Department of Endocrinology

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Department of Endocrinology
Annual Report
2009
EFE - Endocrine Research Unit
Department of Endocrinology
TABLE OF CONTENTS
Preface....................................................................................
4
Endocrine Research Unit Committee.............................................
5
Seven selected research stories from 2009....................................
6
1. ROSE – Risk-stratified Osteoporosis strategy Evaluation: Providing
an osteoporosis service to those at the highest risk....................
6
2. Self-Care Behaviour Treatment in Diabetes................................
7
3. Isolation and differentiation of Chondrocytic Cells Derived from
Human Embryonic Stem Cells Using dlk1/FA1 as a Novel Surface
Marker ................................................................................
8
4. Role of Telomerase enzyme in osteoblast differentiation in vitro
and bone homeostasis in vivo.................................................
9
5. Genetic Variants Involved in Mitochondrial Oxidative Metabolism
are associated with Type 2 Diabetes Mellitus.............................
10
6. Clinical and immunological aspects of B-lymphocyte depletion
with rituximab in Graves´ disease...........................................
11
7. Patient education on retinopathy .............................................
12
The Danish PhD School of Endocrinology.......................................
14
The Danish PhD School of Molecular Metabolism............................
14
Current PhD projects carried out in EFE........................................
The Bone and Calcium Research Group....................................
The Diabetes Research Group.................................................
The Molecular Endocrinology Unit (KMEB).................................
The Pituitary- and Clinical Nutrition Research Group...................
The Thyroid Research Group...................................................
The Clinical Nursing Research Group........................................
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Researchers and technical/administrative staff in EFE
- as per 31 December 2009.........................................................
The Bone and Calcium Research Group....................................
Clinical Nursing Research Group..............................................
The Diabetes Research Group.................................................
The Molecular Endocrinology Unit (KMEB).................................
The Pituitary- and Clinical Nutrition Research Group...................
The Thyroid Research Group...................................................
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Completed PhD theses...............................................................
23
Publications..............................................................................
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Financial support to EFE .............................................................
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3
PREFACE
Our goal is diagnostic treatment based on
scientific knowledge, and therefore it is my
pleasure to ascertain the high number of medical publications – more than 100 this year.
It is also a pleasure to congratulate the 7
ph.d. students who finished their training and
obtained their ph.d. degree. The research
stories presented here are showing that department M is producing interesting results
which can be implemented in the clinical work
for the benefit of patients.
By Professor, Dr. MSci. Henning Beck-Nielsen
Research Manager EFE
In 2009 Torben Hansen, Hagedorn Research
Institute, was appointed adjungated professor at EFE. A warm welcome to Torben.
Indeed, we want to thank everybody who
has contributed to our research, specifically
all the patients who agreed to be at the disposal for science. The same gratefulness applies to all the health control subjects. I hope
that this annual report shows all of you that it
was worth it. I also want to extend my thanks
to all staff, both those who are directly involved in research and those who in their clinical
work enables research to thrive.
Endocrinology Research Unit (EFE) is a venture of all research efforts around endocrinology
concentrated at department of Endocrinology
M, Odense University Hospital.
EFE has its own research lab – clinic for Molecular Endocrinology and Endocrinlogy Treatment (KMEB) and presently, 23 Ph.d. students are trained in EFE. EFE also embraces
two PhD Schools in which a close collaboration between the faculty of Natural Science and
Technology of University of Southern Denmark and the Panum Institute of University of
Copenhagen is taking place.
A special thank to our research secetaries,
who through their daily work secure a smooth
work flow, and who have produced this annual report: Nanett Mosumgaard, Tine Hylle,
Tina Barbisan Hansen, Kristine Michailidis and
Sandra Harris.
Also a warm thank to the Faculty of Health
Science, the hospital management and to the
foundations for their support to the research
activites in endocrinological research.
4
ENDOCRINE RESEARCH UNIT COMITTEE
Marianne Andersen
Consultant, PhD
The Pituitary Gland Resarch
Group
Henning Beck-Nielsen
Professor, Consultant, DMSc
Chairman
The Diabetes Research Group
Kim Brixen
Professor, Consultant, DMSc
The Bone and Calcium
Research Group
Rene Støving
Consultant, PhD
The Pituitary- and Clinical
Nutrition Research Group
Laszlo Hegedüs
Professor, Consultant, DMSc
The Thyroid Research Group
Moustapha Kassem
Professor, Consultant, DMSc
The Molecular Endocrinology
Unit (KMEB)
Anne Holm Nyland
Development Nurse,
MSc in nursing
Clinical Nursing Research Group
Dorthe Nielsen
Nurse, RN, MHS, PhD
The Bone and Calcium Research
Group
Nanett Mosumgaard
Research Secretary
5
SEVEN SELECTED RESEARCH STORIES FROM 2009
- examples of EFE research areas
1
is based on a few simple questions such as “do you
smoke?”, “did your mother or father have osteoporosis?” and data on height, weight and age of the
patient. This tool may allow us to offer DEXA to
high-risk patients with better precision. This is the
basic idea of the study.
ROSE – Risk-stratified Osteoporosis strategy Evaluation:
Providing an osteoporosis service to those at the highest risk
by Katrine Hass Rubin; PT, MHS
and PhD-student; The Bone and
Calcium Metabolic Research Group
Randomized design is necessary
The primary aim of the project is to test if risk-stratified screening for osteoporosis in women aged
65-80 years is effective in preventing fractures. In
order to obtain solid data on this issue, the study is randomized, i.e. 50% of the participants will
be “controls” and 50% will be “screened”. A total
of 15,000 women aged 65-80 years are selected
at random from the Central Person Register and
randomized. All the women will receive the “FRAX
questionnaire” and women in the screening group
with a 10-year probability of major osteoporotic
fracture above 15% are invited to a DEXA-scan. If
osteoporosis is diagnosed, treatment and follow-up
will be carried out in general practice.
While the main question is whether or not this new
strategy is effective, a number of associated questions will also be clarified – if the screening program is cost-effective and the women’s attitudes,
experience and acceptance of the screening program.
Moreover, a second part of the study will investigate the use of ultrasound machines in the assessment of osteoporosis. This part of the study is
scheduled to start in the autumn of 2010.
In January 2010, we have started inclusion of women in a large-scale trial on risk-stratified screening for osteoporosis (ROSE). This study will – as
one of the first in the world – investigate the effect
of a screening program for osteoporosis in postmenopausal women in a randomized design. The
study will include 15,000 women in the Region of
Southern Denmark. The study is supported by the
Region of Southern Denmark and INTERREG and is
performed in collaboration between researchers in
Esbjerg, Kolding, Odense and Kiel.
Osteoporosis is under-diagnosed
Osteoporosis is highly prevalent especially in postmenopausal women and grave consequences for
those patients suffering e.g. hip fractures. Moreover, the costs to society that results from treatment and care of fracture patients are enormous.
Indeed, approximately 45% of all women will suffer at least one fracture during their lifetime where
osteoporosis is a causal factor. In Denmark as in
many other countries, a case-finding strategy is
currently used to identify patients with possible
osteoporosis. Ideally, women with one or more risk
factors should be referred to a DEXA-scan by their
general practitioner. This strategy, however, seems
to result in referral of only few high-risk patients
while many resources are used to examine women
with relatively low fracture risk. Recently, the WHO
Collaborating Centre for Metabolic Bone Diseases at
Sheffield developed the Fracture Risk Assessment
Tool (FRAX®) to improve the case-finding strategy
and help general practitioners in their daily praxis
to calculate the individual risk of fracture in women
and men in order to identify the patients at highest
risk of fracture. FRAX uses clinical risk factors to
predict the 10-year risk of hip fractures and other
fractures in individual patients. Calculation of FRAX
Regional and cross-boarder collaboration
The project is performed in close international collaboration between Odense University Hospital,
Kolding hospital, Hospital of South Western Jutland
(Esbjerg), University of Southern Denmark and Kiel
University Hospital. Moreover, four PhD–students
(or PhD-students-to-be) are currently working on
the study; Mette Rothmann, Teresa Holmberg, Mikkel Høiberg and Katrine Hass Rubin.
The ROSE study will include women in the next
1-2 years. Duration of the study is anticipated to
be 3-6 years depending on e.g. participation rate.
The large amount of data from the project will be
analyzed by 4-8 PhD-students during the years to
come.
6
2
Self-Care Behaviour Treatment
in Diabetes
improvements in long-term glycaemic control and
to establish the most effective regime.
by Lisbeth Minet, Else-Marie Lønvig, Lis Wagner, Jan Erik Henriksen, the Diabetes Research Group
Aim and Methods
The aim of this randomised controlled trial was to
study the effect of a 1 year nurse-led intervention
programme based on Motivational Interviewing
describe by Miller and Rollnick in patients diagnosed with diabetes type 1 DM or type 2 DM. Our
approach was derived from Albert Bandura’s Selfefficacy theory of human intentional acts through
their beliefs in their capability to perform a desired
effect by their actions. All 349 participants included
in the trial received a four days diabetes education
programme before randomisation to an intervention group or a control group. After the education programme both the intervention and control
group were discharged to usual care consisting of
visits to their physician every three months. In addition to usual care the intervention group received five individual sessions in one year given by
diabetes specialist nurses educated in Motivational
Interviewing. The goal of intervention was to help
patient to recognise and address problem areas in
the diabetes self-management. By request the patients in the intervention group were referred to
a tailored counselling in changes of diet, smoking
habit, physical activity and alcohol use. All data are
collected prospectively over the period of 5 years.
Figure 2 illustrate the participants flow throughout
the trial.
Background
The large amount of research in the self-management area testifies to the urgency this factor is given in the diabetes treatment. Self-management
of diabetes involves a number of considerations
and choices that each patient with diabetes takes
on a daily basis. It requires that patients are able
to reconcile their resources, values and preferences with a therapeutic regimen of healthy diet,
exercise, no smoking, low alcohol intake, glucose
monitoring and for some medication. The knowledge of how self-management evolves in the lives
of patient with diabetes is stressed to be essential
in the organization of treatment approaches. This
means that there has been an increased focus on
patient responsibility, as clarified in the attempts to
encourage patients to be active participants in the
diabetes treatment and thereby enabling the patients to control their diabetes. However, the ability
to handle the daily care of diabetes steel seems to
be a challenging task for many patients with diabetes. A patient’s ability to be involved in the daily
routine of diabetes care seems to be grounded in
psychological and motivational factors as well as
educational factors. The inability to conduct selfmanagement activities and to assume responsibility for daily diabetes care is reflected in poor outcomes, which makes the patients more prone to
diabetes-related complications such as blindness,
kidney damage, amputation of lower limbs and
cardio vascular illnesses. Therefore, in research
purposes, it has been of interest to find ways to
strengthen the individual’s belief and competence
to handle their diabetes.
Results
The findings from the qualitative data collection
method indicated the need for involving patients in
setting the objective of therapy to ensure for the
patient a meaningful and applicable treatment that
can be transferred to various everyday situations.
It was suggested that people with diabetes have
specific needs for support in the daily responsibility
of managing the rules of conduct within diet, exercise, blood glucose monitoring, and medication
intake. Health care professionals should be aware
of the difficulties for some vulnerable patients to
handle the responsibility of self-management.
The assessments of quantitative data are ongoing.
Results are expected to be presented June 2010.
A meta-analysis of 47 randomised controlled trials was carried out to establish knowledge about
the existing evidence on the effectiveness of selfmanagement intervention on diabetic control. The
analysis found improvements in glycaemic control
indexed by glycated haemoglobin with a 0.358 %
decrease in HbA1c (95% CI -0.509 to -0.207) in
diabetes patients who received self-care behavioural intervention compared to a control group. This
was especially true under conditions which imply an
intense and individual treatment. However, further
research is needed to establish knowledge about
7
Figure 2
3
Isolation and differentiation
of Chondrocytic Cells Derived
from Human Embryonic Stem
Cells Using dlk1/FA1 as a Novel
Surface Marker
Aim and methods
We aimed in this study to design a clinically relevant
protocol for directing the differentiation of hESC
into chondrocytes based on tracking the dlk1/FA1
expression as a novel mesoderm/chondroprogenitor surface marker. hESC were differentiated as
human embryoid bodies (hEBs) in 3D culture for 10
days in the presence of 50 ng/ml Activin B. FACS
cell sorting was employed to isolate dlk1/FA1+
cells from Activin B-induced EB-outgrowth culture
in serum free medium. hESC-derived dlk1/FA1+
cells were induced to differentiation into chondrocytes by culturing them as a micromass pellets in
the presence of 10 ng/ml TGFβ1.
By Basem M. Abdallah, Lektor. The
molecular Endocrinology Unit (KMEB)
Human embryonic stem cells are considered as a
good source for providing differentiated cells for
cell-based therapy of cartilage degenerative diseases including osteoarthritis and traumatic cartilage injury. However, chondrogenic differentiation
protocols for hESC have limited success and have
been mainly accomplished via co-culture conditions or adding exogenous extracellular proteins. In
order to develop well-defined and efficient protocols for directing hESC differentiation into chondrogenic lineage in vitro, there is a need to identify
novel surface markers that define early stages of
hESC commitment to chondrocytes. Delta-like1/
fetal antigen1 (dlk1/FA1) is a transmembrane protein of the Notch/Delta/Serrata family. Here, we
identified dlk1/FA1 as a novel surface marker for
chondroprogenitor cells that undergoing transition
from proliferating to prehypertrophic chondrocytes
in parallel with the expression of Sox 9 and type IIA
procollagen during mouse limb bone development
(Figure 1). The same pattern of dlk1/FA1 expression was also obtained in hESC-derived cartilage in
vivo (Figure 2, upper panel).
