplinäre Potenziale.

Environmental conditions influence human health and interact with other factors such as DNA, lifestyle, or the social environment. Earth observations from space provide data on the most diverse manifestations of these environmental conditions and make it possible to quantify them spatially. Using two examples - the availability of open and recreational space and the spatial distribution of air pollution - this article presents the potential of Earth observations for health studies. In addition, possible applications for health-related issues are discussed. To this end, we try to outline key points for an interdisciplinary approach that meets the conceptual, data technology, and ethical challenges.

Hemoglobin A1c and retinal arteriolar narrowing in children with type 1 diabetes: the diagnostics of early atherosclerosis risk in kids study.

BACKGROUND/OBJECTIVE: Microvascular alterations play a key role in the development of diabetes complications. Retinal vessel analysis is a unique method to examine microvascular changes in brain-derived vessels. METHODS: Sixty-seven pediatric and adolescent type 1 diabetes patients and 58 healthy control persons (mean age 12.4 ± 2.9 years) underwent non-mydriatic retinal photography of both eyes. Central retinal arteriolar and central retinal venular (CRVE) diameter equivalents as well as the arteriolar-to-venular ratio were calculated using a semiautomated software. All anthropometric and laboratory parameters were measured according to standardized procedures for children. RESULTS: Retinal vessel diameter did not differ between type 1 diabetic children and healthy controls. However, there was an independent association of higher hemoglobin A1c (HbA1c) levels with arteriolar narrowing. Arteriolar narrowing of 5.4 µm was observed with each percent increase in HbA1c. Longer duration of diabetes was associated with wider retinal arterioles. CRVE was not associated with diabetes duration or HbA1c. CONCLUSIONS: Microvascular arteriolar alterations are already present in childhood and may indicate subclinical atherosclerosis and increased risk of diabetes complications later in life. Future research will have to investigate the potential use of retinal vessel diameters for treatment monitoring and guidance of therapy in children.

[Barriers to Accessing HIV Testing Services - A Systematic Literature Review]. / Zugangsschwellen zu HIV-Test-Angeboten ­ Eine systematische Literaturanalyse.

OBJECTIVE: In Germany there are 3,100 new HIV infections per year (2016), mainly homosexual men and intravenous drug users. According to experts from Robert Koch Institute, about 30 % of people with HIV are diagnosed late, well past the optimal moment to start the antiretroviral therapy. The high rate of late presenters seems to be a strong argument for an intensification of voluntary counseling and testing services. The main objective of this literature analysis was to describe the barriers to HIV testing. METHODS: A systematic literature search was done to evaluate current knowledge on theory and practice regarding barriers that keep vulnerable groups from getting tested. The analysis includes all publications between 2000 and 2014 from western industrial states. RESULTS: 132 publications have been included in a full text analysis. Most of these publications present the result of surveys of clients attending counseling and testing services. Hence, we have a clear idea of the elements that are relevant for clients when they decide whether or where to get tested for HIV. First, the individual risk perception influences the decision on getting tested or not. The risk perception can be influenced through public relations and outreach services. All processes within the counseling and testing service should be adapted to assure confidentiality and anonymity. In addition, clients want to have counseling that is accepting and free of prejudices. These elements are therefore important since HIV is often associated with getting stigmatized. Similar concerns regarding stigmatization occur if clie nts have sexual preferences that can be considered as deviant. The clients' fear of stigmatization, judgment and social exclusion requires a high sensitivity for the situation of the clients and acceptance of their lifestyle. CONCLUSION: We have a clear insight into how clients decide on getting tested or not. The factor with the greatest influence in the decision-making process is the individual risk perception and anxiety regarding stigmatization. Stigmatization is suspected as a societal reaction to deviant sexual behavior or to being infected with HIV. Public relations should inform about risk factors and risk perception as well as on confidentiality and anonymity of the service. The use of social media and social networks is highly recommended. New approaches such as home testing could eliminate the concerns regarding confidentiality and anonymity.

A standardized clinical and radiological follow-up of patients with chronic non-bacterial osteomyelitis treated with pamidronate.

