Objective: Type 1 diabetes is associated with autoantibodies to different organs that include the gut. The objective of the study was to determine the risk of developing gastric parietal cell autoimmunity in relation to other autoimmunity in individuals with a family history of type 1 diabetes. Methods: Autoantibodies to the parietal cell autoantigen, H+/K+ ATPase subunit A (ATP4A) was measured in 2218 first-degree relatives of patients with type 1 diabetes, who were prospectively followed from birth for a median of 14.5 years. All were also tested regularly for the development of islet autoantibodies, transglutaminase autoantibodies, and thyroid peroxidase autoantibodies. Results: The cumulative risk to develop ATP4A autoantibodies was 8.1% (95% CI, 6.6–9.6) by age 20 years with a maximum incidence observed at age 2 years. Risk was increased in females (HR, 1.9; 95% CI, 1.3–2.8; p = 0.0004), relatives with the HLA DR4-DQ8/DR4-DQ8 genotype (HR, 3.4; 95% CI, 1.9–5.9; p < 0.0001) and in participants who also had thyroid peroxidase autoantibodies (HR, 3.7; 95% CI, 2.5– 5.5; p < 0.0001). Risk for at least one of ATP4A-, islet-, transglutaminase-, or thyroid peroxidase-autoantibodies was 24.7% (95% CI, 22.6–26.7) by age 20 years and was 47.3% (95% CI, 41.3–53.3) in relatives who had an HLA DR3/DR4-DQ8, DR4-DQ8/ DR4-DQ8, or DR3/DR3 genotype (p < 0.0001 vs. other genotypes). Conclusions: Relatives of patients with type 1 diabetes who have risk genotypes are at very high risk for the development of autoimmunity against gastric and other organs.

No description available.

Background: Diabetic kidney disease is the leading cause of end-stage renal disease. Administration of ACE inhibitors or/and SGLT2 inhibitors show renoprotective effects in diabetic and other kidney diseases. The underlying renoprotective mechanisms of SGLT2 inhibition, especially in combination with ACE inhibition, are incompletely understood. We used longitudinal intravital microscopy to directly elucidate glomerular hemodynamics on a single nephron level in response to the ACE inhibitor enalapril or/and the SGLT2 inhibitor empagliflozin. Methods: Five weeks after the induction of diabetes by streptozotocin, male C57BL/6 mice were treated with enalapril, empagliflozin, enalapril/empagliflozin or placebo for 3 days. To identify hemodynamic regulation mechanisms, longitudinal intravital multiphoton microscopy was employed to measure single nephron glomerular filtration rate (snGFR) and afferent/efferent arteriole width. Results: Diabetic mice presented a significant hyperfiltration. Compared to placebo treatment, snGFR was reduced in response to enalapril, empagliflozin, or enalapril/empagliflozin administration under diabetic conditions. While enalapril treatment caused significant dilation of the efferent arteriole (12.55 ± 1.46 µm vs. control 11.92 ± 1.04 µm, p < 0.05), empagliflozin led to a decreased afferent arteriole diameter (11.19 ± 2.55 µm vs. control 12.35 ± 1.32 µm, p < 0.05) in diabetic mice. Unexpectedly under diabetic conditions, the combined treatment with enalapril/empagliflozin had no effects on both afferent and efferent arteriole diameter change. Conclusion: SGLT2 inhibition, besides ACE inhibition, is an essential hemodynamic regulator of glomerular filtration during diabetes mellitus. Nevertheless, additional mechanisms—independent from hemodynamic regulation—are involved in the nephroprotective effects especially of the combination therapy and should be further explored in future studies.

Current diabetes care practices provide the same amount of care to everyone, regardless of individual needs. The high coverage of continuous glucose monitors (CGMs) in the Type 1 Diabetes (T1D) population can facilitate the implementation of need-based care, which could potentially largely benefit both clinics and patients. This master’s thesis develops and evaluates a simulation model to explore patient flow in T1D clinics using need-based booking, as well as a user interface for running the simulation and collecting output data. The model also serves as a tool for optimizing input parameters for this system. Utilizing Agent-Based Modeling (ABM) and Discrete Event Simulation (DES), the study includes basic validation to ensure reliability. Findings suggest that the model has been perceived as useful as a tool to discover suitable configurations of a need based booking system when used in a T1D clinic, as well as to communicate and visualise potential benefits and effects of using a need-based system for T1D patients. / Nuvarande diabetesvårdsmetoder erbjuder samma vård till alla, oavsett individuella behov. Den höga täckningen av kontinuerliga glukosmätare (CGMs) i befolkningen med Typ 1-diabetes (T1D) kan underlätta införandet av behovsstyrd vård, vilket potentiellt kan gynna både kliniker och patienter i stor utsträckning. Denna masteruppsats utvecklar och utvärderar en simuleringsmodell för att utforska patientflödet i T1D-kliniker med behovsstyrd bokning, samt ett användargränssnitt för att köra simuleringen och samla in utdata. Modellen fungerar också som ett verktyg för att optimera inmatningsparametrar för detta system. Genom att använda agentbaserad modellering (ABM) och diskret händeslestyrd simulering (DES) inkluderar studien grundläggande validering för att säkerställa tillförlitlighet. Resultaten tyder på att modellen har uppfattats som användbar som ett verktyg för att upptäcka lämpliga konfigurationer av ett behovsstyrt bokningssystem i kliniker för T1D, såval som kommunicera och visualisera potentiella fördelar och effekter av att använda behovsstyrda bokningssystem för patienter med T1D diabetes.