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The impact of Diabetes mellitus type 2 and its therapy on Lymphocyte function
Diabetes is the silent killer of modern time. A recent report of the WHO estimates that over 420 million people have diabetes mellitus type 2 (DM2) worldwide, of which almost 300.000 in Croatia. DM2 is a major health risk, because it is associated with several potentially life-threatening co-morbidities, such as cardiovascular disease, kidney disease and non-alcoholic fatty liver disease. An underappreciated complication of DM2 is reduced immune cell function. As a result, patients with DM2 are at increased risk for immune-associated complications ranging from reduced vaccination efficiency to cancer and increased mortality following influenza infection. Surprisingly, very little is known about which immune cells are affected by DM2 and whether current treatments alleviate DM2-induced immune dysfunction.
The overall goal of this project, with acronym DIABOLYC is to determine the specific impact of DM2 on immune cell function and whether its negative effects are reversible with anti-diabetic treatment. To accomplish this goal, we will recruit healthy volunteers and patients with uncontrolled DM2 and isolate leukocytes from their blood. Using phenotypic analysis and functional in vitro assays, we will investigate which immune cells are most affected by DM2 and for what parameters. Lymphocyte dysfunctions will be correlated with key disease parameters of DM2. Blood leukocytes will be analyzed again 6 and 12 months after start of anti-diabetic treatment in patients that reach HbA1c target values. Finally, we will perform whole transcriptome analysis on cells most affected by DM2 before and after treatment, to elucidate key molecular mediators of pathological effects.
In summary, this study will provide valuable new insights in an underappreciated aspect of diabetes mellitus type 2. More importantly, it will allow clinicians to include the immunological risk profile of patients as an additional parameter when considering their best treatment options.
Project name: The impact of Diabetes mellitus type 2 and its therapy on Lymphocyte function
Project identifier: IP-2020-02-7928
Project duration: 01.04.2021 - 30.03.2025
Project budget: HRK 1.388.000
Funding body: Croatian Science Foundation / Hrvatska zaklada za Znanost (HRZZ)
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