Results
We employed dlk1/FA1 as a surface marker to
identify mesodermal/chondroprogenitor cells during human embryonic stem cell (hESC) differentiation. FACS analysis, immunohistochemistry and
real time-PCR showed an association between
dlk1/FA1 expression and the up-regulation of mesoderm specific markers during in vitro differentiation of hESC into embryoid bodies (Ebs). Activation of TGFb emodellin in hEBs outgrowth culture
using Active B markedly induced mesoderm lineage in parallel with up-regulating Dlk1 expression.
Thus, we used FACS cell sorting to enrich for mesoderm/dlk1/FA1+ cells. Interestingly, hESC-derived
dlk1+cells showed to differentiate efficiently into
a pure population of chondrocytic cells when cultured as micromass pellets in a xeno-free system
containing TGFβ1 (Figure 2)
Figure 1
Figure 2
8
4
Role of Telomerase enzyme
in osteoblast differentiation
in vitro and bone homeostasis in vivo
AG, Zürich, Switzerland) scanned bone samples for
the region of interest that is trabecular and cortical bone of proximal tibia. Bone marrow cells were
harvested according to the protocol described by
Peister, with some in house modifications.
By Hamid Saeed, B.Pharm,
Mphil, PhD student, the Molecular Endocrinology Unit (KMEB)
Results
Whole skeletal mount staining of E17.5 days old
embryos revealed mild patterning defects with
delayed ossification in occipital bone, calvarial
sutures, sternubra, metatarsal and caudal vertebrae (Fig.1A). TERC-/- exhibited accelerated agerelated bone loss starting at 3 months of age and
during 12 months follow up period as evidenced by,
DEXA (Fig. 1C) and µ-CT trabecular bone volume
(TBV/TV) in TERC-/- 0.078 ± 0.020 vs wild type
mice (WT) 0.113 ± 0.029 (p< 0.05, n=6)(Fig. 1D).
Stromal (mesenchymal) stem cells (MSC) isolated
from TERC-/- mice exhibited intrinsic defects with
reduced total number of CFU-F and alkaline phosphatase positive (AP+)-CFU-F (Fig.1E)
Introdcution
Osteoporosis is a multifactorial and complex disorder characterized by bone fragility and increased
risk for fractures. One of the principal pathophysiological mechanisms underlying osteoporosis is the
impairment of osteoblastic bone formation during
bone emodelling with aging. In this context, we
have previously demonstrated that age-related and
osteoporosis-related impairment of bone formation
is caused by accumulation of senescent osteogenic
stem cells that impairs bone regeneration capacity,
though; self-renewal capacity of hMSC could be restored by over-expression the hTERT gene in hMSC
thereby enhancing proliferation and in vivo bone
formation capacity. However, in vivo consequences
of defective telomerase activity and shortened telomere on bone stem cells and bone biology are
poorly studied.
Conclusion
Our data demonstrate that telomerase plays an important role in maintenance of stem cell functions
and activation of telomerase in MSC or in a compartment specific manner can be a novel strategy
for abolishing age-related bone loss.
Objective
The aim of this project is to determine the physiological role of telomerase in osteogenic stem cell
proliferation and differentiation to osteoblastic cells
and also its effects on bone homeostasis in vivo
using the TERC knockout mouse model that lacking telomerase activity due to null mutation in RNA
component of telomerase complex.
Methods
17.5day old embryos were de-skinned and eviscerated. Staining was performed in a solution of 90%
ethanol, 5% acetic acid, and 5% H2O supplemented
with 0.005% alizarin red S (Sigma) and 0.015%
alcian blue 8GS (Sigma) for 3 days at 37°C. Total body mass (grams) bone mineral content (milligrams) and bone mineral density (milligrams per
square centimetre) were measured using DEXA
scanner. μCT scanner (viva-CT 40, Scanco Medical
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5
Genetic Variants Involved in
Mitochondrial Oxidative Metabolism are associated with
Type 2 Diabetes Mellitus
Exploring results from a meta-analysis of genome
wide association studies (DIAGRAM Consortium),
we found that among 1284 SNPs in 119 OxPhos
genes, 39 SNPs showed potential association with
T2D (uncorrected p<0.01). SNPs that were in linkage disequilibrium (r2>0.8) were excluded from
further analysis. The resulting 10 SNPs in or near
6 OxPhos genes were genotyped in 3,139 T2D patients and 5,302 controls with normal glucose tolerance.
By Lena Soender Snogdal, Md,
PhD student, the diabetes research
group
Introduction
Type 2 diabetes (T2D) is the most common form of
diabetes and a dramatic increase in prevalence is
being observed worldwide. Like T2D, obesity is an
increasing problem in the Western World and has
taken on epidemic proportions. T2D and obesity is
in part inherited and therefore a lot of research
focuses on finding genetic factors contributing to
the diseases. T2D is characterized by insulin resistance (IR) and failure of the pancreatic beta cells
to compensate for this defect. Several studies have
demonstrated a link between IR and impaired mitochondrial oxidative phosphorylation (OxPhos)
in skeletal muscle. Oxphos consists of respiratory
chain and ATP synthesis (shown in the figure). Recently, mitochondrial defects have also been implicated in beta-cell dysfunction in T2D.
Results
Rs1466100 in COX5B (OR=1.67, p=0.004) and
rs9915302 in COX10 (OR=1.14, p=0.02) were significantly associated with T2D. In a meta-analysis
combining our results with data from an available
subset of the DIAGRAM data, we demonstrated that
three SNPs (rs10775377, rs8077302, rs9915302)
in COX10 and a SNP (rs2267584) in a gene (UPK1A) next to COX6B1 were significantly associated with T2D. In particular, the rs9915302 variant in COX10 showed strong association with T2D
(OR=1.14, p=7.7x10-6). Analysis of quantitative
traits, applying an additive model and adjusting
for age and sex, revealed significant associations (p<0.05) between a surrogate marker (BIGAIR) of insulin secretion and variants in COX5B
(rs11904110) and COX10 (rs10521253), between
fasting plasma glucose and rs11904110 in COX5B,
and 2-h post-OGTT plasma glucose and rs8134542
in NDUFV3 (p<0.05).
Aim and methods
The overall aim of this thesis is to contribute to the
pathological exploration of the genetic risk factors
of T2D with a special focus on mitochondrial dysfunction by genotyping selected single nucleotide
polymorphisms (SNPs). All SNPs have their own
specific rs-number and are specified by which gene
hey are placed in or near by.
DNA string
Conclusion
Our data suggest that genetic variants in or near
genes encoding subunits in complex IV (COX5B,
COX6B1, COX10) contribute to the pathogenesis
of T2D. The observed association of variants in
COX5B, COX10 and NDUFV3, with markers of insulin secretion and postprandial hyperglycaemia,
supports a role for mitochondrial defects in betacell dysfunction in T2D.
In this specific study we hypothesized that single
nucleotide polymorphisms (SNPs) in OxPhos genes
could contribute to the pathogenesis of T2D.
10
6
Clinical
and
immunological
aspects of B-lymphocyte depletion with rituximab in Graves´ disease
ly in the RTX-treated patients. These results support the case that methimazole therapy does not
affect the autoimmune process per se. The specific declines in a subset of autoantibodies may rely
upon the need for intrathyroidal germinal centers
for their production, or the preferential production of these autoantibodies by short-lived plasma
cells. As to the former argument we showed that
B cells were absent from the thyroid 7 days after
RTX therapy 4.
Two patients included in the study had active,
previously treatment refractory GO, both patients
showed a marked improvement in GO severity as
well as activity 5.
Unanticipated from literature review, RTX induced
articular and gastrointestinal adverse events in
three and two of the patients, respectively.
In conclusion, RTX seems to have some efficacy in
GD. However, side effects and high cost disfavours
the use in GD without GO. In our hands, RTX seemed effective in GO. This finding has been confirmed in other small patient series, and is presently
under investigation in randomized placebo-controlled trials.
By Daniel El Fassi, MD, the Thyroid
Research Unit
Graves´ disease (GD) is an autoantibody-mediated
autoimmune disease, which has a prevalence of
around 1-2%. The hyperthyroidism affects various
organ systems, and has a marked impact on quality-of-life. Only around half of the patients achieve remission by an initial 12-18 months course of
antithyroid drugs 1. The remaining half of the patients often require thyroidectomy or radioiodine
treatment, both of which infer a risk of permanent
hypothyroidsm. Marked Graves´ ophthalmopathy
(GO) is present in 5-10% of the patients. The pathogenesis of GO is less clear than that of GD. The
mainstay of current therapy is high-dose glucocorticoid therapy, with retrobulbar irradiation or orbital
surgery as the second-line alternatives. Treatment
responses are often unsatisfactory in GO patients,
and particularly in this condition, novel treatment
modalities are warranted.
We have conducted a controlled but non-randomized and non-blinded study with the main focus
on evaluating the efficacy and safety of the B-lymphocyte depleting agent rituximab (RTX) in GD.
Furthermore, we wished to evaluate immunological
changes occurring after the treatment 2.
We rendered 20 patients with GD euthyroid using
standard methimazole therapy given for around
four months, the last four weeks of which ten of
the patients received weekly infusions of RTX 2.
At the end of follow-up, which was at least one year,
four RTX-treated patients remained euthyroid, while all the non-RTX treated patients had relapsed.
All the patients who maintained euthyroidism had
low baseline TSH-receptor antibody (TRAb) levels.
Upon relapse methimazole therapy was reinitiated.
We were able to evaluate precisely the changes in
autoantibody levels attributable to RTX therapy (Figure). TRAb levels declined in both groups with no
difference between the treatment groups. However,
using a bioassay involving Chinese hamster ovary
cells transfected with the human TSH-receptor the
stimulatory activity of the TRAbs (TSAb activity)
decreased markedly and specifically in RTX-treated
compared to non-RTX treated patients 3. Thyroid
peroxidase antibody levels also declined specifical-
Legend
Antibody levels following treatment with 375 mg/
m2 rituximab at days 1,8,15 and 22 in ten patients
with Graves´ disease who also received methimazole.
Mean values±SEM are shown on a logarithmic scale.
A matched control group received methimazole
only. Immunoglubulin (Ig) G and TRAb levels were
not differentially affected by RTX (open symbols).
IgM levels, thyroid peroxidase antibody (TPOAb)
levels, and the biological activity of the TRAbs
(TSAb) were differentially affected (filled symbols).
In the control group, TPOAb and TSAb levels were
unchanged over time, and IgM levels increased
slightly (data not shown). The dotted line represents the theoretical half-life of IgGs, the Ig subtype to which most TRAbs, TSAbs and TPOAbs belong.
11
7
Patient education
nopathy
on
reti-
For evaluation height, weight and blood pressure was
measured. Blood samples were drawn (HbA1c, low
density lipoprotein, high density lipoprotein, total
cholesterol and triglycerides). Retinal photography
was obtained.
Thirty-seven completed the study. Primary endpoints
of the study were to test the effect of the program
on parameters of lifestyle changes and self-efficacy.
Secondary endpoint was to test the effect of the program on progression in retinopathy.
Primary endpoints were tested by applying T-test
on delta-values in the two groups. No differences
over all between the two groups were found. The
secondary endpoint was change in the degree of retinopathy. There were no significant differences between the groups. Data did not involve the possibility that a patient could have worsening at one eye,
and at the same time improved on the other eye. To
comply with this a score system was made to find
the overall changes in retinopathy (figure 1). Overall
both groups improved.
By Rothmann M, Nyland A.H, Hammelsvang L, Petersen L, Kirketerp
G, Henriksen J.E.
Retinopathy is a common complication of diabetes. A
fourth of the patients with type 2 diabetes have retinal micro vascular changes at time of diagnoses (1).
Furthermore, many patients with type 1 diabetes will
develop retinopathy during to the disease duration
(2).
The aim of the present study was to evaluate a new
nursing practice for diabetic patients with retinopathy.
We wanted to determine if systematic patient education could optimize knowledge of retinopathies, lifestyle changes and self management. Furthermore,
to evaluate if the acquired patient knowledge and capabilities could prevent retinopathy progression and
ultimately save eye-sight.
Fifty patients were randomized to either an intensified educational program or the standard follow-up
procedures in the outpatient clinic. The study period
was two years with evaluation at baseline, after 12
and 24 months whereas focus group interviews were
performed at 12 month only.
The educational program applied to the intervention
group contained 4 lessons of 1½ hours during a three
months period (table 1). Teaching methods were inspired by Aron Antonovskys ‘sense of coherence’ and
an approach on empowerment. Patient’s experiences
were central in an attempt to strength self-management (3,4). Teaching was seen as a pluralistic approach on evidence based practice (5,6).
Figur 1
The control group
The intervention group
Table 1
P.M.
Lesson 1
(week 1)
Lesson 2
(week 2)
Lesson 3
(week 3)
Lesson 4
(week 7)
2.30-3.15
Introduction,
Expectations
of Education
Prevention of
Retinopathy
Treatment of
Retinopathy
Everyday
life and Retinopathy
3.15-3.30
Break
Break
Break
Break
3.30-4.15
Anatomy and
Physiology of
the eye
Prevention of
Retinopathy
and Self-care
Treatment of
Retinopathy,
Cataract,
Glaucoma and
Age-related
Macular Degeneration
Closing
discussion
The themes found in the focus group interviews were
nearly identical, but the weighting and description of
the themes were different (figure 2). Fear of blindness was the only theme described identical at the
time of diagnosis.
The main theme in the two groups differed. “Knowledge” was the most significant theme in the intervention group. Knowledge on retinopathy was described as important in everyday life, indicated as
12
Figur 2
ned. In contrast the intervention group took responsibility in the prevention showed as shared care.
