82623 research outputs found
Sort by
Lifestyle Patterns and Mental Health Problems in Swiss University Students: A Latent Profile Analysis
No full textObjectives: This study examined whether first-year university students with distinct lifestyle profiles experienced varying mental health problems. Design: The study used a cross-sectional design with self-selection sampling. Methods: Sociodemographic, lifestyle behavior, and mental health data from 352 students (age = 20.8 ± 2.56, women = 66.5%) at the University of Basel were analyzed. Logistic regression was conducted to examine associations between lifestyle behaviors and mental disorders. Latent profile analysis was performed to identify classes. Between-class differences were assessed using chi-square and multinomial logistic regression analysis, adjusting for covariates. Results: A higher lifestyle score was associated with reduced prevalences, including depression, anxiety, sleep disorder, obsessive-compulsive disorder (OCD), substance use, and attention-deficit/hyperactivity disorder. An inverse relationship was observed for bipolar disorder. Improved sleep, physical activity, social connections, and lower use of substance use, stress-coping, and screen time were linked to fewer mental health problems. Latent profile analysis identified three lifestyle classes: one healthier and two less healthy (high substance use and isolated). University students in the healthiest class exhibited fewer mental disorders. Employment status and BMI category influenced class membership, whereas age and sex did not. Within two classes, female university students were more likely to screen positive for depression, anxiety, sleep disorder, OCD, and suicidal ideation, whereas male university students exhibited higher substance use. Conclusion: The findings suggest that healthier lifestyle behavior is associated with a reduced prevalence of multiple mental disorders. Including lifestyle medicine in research and implementing it in prevention and treatment is essential, particularly among university students
Investigating the link between nutrient sensing and gametocyte formation in the malaria parasite Plasmodium falciparum
No full textMalaria is an infectious disease and causes over 600’000 deaths annually. To ensure host-to-host transmission, malaria parasites rely on specialized stages, called gametocytes. The formation of these sexual precursor cells is initiated by commitment of asexual blood stage parasites to the sexual differentiation pathway. Plasmodium falciparum, the most virulent of six parasite species infecting humans, employs nutrient sensing to adapt the rate of sexual commitment. The parasite monitors the levels of the host-derived lipid lysophosphatidylcholine (lysoPC) to control the epigenetically regu-lated expression of the transcription factor AP2-G, the master regulator of sexual commitment. The molecular mechanisms linking lysoPC sensing to AP2-G expression, however, are poorly under-stood. In this PhD project, I aimed at identifying factors linking nutrient sensing and sexual commit-ment in P. falciparum. To this end, I investigated the effect of a set of chemical compounds and 12 selected genes on sexual commitment rates. In a first study, I assessed the effect of drug treatment on sexual commitment rates using a high content imaging-based assay to clarify the longstanding question of whether antimalarial drug treatment increases gametocyte formation. By screening a comprehensive set of pharmaceuticals using both drug sensitive and drug resistant parasite strains, we show that drug treatment indeed can increase sexual commitment rates, but only rarely results in a net increase in gametocyte production. Our results suggest that general stress, rather than drug-specific activities, promotes sexual commitment. This finding was crucial to interpret the results of a second study, in which we screened compounds of inhibitor libraries to identify molecules influenc-ing sexual commitment. We then employed mass spectrometry-based cellular thermal shift assays (MS-CETSA) to identify the cellular target of selected hit compounds. Thereby, we identified high-confidence candidate targets and assessed their role during sexual commitment using reverse genet-ics approaches. We found indication for an involvement of cyclic adenosine monophosphate (cAMP)-dependent signaling and protein kinase A (PKA) in regulating commitment to gametocyte formation. Based on reverse genetics experiments and chemical perturbation assays, we hypothesize that PKA acts as a repressor of AP2-G expression under lysoPC-free conditions and thus links nutri-ent sensing to the epigenetic regulation of AP2-G. However, more experiments are required to con-firm this hypothesis. In a third project, we assessed the function the FK506-binding protein 35 (FKBP35) – another putative target of a