Comprehensive analysis of risk factors in offspring of type 2 diabetic patients [Elektronische Ressource] / submitted by Michaela Vossen

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• Publié par: universitat_hamburg
• Publié le: 01 janvier 2010
• Nombre de lectures: 13
• Langue: English
• Poids de l'ouvrage: 2 Mo

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Comprehensive Analysis of Risk Factors
in Offspring of Type 2 Diabetic Patients





Dissertation
for the award of the academic degree

Doctor rerum naturalium (Dr. rer. nat.) in Biochemistry

Department of Biology, Faculty of Mathematics, Informatics and Natural Sciences
of the University of Hamburg






submitted by
Michaela Vossen
from Wuppertal, Germany



Hamburg, December 2010
Aim and Working Hypothesis
Individuals with at least one type 2 diabetic parent have a substantially higher risk
of developing insulin resistance, type 2 diabetes or cardiovascular diseases. Thus,
these individuals can be used not only to identify novel risk markers but also to
recognize early alterations in metabolism.
Therefore, a study of a cohort of 91 apparently healthy type 2 diabetes offspring
was used as a basis for this work which comprised the biostatistical analysis of the
given dataset. The participants were invited on two independent test days. Plasma
samples were collected before and after an oral glucose tolerance test and after the
consumption of a fat-rich breakfast as an oral fat tolerance test. The plasma sam-
ples were used for a comprehensive metabolic profiling. The large dataset of fasting
and postprandial data was analyzed in this thesis with the help of biostatistical
methods. The results were interpreted on the basis of current knowledge and pre-
viously published data.
This thesis focused on four aspects. The first aim was to confirm previously re-
ported association between risk factors and fatty acids, measured in total plasma
and major phospholipid species, for healthy subjects, type 2 diabetes or cardiovas-
cular diseases patients, in the cohort of healthy offspring from type 2 diabetic pa-
tients. Since the role of 3-fatty acids during the development of type 2 diabetes
and cardiovascular diseases remained inconclusive in previous studies, the associa-
tion of plasma 3-fatty acids with insulin resistance parameters was the second as-
pect studied here. The fact that the study focused on the postprandial state and in-
sulin action, allowed, as the third aspect, to analyze plasma triacylglycerol levels
during an oral glucose tolerance test as well as an oral fat tolerance test. The fourth
aspect which has been analyzed was the association between 3-fatty acids and ac-
tive plasminogen activator inhibitor-1 as a marker for fibrinolysis and risk factor for
cardiovascular diseases.
Contents
Contents

List of Figures ................................................................................................. III
List of Tables .. IV
List of Abbreviations ........................................................................................ V
1 Introduction.............................. 1
1.1 Pathophysiology of Hyperglycemia and Insulin Resistance ........................1
1.2 Lipids and their Role in Insulin Resistance ...................................................5
1.3 Postprandial Metabolism .............................................. 10
1.4 Pro-inflammatory Proteins and their Role in Insulin Resistance ............ 13
1.5 Nutritional Aspects of Cardiovascular Risk Factors ................................. 14
2 Materials and Methods .......................................................................... 17
2.1 Study Population ............................ 17
2.2 Analysis of Insulin Resistance Parameters .................. 19
2.3 Analysis of Plasma Fatty Acids .................................................................... 19
2.4 Analysis of Plasma Phospholipid Species ................................................... 20
2.5 Analysis of Lipoproteins ............................................... 21
2.6 Analysis of Pro-Inflammatory Parameters ................. 21
2.7 Statistical Analyses ......................................................................................... 22
3 Results .................................................................... 25
3.1 Metabolic Characterization of the Study Population 25
3.2 Lipids and Insulin Resistance ....................................... 30
3.3 Metabolic Characterization of the Cohort during an OGTT .................. 37
3.4 Lipids during an OGTT ................................................................................ 38
3.5 Postprandial Triacylglycerol and Insulin Resistance.. 42
3.6 Active PAI1 and Cardiovascular Risk ......................................................... 57
4 Discussion .............................................................. 70
4.1 Lipids and Insulin Resistance ....................................................................... 70
4.2 Postprandial Triacylglycerol and Insulin Resistance.. 76
4.3 Active PAI1 and Cardiovascular Risk ......................................................... 81
5 Conclusion .............................................................. 87
I Contents
Appendix ............................................................................................................ I
List of Supplemental Tables .............................. I
Supplemental Tables ......................................................................... II
Acknowledgements ....................... VII
References ....................................................................................................... IX
II