The study has illustrated the need for patient education in relation to retinopathy and the need for
constantly developing new nursing practices to support the patients. The interviews findings confirm
that knowledge on diabetes and retinopathy as well
as openness to the psychological dimension of retinopathy strengthens the patient sense of coherence
resulting in less fear or anxieties (7). Moreover, the
interviews findings illustrated that knowledge on retinopathy, self-care, and self-efficacy in relation to retinopathy are associated to responsibility and motivation to prevention of diabetic complications. Contrary
our quantitative data did not show any significant
effect of the education program. Education had a positive effect on sense of coherence, empowerment,
self-care and self-efficacy in relation to responsibility, ownership and everyday life with diabetes and
retinopathy. The main point in this study might be
that knowledge achieved by patient education seems
to be comprehensible and meaningful. Knowledge is
turned into everyday life.
motivation for metabolic control. The main theme
in the control group was “Responsibility for prevention”. Responsibility should be handled by professionals and they themselves had only a minimum of
responsibility for the prevention. The control group
indicated knowledge on retinopathy, but did not act
according to the knowledge. The patients felt safe,
but it did not reduce their fear of blindness.
Both groups described “accept”. Characteristic of the
two groups were that the control group was resig-
at KMEB Lab
13
THE DANISH PHD SCHOOL OF ENDOCRINOLOGY
www.endocrinology-phd.dk
• To intensify the efforts of the involved instituti ons (Nordic Bioscience and the University of Sou thern Denmark) to educate PhD candidates with
a solid background in medical endocrinology.
• To build up a national and international network
between leading researchers in the field of medi cal endocrinology.
• To build up a national and international network
between leading researchers in the field of me dical endocrinology.
Background
The Danish PhD School of Endocrinology is a new PhD
school established on 1 August 2008 and financed by
the University of Southern Denmark and Nordic Bioscience A/S, Center for Clinical and Basic Research.
The main research areas of the school are application-oriented clinical endocrinology. The disease areas
include calcium metabolic diseases, diabetes mellitus, metabolic syndrome, obesity, cardiovascular risk
factors and fibrosis.
PhD students
The school has now enrolled the first 8 PhD students.
PhD Courses and Curriculum
The head of the PhD school is Professor Henning
Beck-Nielsen, Dept. of Endocrinology, Odense University Hospital. A coordination committee is responsible for proposal and approval of PhD projects and
PhD students.
The aims of the PhD School of Endocrinology are:
• To establish a high-standard, international PhD
programme in medical endocrinology with spe cial emphasis on metabolic diseases with incre ased tissue turnover, such as osteoporosis, oste oarthritis, cardiovascular diseases and fibrosis.
THE DANISH PHD SCHOOL OF MOLECULAR METABOLISM
www.metabolism-phd.dk
laborates with a large number of well-estimated
researchers and private companies both nationally
and internationally.
Background
The Danish PhD School of Molecular Metabolism
is a joint venture between the Faculty of Science
and the Faculty of Health Sciences at the University of Southern Denmark and the Faculty of Health
Sciences, University of Copenhagen. The Danish
PhD School of Molecular Metabolism is organised
with a head, a board, an international Advisory
Board (approx. 20 members) and a national Faculty (approx. 45 members). Chief consultant, professor, MD, DMSc Henning Beck-Nielsen is head of
the Danish PhD School of Molecular Metabolism.
Aims
• To train PhD students in theoretic and practical
methods in the field of molecular metabolism,
i.e. genomics, transcriptomics, proteomics, li pidomics, metabolomics and bioinformatics.
• To train PhD students in using these methods in
the field of cell biology and for clinical applicati on, especially in relation to type 2 diabetes,
obesity and the metabolic syndrome.
• To stimulate ”translational research” by assu ring that more PhD projects stretch from ”mole cule to sick bed”
• To organise a core curriculum covering the abo ve spectrum.
• To strengthen the cooperation between univer sity research, public sector research and indu strial research.
• To build up a national and international network
between leading researchers in the field of mo lecular metabolism.
The School is interdisciplinary and research-focused and employs new cellular methods for the
study of molecular metabolism, especially in connection with diseases in glucose and fat metabolism, i.e. obesity and type 2 diabetes. The school
integrates the entire metabolic spectrum from
genome through transcriptome and proteome to
metabolome. The tehcniques are applied to large,
well-defined cohorts (epidemiology) and clinically representative patient groups (diseases). The
PhD school covers subject areas such as genetics,
physiology, biochemistry, molecular biology, endocrinology and diabetology. The PhD school col-
PhD students
In total the Danish PhD School of Molecular Metabolism has 60 PhD students enrolled.
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CURRENT PHD PROJECTS
The Bone and Calcium Research Group
BMD decrease is seen, with a subsequent small increase or
return to baseline. Still, both the number of vertebral and
peripheral fractures is reduced by approx. 60%.
HR-pQCT is a newly introduced imaging technique to assess
density and micro-architectural morphology of the radius
and tibia offering an evaluation of bone quality potentially
superior to DXA, which could possibly capture changes in
bone morphology underlying the above results. However,
HR-pQCT is yet an unproven technique with the need for
further validation.
Dorthe Nielsen, RN, MHS
The Importance of Patient Education in Groups in Patients with Osteoporosis
- A qualitative and quantitative project.
In this study, we aim to understand the influence of patient
education in relation to patients’ way of coping with osteoporosis in the conduct of every day life. The first part of the
study is a randomised controlled trial, here we hypothesise
that multi-disciplinary education of patients with osteoporosis increases compliance, physical activity and knowledge
on osteoporosis. In part two focus groups are being completed with 4x6 men diagnosed with osteoporosis, to get
the gender perspective. In the last part of the study 20 qualitative interviews are being performed in Odense University
Hospital, DK and Nottingham University Hospital, UK). Focus is held on similarities and differences for patients’ possibilities to act in concrete contexts.
Katrine Hass Rubin, MT, PHS
Risk stratified screening for osteoporosis in the Region of Southern Denmark
The aim of this study is to evaluate whether risk stratified
screening with one of the existing fracture risk tools (FRAX,
OST, SCORE, ORAI ORISIS, OPERA) is an effective methods
to identify post menopausal women with increased fracture
risk. The study was designed as a population-based crosssectional study where 5,000 women, aged 40-90 years,
living in the region of Southern Denmark, were mailed a
self-administered questionnaire concerning risk factors for
osteoporosis. The respondent rate was 84 %. Following studies will be done on the data; Describing the prevalence of
risk factors and the use of DXA-scanning, Validate FRAX in a
Danish population, investigate the correspondence between
and the existing fracture risk tools, evaluate their predictive
values.
Morten Frost Nielsen, MD
SOMA – Study on Male Osteoporosis and Aging
Osteoporosis and fractures in men are a significant public
health problem. The disease is a very heterogeneous clinical entity: some develop osteoporosis in a relatively young
age for idiopathic reasons while others may have secondary
causes.
Some 10.000 men aged 60-75 received a questionnaire by
mail in 2004. The questionnaire was designed to capture
potential factors that could be related to the development of
osteoporosis or increase fracture risk. Respondent were all
enrolled in a nested case-control study of causes of fragility
fractures in men. In cases as well as controls, BMD, hormonal status etc are evaluated.
The study is expected to improve our knowledge on male
osteoporosis including in particular risk factors for fragility
fractures.
The Diabetes Research Group
Lisbeth Minet, Physiotherapist, MHS
Self-care behaviour treatment in patients with type
2 diabetes
The aim of the project is to study the long-term effect of a
motivational intervention program based on cognitive-behavioural strategies in patients with diabetes. A randomized
controlled trial with 400 patients with type 2 diabetes is
carried out at an endocrinology unit. The sample size was
determined by a power calculation based on a standard
deviation of 1.15 in the HbA1c-value and a 5% two-sided
significance level. The power is set to 90 %. Assessments
are made at baseline, follow-up 1 year and follow-up 2 year.
Statistical analysis will be used to compare end points between the two groups.The effect will be evaluated on both
physiological and psychosocial parameters.
Stinus Hansen, MD
The effects of parathyroid hormone on bone structure assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT)
Parathyroid hormone (PTH) is a key hormone in bone remodeling with either catabolic or anabolic actions depending
on exposure. The continuously elevated PTH in primary
hyperparathyroidism (PHPT) increased bone turn over, the
risk of fracture and decreases bone mineral density (BMD)
in both the spine and peripheral skeleton when measured
with dual energy absorptiometry (DXA). As opposed to this
18 month of treatment with once daily biosynthetic PTH injections in patients with osteoporosis, increases spine BMD
by approx. 10% whereas in the hip and forearm an initial
Birgitte Vind, MD
Studies of molecular mechanisms behind insulin resistance in type 2 diabetes
The ph.d. study comprises two different projects which address the pathogenetic features behind insulin resistance
15
and glucose metabolism in type 2 diabetes from different
angles. In the first project glucose metabolism is examined
by means of a hyperinsulinemic clamp at euglycemic and
hyperglycemic conditions respectively in order to evaluate
the effect of glycemia on the activities of relevant intramyocellular enzymes. In the second project the effect of training
on insulin resistance and selected metabolic parameters is
evaluated in a group of type 2 diabetic subjects compared
with obese controls.
Material and methods:
360 obese women with BMI> 30 are randomised to lifestyle intervention (n=180) or control group (n=180).
The intervention is composed of individual dietarian
counselling and physical training. The physical training
includes weekly aerobic lessons in a fitness centre and
coaching in small groups. Both groups will be examined
during pregnancy with extra ultrasound scanning of the
fetus and measuring of weight, blood pressure, and metabolic markers.
Lena Sønder Snogdal, MD
Genetic Variants and Phenotypic Characteristics of
Patients with Type 2 Diabetes Mellitus
Xiaolu Zhao, MSc
Mass spectrometry-based quantitative proteomics
in the study of mitochondrial dysfunction in muscle
in type 2 diabetes
The aim of this PhD study is to get a further insight in the
field of Type 2 Diabetes (T2D) and genetics. T2D is a disease of worldwide increasing incidence and prevalence. It
is caused both by genetic and environmental factors. There
is an ongoing intensive research in the genetic field. Hopefully this work can add new knowledge into this field.
Therefore the project consists of several arms:
1. Collecting DNA and clinical data from a cohort of T2D
patients and non-diabetic controls in Odense
2. A candidate gene study of genes related to mitochondrial dysfunction and oxidative phosphorylation in DNA from
existing cohorts from Odense and Steno Diabetes Center
3. A second candidate gene study of genes related to lipid
droplets on existing cohorts from Odense and Steno Diabetes Center and on my own cohort
4. A third study of genes already associated to T2D in a
specific group of patients from Odense who has previously
been examined by hyperinsulinaemic clamps on muscle
biopsies.
Mitochondria are the primary energy-generating systems
in eukaryotes. They play a crucial role in oxidative metabolism including carbohydrate metabolism, fatty acid
oxidation and urea cycle, as well as in calcium signaling
and apoptosis. Mitochondria dysfunction is centrally involved in a number of human pathologies, such as type
2 diabetes (T2D). Abnormalities in mitochondrial oxidative phosphorylation (OXPHOS) activity are believed to
contribute to fat accumulation and insulin resistance in
skeletal muscle of patients with T2D. To which extent
this is caused by post-translational modifications (PTMs)
of OXPHOS proteins remains undetermined. Mass spectrometry-based proteomic analysis is a powerful tool for
global profiling and quantification of proteins and their
PTMs. Therefore, the aim of this project is to establish
methods for application of mass spectrometry -based
quantitative proteomics and phosphoproteomics in mitochondria isolated from human skeletal muscle biopsies,
and apply these methods in identifying OXPHOS proteins
with altered expression and/or phosphorylation in muscle
mitochondria from patients with T2D.
Christina Anne Vinter, MD
LIFESTYLE AND PREGNANCY: The clinical effect of
lifestyle intervention during pregnancy in obese
women
Steffen Bak, MD
Phosphoproteomic characterisation of mitochondrial dysfunction and insulin resistance in type 2
diabetes. From molecule to diabetes
Aims
1. To study the effects of diet and physical training during
pregnancy among Danish obese women. Primary outcomes: Rate of caesarean section, gestational diabetes
mellitus, hypertension/preeclampsia, LGA, and admission
to neonatal intensive care unit.
2. To describe the metabolic effects of lifestyle intervention during pregnancy.
Background:
Obesity in pregnancy is related to higher maternal morbidity and perinatal morbidity and mortality. The risk of
gestational diabetes, hypertensive complications, caesarean section, induction of labour, and children born
large for gestational age (LGA) is increased with increasing maternal BMI.
The central hypothesis of this project is that reversible
phosphorylation of mitochondrial proteins contributes
to the regulation of a number of mitochondrial processes, and that abnormalities in this regulation play a role
for the link between mitochondrial dysfunction and IR.
Such abnormalities could be due to altered signaling to
mitochondrial phosphoproteins in response to insulin and
acute exercise in the presence of hyperglycemia (T2D)
and obesity.
The overall goal of my project is to characterize reversible
phosphorylation of mitochondrial proteins in human skeletal muscles in response to insulin and acute exercise,
and how potential abnormalities in the phosphorylation
of mitochondrial proteins in response to these stimuli in
obesity and T2D relate to defects in insulin-stimulated
glucose metabolism and insulin signaling.
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The Molecular Endocrinology Unit (KMEB)
expression of telomerase gene (hTERT) in hMSC leads to
rescuing the senescent phenotype of hMSC and also enhanced their differentiation capacity. The biological function of telomerase activity regarding mMSC diff & bone
formation is not known. Therefore, the aim of this project is to understand the physiological role of telomerase
in osteogenic stem cell proliferation and differentiation
and also its effects on bone homeostasis in vivo by using
TERC knockout mouse model that lacks telomerase activity due to null mutation in RNA component (TERC).