commitment-inducing compound – by combining reverse genetics with transcriptional and proteomic profiling. While we did not find evidence for a role in sexual commitment, we show that limiting FKBP35 levels are lethal to P. falciparum and result in a delayed death-like phenotype that is characterized by defective ribosome homeostasis and stalled protein synthesis. Our data furthermore suggest that the antiplasmodial activity of the well-characterized FKBP inhibitor FK506 is independent of FKBP35, which has implications for the de-velopment of FK506-derived molecules as antimicrobial drugs. In summary, this thesis offers a test-able model to further investigate the link between nutrient sensing and sexual commitment and pro-vides new insights into the function of FKBP35
Evaluation of phenotypic heterogeneity and the role of MRC2 in leukemic stem cells
No full textAcute myeloid leukemia (AML) is a blood malignancy affecting people from all age categories
yet most frequently elderly people (older than 65-year-old). Therapy options have improved
over the last decades but AML still remain lethal in many cases despite many patients
achieving apparent remission. Indeed, patients often relapse and such reoccurrence
becomes harder to treat due to the development of therapy resistance and the selection of
specific more aggressive subclones. AML was the first malignancy to support the theory of
cancer stem cells and is widely described for its hierarchical structure. In fact, AML is known
to originate and relapse from a rare cell subpopulation of leukemic cells called leukemic stem
cells (LSC). AML and their LSC are very heterogeneous on the transcriptomic and
phenotypic level which makes it challenging to eradicate these cells. Currently, efforts are
made by many research groups to determine how to selectively and specifically target LSC.
Not only would this improve our knowledge on their biology but this could potentially greatly
improve clinical care.
In this thesis, we improved knowledge on LSC biology and highlighted a potential new
vulnerability. We discovered that MRC2 is overexpressed in AML and specifically enriched
cells with LSC properties. RNA-sequencing of MRC2+ vs. MRC2- cells revealed the former
population to have, on the transcriptomic level, a stemness signature that is highly
concordant with our in vitro and in vivo assays indicating positive cells to be more clonogenic
in colony forming unit (CFU) assay and patient-derived xenograft (PDX) models, respectively.
MRC2+ cells are functionally involved in collagen uptake, which engages cells metabolically.
In depth in silico analyses revealed proline dehydrogenase (PRODH) as overexpressed in
MRC2+ LSC. Importantly, PRODH inhibition impaired cell viability and stemness (with no
effect on healthy cells) and synergized with the BCL-2 inhibitor venetoclax. Furthermore,
TGF-β1 was discovered as a strong inducer of MRC2 expression/function in AML.
In a related second project, variables influencing leukemic engraftment in PDX models were
studied in an attempt to further improve these models that are essential for functional studies
of human AML. Noticeably, we discovered an improved leukemic engraftment in female vs.
male NSG animals when injected with the exact same cell dose of primary sample in both
primary and secondary transplant assays. This importantly made us reconsider how to
continue with PDX models and, by only relying on female NSG mice, we further discovered
that AML samples from the adverse risk group, with high FLT3-ITD ratio or with high LSC
content had shorter time to engraft in female NSG mice. Our extended incubation period
allowed us to appreciate engraftment in samples previously considered non-engraftable such
as from favorable molecular risk groups. These observations are helpful as they mimic well
clinical settings and furthermore allow comprehensive studies of AML biology in in vivo
settings
Monitoring and control of "Anopheles" vectors in the context of residual malaria transmission in Ulanga, Tanzania
Get PDFThe global burden of malaria is disproportionately high in sub Saharan Africa (SSA) where prolific cases and deaths affect some of the world’s poorest populations. However, historically, malaria was widespread in virtually all habitable regions of the world. The current global map of malaria risk can be attributed to three factors: (i.) SSA was largely sidestepped during the Global Malaria Eradication Programme (GMEP), the first global attempt to interrupt completely widespread endemic malaria transmission. (ii.) Majority of SSA countries lack adequate resources and robust health systems that can support effective and consistent malaria control programmes necessary for malaria elimination. (iii.) A hot-humid tropical and sub-tropical climate supports breeding of some of the most effective malaria vector populations. In