Diabetesinstitut Heidelberg

Trientine dihydrochloride (TETA-2HCl) is an established treatment for Wilson disease. We assessed different dissolution profiles of TETA-2HCl capsules on the pharmacokinetics (PK) of trientine (TETA) and on direct copper (Cu) parameters. In this open-label, randomized, two way cross-over study, 24 healthy subjects received two single oral doses of 600mg TETA-2HCl with a washout of at least one week; one dose with a fast and one dose with a slow dissolution profile. Blood and urine samples were collected up to 48h for analysis of plasma TETA and its metabolites, N1-acetyltriethylenetetramine (MAT) and N1-N10-diacetyltriethylenetetramine (DAT), serum Cu, ceruloplasmin (Cp) and urinary Cu excretion (UCE). The effect of dissolution profile on the PK was assessed through the ratio of geometric mean ratios (GMRs) and two-sided 90%-confidence intervals (CI) of the fast vs. slow dissolution profile. The Cmax of TETA was comparable for the two products (GMR 95.81%; CI 83.87-109.46%) while AUC0 - inf was slightly lower for the capsules with fast dissolution profile (GMR 90.65; 90% CI 78.32-104.91%). PK parameters were similar for the metabolites of TETA. Additionally, serum Cu and Cp concentrations remained stable over the 12h period after dosing and were comparable between the two products, as was UCE. The pharmacokinetic profiles of TETA after administration of TETA-2HCl capsules with fast and slow dissolution characteristics were similar. Though the lower 90%-CI for AUC0-inf was outside the formal bioequivalence ranges, differences were small (9%) and not considered clinically relevant. A difference in dissolution profile did not affect copper parameters and tolerability.

BackgroundConspicuous color patterns are traditionally believed to advertise the toxicity of prey to potential predators. However, many aposematic species show drastic variation in coloration, indicating the possibility of other functions of coloration such as intraspecific communication. To study these other functions, we can investigate the influence of intrinsic (e.g., sex) and external factors (e.g., climate) on color variation. We used the aposematic European fire salamander (Salamandra salamandra) to study drivers of variation in the yellow-to-black ratio of the dorsal coloration based on citizen science data available in a new online database.ResultsOur results suggest a widespread sexual dichromatism in fire salamanders in Germany with males displaying a larger yellow-to-black ratio, i.e. are more yellow, than females. This dichromatism persisted even after correcting for a sex-difference in body shape that accounts for some of the variation in the yellow-to-black ratio. Among six investigated putative drivers of this color variation, the proportion of the aposematic yellow coloration increased with latitude but showed no association with other environmental variables such as temperature or the productivity of the habitat.ConclusionsIntegrating citizen science data in this study enabled a comparison of fire salamander populations across large parts of their distribution and highlights widespread sexual dichromatism. Future studies should further investigate potential mechanisms of mate choice in fire salamanders and other selective forces on coloration such as differential predation pressure between both sexes or the role in crypsis. Lastly, multi-national studies supported by citizen science data could fully unravel the extent of color variation in this species.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12862-025-02461-0.

There is limited published information on outcome adjudication in heart failure (HF) trials, particularly in heart failure with preserved ejection fraction (HFpEF). The study sought to compare investigator reports with clinical events committee (CEC) adjudication and assess the impact of the SCTI (Standardized Data Collection for Cardiovascular Trials) criteria. In the EMPEROR-Preserved (EMPagliflozin outcome tRial in Patients with chronic heart Failure With Preserved Ejection Fraction) trial, we compared investigator reports with CEC for concordance, treatment effect on primary composite outcome events and components (first event primary heart failure hospitalization [HHF] or cardiovascular [CV] mortality), prognosis after first HHF, total HHF, and trial duration with and without SCTI criteria. The CEC confirmed 67.4% investigator-reported events for the primary outcome (CV mortality 82.7%, HHF 66.3%). The HR for treatment effect did not differ between adjudication methods for the primary outcome: investigator reports (HR: 0.77; 95%CI: 0.69-0.87), CEC (HR: 0.79; 95%CI: 0.69-0.90), its components, or total HHFs. The prognosis after the first HHF for all-cause mortality and CV mortality also did not differ between investigator reports and the CEC, nor did investigator reports and HHFs with a different CEC cause. SCTI criteria were present in 92% of CEC HHFs with a similar treatment effect to non-SCTI criteria. The investigator-reported primary events reached the protocol target number 6months earlier than the CEC (7months with full SCTI criteria). Investigator adjudication is an alternative to a CEC with similar accuracy and faster event accumulation in HFpEF. The use of granular (SCTI) criteria did not improve trial performance. Our data suggest that a broader definition of an HHF event could be particularly beneficial in HFpEF clinical trials. (EMPagliflozin outcome tRial in Patients with chronic heart Failure With Preserved Ejection Fraction; NCT03057951).