Lasse Kjær, MSc
The potential for the generation of nerve cells from
human embryonic stem cells
Human embryonic stem cells (hESCs) have the ability for
unlimited self-renewal and the potential for generating
all cell types of the human adult body. By these virtues
they present a prospective source of cells for treatment
of diseases resulting from cellular, such as Parkinson’s disease. In this thesis it was shown that the hESC lines OD3
and HUES9 had a normal karyotype and were maintained
in the undifferentiated state. Differentiation of the cell
lines revealed that OD3 had a predisposition for generation of the mesodermal germlayer, and HUES9 for the
ectodermal germlayer. Inhibition of the TGF-b/Activin/
Nodal and BMP signalling pathways during differentiation
was found to promote generation of neuroectoderm. It
was furthermore found that exogenous Retinoic acid resulted in a concentration dependent acquisition of neural
rostrocaudal identity and was found to increase the number of tyrosine hydroxylase positive neurons for certain
concentrations of RA.
Maria E. O. Nielsen, MSc
Identification and characterization of membrane
marker proteins selective for adipogenesis, chondrogenesis, and osteogenesis in human mesenchymal stem cells using quantitative proteomics and
live-cell imaging in combination with RNA interference
We have identified and quantified proteins from plasma
membrane selective for adipogenesis and osteogenesis
using a high-through put proteomics strategy. By comparing the protein profiles for each differentiation pathway
it is possible to distinguish which proteins are selectively
up- or down-regulated in each of the two differentiation
processes. These proteins will be validated with fluorescence microscopy among others methods.
Ann Dorte Storm Pørneki, MSc
Derivation of pancreatic progenitor cells from human embryonic stem cells
Kenneth Hauberg Larsen, MSc
Differentiation of human embryonic stem cells into
osteogenic precursor cells through mesodermal induction
A transplantable source of β-cells for the treatment of
Diabetes type I could be obtained from the directed in vitro differentiation of human embryonic stem cells (hESC).
To achieve the goal of functional cells for therapy it is necessary to recapitulate the embryonic development and
to direct the hESC through the various developmental
stages along the path to mature β-cells. The first step
in this directed in vitro differentiation is the induction of
definitive endoderm. This is accomplished by a combination of high TGF-β/Activin A signalling and low PI3Ksignalling. The aim is to differentiate these endodermal
progenitor cells further towards cells with markers of foregut and ultimately to pancreas progenitor cells.
Human mesenchymal stem cells or bone marrow derived
marrow stromal cells (hMSC) represents a group of stem
cells located in the bone marrow stroma. They are capable of multilineage differentiation into various mesodermlike cells such as adipocytes, chondrocytes, myoblasts
and osteoblasts. MSCs are important candidates to be
employed in cell-based therapy for a variety of diseases
ranging from osteogenesis imperfecta, bone and cartilage
defects, and achilles tendon repair. The focus of our group
is to understand the cellular and molecular mechanisms
controlling bone formation. This is relevant since one major disease affecting the elderly population: osteoporosis
is the result of age-related bone loss due to decreased
bone formation. Recently, our group has employed large
scale screening strategies of geneomics and proteomics
in order to identify factors controlling bone formation as
well as novel markers associated with osteoblastic phenotype in vitro. The aim of this study is to functionally verify novel markers identified by SILAC-based proteomics
and to study their possible regulatory role during osteoblast differentiation, as well as their possible use for isolating specific cell populations of hMSC with bone forming
phenotype. We will employ a variety of methods to verify
Hamid Saeed, Msc
The Physiological role of telomerase enzyme in
osteoblast differentiation in vitro and bone homeostasis in vivo
Osteoporosis is a multifactorial and multifaceted disorder
leading to an increased risk for osteoporotic fractures.
Senescent micro-environment due to aging coupled with
telomerase deficiency resulted in accumulation of senescent osteogenic stem cells that imprecise the differentiation of mesenchymal stem cells. It is well documented
that telomerase activity is one of the limiting factors that
accelerated cellular senescence and decreased organ
regeneration. We have demonstrated that ectopic over-
17
these results and to identify important and relevant markers. Cell sorting of specific populations that are positive
for potential markers will be examined for their in vitro
and in vivo differentiation. In order to identify a possible
role of these markers in osteoblast differentiation, we will
block or over express these proteins, and study the effects on osteoblast differentiation. Furthermore we aim to
functionally test the osteogenic potential of prospectively
isolated hMSC in vivo employing novel 3D-osteoconductive scaffolds. Traditionally, we have employed hydroxyapatite/tricalcium phosphate (HA/TCP). Recently and
through collaboration with several biotech companies,
University of Aarhus, and the iNANO center, we have access to a variety of novel scaffolds. We will test the ability of these scaffolds to enhance bone formation of the
prospectively isolated cell and to compare the efficiency
of bone formation with that observed in HA/TCP using
histomorphometric methods developed in our lab.
have recently confirmed that this mechanism also seem
to occur in HBM patients from Fyn.
To further investigate the mechanism behind HBM caused
by mutation in Lrp5, we are studying the effects of serum
obtained from these patients on mesenchymal stem cells
(MSC). These results show that serum from HBM patients
promote the differentiation of MSC into osteoblasts while
inhibiting differentiation into adipocytes. These differences seem not to depend on serotonin and we are studying
what alternative components of serum causes these effects.
Abbas Jafari Kermani, MSc
Identification of kinases that determine differentiation of Human Mesenchymal Stem Cells into osteoblastic cells and their use as therapeutic targets for
modifying osteoblast differentiation and enhancing
bone formation
Human Mesenchymal Stem Cells have the potential to be
differentiated into a variety of cell types including osteoblasts and they are considered as a very attractive cell
type to be used in cell therapy of bone related diseases.
Looking into the mechanisms which govern osteogenic
differentiation of MSCs is of great importance, as this can
lead to development of new drugs, as well as, strategies
to improve bone forming ability of these cells.
Therefore, the aim of this project is to identify kinases
which control osteoblastic differentiation of hMSCs, using
a high-throughput siRNA library screening, using a library
which contains 3 different siRNAs for each of the ~800
known kinases represented in the human genome. In order to assess the effect of each kinase knock down on the
osteoblastic differentiation of hMSCs, Alkaline phosphatase activity will be quantified. Having identified kinases
that positively or negatively influence osteoblastic differentiation, we will perform verification experiments, both
in vitro and in vivo.
Tom E. Andersen, MSc
Regulation of bone mass by Lrp5 and the influence
of Lrp5-T253I in bone remodelling
Bone is a dynamic tissue that undergoes a balanced process of bone formation (mediated by bone forming cells;
osteoblasts) and bone resorption (mediated by bone resorbing cells; osteoclasts). This bone remodelling occurs
throughout life and constantly adjusts the strength of
the bones to conform to the physical stress of weight
load on the bones. Disturbance of this process gives
rise to diseases in the skeletal system with either increased (high bone mass, HMB) or decreased bone mass
(osteoporosis). As the life expectancy of the population
in the modern world is constantly increasing and because
osteoporosis is a common disease especially in elderly
people, the number of people suffering from osteoporosis
is expected to increase in the future. At present, treatment of osteoporosis primarily targets bone resorption
by inhibiting the osteoclasts. Often however the primary
cause of osteporosis is not due to high bone resorption by
osteoclasts but due to too low bone formation by osteoblasts. To date only a single treatment (PTH approved by
FDA, 2006) targets osteoblasts in order to increase bone
formation. It is therefore much needed to reach a better understanding of how mature osteoblasts regulate the
bone mass and how to increase their bone forming ability.
The Pituitary – and Clinical Nutrition
Research Group
Kristian Wraae, MD
Odense Androgen and Growth Factor Study in Elderly Men
The project is a clinical investigation of 800 men between
60 and 75 years of age. Primarily, we investigated the relationship between androgens, growth factors and other
hormones, on one hand, and body composition (muscle,
fat and bone) and physical ability (strength and physical
performance) on the other hand. Moreover, we investigate the importance of various genes and lifestyle factors
for the correlation between hormones and body composition/physical ability. In addition, the study will answer
questions regarding aging and the causes of decreasing
androgen levels and growth factor levels in the blood.
The LRP5 protein belongs to the low density lipoprotein
receptor (LDLR) family, which are cell surface proteins
that bind and internalize ligands. LRP5 function as a coreceptor of wnt factors and recently it was shown also
to regulate the level of serotonin in blood from the gut.
People having an inactivating mutation in Lrp5 suffer
from severe osteoporosis while people having an activating mutation have HBM. This occurs by an effect of these
mutations on the circulating levels of serotonin in blood
which affects proliferation of osteoblasts in bone. We
18
Louise Frederiksen, MD
Odense Androgen Study - The effect of Testim and
training in a population based, randomized, placebo controlled, double blinded study on hypogonadal men
Søren Fast, MD, PhD student
The effect of pretreatment with 0.1 mg of recombinant human TSH (rhTSH) on thyroid 131I uptake
and goitre volume reduction, following 131I-therapy for non-toxic benign nodular goitre. A randomized double blinded, placebo-controlled trial
Testosterone is widely used to treat relative hypogonadism in elderly males, but the indication for treatment
and safety of treatment is still being debated.
This study will examine the effect of testosterone (gel) on
body composition, insulin sensitivity, physical performance, muscle strength, sexual function and quality of life.
The study duration is 6 months. 60 males (60-78 years) are randomized into groups (testosterone, placebo
and strength training) and the strength training group
is further randomized to placebo or testosterone after 3
months.
Examination program, including physical testing, MRI
spectroscopy, DXA and euglyceamic clamp will be conducted every three months.
The main objective of this study is to examine whether
the amplification of 131I-therapy with 0.1 mg of rhTSH
allows a 131I-dose reduction, from 100 Gy to 50 Gy, in
non-toxic nodular goitre patients. In addition the optimal
time interval between rhTSH administration and 131Itherapy is studied.
The Clinical Nursing Research Group
Mette Rothmann, cand.scient.san
Risk stratified screening for osteoporosis in Region
Syddanmark – a study focusing on the patient perspective.
The Thyroid Research Group
The purpose is to focus on the significance, the procedure and the experience obtained by participating in a
screening process. As part of this study women’s own
assessments of risk of bone fractures as well as other factors of influence will be evaluated. The hypothesis is that
the patient perspective is important if current screening
programmes are to be implemented successfully, and this
study will provide knowledge both to be used for targeted
information about a screening programme as well as
communication of and follow-up on the screening result.
Daniel El-Fassi, MD, PhD student
Clinical and immunological aspects of B-lymphocyte depletion in Graveś disease
We have conducted a controlled, clinical study evaluating the effect of B lymphocyte depletion with rituximab
on autoantibody levels, autoantibody specificity, thyroid
function, and ophthalmic findings in Graves’ disease.
Further studies adressing changes in the immune functions of the patients are ongoing.
Thyroid examination
19
RESEARCHERS AND TECHNICAL/ADMINISTRATIVE STAFF IN EFE AS PER 31 DECEMBER 2009
Anne Holm Nyland, MSc in nursing, RN (clinical development nurse, Department of Endocrinology, Odense
University Hospital)
Lillian Petersen (nurse, Department of Endocrinology,
Odense University Hospital)
Lene Borgen Esman, (nurse, Department of Endocrinology, Odense Univesity Hospital)
Carina Rebsdorf, (nurse, Department of Endocrinology,
Odense Univesity Hospital)
The Bone and Calcium Research Group
Researchers
Kim Torsten Brixen, Associate Professor, PhD (consultant, Department of Endocrinology, Odense University
Hospital)
Pernille Hermann, PhD (consultant, Department of Endocrinology, Odense University Hospital)
PhD students
PhD student
Dorthe Nielsen, RN (MHS, PhD-student. University of
Southern Denmark)
Morten Frost Nielsen, MD (Department of Endocrinology, Odense University Hospital)
Katrine Hass Rubin, Pt, MHS, (Department of Endocrinology, Odense University Hospital)
Stinus Hansen, MD (Department of Endocrinology,
Odense University Hospital)
Mette Rothmann (nurse, Department of Endocrinology,
Odense University Hospital)
The Diabetes Research Group
Researchers
Henning Beck-Nielsen, Professor, DMSc, head of research (consultant, Department of Endocrinology, Odense University Hospital)
Michael Gaster, MD, PhD (Assistant Research Professor,
KMEB, Department of Endocrinology, Odense University
Hospital)
Jan Erik Henriksen, MD, PhD (consultant, Department
of Endocrinology, Odense University Hospital)
Ole Hother-Nielsen, DMSc (consultant, Department of
Endocrinology, Odense University Hospital)
Kurt Højlund, MD, PhD (Senior House Officer, Department of Endocrinology, Odense University Hospital)
Dorte Møller Jensen, PhD (Senior House Officer, Department of Endocrinology, Odense University Hospital)
Tine Thingholm, MSc, PhD (Department of Endocrinology, Odense University Hospital)
Knud Yderstræde, PhD (consultant, Department of Endocrinology, Odense University Hospital)
Torben Hansen, MD, PhD (adj. Professor, Department of
Endocrinology, Odense University Hospital, University of
Southern Denmark and Steno Diabetes Center)
Aase Handberg, DMSc, PhD (Ass. professor, Department of Endocrinology, Odense University Hospital and
Unviersity of Southern Denmark)
External researchers
Signe Beck-Nielsen, MD (House Officer, Afd. H, OUH +
Esbjerg Centralsygehus)
Ellen Hamborg-Petersen, MD (House Officer, Esbjerg
Centralsygehus)
Claus Lohman Brasen, MD (Department of Biochemistry, Pharmacology and Genetics, Odense University Hospital)
Lars Folkestad, MD, (Esbjerg Central Hospital)
Mikkel Høiberg, MD, Kristiansand, Norge
Technical/administrative staff
Donna Arbuckle-Lund (technologist), Elsebeth Byrge
(secretary), Sandra Harris Nielsen (secretary), Anette
R. Madsen (technologist), Steffanie Anthony Christensen (technologist), Elizabeth Hanmann (technologist), Lotte Hørlyck (technologist), Jeanette Lindegaard (technologist), Jane Nielsen (technologist), Jane
Nielsen (technologist), Mette Brøchner Hansen (technologist).
