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Associations of Liver Dysfunction with Glucose Intolerance and All-Cause Mortality in a General Population

  • Liver dysfunctions are commonly associated with diabetes and mortality in the general population. However, previous studies lack to define these disorders with hepatic markers from MRI, which have been shown to be more accurate and sensitive than hepatic ultrasound and laboratory markers. Further, previous studies defining different categories of prediabetes by oral glucose tolerance states revealed controversial findings. Hence, this dissertation contributed to understand the associations of liver dysfunctions with glucose intolerance states and all-cause mortality in the general population. In the first part of the dissertation, the associations of MRI-related hepatic steatosis and hepatic iron overload with prediabetes were investigated. Prediabetes was categorized into IFG, IGT, (alone or in combination) or previously unknown type 2 diabetes mellitus using OGGT data, as suggested by the ADA. For analyses, we included 1632 subjects with MRI who participated in an OGTT and reported no type 2 diabetes mellitus. We found that hepatic steatosis was positively associated with continuous markers of glucose metabolism. Similarly, subjects with hepatic steatosis as defined by MRI had a higher relative risk ratio to be in the prediabetes groups (i-IFG, i-IGT and IFG + IGT) or having undiagnosed diabetes than individuals without this condition. The observed associations were more obvious for MRI-derived hepatic steatosis compared to ultrasound. In comparison to hepatic steatosis, we found that MRI-assessed hepatic iron overload was positively associated only with both 2-hour plasma glucose and the combined IFG + IGT category. There were no significant associations between hepatic iron overload and other glucose tolerance states or biomarkers of glucose metabolism, regardless of possible confounding factors. In the second part, the associations of liver volume and other markers of hepatic steatosis with all-cause mortality in the general population were investigated. We included 2769 middle-aged German subjects with a median follow-up of 8.9 years (23,898 person-years). Serum liver enzymes and FIB-4 score were used as quantitative markers, while MRI measurements of liver fat content and total liver volume included as qualitative markers of hepatic steatosis. Compared to other markers of hepatic steatosis, larger liver volumes were significantly associated with a nearly three-fold increase in the long-term risk of all-cause mortality. Furthermore, this association was consistent across all subgroups considered (men vs. women; presence or absence of metabolic syndrome or type 2 diabetes at baseline). A positive association between FIB-4 score and all-cause mortality was found both in the entire cohort and in women. Likewise, positive associations of higher serum AST and GGT levels with all-cause mortality were found in the entire cohort and in men. To conclude, this dissertation acknowledges the fact that prevention and early intervention of liver dysfunction has major impact to reduce the burden of public health problems. Thus, our findings suggest that hepatic markers contributes to an increased risk of prediabetes and all-cause mortality, which might be helpful to identify high risk groups who need closer attention with respect to prevention of liver disorders and diabetes.

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Metadaten
Author:Dr. rer. Med Muhammad Naeem
URN:urn:nbn:de:gbv:9-opus-79653
Title Additional (German):Assoziationen von Leberfunktionsstörungen mit Glukoseintoleranz und Gesamtmortalität in einer Allgemeinbevölkerung
Referee:Prof. Dr. Henry Völzke, Prof. Dr. med. Ali Aghdassi, PD Dr. Till Ittermann
Advisor:Prof. Dr. med. Ali Aghdassi
Document Type:Doctoral Thesis
Language:English
Year of Completion:2023
Date of first Publication:2023/03/20
Granting Institution:Universität Greifswald, Universitätsmedizin
Date of final exam:2023/02/21
Release Date:2023/03/20
GND Keyword:hepatic markers,MRI, General populations
Faculties:Universitätsmedizin / Institut für Community Medicine
DDC class:600 Technik, Medizin, angewandte Wissenschaften / 610 Medizin und Gesundheit