Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Aberer, F.
Effect of tight glycemic control in in- and outpatient settings in different patient populations.
A retrospective analysis to evaluate the impact of hyperglycemia in patients with acute myeloid leukemia and Graft-versus-Host disease and
Results from a prospective randomized pilot trial focusing on the management of hyperglycemia in patients with Graft-versus-Host disease using a decision support system for insulin therapy (GlucoTab)
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Graz Medical University; 2017. pp.
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Mader Julia
- Sourij Harald
- Wölfler Albert
- Altmetrics:
- Abstract:
- Background: Hyperglycemia represents a risk factor for complications and mortality in hospitalized patients independently from an underlying diabetic disease. Data on hyperglycemia contributing to outcome in patients with hematological disease is sparse and needs more attention. Acute myeloid leukemia is a malignant disease of the hematopoietic system leading to uncontrolled formation of immature myeloid cells. This condition leads untreated to potentially life-threatening bleeding and infectious complications. The most established curative therapeutic option for AML includes allogeneic hematopoietic stem cell transplantation (HSCT). About 1 third of patients who underwent HSCT develop a so called graft-versus-host disease (GvHD) which is a potentially life-threatening condition appearing after HSCT. GvHD represents an immunotoxic reaction of donor cells to recipient´s tissue, leading to immune reactions, severe inflammatory processes and tissue necrosis, mainly affecting the gastrointestinal tract, the skin and the liver. As first-line therapy for GvHD contains high-dose systemic steroid therapy, about half of patients develop steroid induced hyperglycemia. The impact of hyperglycemia on outcome of patients with AML and GvHD is not sufficiently investigated. Furthermore it still remains unclear whether a tight glycemic control of hyperglycemia might contribute to a better prognosis in patients with AML and GvHD. Material and Methods: We performed two retrospective trials including patients with AML and separately GvHD, aiming to investigate the influence of hyperglycemia on different outcome endpoints. In the AML-study 159 patients with AML undergoing HSCT were included. Within the first 28 days after HSCT glucose parameters were documented. According to mean glycemia, patients were allocated to three different glucose categories and outcome was investigated according to the extent of hyperglycemia after HSCT. The second retrospective trial focused on 104 patients who received high dose steroid therapy for GvHD. During time of steroid therapy glucose values were collected and according to mean glucose risk for mortality and other outcome parameters were calculated. Furthermore, in this cohort a score was established which took the glycemic status during the first 3 days after steroid initiation and whether patients responded to steroid therapy within 7 days or not, into account. Additionally, we performed a prospective randomized trial which included 10 patients with GvHD to determine whether an automated decision support system for insulin therapy (GlucoTab®) can be established effectively and safely for the treatment of steroid induced hyperglycemia in patients with GvHD. Results: In the AML study we were able to demonstrate that hyperglycemia during the first month after HSCT contributed decisively and independently to a higher mortality. In the GvHD study results were similarly impressive showing a clear and independent correlation of glycemic status on adverse outcome. Additionally, our implemented score (based on 3-day hyperglycemia and lack of response to steroids) showed to be highly predictive for mortality. The prospective pilot study demonstrated that GlucoTab could be established safely and effectively for the treatment of steroid induced hyperglycemia in patients with GvHD. Conclusion: Both retrospective analyses identified hyperglycemia to be a prominent and independent risk factor for overall mortality. Whether hyperglycemia is just a predictor for adverse outcome or might be a modifiable risk factor has to be evaluated in larger multicenter studies. Perhaps, management of hyperglycemia using GlucoTab might contribute to an improvement of glycemia in this indicated population.