Clinical Nursing Research Group
PhD students
Charlotte Mose (head nurse, Department of Endocrinology, Odense University Hospital
Lone Hammelsvang (nurse, Department of Endocrinology, Odense University Hospital)
Helle Vagner Nielsen (nurse, Department of Endocrinology, Odense University Hospital)
Lisbeth Minet, PT, MHS, Ph.D.-student (Department of
Endocrinology, Odense University Hospital)
Birgitte Vind, MD (Department of Endocrinology, Odense University Hospital)
Christina Anne Vinter, MD, (Department of Gynaecology, Odense University Hospital)
20
PhD students
Xiaolu Zhao, MSc, (Institute of Biochemistry and Molecular Biology, University of Southern Denmark)
Lena Sønder Snogdal, MD (Department of Endocrinology, Odense University Hospital)
Steffen Bak, MSc (Dept. of Biochemistry and Molecular
Biology, University of Southern Denmark)
Ann Dorte Pørneki, MSc (KMEB, Department of Endocrinology, Odense University Hospital)
Hamid Saeed, Msc, (KMEB, Department of Endocrinology, Odense University Hospital)
Tom E. Andersen, MSc (KMEB, Department of Endocrinology, Odense University Hospital)
Maria E. O. Nielsen, Msc (CEBI, University of Southern
Denmark & KMEB, Department of Endocrinology, Odense
University Hospital)
Abbas Jafari Kermani, MSc (Institute of Medical Biology, University of Southern Denmark)
Diyako Qânie, MSc (KMEB, Department of Endocrinology, Odense University Hospital)
External researchers
Klaus Brusgaard, MSc, PhD (molecular biologist, Department of Clinical Biochemistry, Genetics and Pharmacology, Odense University Hospital)
Klaus Levin, MD, PhD (staff specialist, Svendborg Hospital)
Pernille Poulsen, PhD (post.doc., Steno Diabetes Center, Gentofte)
Henrik Støvring, MSc (Institute of Public Health, General
Practice Research Unit, University of Southern Denmark)
Jørgen Wojtaszenski, PhD, (Institute of August Krogh,
University of Copenhagen)
Other students
Pernille Rasmussen, Thesis student
Mohamed Abdelgawad, Research Trainee
Olena Kucheryavenko, Research Trainee
Technical/administrative staff
Nanett Mosumgaard (research secretary), Charlotte
Olsen (technologist), Lone Hansen (technologist), Vibe
Vestergaard (research nurse), Ewa Romancsuk ( research nurse), Kristine Michailidis (research secretary), Irene Lynfort (technologist), Jeanett Agergaard
(technologist), Ariane Minet (MSc)
Technical/administrative staff
Tina Hansen Barbisan (research secretary), Tina K.L.
Nielsen (technologist), Bianca Jørgensen (technologist), Stephanie Shouse (technologist), Helle Hansen
(assistant), Lone Christiansen (technologist)
The Molecular Endocrinology Unit (KMEB)
Researchers
Moustapha Kassem, Professor, DMSc, PhD (consultant,
KMEB, Department of Endocrinology, Odense University
Hospital)
Basem Abdallah, MSc, PhD, Lecturer (KMEB, Department of Endocrinology, Odense University Hospital)
Jorge Burns, MSc, PhD, Assistant Research Professor
(KMEB, Department of Endocrinology, Odense University
Hospital)
Nicholas Ditzel, Research Assistant (KMEB, Department
of Endocrinology, Odense University Hospital )
Linda Harkness, MPhil, Research Assistant (KMEB, Department of Endocrinology, Odense University Hospital)
Weimin Qiu, Assistant Research Professor (KMEB, Department of Endocrinology, Odense University Hospital)
Kenneth Hauberg, Research assistant (KMEB, Department of Endocrinology, Odense University Hospital)
Li Chen, Assistant research professor (KMEB, Department of Endocrinology, Odense University Hospital)
Amer Mahmood, Research assistant (KMEB, Department of Endocrinology, Odense University Hospital)
Lars Peter Kristensen, Research assistant (KMEB, Department of Endocrinology, Odense University Hospital)
21
The Pituitary- and Clinical Nutrition Research Group
The Thyroid Research Group
Researchers
Laszlo Hegedüs, DMSc (Professor, consultant, Department of Endocrinology, Odense University Hospital)
Steen Joop Bonnema, MD, PhD (Consultant, Department of Endocrinology, Odense University Hospital)
Thomas Heiberg Brix, MD, PhD (Senior House Officer,
Department of Endocrinology, Odense University Hospital)
Pia Skov Hansen, MD, PhD (Post.doc., Department of
Endocrinology, Odense University Hospital, and Institute
of Public Health, Epidemiology, University of Southern
Denmark)
Helle Døssing, MD, PhD (consultant, Department of
Oto-rhino-laryngology, Odense University Hospital)
Viveque Egsgaard Nielsen, MD, PhD (Department of
Oto-rhino-laryngology, Århus University Hospital)
Anina L. Jensen, BSc (Department of Endocrinology,
Odense University Hospital)
Frans B. Kristensen, MD (Senior Registrar, Department
of Endocrinology, Odense University Hospital)
Researchers
Marianne Andersen, PhD (consultant, Department of
Endocrinology, Odense University Hospital)
Rene Klinkby Støving, PhD (consultant, Department of
Endocrinology, Odense University Hospital)
Dorte Glintborg, MD, PhD (Medical Department, Kolding
Hospital)
Torben Leo Nielsen (House Officer, Medical Department, Odense University Hospital)
Magdalena Andries, MD (House Officer, Medical Department, Odense University Hospital)
Laima Saudaskiene (House Officer, Medical Department, Odense University Hospital)
Alin Andries, MD (Department of Endocrinology, Odense
University Hospital)
Laura Vad Winkler, MD (Medical Department, Svendborg Hospital)
Ida Ringsborg Madsen, MD (Department of Endocrinology, Odense Univesity Hospital)
Stina Bolette Martin, MD (Department of Endocrinology, Odense Univesity Hospital)
Linnéa E. Lingqvist, MD (Department of Endocrinology,
Odense University Hospital)
PhD students
Daniel El-Fassi, MD (Department of Endocrinology,
Odense University Hospital)
Søren Fast, MD (Department of Endocrinology, Odense
University Hospital)
PhD students
Kristian Wraae, MD (Department of Endocrinology,
Odense University Hospital)
Louise Frederiksen, MD (Department of Endocrinology,
Odense University Hospital)
Hanne Mumm, MD (Department of Endocrinology,
Odense University Hospital
External researchers
Finn N. Bennedbæk, MD, PhD (Consultant, Department
of Endocrinology, Herlev Hospital, University of Copenhagen)
Malene Boas, MD (clinical assistant, PhD student House
Officer, Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen)
Esther Jensen, MD (consultant, Department of Clinical
Biochemistry, Hillerød Hospital)
Claus H. Nielsen, MD, MSc, PhD (Consultant, Institute
of Inflammation Research, Rigshospitalet, University of
Copenhagen)
Torquil Watt, MD (PhD student, Endocrine Clinic, Abdominal Center, Rigshospitalet)
Terry J. Smith, MSD, PhD (Department of Ophtamology
an Visual Sciences, Kellogg Eye Center and Department
of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, USA)
Birte Kristensen, MSc (Clinical Assistant, Institute of
Inflammation Research, Rigshospitalet, Copenhagen, and
Department of Endocrinology, Odense University Hospital)
External researchers
Thue Kvorning, MSc (Institute of Sport Sciences and
Biomechanics, University of Southern Denmark)
Klavs Madsen (Institute of Sport Sciences and Biomechanics, University of Southern Denmark)
Claus Hagen, DMSc (consultant, Department of Endocrinology, Gentofte Hospital)
Jan Frystyk, PhD (consultant, Medical Research Laboratories, Aarhus University Hospital)
Allan Flyvbjerg (Professor, consultant, Medical Research
Laboratories, Clinical Institute, Aarhus University Hospital)
Joanna Ganc-Petersen (Senior House Officer, Department of Orthopaedic Surgery, Fredericia Hospital)
Kirsten Hørder, MD (consultant, Center for Eating Disorders, Odense University Hospital)
Niels Bilenberg, MD (professor, Department of Child
Psychiatry, Odense University Hospital)
Per Nøhr-Jensen, MD (consultant, Center for Eating
Disorders, Odense University Hospital)
Technical/administrative staff
Ellen Andersen (technologist), Henny Hansen (technologist), Annagrethe Jeppesen (technologist), Susanne Møller (technologist), Berit Knold (dietician),
Mette Hansen (clinical assistant).
22
COMPLETED PHD THESES
Jesper Ryg
The Frail Hip. A study on the risk of second hip
fracture, prevalence of osteoporosis and adherence
to treatment in patients with recent hip fracture.
Malthe Kristiansen
Isolation and characterisation of human mesenchymal stem cells from bone marrow and their potential use in therapy.
Iben Brock Jacobsen
New Aspects of insulin treatment in type 1 diabetes.
Amer Mahmood
Differentiation of human embryonic stem cells into
osteogenic precursor cells through mesodermal induction.
Martin Mogensen
Mitochondrial function in patients with type 2 diabetes.
Lars Peter Kristensen
Using quantitative proteomics methods for studying the secreteome of human mesenchymal stem
cells during osteoblast differentiation.
Mikael Kjær Poulsen
Prevalence of macrovascular disease in Type 2 Diabetes Mellitus: Left ventricular diastolic dysfunction, myocardial ischemia and peripheral vascular
insufficiency.
Stem cell research
23
PUBLICATIONS
(peer reviewed papers and book chapters)
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Abdallah, Basem ; Kassem, Moustapha. I: Journal of Cellular Physiology. 2009 ; vol. 218, nr. 1, Jan. United States. s.
9-12 /The use of mesenchymal (skeletal) stem cells for treatment of degenerative diseases: current status and future perspectives.
Abrahamsen, B ; Eiken, P ; Brixen, K. I: Journal of Internal
Medicine. 2009 ; vol. 265, nr. 5, 2009-May. England. s.
581-92 / Atrial fibrillation in fracture patients treated with
oral bisphosphonates.
Bay-Jensen, Anne-Christine ; Tabassi, Nadine ; Sondergaard, Lene ; Andersen, Thomas ; Dagnaes-Hansen, Frederik ;
Garnero, Patrick ; Kassem, Moustapha ; Delaisse, Jean-Marie. I:
Arthritis Research & Therapy. 2009 ; vol. 11, nr. 1, 2009-Jan-20. s.
R9 / The response to estrogen deprivation on cartilage collagen degradation markers; CTX-II is unique compared to other markers of
collagen turnover.
Beck-Nielsen, Signe ; Jacobsen, Bendt ; Gram, Jeppe ; Brixen, Kim
; Jensen, Tina Kold. I: European Journal of Endocrinology. 2009 ;
vol. 160, nr. 3, s. 491-497 / Incidence and prevalence of nutritional
and hereditary rickets in southern Denmark.
Beck-Nielsen, Signe ; Jensen, Tina Kold ; Gram, Jeppe ; Brixen,
Kim ; Brock-Jacobsen, Bendt. I: European Journal of Pediatrics.
2009 ; vol. 168, nr. 8, August. s. 941-949 / Nutritional rickets in
Denmark : a retrospective review of children’s medical records
from 1985 to 2005.
Bellantuono, Ilaria ; Aldahmash, Abdullah ; Kassem, Moustapha.
I: Biochimica et Biophysica Acta. 2009 ; vol. 1792, nr. 4, 2009-Apr.
Netherlands. s. 364-70 / Aging of marrow stromal (skeletal) stem
cells and their contribution to age-related bone loss.
Boas, Malene ; Hegedüs, Laszlo ; Feldt-Rasmussen, Ulla ; Skakkebaek, Niels E ; Hilsted, Linda ; Main, Katharina M. I: Journal of
Clinical Endocrinology and Metabolism. 2009 ; vol. 94, nr. 10,
2009-Oct. United States. s. 4031-5 / Association of thyroid gland
volume, serum insulin-like growth factor-I, and anthropometric variables in euthyroid prepubertal children.
Boesgaard, Trine Welløv ; Gjesing, Anette Prior ; Grarup, Niels
; Rutanen, Jarno ; Jansson, Per-Anders ; Hribal, Marta Letizia ;
Sesti, Giorgio ; Fritsche, Andreas ; Stefan, Norbert ; Staiger, Harald
; Häring, Hans ; Smith, Ulf ; Laakso, Markku ; Pedersen, Oluf ;
Hansen, Torben ; EUGENE2 Consortium. I: PLoS ONE. 2009 ; vol.
4, nr. 9, 2009-null. United States. s. e7236 / Variant near ADAMTS9
known to associate with type 2 diabetes is related to insulin resistance in offspring of type 2 diabetes patients - EUGENE2 study.
Bonnema, Steen J ; Hegedüs, Laszlo. I: Current opinion in endocrinology, diabetes, and obesity. 2009 ; vol. 16, nr. 5, 2009-Oct. England. s. 379-84 / A 30-year perspective on radioiodine therapy of
benign nontoxic multinodular goiter.