OBJECTIVES: Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory disorder of the skeletal system. Treatment with NSAIDs is generally effective in the majority of patients, however, a sizeable proportion of patients have persistent disease and subsequent treatment strategies are required. The aim of this study was to characterise the clinical and radiological disease course in CNO patients treated with the bisphosphonate pamidronate (PAM). METHODS: Eight CNO patients refractory to NSAIDs, glucocorticoids and sulfasalazine were treated with 6 cycles of PAM in four-weekly intervals. The disease course was assessed by clinical examination and whole-body (WB) MRI at standardised time points during the treatment phase and in a 6 months follow-up. RESULTS: Seven patients were in complete clinical remission after 6 applications of PAM. WB MRIs showed regression of inflammatory lesions in 7 patients with complete remission in only one patient and partial remission in 6 patients. One patient developed radiological progression despite a marked improvement of clinical symptoms. In the follow-up after PAM therapy, 3 patients developed MRI confirmed relapse. Additional applications of PAM induced a sustained clinical remission and partial radiological response in two of them. Mild temporary adverse effects were noted in 5 patients. CONCLUSIONS: Our study highlights that PAM is effective in controlling clinical symptoms (e.g. pain) in CNO patients. However, subclinical bone inflammation was still detectable by MRI in most of the patients and disease progression was noticed in some patients after cessation of PAM.

Diabetes care and outcomes of pediatric refugees and migrants from Ukraine and Syria/Afghanistan with type 1 diabetes in German-speaking countries.

Introduction: Currently, over two million war refugees live in Germany. Exposure to war and flight is associated with a high burden of diseases, not limited to mental disorders and infections. We aimed to analyze diabetes treatment and outcomes of pediatric refugees and migrants from Ukraine and Syria/Afghanistan with type 1 diabetes (T1D) in German-speaking countries. Materials and methods: We included patients with T1D documented between January 2013 and June 2023 in the German/Austrian/Luxembourgian/Swiss DPV registry, aged < 20 years, born in Ukraine [U], in Syria or Afghanistan [S/A], or without migration background [C]. Using logistic, linear, and negative binomial regression models, we compared diabetes technology use, BMI-SDS, HbA1c values, as well as severe hypoglycemia and DKA rates between groups in the first year of treatment in the host country. Results were adjusted for sex, age, diabetes duration, and time spent in the host country. Results: Among all patients with T1D aged < 20 years, 615 were born in Ukraine [U], 624 in Syria or Afghanistan [S/A], and 28,106 had no migration background [C]. Compared to the two other groups, patients from Syria or Afghanistan had a higher adjusted BMI-SDS (0.34 [95%-CI: 0.21-0.48] [S/A] vs. 0.13 [- 0.02-0.27] [U] and 0.20 [0.19-0.21] [C]; all p<0.001), a lower use of CGM or AID system (57.6% and 4.6%, respectively [S/A] vs. 83.7% and 7.8% [U], and 87.7% and 21.8% [C], all p<0.05) and a higher rate of severe hypoglycemia (15.3/100 PY [S/A] vs. 7.6/100 PY [C], and vs. 4.8/100 PY [U], all p<0.05). Compared to the two other groups, patients from Ukraine had a lower adjusted HbA1c (6.96% [95%-CI: 6.77-7.14] [U] vs. 7.49% [7.32-7.66] [S/A] and 7.37% [7.36-7.39] [C], all p<0.001). Discussion: In their first treatment year in the host country, young Syrian or Afghan refugees had higher BMI-SDS, lower use of diabetes technology, higher HbA1c, and a higher rate of severe hypoglycemia compared to young Ukrainian refugees. Diabetologists should be aware of the different cultural and socioeconomic backgrounds of refugees to adapt diabetes treatment and education to specific needs.

YOLO object detection models can locate and classify broad groups of flower-visiting arthropods in images.

Develoment of image recognition AI algorithms for flower-visiting arthropods has the potential to revolutionize the way we monitor pollinators. Ecologists need light-weight models that can be deployed in a field setting and can classify with high accuracy. We tested the performance of three deep learning light-weight models, YOLOv5nano, YOLOv5small, and YOLOv7tiny, at object recognition and classification in real time on eight groups of flower-visiting arthropods using open-source image data. These eight groups contained four orders of insects that are known to perform the majority of pollination services in Europe (Hymenoptera, Diptera, Coleoptera, Lepidoptera) as well as other arthropod groups that can be seen on flowers but are not typically considered pollinators (e.g., spiders-Araneae). All three models had high accuracy, ranging from 93 to 97%. Intersection over union (IoU) depended on the relative area of the bounding box, and the models performed best when a single arthropod comprised a large portion of the image and worst when multiple small arthropods were together in a single image. The model could accurately distinguish flies in the family Syrphidae from the Hymenoptera that they are known to mimic. These results reveal the capability of existing YOLO models to contribute to pollination monitoring.

