The effects of a very low calorie diet and exercise in obese type 2 diabetes mellitus patients
Snel, M.
Citation
Snel, M. (2011, September 1). The effects of a very low calorie diet and exercise in obese type 2 diabetes mellitus patients. Retrieved from https://hdl.handle.net/1887/17801
Version: Corrected Publisher’s Version
License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden
Downloaded from: https://hdl.handle.net/1887/17801
Note: To cite this publication please use the final published version (if
applicable).
The Effects of a Very Low Calorie Diet and Exercise in Obese Type 2 Diabetes Mellitus Patients
Marieke Snel
ISBN: 978-94-6169-102-6
Cover Design: Els Kok, Meeple, Den Haag.
Lay-out and print: Optima Grafische Communicatie, Rotterdam.
This thesis was partly financially supported by Roba Metals B.V., IJsselstein and Nutrition and Santé, Antwerpen, Belgium.
Publication of this thesis was financially supported by the research fund of the Bronovo hospital, Den Haag.
© 2011, Marieke Snel, Leiden, The Netherlands. All rights reserved. No part of this thesis may be reproduced or transmitted in any form, by any means, without prior written permission of the author.
The Effects of a Very Low Calorie Diet and Exercise in Obese Type 2 Diabetes Mellitus Patients
Proefschrift
ter verkrijging van
de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof. mr. P.F. van der Heijden,
volgens besluit van het College voor Promoties te verdedigen op
donderdag 1 september 2011 klokke 13.45 uur
door
Marieke Snel
geboren te Delft in 1979
PrOMOTiECOMMiSSiE
Promotor: Prof. dr. A.E. Meinders Prof. dr. H. Pijl Co-promotor: Dr. I.M. Jazet
Overige Leden: Dr. E.J.P. de Koning
Prof. dr. P. Schrauwen, Universiteit Maastricht Prof. dr. F.L.J. Visseren, Universiteit Utrecht
5
COnTEnTS
List of Abbreviations 7
Chapter 1 Introduction and outline of the thesis 11
Chapter 2 Ectopic fat and insulin resistance: pathophysiology and effect of diet and lifestyle interventions
35
Chapter 3 Adding exercise to a 16-week very low calorie diet in obese, insulin- dependent type 2 diabetes mellitus patients improves metabolic flexibility, VO2max and mitochondrial copy number in skeletal muscle
61
Chapter 4 Quality of life is improved for at least 18 months by the addition of exercise to a 16-week very low calorie diet in obese patients with type 2 diabetes mellitus
75
Chapter 5 Immediate and long-term effects of addition of exercise to a 16-week very low calorie diet on low-grade inflammation in obese, insulin-dependent type 2 diabetes mellitus patients
89
Chapter 6 Prolonged caloric restriction in obese patients with type 2 diabetes mellitus decreases myocardial triglyceride content and improves myocardial function
105
Chapter 7 Sustained cardiac remodeling after a 16-week very low calorie diet in type 2 diabetes mellitus patients
119
Chapter 8 Long-term beneficial effect of a 16-week very low calorie diet on pericardial fat in obese type 2 diabetes mellitus patients
131
Chapter 9 Summary and conclusions 143
Chapter 10 Samenvatting 157
Curriculum Vitae 171
List of publications 173
7
LiST Of AbbrEViATiOnS
ACP American college of Physicians ADA American Diabetes Association AGE advanced glycation end products ALT alanine aminotransferase
AMPK adenosine monophosphate-activated kinase AST aspartate aminotransferase
AS160 Akt substrate 160
ATM adipose tissue macrophage au arbitrary units
BMI body mass index
CPT1 carnitine-palmitoyl transferase 1 CR caloric restriction
CT computertomografie CVD cardiovascular disease DAG diacylglycerol
E exercise
E/A ratio early and atrial diastolic filling phase ratio EASD European association for the study of diabetes ECG electrocardiogram
E/Ea estimated left ventricular filling pressure EDV end-diastolic volume
EGP endogenous glucose production ELISA enzyme-linked immunosorbent assay ESV end-systolic volume
FAT/CD36 fatty acid transporter CD36 FATP fatty acid transport protein FABP fatty acid binding protein FFA free fatty acid
FM fat mass
FOXO forkhead box protein O FPG fating plasma glucose GLM general linear model γ-gt gamma-glutamyl transferase GLUT2 glucose transporter protein 2 GLUT4 glucose transporter protein 4 GS glycogen synthase
GSK3 glycogen synthase kinase 3
8
Abbreviations
G6Pase glucose-6-phosphatase catalytic subunit HADS hospital anxiety and depression score HbA1c hemoglobin A1c (glycosylated hemoglobin) HDL high-density lipoprotein
HIR hepatic insulin resistance
1H-MRS proton magnetic resonance spectroscopy
HOMA-IR homeostatic model assessment of insulin resistance HPLC high-performance liquid chromatography
hsCRP high sensitive c-reactive protein IGT impaired glucose tolerant IHL intrahepatic lipids IL interleukin
IMCL intramyocellular lipid IFNγ interferon gamma IR insulin receptor
IRS insulin receptor substrate LBM lean body mass
LC-CoA long chain fatty acid-CoA LDL low density lipoprotein
LUMC Leiden university medical center LV left ventricle
LVEDVI left ventricle end-diastolic volume index LVEF left ventricular ejection fraction MCRI metabolic clearance rate of insulin MFI20 multidimensional fatigue index 20 MRI magnetic resonance imaging mtDNA mitochondrial DNA
mTORC1 mammalian target of rapamycin complex 1 NAFLD non-alcoholic fatty liver disease
NASH non-alcoholic steatohepatitis NGT normal glucose tolerant NHP Nottingham health profile NOGD non-oxidative glucose disposal NS non significant
OGTT oral glucose tolerance test ORO oil red o
PCR polymerase chain reaction PI3K phosphatidylinositol 3-kinase
PIP2 phosphatidylinositols-4,5-bisphophate
9 Abbreviations
PIP3 phosphatidylinositols-3,4,5-trisphophate PDK phosphatidylinositol dependent protein kinase PKB/AKT Protein kinase B/AKT
PKC protein kinase C ppm parts per million
PRAS40 Proline rich Akt substrate 40 kDa QoL quality of life
Ra rate of appearance Rd rate of disappearance SEM standard error of the mean SF36 short form 36
SU sulfonylureum
TC total cholesterol
TE echo time
TG triglyceride
TNFα tumor necrosis factor α TR repetition time
T2DM type 2 Diabetes Mellitus
UKPDS United Kingdom Prospective Diabetes Study VLCD very low calorie diet
VLDL very low density lipoprotein VO2max maximum aerobic capacity WHO World Health Organization