Bouatia-Naji, Nabila ; Bonnefond, Amélie ; Cavalcanti-Proença,
Christine ; Sparsø, Thomas ; Holmkvist, Johan ; Marchand, Marion ; Delplanque, Jérôme ; Lobbens, Stéphane ; Rocheleau, Ghislain ; Durand, Emmanuelle ; De Graeve, Franck ; Chèvre, JeanClaude ; Borch-Johnsen, Knut ; Hartikainen, Anna-Liisa ; Ruoko-
24
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nen, Aimo ; Tichet, Jean ; Marre, Michel ; Weill, Jacques ; Heude,
Barbara ; Tauber, Maithé ; Lemaire, Katleen ; Schuit, Frans ; Elliott,
Paul ; Jørgensen, Torben ; Charpentier, Guillaume ; Hadjadj, Samy ;
Cauchi, Stéphane ; Vaxillaire, Martine ; Sladek, Robert ; Visvikis-Siest, Sophie ; Balkau, Beverley ; Lévy-Marchal, Claire ; Pattou, François ; Meyre, David ; Blakemore, Alexandra I F ; Jarvelin,
Marjo-Riita ; Walley, Andrew J ; Hansen, Torben ; Dina, Christian ;
Pedersen, Oluf ; Froguel, Philippe. I: Nature Genetics. 2009 ; vol.
41, nr. 1, 2009-Jan. United States. s. 89-94 / A variant near MTNR1B is associated with increased fasting plasma glucose levels
and type 2 diabetes risk.
Boström, Pontus ; Andersson, Linda ; Li, Lu ; Perkins, Rosie ;
Højlund, Kurt ; Borén, Jan ; Olofsson, Sven-Olof. I: Biochemical
Society Transactions. 2009 ; vol. 37, nr. Pt 5, Oct. England. s. 981-5
/ The assembly of lipid droplets and its relation to cellular insulin
sensitivity.
Brand, Oliver J ; Barrett, Jeffrey C ; Simmonds, Matthew J ; Newby,
Paul R ; McCabe, Christopher J ; Bruce, Christopher K ; Kysela,
Boris ; Carr-Smith, Jackie D ; Brix, Thomas ; Hunt, Penny J ; Wiersinga, Wilmar M ; Hegedüs, Laszlo ; Connell, John ; Wass, John
A H ; Franklyn, Jayne A ; Weetman, Anthony P ; Heward, Joanne M
; Gough, Stephen C L. I: Human Molecular Genetics. 2009 ; vol.
18, nr. 9, 2009-May-1. England. s. 1704-13 / Association of the thyroid stimulating hormone receptor gene (TSHR) with Graves’ disease.
Brix, Thomas Heiberg ; Hansen, Pia Skov ; Kyvik, Kirsten Ohm ;
Hegedüs, Laszlo. I: Journal of Clinical Endocrinology and Metabolism. 2009 ; vol. 94, nr. 11, 2009-Nov. United States. s. 4439-43 /
Aggregation of thyroid autoantibodies in twins from opposite-sex
pairs suggests that microchimerism may play a role in the early stages of thyroid autoimmunity.
Brix, Thomas Heiberg ; Hansen, Pia Skov ; Bennedbak, Finn Noe ;
Bonnema, Steen Joop ; Kyvik, Kirsten Ohm ; Ørstavik, Karen Helene ; Hegedüs, Laszlo. I: Twin Research and Human Genetics.
2009 ; vol. 12, nr. 5, 2009-Oct. Australia. s. 502-6 / X Chromosome
inactivation pattern is not associated with interindividual variations
in thyroid volume: a study of euthyroid danish female twins.
Brixen, Kim ; Kroustrup, Jens Peter. I: Medicinsk kompendium. /
red. Ove B Schaffalitzky de Muckadell ; Stig Haunsø ; Hendrik
Vildstrup. Bd. 2 17. udg. Nyt Nordisk Forlag / Schønberg Forlag /
Arnold Busck, 2009. s. 2389-2392 / Multiple endokrine neoplasier.
Brixen, Kim. I: Praktisk medicin. / red. Hansen Jens Georg. Dagens
medicin Bøger, 2009. s. 207-263 / Endokrine sygdomme.
Charni-Ben Tabassi, N ; Richardot, P ; Toh, L ; Marotte, H ; Jensen,
Anne-Christine Bay ; Miossec, P ; Garnero, P. I: Annals of the
Rheumatic Diseases. 2009 ; vol. 68, nr. 3, 2009-Mar. England. s.
451-2 / Circulating nitrated N-telopeptide of type III collagen
(IIINys) as a biochemical marker of oxidative-related synovial tissue metabolism in rheumatoid arthritis.
Chen, Muwan ; Feng, Wenzhou ; Cao, Hui ; Zou, Lijin ; Chen,
Chungui ; Baatrup, Anette ; Nielsen, Anne Bay ; Li, Haisheng ;
Kassem, Moustapha ; Zou, Xuenong ; Bünger, Cody. I: Journal of
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ethnopharmacology. 2009 ; vol. 125, nr. 1, 2009-Aug-17. Ireland. s.
75-82 / A traditional Chinese medicine formula extracts stimulate
proliferation and inhibit mineralization of human mesenchymal
stem cells in vitro.
Christensen, Signe Engkjær ; Nissen, Peter H ; Vestergaard, Peter ;
Heickendorff, Lene ; Rejnmark, Lars ; Brixen, Kim ; Mosekilde,
Leif. I: Clinical Endocrinology. 2009 ; vol. 71, 2009-Feb-25. s. 798807 / Skeletal consequences of familial hypocalciuric hypercalcaemia versus primary hyperparathyroidism.
Clausen, Tine D ; Mathiesen, Elisabeth R ; Hansen, Torben ; Pedersen, Oluf ; Jensen, Dorte M ; Lauenborg, Jeannet ; Schmidt,
Lone ; Damm, Peter. I: Journal of Clinical Endocrinology and Metabolism. 2009 ; vol. 94, nr. 7, 2009-Jul. United States. s. 2464-70
/ Overweight and the metabolic syndrome in adult offspring of women with diet-treated gestational diabetes mellitus or type 1 diabetes.
Dahl, Sandra Rinne ; Kleiveland, Charlotte Ramstad ; Kassem,
Moustapha ; Lea, Tor ; Lundanes, Elsa ; Greibrokk, Tyge. I: Journal
of chromatography. A. 2009 ; vol. 1216, nr. 22, 2009-May-29.
Netherlands. s. 4648-54 / Determination of thromboxanes, leukotrienes and lipoxins using high-temperature capillary liquid chromatography-tandem mass spectrometry and on-line sample preparation.
Douglas, Raymond S ; Tsirbas, Angelo ; Gordon, Mark ; Lee, Diana
; Khadavi, Nicole ; Garneau, Helene Chokron ; Goldberg, Robert A ;
Cahill, Kenneth ; Dolman, Peter J ; Elner, Victor ; Feldon, Steve
; Lucarelli, Mark ; Uddin, Jimmy ; Kazim, Michael ; Smith, Terry J
; Khanna, Dinesh ; Hegedüs, Laszlo ; International Thyroid Eye
Disease Society. I: Archives of Ophthalmology. 2009 ; vol. 127, nr.
9, 2009-Sep. United States. s. 1155-60 / Development of criteria
for evaluating clinical response in thyroid eye disease using a modified Delphi technique.
Douglas, Raymond S ; Brix, Thomas H ; Hwang, Catherine J ; Hegedüs, Laszlo ; Smith, Terry J. I: Journal of Clinical Endocrinology and Metabolism. 2009 ; vol. 94, nr. 5, 2009-May. United States. s. 1797-802 / Divergent frequencies of IGF-I receptor-expressing blood lymphocytes in monozygotic twin pairs discordant for
Graves’ disease: evidence for a phenotypic signature ascribable to
nongenetic factors.
Eastell, Richard ; Nickelsen, Thomas ; Marin, Fernando ; Barker,
Clare ; Hadji, Peyman ; Farrerons, Jordi ; Audran, Maurice ; Boonen, Steven ; Brixen, Kim ; Melo Gomes, Jose ; Obermayer-Pietsch,
Barbara ; Avramidis, Avraam ; Sigurdsson, Gunnar ; Glüer, Claus
C. I: Journal of Bone and Mineral Research. 2009 ; vol. 24, nr. 4,
Apr. s. 726-36 / Sequential Treatment of Severe Postmenopausal
Osteoporosis Following Teriparatide: Final Results of the Randomized, Controlled European Study of Forsteo (EUROFORS): Trial
registration: clinicaltrials.gov identifier NCT00191425 (Trial regi
stration date: 12 September 2005).
Fast, Søren ; Nielsen, Viveque Egsgaard ; Grupe, Peter ; Bonnema,
Steen Joop ; Hegedüs, Laszlo. I: Journal of Nuclear Medicine. 2009
; vol. 50, nr. 5, 2009-May. United States. s. 732-7 / Optimizing 131I
Uptake After rhTSH Stimulation in Patients with Nontoxic Multinodular Goiter : Evidence from a Prospective, Randomized, DoubleBlind Study.
Fast, Søren ; Nielsen, Viveque ; Bonnema, Steen ; Hegedus, Laszlo.
I: European Journal of Endocrinology. 2009 ; vol. 160, nr. 4, s. 517528 / Time to reconsider nonsurgical therapy of benign nontoxic
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multinodular goitre. Focus on recombinant human TSH (rhTSH)
augmented radioiodine therapy.
Fast, Søren ; Nielsen, Viveque Egsgaard ; Grupe, Peter ; Bonnema,
Steen Joop ; Hegedüs, Laszlo. I: Journal of Nuclear Medicine. 2009
; vol. 50, nr. 5, 2009-May. United States. s. 732-7 / Optimizing 131I
Uptake After rhTSH Stimulation in Patients with Nontoxic Multinodular Goiter : Evidence from a Prospective, Randomized, DoubleBlind Study.
Faerch, Kristine ; Vaag, Allan ; Holst, Jens J ; Hansen, Torben ;
Jørgensen, Torben ; Borch-Johnsen, Knut. I: Diabetes Care. 2009
; vol. 32, nr. 3, 2009-Mar. United States. s. 439-44 / Natural history
of insulin sensitivity and insulin secretion in the progression from
normal glucose tolerance to impaired fasting glycemia and impaired
glucose tolerance: the Inter99 study.
Finucane, F ; Luan, J ; Wareham, N ; Sharp, S ; O’Rahilly, S ;
Balkau, B ; Flyvbjerg, A ; Walker, M ; Højlund, K ; Nolan, J ; (on
behalf of the European Group for the Study of Insulin Resistance:
Relationship between Insulin Sensitivity and Cardiovascular Disease Risk Study Group) ; Savage, D. I: Diabetologia. 2009 ; vol.
52, nr. 11, 2009-Sep-12. s. 2345-2349 / Correlation of the leptin
: adiponectin ratio with measures of insulin resistance in non-diabetic individuals.
Frederiksen, L ; Nielsen, T L ; Wraae, K ; Hagen, C ; Frystyk, J ;
Flyvbjerg, A ; Brixen, K ; Andersen, M. I: Journal of Clinical Endocrinology and Metabolism. 2009 ; vol. 94, nr. 10, 2009-Oct. United States. s. 4010-5 / Subcutaneous rather than visceral adipose tissue is associated with adiponectin levels and insulin resistance in
young men
Gastaldelli, Amalia ; Kozakova, Michaela ; Højlund, Kurt ; Flyvbjerg, Allan ; Favuzzi, Angela ; Mitrakou, Asimina ; Balkau, Beverley ; RISC Investigators. I: Hepatology. 2009 ; vol. 49, nr. 5, 2009May. United States. s. 1537-44 / Fatty liver is associated with insuqlin resistance, risk of coronary heart disease, and early atherosclerosis
in a large European population
Gaster, Michael. I: Biochemical and Biophysical Research Communications. 2009 ; vol. 382, nr. 4, 2009-May-15. United States. s.
766-70 / Reduced lipid oxidation in myotubes established from
obese and type 2 diabetic subjects.
Gaster, Michael. I: Biochemical and Biophysical Research Communications. 2009 ; vol. 387, nr. 4, 2009-Oct-2. United States. s. 651-5
/ Reduced TCA flux in diabetic myotubes: A governing influence on
the diabetic phenotype?
Gjerstorff, Morten ; Burns, Jorge S ; Nielsen, Ole ; Kassem, Moustapha ; Ditzel, Henrik. I: American Journal of Pathology. 2009 ;
vol. 175, nr. 1, 2009-Jul. United States. s. 314-23 / Epigenetic moqdulation of cancer-germline antigen gene expression in tumorigenic
human mesenchymal stem cells: implications for cancer therapy.
Gjesing, Anette P ; Sparsø, Thomas ; Borch-Johnsen, Knut ; Jørgensen, Torben ; Pedersen, Oluf ; Hansen, Torben ; Olsen, Niels V.
I: PLoS ONE. 2009 ; vol. 4, nr. 9, 2009-null. United States. s. e7206
/ No consistent effect of ADRB2 haplotypes on obesity, hypertension and quantitative traits of body fatness and blood pressure
among 6,514 adult danes.
Glintborg, Dorte ; Andersen, Marianne ; Richelsen, Bjørn ; Bruun,
Jens M. I: Clinical Endocrinology. 2009 ; vol. 71, nr. 5, 2009Nov. England. s. 652-8 / Plasma monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha are
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increased in patients with polycystic ovary syndrome (PCOS) and
associated with adiposity, but unaffected by pioglitazone treatment.
Glintborg, Dorte ; Andersen, Marianne. I: ved ikke. 2009 / Medicinske sygdomme og tilstande med relevans for tandlægens kliniske
hverdag. Hypofyse- og binyresygdomme.