Seasonal and Diurnal Variation of Land Surface Temperature Distribution and Its Relation to Land Use/Land Cover Patterns.

The surface urban heat island (SUHI) affects the quality of urban life. Because varying urban structures have varying impacts on SUHI, it is crucial to understand the impact of land use/land cover characteristics for improving the quality of life in cities and urban health. Satellite-based data on land surface temperatures (LST) and derived land use/cover pattern (LUCP) indicators provide an efficient opportunity to derive the required data at a large scale. This study explores the seasonal and diurnal variation of spatial associations from LUCP and LST employing Pearson correlation and ordinary least squares regression analysis. Specifically, Landsat-8 images were utilized to derive LSTs in four seasons, taking Berlin as a case study. The results indicate that: (1) in terms of land cover, hot spots are mainly distributed over transportation, commercial and industrial land in the daytime, while wetlands were identified as hot spots during nighttime; (2) from the land composition indicators, the normalized difference built-up index (NDBI) showed the strongest influence in summer, while the normalized difference vegetation index (NDVI) exhibited the biggest impact in winter; (3) from urban morphological parameters, the building density showed an especially significant positive association with LST and the strongest effect during daytime.

Empiric recommendations for population disaggregation under different data scenarios.

High-resolution population mapping is of high relevance for developing and implementing tailored actions in several fields: From decision making in crisis management to urban planning. Earth Observation has considerably contributed to the development of methods for disaggregating population figures with higher resolution data into fine-grained population maps. However, which method is most suitable on the basis of the available data, and how the spatial units and accuracy metrics affect the validation process is not fully known. We aim to provide recommendations to researches that attempt to produce high-resolution population maps using remote sensing and geospatial information in heterogeneous urban landscapes. For this purpose, we performed a comprehensive experimental research on population disaggregation methods with thirty-six different scenarios. We combined five different top-down methods (from basic to complex, i.e., binary and categorical dasymetric, statistical, and binary and categorical hybrid approaches) on different subsets of data with diverse resolutions and degrees of availability (poor, average and rich). Then, the resulting population maps were systematically validated with a two-fold approach using six accuracy metrics. We found that when only using remotely sensed data the combination of statistical and dasymetric methods provide better results, while highly-resolved data require simpler methods. Besides, the use of at least three relative accuracy metrics is highly encouraged since the validation depends on level and method. We also analysed the behaviour of relative errors and how they are affected by the heterogeneity of the urban landscape. We hope that our recommendations save additional efforts and time in future population mapping.

Screening for hypophosphatasia: does biochemistry lead the way?

OBJECTIVES: Patients with childhood hypophosphatasia (HPP) often have unspecific symptoms. It was our aim to identify patients with mild forms of HPP by laboratory data screening for decreased alkaline phosphatase (AP) within a pediatric population. METHODS: We conducted a retrospective hospital-based data screening for AP activity below the following limits: Girls: ≤12 years: <125 U/L; >12 years: <50 U/L Boys: ≤14 years: <125 U/L; >14 years: <70 U/L. Screening positive patients with otherwise unexplained hypophosphatasemia were invited for further diagnostics: Re-test of AP activity, pyridoxal 5'-phosphate (PLP) in hemolyzed whole blood, phosphoethanolamine (PEA) in serum and urine, and inorganic pyrophosphate in urine. Sequencing of the ALPL gene was performed in patients with clinical and/or laboratory abnormalities suspicious for HPP. RESULTS: We assessed a total of 14,913 samples of 6,731 patients and identified 393 screening-positive patients. The majority of patients were excluded due to known underlying diseases causing AP depression. Of the 30 patients who participated in the study, three had a decrease in AP activity in combination with an increase in PLP and PEA. A heterozygous ALPL mutation was detected in each of them: One patient with a short stature was diagnosed with childhood-HPP and started with enzyme replacement therapy. The remaining two are considered as mutation carriers without osseous manifestation of the disease. CONCLUSIONS: A diagnostic algorithm based on decreased AP is able to identify patients with ALPL mutation after exclusion of the differential diagnoses of hypophosphatasemia and with additional evidence of increased AP substrates.