Mesenchymal stem cells (MSCs) are a family of multipotent stem cells that show self-renewal under proliferation, multilineage differentiation, immunomodulation, and trophic function. Thus, these cells, such as adipose tissue-derived mesenchymal stem cells (ADSCs), bone marrow-derived MSCs (BM-MSCs), and umbilical cord-derived mesenchymal stem cells (UC-MSCs), carry great promise for novel clinical treatment options. However, the challenges associated with the isolation of MSCs and the instability of their in vitro expansion remain significant barriers to their clinical application. The plasma membrane-spanning P-glycoprotein ATP-binding cassette subfamily B member 5 positive MSCs (ABCB5+ MSCs) derived from human skin specimens offer a distinctive advantage over other MSCs. They can be easily extracted from the dermis and expanded. In culture, ABCB5+ MSCs demonstrate robust innate homeostasis and a classic trilineage differentiation. Additionally, their ability to modulate the recipients' immune system highlights their potential for allogeneic applications in regenerative medicine. In this review, we primarily discuss the differentiation potential of ABCB5+ MSCs and their perspectives in regenerative medicine.

The use of diabetes technologies is increasing worldwide, with health systems facilitating improved access to devices. Continuous glucose monitoring is a complex intervention that provides information on glucose concentration, rate and direction of change, historical data and alerts and alarms for extremes of glucose. These data do not themselves change glycaemia and require translation to a meaningful action for impact. It is, therefore, crucial that such systems advance to better meet the needs of individuals using them. Narrative review of the use of, engagement with, limitations and unmet needs of continuous glucose monitoring systems. CGM devices have made a significant contribution to the self-management of diabetes; however, challenges with access and user experience persist, with multiple limitations to uptake and benefit. These limitations include physical size and implementation, with associated stigma, alarm fatigue, sleep disturbance and the challenge of addressing large volumes of real-time data. Greater personalisation throughout the continuous glucose monitoring journey, with a focus on usability, may improve the benefits derived from the device and reduce the burden of self-management. Healthcare professionals may have unconscious biases that affect the provision of continuous glucose monitors due to deprivation, education, age, ethnicity and other characteristics. Continuous glucose monitoring exerts a dose-dependent response; the more it is used, the more effective it is. For optimal use, continuous glucose monitors must not just reduce the burden of management in one dimension but facilitate net improvement in all domains of self-management for all users.

The DDG clinical practice guidelines are updated regularly during the second half of the calendar year. Please ensure that you read and cite the respective current version. Part 1 of the clinical practice guideline Change 1: An additional section on the prevalence and incidence of type 2 diabetes in Germany has been added. Reason: These current figures highlight the medical, psychosocial and health policy significance of this complex disease. Change 2: On the basis of current data, the various risk factors and their structured assessment (including the increasing importance of fatty liver) for the development of cardiovascular and renal complications are again highlighted. Reason: For an individual therapy decision, the in-depth risk assessment is very helpful Supporting reference: [6-7] Change 3: The short diagnostics section has been brought forward Reason: More logical order of sections Change 4: The section on plasma glucose self-measurement was supplemented to include the possibilities and possible necessity of using CGM in people with type 2 diabetes Reason: The treatment of people with type 2 diabetes is becoming more individual and therefore more complex. Temporary information about TiR and TuR can at minimum be helpful in the treatment decision. This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.