Gulmez, Sinem Ezgi ; Lassen, Annmarie Touborg ; Aalykke, Claus ;
Dall, Michael ; Andries, Alin ; Andersen, Birthe Søgaard ; Hansen,
Jane Møller ; Andersen, Morten ; Hallas, Jesper. I: British Journal
of Clinical Pharmacology. 2009 ; vol. 67, nr. 4, 2009-Apr. England.
s. 460-5 / Do statins protect against upper gastrointestinal bleeding?
Grau, K ; Hansen, Torben ; Holst, C ; Astrup, A ; Saris, W H M ;
Arner, P ; Rössner, S ; Macdonald, I ; Polak, J ; Oppert, J-M ;
Langin, D ; Martinez, J A ; Pedersen, O ; Sørensen, T I A. I: International Journal of Obesity. 2009 ; vol. 33, nr. 11, 2009-Nov. England. s. 1227-34 / Macronutrient-specific effect of FTO rs9939609
in response to a 10-week randomized hypo-energetic diet among
obese Europeans.
Grunnet, Louise G ; Brøns, Charlotte ; Jacobsen, Stine ; Nilsson,
Emma ; Astrup, Arne ; Hansen, Torben ; Pedersen, Oluf ; Poulsen,
Pernille ; Quistorff, Bjørn ; Vaag, Allan. I: Journal of Clinical Endocrinology and Metabolism. 2009 ; vol. 94, nr. 2, 2009-Feb. United
States. s. 596-602 / Increased recovery rates of phosphocreatine and
inorganic phosphate after isometric contraction in oxidative muscle
fibers and elevated hepatic insulin resistance in homozygous carriers of the A-allele of FTO rs9939609.
Grunnet, Louise G ; Nilsson, Emma ; Ling, Charlotte ; Hansen, Torben ; Pedersen, Oluf ; Groop, Leif ; Vaag, Allan ; Poulsen, Pernille.
I: Diabetes. 2009 ; vol. 58, nr. 10, 2009-Oct. United States. s. 24028 / Regulation and function of FTO mRNA expression in human
skeletal muscle and subcutaneous adipose tissue.
Hansen, S J ; Nielsen, Morten M. ; Ryg, J ; Wraae, K ; Andersen,
Marianne ; Brixen, K. I: Acta Radiologica. 2009 ; vol. 50, nr. 6,
2009-Jun-1. s. 658-63 / Radiographic Absorptiometry as a Screening Tool in Male Osteoporosis : Results from the Odense Androgen Study.
Hald, Andreas ; Hansen, RR ; Thomsen, MW ; Ding, Ming ; Croucher, PI ; Gallagher, O ; Ebetino, FH ; Kassem, Moustapha ; Heegaard, AM. I: International Journal of Cancer. 2009 ; vol. 125, nr. 5,
2009 Mar 19. s. 1177-1185
/ Cancer-induced bone loss and associated pain-related behavior is
reduced by risedronate but not its phosphonocarboxylate analog
NE-10790
Heile, Anna M B ; Wallrapp, Christine ; Klinge, Petra M ; Samii,
Amir ; Kassem, Moustapha ; Silverberg, Gerald ; Brinker, Thomas.
I: Neuroscience letters. 2009 ; vol. 463, nr. 3, 2009-Oct-9. Ireland.
s. 176-81 / Cerebral transplantation of encapsulated mesenchymal
stem cells improves cellular pathology after experimental traumatic
brain injury.
Hegedüs, Laszlo ; Brix, Thomas H ; Paschke, Ralf. I: Thyroid. 2009
; vol. 19, nr. 3, 2009-Mar. United States. s. 209-11 / Etiology of
simple goiter.
Hegedüs, Laszlo. I: Endocrinology & Metabolism Clinics of North
America. 2009 ; vol. 38, nr. 2, 2009-Jun. United States. s. 355-71, ix
/ Treatment of Graves’ hyperthyroidism: evidence-based and emerging modalities.
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Henriksen, Kim ; Byrjalsen, Inger ; Nielsen, Rasmus H ; Madsen,
Andreas N ; Larsen, Leif K ; Christiansen, Claus ; Beck-Nielsen,
Henning ; Karsdal, Morten A. I: European Journal of Pharmacology.
2009 ; vol. 616, nr. 1-3, 2009-Aug-15. Netherlands. s. 340-5 / A
comparison of glycemic control, water retention, and musculoskeletal effects of balaglitazone and pioglitazone in diet-induced obese
rats.
Holmkvist, Johan ; Banasik, Karina ; Andersen, Gitte ; Unoki, Hiroyuki ; Jensen, Thomas Skot ; Pisinger, Charlotta ; Borch-Johnsen,
Knut ; Sandbaek, Annelli ; Lauritzen, Torsten ; Brunak, Sören ; Maeda,
Shiro ; Hansen, Torben ; Pedersen, Oluf. I: PLoS ONE. 2009 ; vol.
4, nr. 6, 2009-null. United States. s. e5872 / The type 2 diabetes
associated minor allele of rs2237895 KCNQ1 associates with reduced insulin release following an oral glucose load
Home, Philip D ; Pocock, Stuart J ; Beck-Nielsen, Henning ; Curtis,
Paula S ; Gomis, Ramon ; Hanefeld, Markolf ; Jones, Nigel P ; Komajda, Michel ; McMurray, John J V ; RECORD Study Team. I:
Lancet. 2009 ; vol. 373, nr. 9681, 2009-Jun-20. England. s. 212535 / Rosiglitazone evaluated for cardiovascular outcomes in oral
agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial.
Højlund, Kurt ; Birk, Jesper B ; Klein, Ditte K ; Levin, Klaus ; Rose,
Adam J ; Hansen, Bo F ; Nielsen, Jakob N ; Beck-Nielsen, Henning
; Wojtaszewski, Jørgen F P. I: Journal of Clinical Endocrinology and
Metabolism. 2009 ; vol. 94, nr. 11, 2009-Nov. United States. s.
4547-56 / Dysregulation of glycogen synthase COOH- and NH2terminal phosphorylation by insulin in obesity and type 2 diabetes
mellitus.
Højlund, Kurt ; Birk, Jesper B ; Klein, Ditte K ; Levin, Klaus ; Rose,
Adam J ; Hansen, Bo F ; Nielsen, Jakob N ; Beck-Nielsen, Henning
; Wojtaszewski, Jørgen F P. I: Journal of Clinical Endocrinology and
Metabolism. 2009 ; vol. 94, nr. 11, 2009-Nov. United States. s.
4547-56 / Dysregulation of glycogen synthase COOH- and NH2terminal phosphorylation by insulin in obesity and type 2 diabetes
mellitus. / Forskning:
Højlund, Kurt ; Bowen, Benjamin P ; Hwang, Hyonson ; Flynn,
Charles R ; Madireddy, Lohith ; Thangiah, Geetha ; Meyer, Christian ; Mandarino, Lawrence J ; Yi, Zhengping. I: Journal of Proteome Research. 2009 ; vol. 8, nr. 11, 2009-Sep-18. s. 4954-65 / In
vivo Phosphoproteome of Human Skeletal Muscle Revealed by
Phosphopeptide Enrichment and HPLC-ESI-MS/MS.
Ibsen, Hans ; Jørgensen, Torben ; Jensen, Gorm B ; Jacobsen, Ib
Abildgaard. I: Ugeskrift for læger. 2009 ; vol. 171, nr. 24, 2009-Jun8. Denmark. s. 1998-2000 / Hypertension--forekomst og behandling.
Jacobsen, Iben Brock ; Henriksen, J E ; Hother-Nielsen, O ; Vach,
W ; Beck-Nielsen, H. I: Diabetes Research and Clinical Practice.
2009 ; vol. 86, nr. 1, 2009-Oct. Ireland. s. 1-10 / Evidence-based
insulin treatment in type 1 diabetes mellitus.
Jacobsen, Iben Brock ; Henriksen, Jan Erik ; Beck-Nielsen, Henning. I: Basic & Clinical Pharmacology & Toxicology. 2009 ; vol.
105, nr. 3, 2009-Sep. Denmark. s. 145-9 / The effect of metformin in
overweight patients with type 1 diabetes and poor metabolic control.
Jensen, Thomas ; Dolatshahi-Pirouz, Alireza ; Foss, Morten ; Baas,
Jørgen ; Lovmand, Jette ; Duch, Mogens ; Pedersen, Finn Skou ;
57.
58.
59.
60.
61.
62.
63.
64.
65.
Kassem, Moustapha ; Bünger, Cody ; Søballe, Kjeld ; Besenbacher,
Flemming. I: Colloids and surfaces. B, Biointerfaces. 2009 ; vol. 75,
nr. 1, 2010-Jan-1. Netherlands. s. 186-93 / Interaction of human mesenchymal stem cells with osteopontin coated hydroxyapatite surfaces.
Jensen, Dorte M ; Damm, Peter ; Ovesen, Per ; Mølsted-Pedersen,
Lars ; Beck-Nielsen, Henning ; Westergaard, Jes G ; Moeller, Margrethe ; Mathiesen, Elisabeth R. I: Diabetes Care. 2009 ; vol. 33, nr.
1, 2010-Jan. United States. s. 90-4 / Microalbuminuria, preeclampsia, and preterm delivery in pregnant women with type 1 diabetes: results from a nationwide Danish study.
Jensen, Dorte M ; Korsholm, Lars ; Ovesen, Per ; Beck-Nielsen,
Henning ; Moelsted-Pedersen, Lars ; Westergaard, Jes G ; Møller,
Margrethe ; Damm, Peter. I: Diabetes Care. 2009 ; vol. 32, nr. 6,
2009-June. s. 1046-1048 / Peri-conceptional HbA1c and risk of serious adverse pregnancy outcome in 933 women with type 1 diabetes.
Jägerström, Sara ; Polesie, Sam ; Wickström, Ylva ; Johansson,
Bengt R ; Schröder, Henrik D ; Højlund, Kurt ; Boström, Pontus.
I: Cell Biology International. 2009 ; vol. 33, nr. 9, Sep. Netherlands.
s. 934-40 / Lipid droplets interact with mitochondria using
SNAP23.
Jørgensen, Gitte Maria ; Vind, Birgitte ; Nybo, Mads ; Rasmussen,
Lars Melholt ; Højlund, Kurt. I: European Journal of Endocrinology. 2009 ; vol. 161, nr. 1, 2009-Jul. England. s. 95-101 / Acute hyperinsulinemia decreases plasma osteoprotegerin with diminished
effect in type 2 diabetes and obesity.
Karsdal, M A ; Henriksen, K ; Leeming, D J ; Mitchell, P ; Duffin, K
; Barascuk, N ; Klickstein, L ; Aggarwal, P ; Nemirovskiy, O ; Byrjalsen, I ; Qvist, P ; Bay-Jensen, A C ; Dam, E B ; Madsen, S H ;
Christiansen, C. I: Biomarkers. 2009 ; vol. 14, nr. 3, 2009-May.
England. s. 181-202 / Biochemical markers and the FDA Critical
Path: how biomarkers may contribute to the understanding of pathophysiology and provide unique and necessary tools for drug development.
Kjaerskov, Mette Wanscher ; Comstedt, Lisbeth Rosholm ; Bygum,
Anette ; Yderstraede, Knud Bonnet. I: Ugeskrift for læger. 2009 ;
vol. 171, nr. 22, 2009-May-25. Denmark. s. 1864-5 / Penil kalcifylaksi.
Koutnikova, Hana ; Laakso, Markku ; Lu, Lu ; Combe, Roy ; Paananen, Jussi ; Kuulasmaa, Teemu ; Kuusisto, Johanna ; Häring, HansUlrich ; Hansen, Torben ; Pedersen, Oluf ; Smith, Ulf ; Hanefeld,
Markolf ; Williams, Robert W ; Auwerx, Johan. I: PLoS Genetics.
2009 ; vol. 5, nr. 8, 2009-Aug. United States. s. e1000591 / Development of a type 2 diabetes risk model from a panel of serum
biomarkers from the Inter99 cohort. Identification of the UBP1
locus as a critical blood pressure determinant using a combination
of mouse and human genetics.
Kring, Sofia I I ; Werge, Thomas ; Holst, Claus ; Toubro, Søren ;
Astrup, Arne ; Hansen, Torben ; Pedersen, Oluf ; Sørensen, Thorkild
I A. I: PLoS ONE. 2009 ; vol. 4, nr. 8, 2009-null. United States.
s. e6696 / Polymorphisms of serotonin receptor 2A and 2C genes
and COMT in relation to obesity and type 2 diabetes.
Kristensen, Ida Bruun ; Møller, Hanne ; Kjaerskov, Mette Wanscher
; Yderstraede, Knud ; Møller, Michael Boe ; Bergmann, Olav J. I:
Acta Dermato Venereologica. 2009 ; vol. 89, nr. 2, 2009-null. Sweden. s. 175-7 7 Myeloid sarcoma developing in pre-existing pyoderma gangrenosum.
27
66.
67.
68.
69.
70.
71.
72.
73.
74.
75.
76.
Kronborg, CN ; Hallas, J ; Jacobsen, Ib Abildgaard. I: American
Journal of Hypertension. 2009 ; vol. 3, nr. 1, s. 19-24 / Prevalence,
wawreness and control of arterial hypertension in Denmark.
Lauenborg, Jeannet ; Grarup, Niels ; Damm, Peter ; Borch-Johnsen,
Knut ; Jørgensen, Torben ; Pedersen, Oluf ; Hansen, Torben. I: Journal of Clinical Endocrinology and Metabolism. 2009 ; vol. 94, nr. 1,
2009-Jan. United States. s. 145-50 / Common type 2 diabetes risk
gene variants associate with gestational diabetes.