Frequency of Ketoacidosis at Diagnosis of Pediatric Type 1 Diabetes Associated With Socioeconomic Deprivation and Urbanization: Results From the German Multicenter DPV Registry.

OBJECTIVE: To investigate whether socioeconomic deprivation and urbanization are associated with the frequency of diabetic ketoacidosis (DKA) at diagnosis of pediatric type 1 diabetes. RESEARCH DESIGN AND METHODS: Children and adolescents aged ≤18 years, living in Germany, with newly diagnosed type 1 diabetes documented between 2016 and 2019 in the Diabetes Prospective Follow-up Registry (DPV; Diabetes-Patienten-Verlaufsdokumentation), were assigned to a quintile of regional socioeconomic deprivation (German Index of Socioeconomic Deprivation) and to a degree of urbanization (Eurostat) by using their residence postal code. With multiple logistic regression models, we investigated whether the frequency of DKA at diagnosis was associated with socioeconomic deprivation or urbanization and whether associations differed by age-group, sex, or migration status. RESULTS: In 10,598 children and adolescents with newly diagnosed type 1 diabetes, the frequency of DKA was lowest in the least deprived regions (Q1: 20.6% [95% CI 19.0-22.4], and increased with growing socioeconomic deprivation to 26.9% [25.0-28.8] in the most deprived regions [Q5]; P for trend <0.001). In rural areas, the frequency of DKA at diagnosis was significantly higher than in towns and suburbs (intermediate areas) or in cities (27.6% [95% CI 26.0-29.3] vs. 22.7% [21.4-24.0], P < 0.001, or vs. 24.3% [22.9-25.7], P = 0.007, respectively). The results did not significantly differ by age-group, sex, or migration background or after additional adjustment for socioeconomic deprivation or urbanization. CONCLUSIONS: This study provides evidence that prevention of DKA at diagnosis by means of awareness campaigns and screening for presymptomatic type 1 diabetes should particularly target socioeconomically disadvantaged regions and rural areas.

Diabetic Ketoacidosis at Manifestation of Type 1 Diabetes in Childhood and Adolescence­Incidence and Risk Factors.

BACKGROUND: Diabetic ketoacidosis (DKA) is a potentially life-threatening metabolic disorder that can occur with manifestation of type 1 diabetes mellitus (T1D). The aim of this study was to analyze the incidence of DKA at the time of the diagnosis of T1D in childhood and adolescence, the risk factors, and regional approaches to reduce the incidence of ketoacidosis. METHODS: We investigated the proportion of patients under 18 years of age with DKA (defined as pH <7.3, severe DKA pH <7.1) at the manifestation of T1D in Germany in the period 2000-2019, based on data from the German-Austrian registry of diabetes (Diabetes-Patienten-Verlaufsdokumentation, DPV). The influence of the following factors was evaluated: year of manifestation, age, sex, family history of migration (MiH), and distance from the hospital. Moreover, data from the region with and the region without a pilot screening project from 2015 onwards were compared. RESULTS: Of the 41 189 patients with manifestation of T1D, 19.8% presented with DKA (n = 8154, slight increase [p <0.001] over the study period) and 6.1% (n = 2513) had severe DKA. Children under 6 years of age had DKA more often than adolescents (12-17 years) (21.7% versus 18.6%, OR 1.22 {95% CI: [1.14; 1.30]}). Girls had a higher rate of DKA than boys (20.5% versus 19.2%, OR 1.10 [1.03; 1.14]), and patients with MiH were more likely to have DKA than those without MiH (21.4% versus 18.2%, OR 1.40 [1.32; 1.48]). In the region with a pilot screening project, the DKA rate stayed the same, at 20.6%, while in the control region the rate was 22.7% with a decreasing tendency. CONCLUSION: The frequency of DKA at the time of diagnosis of T1D did not decrease between 2000 and 2019 and increased towards the end of the observation period. Children with MiH, children under 6, and girls were at a higher risk of DKA.

Coeliac disease is associated with depression in children and young adults with type 1 diabetes: results from a multicentre diabetes registry.