addition, designs of most traditional African huts particularly in the rural settings where malaria transmission tends to be high often allow easy entry of mosquitoes through openings on doors, windows and eaves. Such houses have often been associated with increased human-mosquito interactions and risk of malaria. Many African cultural traditions, perceptions, beliefs and practices have been found to be counter-effective to malaria control initiatives. For example, gatherings outdoors in the evenings during events such as funerals tend to expose people to mosquito bites and greatly undermine the effectiveness of ITNs. Across many high burden areas, measures to protect people from malaria infection include use of insecticides treated nets (ITNs) and the indoor residual spraying (IRS) with insecticides. In areas where campaigns by the two core interventions have been implemented effectively, there has been dramatic reductions of malaria transmission and a general decline of the burden of disease. However, despite being highly effective, vector control faces some major challenges that primarily include resistance to insecticides by local vector populations and mosquito behavioural avoidance of the indoor-based insecticidal interventions typically manifested by increased outdoor biting. The World Health Organisation (WHO) warns of stagnated global progress of malaria. Evidence suggests reduced effectiveness of ITNs and IRS across malarious parts. There is increased skepticism by malariologists regarding malaria elimination by the status quo majorly through relying heavily on ITNs and IRS. Going forward, the WHO encourages review and reassessments of the effectiveness of ITNs and IRS across malarious areas and recommends efforts to determine gaps in effective protection against malaria vectors in the context of universal coverage by the core vector control tools. This PhD took advantage of population-wide ITN and IRS studies in Ulanga, a rural area in south-eastern Tanzania, one among the highest burden countries, and investigates, discusses and reflects on the effectiveness of the core vector control and potential of residual malaria transmission. Findings of this PhD suggest that in a typical SSA setting where malaria transmission is endemic and where transmission is primarily by An. funestus and An. arabiensis that bite both indoors and outdoors, ITNs afford high protection against malaria transmission. Malaria control programmes should therefore ensure high household ownership and use of efficacious ITNs across all malarious areas. Strategies that promote high use of ITNs in the households by each member over all the times when they are in their sleeping spaces at night need to be encouraged to guarantee optimal protection by ITNs for everyone in the population. IRS with the use of effective insecticides such as clothianidin and that function by a different mode of action from that of pyrethroids can be employed to mitigate the spread of Anopheles resistance to pyrethroids and help complement ITNs to drive higher effectiveness for vector control and greater impact on malaria transmission. Appropriate IRS deployment strategies need to be employed to ensure that pyrethroid insecticides are not used alongside ITNs, and that insecticides with similar modes of action are not used in the same locations but instead insecticides with dissimilar modes of action are used alternatingly or in combinations. Sampling tools for estimating human biting by local malaria vector populations need to be considered on a case-by-case basis appreciating fundamental limitations of exposure-free mosquito traps for specific entomological survey tasks in different settings. HLC should be preferred over exposure-free traps where the purpose of surveying mosquitoes is to quantify absolute estimates of malaria risk more specifically the EIR. HLC-standardised entomological metrics estimated from catches by exposure-free mosquito traps may be used for evaluating malaria vector control interventions and for monitoring changes in behaviours in Anopheles populations including possible shifts in species composition, biting behaviours and occurrence or spread of insecticide resistance
Mechanistic interrogation of amoeboid T cell migration reveals a novel role for the VPS34-PIKfyve pathway in the regulation of cell speed
Get PDFThis thesis explores the intricate regulatory mechanisms governing amoeboid cell migration. It follows a cumulative format, beginning with an introduction, followed by a section delineating the aims of this thesis. The results chapter is divided into four sections (Sections I-IV), comprising a preprint, a set of unpublished data, and two published research articles. The final chapter, "Conclusion & Future Perspectives" relates the presented findings to a broader context and outlines possible directions for future studies.
