Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Tripolt, N.
The impact of multifactorial risk factor intervention, vitamin D and probiotic supplementation on novel and established cardiovascular surrogate measures in subjects with disturbed glucose metabolism
[ Dissertation ] Medical University of Graz; 2012. pp. 141
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- Autor*innen der Med Uni Graz:
- Tripolt Norbert
- Betreuer*innen:
- Sourij Harald
- Stadlbauer-Köllner Vanessa
- Altmetrics:
- Abstract:
- Introduction: Individuals with so-called pre-diabetes are at high risk to experience an adverse cardiovascular event in their life. Therefore, treatments and interventions aiming to reduce these events are of great interest. In the first part of my thesis programme, we focused on novel cardiovascular surrogate parameters and how they are affected by multifactorial risk factor intervention. For the second part we investigated the impact of vitamin D and probiotic supplementation, respectively on surrogate measures. Methods: We carried out a prospective, open 2 years clinical trial (CARDIONOR-study) including 97 patients with type 2 diabetes (T2DM). Whilst we have investigated the impact of the multifactorial intervention on intima media thickness (IMT) in the whole population, we have assessed 3 novel cardiovascular surrogate measurements (arginine bioavailability ratios, the reactive hyperaemia index (RHI) and endothelial progenitor cells) in subsets of our study population. In addition, we performed a randomized-controlled pilot study including 30 subjects with metabolic syndrome to investigate the impact of Lactobacillus casei Shirota (LcS) supplementation on glucose tolerance and indices of insulin sensitivity and beta-cell function. Moreover, we performed a randomized-controlled study in coronary artery disease patients with post-challenge hyperglycemia (pcHG) and vitamin d deficiency to investigate the effect of vitamin d supplementation on endothelial function. Additionally, an analysis of 2565 patients of the LURIC study was performed to elucidate whether the association of 25(OH) vitamin D levels with mortality is the same in various stages of glucometabolic disturbances. Results:CARDIONOR: Intensified risk factor management significantly improved global arginine bioavailability ratio (GABR) and arginine to ornithine ratio (AOR). A significant improvement was only seen in patients with short diabetes duration (<5 years) whereas in patients with longer diabetes duration improvement did not reach statistical significance. In addition the change of GABR was inversely correlated with mean intima media thickness.IMT significantly reduced from baseline to 2 year. Mean cIMT correlates at baseline significantly with age, and duration of diabetes as well as systolic blood pressure. In contrast, no significant changes in the number of CD34+CD133+VEGFR2 and the reactive hyperemia index could be observed from Baseline to 3 months while risk factor management was intensified. Intervention study (LcS): Insulin sensitivity index (ISI) was significantly improved after 3 months of probiotic supplementation but not significantly different to the control group. No improvements were seen in further indices of insulin sensitivity and beta-cell function. Intervention study (vitamin D): At the end of the trial, no significant changes in the vitamin d group in FMD and NMD compared to the placebo group were observed. Cohort analysis: Patients with T2DM had the lowest mean 25(OH)D levels followed by the post-challenge hyperglycemia (pcHG) group and normal glucose tolerance group (NGT). Conclusion: We demonstrate that multifactorial risk factor intervention significantly improved IMT as well as the GABR and AOR in patients with type 2 diabetes. The intake of LcS for 12 weeks in subjects with metabolic syndrome did not clearly affect insulin sensitivity or beta-cell function in our pilot trial. The trial investigating the supplementation of vitamin d for 12 weeks in subjects with CAD, post-challenge hyperglycemia or early T2DM and vitamin d deficiency had to be terminated early due to the inability to recruit. However, at this time no trend in favour of vitamin D with regard to FMD has been observed. In our cohort analysis we display that 25(OH)D levels are associated with increased mortality in normal glucose tolerance, post-challenge hyperglycemia as well as diabetic patients.