AIMS: To analyse the association between coeliac disease (CD) and depression in children, adolescents, and young adults with type 1 diabetes (T1D). METHODS: We included 79,067 T1D patients aged 6-20 years, with at least six months of diabetes duration, and treatment data between 1995 and 2019 were documented in the diabetes patient follow-up registry. We categorized patients into four groups: T1D only (n = 73,699), T1 + CD (n = 3379), T1D + depression (n = 1877), or T1D + CD + depression (n = 112). RESULTS: CD and depression were significantly associated (adjusted OR: 1.25 [1.03-1.53]). Females were more frequent in both the depression and the CD group compared with the T1D only group. Insulin pumps were used more frequently in T1D + CD and T1D + depression compared with T1D only (both p < .001). HbA1c was higher in T1D + depression (9.0% [8.9-9.0]), T1D + CD + depression (8.9% [8.6-9.2]), both compared with T1D only (8.2% [8.2-8.2], all p < .001). We found comorbid autism, attention deficit hyperactivity disorder, anxiety, schizophrenia, and eating disorders more frequently in the T1D + CD + depression group compared with T1D only (all p < .001). CONCLUSIONS: CD and depression are associated in young T1D patients. The double load of T1D and CD may lead to an increased risk for depression. Depression was associated with additional psychological and neurological comorbidities. Aside from imperative CD screening after T1D diagnosis and regular intervals, depression screening might be helpful in routine care, especially in patients with diagnosed CD.

Incidence of COVID-19 and Risk of Diabetic Ketoacidosis in New-Onset Type 1 Diabetes.

OBJECTIVES: With this study, our aim was to quantify the relative risk (RR) of diabetic ketoacidosis at diagnosis of type 1 diabetes during the year 2020 and to assess whether it was associated with the regional incidence of coronavirus disease 2019 (COVID-19) cases and deaths. METHODS: Multicenter cohort study based on data from the German Diabetes Prospective Follow-up Registry. The monthly RR for ketoacidosis in 2020 was estimated from observed and expected rates in 3238 children with new-onset type 1 diabetes. Expected rates were derived from data from 2000 to 2019 by using a multivariable logistic trend regression model. The association between the regional incidence of COVID-19 and the rate of ketoacidosis was investigated by applying a log-binomial mixed-effects model to weekly data with Germany divided into 5 regions. RESULTS: The observed versus expected frequency of diabetic ketoacidosis was significantly higher from April to September and in December (mean adjusted RRs, 1.48-1.96). During the first half of 2020, each increase in the regional weekly incidence of COVID-19 by 50 cases or 1 death per 100 000 population was associated with an increase in the RR of diabetic ketoacidosis of 1.40 (95% confidence interval, 1.10-1.77; P = .006) and 1.23 (1.14-1.32; P < .001), respectively. This association was no longer evident during the second half of 2020. CONCLUSIONS: These findings suggest that the local severity of the pandemic rather than health policy measures appear to be the main reason for the increase in diabetic ketoacidosis and thus the delayed use of health care during the pandemic.

Short-Term Effects of Growth Hormone on Lipolysis, Glucose and Amino Acid Metabolism Assessed in Serum and Microdialysate of Healthy Young Men.

OBJECTIVE: We investigated direct effects of a therapeutic growth hormone dose on lipolysis, glucose and amino acid metabolism. METHODS: This crossover microdialysis trial involved six healthy male volunteers receiving single subcutaneous injections of both growth hormone (0.035 mg/kg) and placebo (0.9% sodium chloride). The investigation comprised three test days with standard diet. The first day served for adaptation, the second and third one for determining study data during 9 night hours with or without growth hormone. Abdominal subcutaneous microdialysate and blood were continuously collected and forwarded to a separate room next door where hourly taken samples were centrifuged and frozen until analysed. RESULTS: Growth hormone achieved the peak serum level after 3 h followed by a plateau-like course for the next 6 h. Glycerol in microdialysate started to rise 2 h following growth hormone injection achieving significance compared to placebo after 9 h (P<0.05). Serum glycerol increased 4 h after growth hormone administration achieving significance after 6 h (P<0.05). Glucose and amino acid concentrations showed neither in microdialysate nor in serum significant differences between growth hormone and placebo. Serum values of insulin and C-peptide revealed no significant difference between growth hormone and placebo. SUMMARY AND CONCLUSION: As the result of a high single subcutaneous dose of GH, persistent lipolysis can be shown in continuously collected microdialysate and blood, but no indication for gluconeogenesis or protein anabolism.

Elevated Plasma Vitamin B12 in Patients with Hepatic Glycogen Storage Diseases.