In the results Section I, titled “Engagement of the VPS34–PIKfyve Axis at the Uropod Promotes Fast Amoeboid Migration”, we reveal a novel role of the VPS34–PIKfyve lipid kinase pathway on endo-lysosomes at the uropod of migrating T cells. The findings, detailed in a preprint accompanied by extended data, underscore the necessity of VPS34 and PIKfyve activity for rapid migration of T cells. VPS34 and PIKfyve promote myosin IIA and retrograde actin flow, which are critical for T cell propulsion. Notably, this effector function of the VPS34–PIKfyve axis on amoeboid migration speed is conserved across myeloid cells, and the social amoeba Dictyostelium discoideum. This section encapsulates the main outcomes of my doctoral research.
Section II of the results, titled “Interrogation of Chemokine-Induced Metabolism in Naïve CD8+ T cells”, unveils findings from an investigation into the chemokine-induced metabolic alterations in T cells in a set of unpublished data. These results elucidate alterations in glycolytic metabolism and mitochondrial respiration initiated by chemokines and provide first insights into the scope of chemokine-induced metabolic rewiring.
The results in Section III, titled “Acetate Modulates Memory CD8+ T Cell Effector Function, Survival, and Migration During Bacterial Infections”, contain a published manuscript that explores the modulatory effects of acetate on memory CD8+ T cell function during bacterial infections. In this context, an investigation unraveled an
inhibitory effect of acetate on the migration of memory CD8+ T cells in vitro, aligning with alterations in cell numbers at sites of acetate treatment in vivo.
Lastly, Section IV, titled “Development of a Volatile Metabolomics Platform for Dendritic Cells to Investigate Cellular Metabolism in Real-Time”, comprises a published manuscript describing the development of a platform capable of real-time monitoring of dendritic cell metabolism in the volatile phase. We demonstrate the ability of this novel experimental platform to discern varying metabolic states of dendritic cells and trace the incorporation of isotopically labeled glucose
Vor dem Vergessen: Verbesserung der Früherkennung der Alzheimer-Krankheit durch innovative kognitive und strukturelle Marker
Get PDFDie Demenz und insbesondere die Alzheimer-Krankheit (AK) als ihre Hauptursache stellen eine der grössten gesundheitlichen Herausforderungen des 21. Jahrhunderts dar. Die frühzeitige Identifikation der kognitiven und strukturellen Veränderungen, die mit der AK einhergehen, ist daher von ausserordentlichem Interesse. Charakteristisch für die AK ist das fortschreitende Verteilungsmuster neurofibrillärer Bündel (NFT), beginnend im medialen perirhinalen Kortex (mPRC), sich ausbreitend über den entorhinalen Kortex (ERC) mit späterer Beteiligung des lateralen perirhinalen Kortex (lPRC), Hippocampus und Rest des Gehirns. Angesichts des engen Zusammenhangs zwischen der Ansammlung von NFT und Nervenzellverlust in betroffenen Regionen, erweist sich der mPRC bzw. der perirhinale Kortex (PRC) als vielversprechender struktureller und kognitiver Marker für die Frühdiagnostik der AK.
Studie I präsentierte eine neue visuelle Diskriminationsaufgabe zur Bewertung der PRC-Funktion. In einer Pilotstudie wurden optimale Testitems für die Differenzierung zwischen einer frühen Alzheimer-Gruppe (N=50) und gesunden Kontrollen (N=50) identifiziert. Eine nachfolgende Validierungsstudie setzte den adaptierten Test an einer Stichprobe mit einer frühen Alzheimer-Gruppe (N=27), gesunden Kontrollen (N=25) und einer Depressionsgruppe (N=26) ein. Die Ergebnisse zeigten, dass die Testleistung erfolgreich zwischen der Alzheimer-Gruppe und gesunden Kontrollen unterscheiden konnte. Die Analyse der ergänzende MRT-Bildgebung wies signifikante Unterschiede in der kortikalen Dicke des mPRC und ERC in der Alzheimer-Gruppe im Vergleich zu den anderen zwei Gruppen auf. Zusätzlich konnte die Testleistung mittels voxel-basierter Morphometrie mit parahippocampalen Regionen, inkl. PRC und ERC, in Verbindung gebracht werden.
