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How Gestational Diabetes Mellitus Affects the Microcirculation and Vasomotion of Newborns and Their Mothers

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How Gestational Diabetes Mellitus Affects the Microcirculation and Vasomotion of Newborns and Their Mothers Aus der Kinderlinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital Klinik der Ludwig-Maximilans-Universität München Direktor: Prof. Dr. med. Dr. sci. nat. Christoph Klein How gestational diabetes mellitus affects the microcirculation and vasomotion of newborns and their mothers Dissertation zum Erwerb des Doktorgrades der Medizin an der Medizinischen Fakultät der Ludwig-Maximilians-Universität zu München vorgelegt von Ann-Kristin Grzybowski aus Meerbusch 2019 Mit Genehmigung der Medizinischen Fakultät der Universität München Berichterstatterin: Prof. Dr. med. Orsolya Genzel-Boroviczény Mitberichterstatter: Prof. Dr. Andreas Holzinger Prof. Dr. Sibylle Ziegler Mitbetreuung durch die promovierte Mitarbeiterin: Dr. med Alexandra Puchwein-Schwepcke Dekan: Prof. Dr. med. dent. Reinhard Hickel Tag der mündlichen Prüfung: 11.04.2019 Eidesstattliche Versicherung Grzybowski, Ann-Kristin Name, Vorname Ich erkläre hiermit an Eides statt, dass ich die vorliegende Dissertation mit dem Thema "How gestational diabetes mellitus affects the microcirculation and vasomotion of newborns and their mothers" selbständig verfasst, mich außer der angegebenen keiner weiteren Hilfsmittel bedient und alle Erkenntnisse, die aus dem Schrifttum ganz oder annähernd übernommen sind, als solche kenntlich gemacht und nach ihrer Herkunft unter Bezeichnung der Fundstelle einzeln nachgewiesen habe. Ich erkläre des Weiteren, dass die hier vorgelegte Dissertation nicht in gleicher oder in ähnlicher Form bei einer anderen Stelle zur Erlangung eines akademischen Grades eingereicht wurde. Hamburg, 11.02.2020 Ann-Kristin Grzybowski Ort, Datum Unterschrift Doktorandin/Doktorand TABLE OF CONTENTS 1. Introduction ...................................................................................................................................... 1 1.1. Definition of gestational diabetes ............................................................................................. 1 1.2. Epidemiology of gestational diabetes in Germany.................................................................... 1 1.3. Diagnosis .................................................................................................................................... 1 1.4. Risk factors ................................................................................................................................. 2 1.5. Pathophysiology of gestational diabetes .................................................................................. 3 1.6. Genetics of GDM ........................................................................................................................ 4 1.7. Consequences of gestational diabetes for the child ................................................................. 4 1.7.1. Direct consequences........................................................................................................... 4 1.7.2. Long-term consequences ................................................................................................... 5 1.8. Consequences for the mother ................................................................................................... 5 1.8.1. Direct consequences........................................................................................................... 5 1.8.2. Long-term consequences ................................................................................................... 5 1.9. Treatment .................................................................................................................................. 6 1.9.1. Self-monitoring of blood glucose ....................................................................................... 6 1.9.2. Dietetic treatment .............................................................................................................. 7 1.9.3. Insulin Treatment ............................................................................................................... 8 1.10. Microcirculation ...................................................................................................................... 9 1.11. Definition ................................................................................................................................. 9 1.12. Microcirculation in newborn infants ..................................................................................... 10 1.13. Microcirculatory dysfunction ................................................................................................ 11 1.14. The microcirculatory dysfunction in diabetes ....................................................................... 12 1.15. Role of microcirculatory dysfunction in gestational diabetes............................................... 14 1.15.1. The fetoplacental unit – a unique system ...................................................................... 14 1.15.2. The fetoplacental unit in gestational diabetes .............................................................. 15 1.2. Methods of evaluating the microcirculation .............................................................................. 17 1.3. Goals of the dissertation.......................................................................................................... 20 2. Methods .......................................................................................................................................... 21 2.1. Study design and study group ................................................................................................. 21 2.2. Assessment of the microcirculation ........................................................................................ 22 2.2.1. SDF imaging ...................................................................................................................... 22 2.2.2. MicroScan™ ...................................................................................................................... 23 2.2.3. Sites for SDF measurements ............................................................................................. 23 2.2.4. Performance of measurements ........................................................................................ 24 2.2.5. Analysis ............................................................................................................................. 26 2.2.6. Statistical evaluation......................................................................................................... 29 3. Results ............................................................................................................................................. 30 3.1. Clinical data.............................................................................................................................. 30 3.1.1. Patient collective .............................................................................................................. 31 3.1.2. Birth modus ...................................................................................................................... 31 3.1.3. APGAR score ..................................................................................................................... 31 3.1.4. Macrocirculatory parameters and O2 saturation............................................................. 31 3.1.5. Therapy ............................................................................................................................. 31 3.2. Microcirculatory parameters of the children .......................................................................... 33 3.2.1. Functional Vascular Density (FVD).................................................................................... 33 3.2.2. Vessel surface ................................................................................................................... 33 3.2.3. Percentage of small, medium and large vessel diameter ................................................ 33 3.3. Microvascular flow index of the children ................................................................................ 36 4. Discussion ....................................................................................................................................... 41 4.1. Overview .................................................................................................................................. 41 4.2. Study design ............................................................................................................................. 41 4.3. Method .................................................................................................................................... 42 4.4. Analysis .................................................................................................................................... 43 4.5. Is there a difference of the microcirculation parameters between women with GDM compared to women without GDM? ................................................................................................. 45 4.6. Is there a difference of the microcirculation parameters between newborns of mothers with GDM compared to newborns with mothers without GDM? ............................................................. 46 4.7. How does the vasomotion behave in newborns? ................................................................... 47 4.8. Is there a difference of the vasomotion in newborns with exposition to GDM compared to newborns
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