Background: Hepatic glycogen storage diseases (GSDs) are inborn errors of metabolism affecting the synthesis or breakdown of glycogen in the liver. This study, for the first time, systematically assessed vitamin B12 status in a large cohort of hepatic GSD patients. Methods: Plasma vitamin B12, total plasma homocysteine (tHcy) and methylmalonic acid concentrations were measured in 44 patients with hepatic GSDs and compared to 42 healthy age- and gender-matched controls. Correlations of vitamin B12 status with different disease markers of GSDs (including liver transaminase activities and triglycerides) as well as the vitamin B12 intake were studied. Results: GSD patients had significantly higher plasma vitamin B12 concentrations than healthy controls (p = 0.0002). Plasma vitamin B12 concentration remained elevated in GSD patients irrespective of vitamin B12 intake. Plasma vitamin B12 concentrations correlated negatively with triglyceride levels, whereas no correlations were detected with liver transaminase activities (GOT and GPT) in GSD patients. Merging biomarker data of healthy controls and GSD patients showed a positive correlation between vitamin B12 status and liver function, which suggests complex biomarker associations. A combined analysis of biomarkers permitted a reliable clustering of healthy controls versus GSD patients. Conclusions: Elevated plasma concentration of vitamin B12 (irrespective of B12 intake) is a common finding in patients with hepatic GSD. The negative correlation of plasma vitamin B12 with triglyceride levels suggests an influence of metabolic control on the vitamin B12 status of GSD patients. Elevated vitamin B12 was not correlated with GOT and GPT in our cohort of GSD patients. Merging of data from healthy controls and GSD patients yielded positive correlations between these biomarkers. This apparent dichotomy highlights the intrinsic complexity of biomarker associations and argues against generalizations of liver disease and elevated vitamin B12 in blood. Further studies are needed to determine whether the identified associations are causal or coincidental, and the possible impact of chronically elevated vitamin B12 on GSD.

Diabetes management in Wolcott-Rallison syndrome: analysis from the German/Austrian DPV database.

BACKGROUND: Wolcott-Rallison syndrome (WRS) is characterized by permanent early-onset diabetes, skeletal dysplasia and several additional features, e.g. recurrent liver failure. This is the first multicentre approach that focuses on diabetes management in WRS. We searched the German/Austrian Diabetes-Patienten-Verlaufsdokumentation (DPV) registry and studied anthropometric characteristics, diabetes treatment, glycaemic control and occurrence of severe hypoglycaemia (SH) and diabetic ketoacidosis (DKA) in 11 patients with WRS. Furthermore, all local treatment centres were personally contacted to retrieve additional information on genetic characteristics, migration background and rate of consanguinity. RESULTS: Data were analysed at diabetes onset and after a median follow-up period of 3 (1.5-9.0) years (time from diagnosis to latest follow-up). Median age at diabetes onset was 0.2 (0.1-0.3) years, while onset was delayed in one patient (aged 16 months). Seventy percent of patients manifested with DKA. At follow-up, 90% of patients were on insulin pump therapy requiring 0.7 [0.5-1.0] IU of insulin/kg/d. More than two third of patients had HbA1c level ≥ 8%, 40% experienced at least one episode of SH in the course of the disease. Three patients died at 0.6, 5 and 9 years of age, respectively. To the best of our knowledge three patients carried novel mutations in EIF2AK3. CONCLUSION: Insulin requirements of individuals with WRS registered in DPV appear to be comparable to those of preschool children with well-controlled type 1 diabetes, while glycaemic control tends to be worse and episodes of SH tend to be more common. The majority of individuals with WRS in the DPV registry does not reach glycaemic target for HbA1c as defined for preschool children (< 7.5%). International multicentre studies are required to further improve our knowledge on the care of children with WRS.

Using the Lifeworld Approach to Improve HIV Testing.

Major guidelines for HIV recommend that testing should be provided in a way that is adapted to the lifeworld of groups at risk. However, precise definitions as to what adaption to the lifeworld means are missing. Therefore, this research project evaluated how the lifeworld approach can be operationalized in regard to HIV testing and how voluntary counseling and testing services can use this approach to improve efficacy. A survey for VCT providers in Germany showed a limited number of factors influencing the adaption to the lifeworld of groups at risk. The opening hours, the number of languages used in public relations, and the comfort of the waiting zone are important for all clients. For men who have sex with men, information material for use in social networks and peer volunteers are relevant. Intravenous drug users are concerned with participation, (low) costs, and counseling. For migrants, continuing staff training and anonymity are important.