Studie II untersuchte die Übereinstimmung zwischen zwei Ratern bei der manuellen Segmentierung parahippocampaler Regionen (mPRC, lPRC und ERC) in strukturellen MRT-Bildern (N=44). Das verwendete manuelle Segmentierungsprotokoll ermöglichte es den Ratern, bemerkenswert ähnliche Werte für die kortikale Dicke zu erzielen. Angesichts des hohen Zeitaufwands für die manuelle Segmentierung in Studie II, wurde in Studie III ein automatisiertes Segmentierungstool für die Berechnung der kortikale Dicke parahippocampaler Regionen (z.B. mPRC und ERC) erstellt. Das Modell wurde auf einem Trainingsdatensatz (N=126) mit manuell segmentierten Labels trainiert und wurde anschliessend auf einen unabhängigen Testdatensatz angewendet (N=103; Stichprobe aus der Studie von Krumm et al., 2016). Wir fanden eine hohe Übereinstimmung zwischen den manuell und automatisiert generierten Werten für die kortikale Dicke. Analog zu den Befunden von Krumm et al. (2016) zeigte sich eine
signifikante Atrophie in der Alzheimer-Gruppe im Vergleich zu gesunden Kontrollen im mPRC, ERC und lPRC. Beim Vergleich einer amnestischen mild cognitive impairment Gruppe mit den gesunden Kontrollen fand sich ein signifikanter Unterschied im ERC, jedoch nicht, wie bei Krumm et al. (2016), auch im mPRC.
Die Ergebnisse präsentieren den neu entwickelten spezifischen PRC-Funktionstest sowie das automatisierte Segmentierungstool zur Beurteilung der kortikalen Dicke des mPRC, als wertvolle Instrumente, um die Alzheimer-Forschung voranzutreiben. Der künftige Einsatz in Langzeitstudien, um dadurch entscheidend zur Verbesserung der Früherkennung und Diagnostik der AK beizutragen wird reflektiert und diskutiert
Mündliches Argumentieren in der Politischen Bildung
Get PDFDie Fähigkeit zu argumentieren wird für die Beteiligung an politischen und gesellschaftlichen Aushandlungsprozessen vorausgesetzt. Damit für jede Person eine Teilnahme möglich ist, soll die Fähigkeit allgemein in der Schule und fachspezifisch im Unterricht der Politischen Bildung gefördert werden.
Die Autorin klärte im Rahmen dieses Dissertationsprojekts für die Politische Bildung die Fähigkeit zu argumentieren und trug die Möglichkeiten zu dessen Förderung im Unterricht theoriebasiert zusammen. Für den empirischen Teil erstellte sie ein Forschungsdesign, um einerseits die Struktur und die Komplexität in Argumentationen von Diskussionen mit zugewiesenen Positionen zu erfassen und um andererseits zu erkennen, inwiefern Begriffe des
Politischen in einem Debattenausschnitt verwendet werden.
Dazu videografierte die Autorin in zwei Berufsschulklassen je fünf Debatten aus dem Spiel «ja – nein – vielleicht?» (Zentrum für Demokratie Aarau et al., 2014–2015) während des Schuljahrs 2014/2015 und transkribierte sie. Die Themen der Debatten wurden mit der Berufsschullehrperson gemeinsam festgelegt. Die Transkripte analysierte sie mit der Gesprächsanalyse nach Przyborski (2004) und mit der qualitativen Inhaltsanalyse nach Kuckartz & Rädiker (2022) hinsichtlich Struktur und Komplexität. Für die qualitative Inhaltsanalyse erstellte sie jeweils deduktiv Kategoriensysteme zur Kodierung und entwickelte sie induktiv weiter. Für die Analyse der Verwendung von Begriffen des Politischen wendete sie die Methode der Objektiven Hermeneutik an.
Die Datenanalysen zeigen, dass über das betrachtete Schuljahr hinweg keine Veränderungen in der Verteilung der unterschiedlichen argumentativen Züge (Struktur) sowie in der Komplexität feststellbar waren. Begriffe des Politischen wurden innerhalb der Debatte teilweise verwendet und weiterentwickelt.
Basierend auf der Theorie und den Resultaten aus der Empirie wird davon ausgegangen, dass zur Förderung der Fähigkeit zu argumentieren zusätzlich zu einem Probehandeln, das in diesem Dissertationsprojekt in Form von Debatten mit der Methode Fischteich (fishbowl) durchgeführt wurde, auch eine Vermittlung von Argumentations- und Fachwissen sowie die
Reflexion dieses Wissens notwendig sind. Dies bleibt empirisch zu prüfen
Dynamic association of human Ebp1 with the 80S ribosome
No full textRibosomes are the macromolecular machines at the heart of protein synthesis. From the peptidyl transferase center, a nascent polypeptide chain is channeled through the ribosome exit tunnel and emerges into the cellular environment. To efficiently modulate mRNA translation, various ribosome-associated factors directly engage with ribosomes. Remarkably, the exit tunnel is a hotspot where chaperons, targeting complexes, and N-terminal processing factors direct to fine-tune the cellular destiny of a newly translated polypeptide. Despite many ribosome-associated factors interacting with the ribosome exit tunnel being known, our understanding of how the spatiotemporal coordination and molecular interactions of N-terminal processing, folding, and targeting of the emerging nascent chain are achieved remains unclear.
The ErbB3 receptor-binding protein (Ebp1) is a highly conserved, abundantly expressed, multifunctional protein. Predominantly studied for its role in cancer progression and transcriptional control, several authors reported a still unclear role in translation control (Nguyen et al. 2018; Monie et al. 2007; Squatrito et al. 2006; Kowalinski et al. 2007). Ebp1 shares high structural homology with the yeast Arx1 protein, a fundamental component of the pre-60S ribosomal subunit export complex, and MetAP-like proteins, N-terminal processing enzymes with a co-translational mechanism (Akbar, Bhakta, and Sengupta 2021; Bhakta, Akbar, and Sengupta 2019; Basil Johannes Greber et al. 2016; Bradatsch et al. 2012). Despite sharing high structural and moderate sequence conservation with MetAPs and Arx1, Ebp1 lacks the catalytic aminopeptidase activity necessary for the excision of a nascent chain N-terminal methionine and appears not to be involved in ribosome biogenesis (Monie et al. 2007; Kowalinski et al. 2007). Instead, Ebp1’s role in translation is only marginally understood.
Expansion segments (ES) are eukaryotic-specific insertions in the rRNA still marginally characterized and poorly understood. The most extended expansion segment, the ES27L of the large ribosomal subunit, has long been known to recruit ribosome-associated factors to the exit tunnel (Beckmann et al. 2001). Arx1 recruits the ES27L to support the nuclear export of pre-60S ribosomes in yeast, and MetAPs require association with ES27L to carry out their aminopeptidase excision of N-terminal methionines (Fujii et al. 2018; Shankar et al. 2020; Basil Johannes Greber et al. 2016; Bradatsch et al. 2012). Yet, the mechanistic role of ES27L in associating dynamically with factors and supporting their engagement with the exit tunnel is mainly unknown. As it might be conserved in the Arx1 and MetAP association with ribosomes, Ebp1 could help clarify the ES27L dynamics.
Therefore, the goals of my Ph.D. project were to characterize human Ebp1 in complex with the 80S ribosome by cryo-EM and analyze the molecular details of the interaction. The Ebp1-80S ribosome structural perspective could provide elements for the functional characterization of Ebp1 and its orthologs Arx1 and MetAPs. Characterizing the ES27L dynamics with Ebp1 and human ribosomes was a key goal of my Ph.D. project. Finally, the potential coordination of ES27L dynamics with Ebp1 and ribosomal subunit conformations carried the possibility of better understanding the functioning of ES27L
Development of novel diagnostic tools for behavioural variant frontotemporal dementia
Get PDFBehavioural variant frontotemporal dementia (bvFTD) is one of the most common early-onset dementia with the first symptoms occurring before the age of 65. Due to the lack of reliable biomarkers, neuropsychological assessment plays a crucial role in bvFTD diagnosis. In 2011 revised diagnostic criteria for bvFTD showed high sensitivity to the early bvFTD symptoms. However, bvFTD is still often misdiagnosed with other neurodegenerative and psychiatric disorders, especially at the early stages of the disease. The aim of this dissertation was to provide clinicians with new diagnostic tools that can increase diagnostic accuracy of early bvFTD. The focus lay on two diagnostic domains, (1) behavioural disorders as outlined in the current diagnostic criteria and (2) Theory of Mind, a subdomain of social cognition often impaired in bvFTD patients even before other behavioural or cognitive symptoms occur. As a result, two diagnostic instruments were developed. The first one is the Behavioural Dysfunctional Questionnaire, the first behavioural scale operationalising the current diagnostic criteria in form of a standardised informant-report questionnaire. The second one is the Basel Version of The Awareness of Social Inference Test – Theory of Mind, a video-based test assessing Theory of Mind ability close to real-life setting and fulfilling the requirements on clinical tools. The implementation of the developed tools in clinical evaluations of the patients with suspect on bvFTD can increase the diagnostic accuracy but also contribute to better understanding of symptoms’ development and progression. This dissertation describes the development of these tools and discusses the possible effects of their implementation for diagnosis and therapy strategies of bvFTD
Die Effekte einer Lebensstilintervention auf den HbA1c, Antidiabetika und anthropometrische Daten bei Patienten mit Diabetes mellitus Typ 2
No full textHintergrund: Typ-2-Diabetes mellitus (T2D) ist ein globales Gesundheitsproblem mit steigender Prävalenz. Er führt oft zu Komplikationen wie Herz-Kreislauf-Erkrankungen und Nierenversagen. T2D ist durch Insulinresistenz und unzureichende Insulinproduktion gekennzeichnet, wobei Übergewicht und Bewegungsmangel wichtige Risikofaktoren darstellen. Eine effektive Behandlung umfasst Lebensstiländerungen und medikamentöse Therapien, die Blutzuckerkontrolle verbessern und positive Effekte auf Blutdruck und Lipidprofil haben. Lebensstilinterventionen zeigen vielversprechende Ergebnisse bei der Senkung des Blutzuckerspiegels und der Verbesserung der glykämischen Kontrolle.
Methoden: Die Intervention wird in einer monozentrischen, offenen, pragmatischen, zweiarmigen, randomisierten, kontrollierten Studie mit einem Stichprobenverhältnis von 1:1 evaluiert. Alle Patienten (n = 100) erhalten die Standardtherapie für T2D. Die Interventionsgruppe erhält ein Jahr lang persönliches Gesundheitscoaching per Telefon und Zugang zu einer Smartphone- und Web-App. Die Kontrollgruppe erhält Zugang zur App und eine einmalige schriftliche Empfehlung zu Ernährung und Bewegung. Untersucht werden HbA1c, BMI, WHR und Antidiabetika. Messungen erfolgen zu Beginn, nach 27 und 54 Wochen. Lineare gemischte Modelle analysieren die Ergebnisse.
Ergebnisse: Die dbcoach-Studie zeigt signifikante Verbesserungen der HbA1c-Werte im Zeitverlauf (p < .001), aber keine Unterschiede zwischen den Gruppen (p = .985). Beide Gruppen zeigen eine Senkung der HbA1c-Werte. Der BMI sinkt signifikant über die Zeit (p < .001), jedoch ohne signifikanten Unterschied zwischen den Gruppen (p = .963). Die Medikamentenanalyse zeigt ähnliche Einnahmen in beiden Gruppen, mit signifikanten Unterschieden bei SGLT-2-Inhibitoren zugunsten der Interventionsgruppe (p = .012).
Schlussfolgerung: Die Ergebnisse betonen die Notwendigkeit kontinuierlicher Betreuung und weiterer Massnahmen zur langfristigen Optimierung der Blutzuckerkontrolle und zur Reduktion des Medikamentenbedarfs