Lauridsen, Mette Høj ; Boesgaard, Trine Welløv ; Pedersen, Oluf
Borbye ; Hansen, Torben ; Hertz, Birgitte. I: Ugeskrift for læger.
2009 ; vol. 171, nr. 23, 2009-Jun-1. Denmark. s. 1923-4 / Spædbørnsdiabetes kan ofte behandles med sulfonylurinstof i stedet for
insulin.
Lefort, Natalie ; Yi, Zhengping ; Bowen, Benjamin ; Glancy, Brian
; De Filippis, Eleanna A ; Mapes, Rebekka ; Hwang, Hyonson ;
Flynn, Charles R ; Willis, Wayne T ; Civitarese, Anthony ; Højlund,
Kurt ; Mandarino, Lawrence J. I: Journal of Proteomics. 2009 ; vol.
72, nr. 6, Aug-20. Netherlands. s. 1046-60 / Proteome profile of
functional mitochondria from human skeletal muscle using onedimensional gel electrophoresis and HPLC-ESI-MS/MS.
Liedert, Astrid ; Kassem, Moustapha ; Claes, Lutz ; Ignatius, Anita.
I: Biochemical and Biophysical Research Communications. 2009 ;
vol. 387, nr. 2, 2009-Sep-18. United States. s. 289-93 / Mechanosensitive promoter region in the human HB-GAM gene
Madsen, S H ; Sondergaard, B C ; Jensen, Anne-Christine Bay ;
Karsdal, M A. I: Scandinavian Journal of Rheumatology. 2009 ; vol.
38, nr. 3, Norway. s. 222-6 / Cartilage formation measured by a
novel PIINP assay suggests that IGF-I does not stimulate but maintains cartilage formation ex vivo.
Madsen, Ida Ringsborg ; Hørder, Kirsten ; Støving, René Klinkby.
I: Journal of Psychosomatic Obstetrics and Gynaecology. 2009 ;
vol. 30, nr. 2, Jun. England. s. 122-6 / Remission of eating disorder
during pregnancy : five cases and brief clinical review.
Mercader, Josep ; Ribot, Joan ; Murano, Incoronata ; Feddersen,
Søren ; Cinti, Saverio ; Madsen, Lise ; Kristiansen, Karsten ; Bonet,
M Luisa ; Palou, Andreu. I: American Journal of Physiology: Endocrinology and Metabolism. 2009 ; vol. 297, nr. 1, 2009-Jul. United
States. s. E184-93 / Haploinsufficiency of the retinoblastoma protein gene reduces diet-induced obesity, insulin resistance, and hepatosteatosis in mice.
Mogensen, M ; Vind, B F ; Højlund, K ; Beck-Nielsen, H ; Sahlin,
K. I: Diabetes, Obesity and Metabolism. 2009 ; vol. 11, nr. 9, Sep.
England. s. 874-83 / Maximal lipid oxidation in patients with type 2
diabetes is normal and shows an adequate increase in response to
aerobic training.
Mosekilde, Leif ; Brixen, Kim ; Jespersen, Bente ; Kassem, Moustapha ; Vestergaard, Peter. I: Medicinsk kompendium. / red. Ove B
Schaffalitzky de Muckadell ; Stig Haunsø ; Hendrik Vildstrup. Bd. 2
17. udg. Nyt Nordisk Forlag / Schønberg Forlag / Arnold Busck,
2009. s. 2247-2333 / Calciummetaboliske sygdomme og forstyrrelser i fosfat- og magnesiumstofskiftet.
Muscelli, Elza ; Kozàkovà, Michaela ; Flyvbjerg, Allan ; Kyriakopoulou, Konstantina ; Astiarraga, Brenno D ; Glintborg, Dorte ;
Konrad, Thomas ; Favuzzi, Angela ; Petrie, Jhon ; RISC investigators. I: American Journal of Hypertension. 2009 ; vol. 22, nr. 4,
2009-Apr. United States. s. 364-70 / The effect of menopause on
carotid artery remodeling, insulin sensitivity, and plasma adiponectin in healthy women.
77.
78.
79.
80.
81.
82.
83.
84.
85.
86.
87.
Nehlin, Jan ; Barington, Torben. I: Biogerontology. 2009 ; vol. 10,
nr. 4, 2009-Aug. Netherlands. s. 339-76 / Strategies for future histo
compatible stem cell therapy.
Nielsen, Jacob F ; El Fassi, Daniel ; Nielsen, Claus H ; Hegedüs,
Laszlo ; Lauer, Simeon A ; Silkiss, Rona Z ; Prause, Jan U. I: Acta
Ophthamologica (Online). 2009 ; vol. 87, nr. 8, 2009-Nov. England.
s. 927-9 / Evidence of orbital B and T cell depletion after rituximab
therapy in Graves’ ophthalmopathy.
Nielsen, Claus H ; Brix, Thomas H ; Leslie, R Graham Q ; Hegedüs,
Laszlo. I: Clinical Immunology. 2009 ; vol. 133, nr. 2, 2009-Nov.
United States. s. 218-27 / A role for autoantibodies in enhancement
of pro-inflammatory cytokine responses to a self-antigen, thyroid
peroxidase.
Nielsen, Jacob F ; El Fassi, Daniel ; Nielsen, Claus H ; Hegedüs,
Laszlo ; Lauer, Simeon A ; Silkiss, Rona Z ; Prause, Jan U. I: Acta
Ophthamologica (Online). 2009 ; vol. 87, nr. 8, 2009-Nov. England.
s. 927-9 / Evidence of orbital B and T cell depletion after rituximab
therapy in Graves’ ophthalmopathy.
Nissen, Nis ; Madsen, Jonna Skov ; Bladbjerg, Else-Marie ; Beck
Jensen, J E ; Jørgensen, N R ; Langdahl, B ; Abrahamsen, B ; Brixen, Kim. I: Calcified Tissue International. 2009 ; vol. 84, nr. 4, 2009Apr. United States. s. 276-85 /No association between hip geometry
and four common polymorphisms associated with fracture : the Danish osteoporosis prevention study.
Pedersen, Oluf; Beck-Nielsen, Henning, Poulsen, Mandrup Thomas, Flyvbjerg, A. I: Medicinsk kompendium. / red. Ove B Schaffalitzky de Muckadell ; Stig Haunsø ; Hendrik Vildstrup. Bd. 2 17.
udg. Nyt Nordisk Forlag / Schønberg Forlag / Arnold Busck, 2009.
s. 2389-2392 / Diabetes Mellitus/Hypoglycæmi
Pilgaard, K ; Jensen, C B ; Schou, J H ; Lyssenko, V ; Wegner, L ;
Brøns, C ; Vilsbøll, T ; Madsbad, S ; Holst, J J ; Vølund, A ; Poulsen,
P ; Groop, L ; Pedersen, O ; Hansen, Torben ; Vaag, A A. I: Diabetologia. 2009 ; vol. 52, nr. 7, 2009-Jul. Germany. s. 1298-307 / The
T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production
in young healthy men.
Poulsen, Mikael ; Henriksen, Jan ; Dahl, Jordi ; Johansen, Allan ;
Møller, Jacob ; Gerke, Oke ; Vach, Werner ; Haghfelt, Torben ;
Beck-Nielsen, Henning ; Høilund-Carlsen, Poul. I: Journal of Nuclear Cardiology. 2009 ; vol. 16, nr. 6, s. 878-887 / Myocardial
ischemia, carotid, and peripheral arterial disease and their interrelationship in type 2 diabetes patients.
Poulsen, Pernille ; Grunnet, Louise G ; Pilgaard, Kasper ; Storgaard,
Heidi ; Alibegovic, Amra ; Sonne, Mette P ; Carstensen, Bendix ;
Beck-Nielsen, Henning ; Vaag, Allan. I: Diabetes. 2009 ; vol. 58,
nr. 6, June. s. 1350-1355 / Increased risk of Type 2 diabetes in Elderly Twins.
Prokhorova, Tatyana A ; Rigbolt, Kristoffer T G ; Johansen, Pia T
; Henningsen, Jeanette ; Kratchmarova, Irina ; Kassem, Moustapha ;
Blagoev, Blagoy. I: Molecular and Cellular Proteomics. 2009 ; vol.
8, nr. 5, May. United States. s. 959-70 7 Stable isotope labeling by
amino acids in cell culture (SILAC) and quantitative comparison
of the membrane proteomes of self-renewing and differentiating hu
man embryonic stem cells.
Radha, V ; Ek, J ; Anuradha, S ; Hansen, Torben ; Pedersen, O ;
Mohan, V. I: Journal of Clinical Endocrinology and Metabolism.
2009 ; vol. 94, nr. 6, 2009-Jun. United States. s. 1959-65 / Identifi-
88.
89.
90.
91.
92.
93.
94.
28
cation of novel variants in the hepatocyte nuclear factor-1alpha gene
in South Indian patients with maturity onset diabetes of young.
Rathcke, Camilla Noelle ; Holmkvist, Johan ; Jørgensen, Torben ;
Borch-Johnsen, Knut ; Hansen, Torben ; Pedersen, Oluf Borbye ;
Vestergaard, Henrik. I: PLoS ONE. 2009 ; vol. 4, nr. 5, 2009-null.
United States. s. e5469 / Variation in CHI3LI in relation to type 2
diabetes and related quantitative traits.
Reiling, Erwin ; van Vliet-Ostaptchouk, Jana V ; van ‘t Riet, Esther
; van Haeften, Timon W ; Arp, Pascal A ; Hansen, Torben ; Kremer,
Dennis ; Groenewoud, Marlous J ; van Hove, Els C ; Romijn, Johannes A ; Smit, Jan W A ; Nijpels, Giel ; Heine, Robert J ; Uitterlinden, André G ; Pedersen, Oluf ; Slagboom, P Eline ; Maassen,
Johannes A ; Hofker, Marten H ; ‘t Hart, Leen M ; Dekker, Jacqueline M. I: European Journal of Human Genetics. 2009 ; vol. 17,
nr. 8, 2009-Aug. England. s. 1056-62 / Genetic association analysis
of 13 nuclear-encoded mitochondrial candidate genes with type II
diabetes mellitus: the DAMAGE study.
Richardot, P ; Charni-Ben Tabassi, N ; Toh, L ; Marotte, H ; Jensen,
Anne-Christine Bay ; Miossec, P ; Garnero, P. I: Osteoarthritis and
Cartilage. 2009 ; vol. 17, nr. 10, 2009-Oct. England. s. 1362-/ Nitrated type III collagen as a biological marker of nitric oxide-mediated synovial tissue metabolism in osteoarthritis.
Rose, C S ; Grarup, N ; Krarup, N T ; Poulsen, P ; Wegner, L ;
Nielsen, T ; Banasik, K ; Faerch, K ; Andersen, G ; Albrechtsen, A ;
Borch-Johnsen, K ; Clausen, J O ; Jørgensen, T ; Vaag, A ; Pedersen,
O ; Hansen, Torben. I: Diabetologia. 2009 ; vol. 52, nr. 10, 2009Oct. Germany. s. 2122-9 / A variant in the G6PC2/ABCB11 locus is
associated with increased fasting plasma glucose, increased basal
hepatic glucose production and increased insulin release after oral
and intravenous glucose loads.
de Rooij, Susanne R ; Dekker, Jacqueline M ; Kozakova, Michaela
; Mitrakou, Asimina ; Melander, Olle ; Gabriel, Rafael ; Guidone,
Caterina ; Højlund, Kurt ; Murphy, Matthew S ; Nijpels, Giel ; RISC
Group Investigators. I: European Journal of Endocrinology. 2009
; vol. 161, nr. 2, 2009-Aug. England. s. 223-30 / Fasting insulin has
a stronger association with an adverse cardiometabolic risk profile
than insulin resistance: the RISC study.
Rung, Johan ; Cauchi, Stéphane ; Albrechtsen, Anders ; Shen, Lishuang ; Rocheleau, Ghislain ; Cavalcanti-Proença, Christine ; Bacot, François ; Balkau, Beverley ; Belisle, Alexandre ; Borch-Johnsen, Knut ; Charpentier, Guillaume ; Dina, Christian ; Durand, Emmanuelle ; Elliott, Paul ; Hadjadj, Samy ; Järvelin, Marjo-Riitta ;
Laitinen, Jaana ; Lauritzen, Torsten ; Marre, Michel ; Mazur, Alexander ; Meyre, David ; Montpetit, Alexandre ; Pisinger, Charlotta ;
Posner, Barry ; Poulsen, Pernille ; Pouta, Anneli ; Prentki, Marc ;
Ribel-Madsen, Rasmus ; Ruokonen, Aimo ; Sandbaek, Anelli ; Serre, David ; Tichet, Jean ; Vaxillaire, Martine ; Wojtaszewski, Jørgen
F P ; Vaag, Allan ; Hansen, Torben ; Polychronakos, Constantin ;
Pedersen, Oluf ; Froguel, Philippe ; Sladek, Robert. I: Nature Genetics. 2009 ; vol. 41, nr. 10, 2009-Oct. United States. s. 1110-5 / Genetic variant near IRS1 is associated with type 2 diabetes, insulin
resistance and hyperinsulinemia.
Ryg, Jesper ; Rejnmark, Lars ; Overgaard, Soren ; Brixen, Kim ;
Vestergaard, Peter. I: Journal of Bone and Mineral Research. 2009
; vol. 24, nr. 7, July. s. 1299-1307 / Hip Fracture Patients at Risk of
Second Hip Fracture-A Nationwide Population-Based Cohort Study
of 169,145 Cases During 1977-2001.
95. Salanti, Georgia ; Southam, Lorraine ; Altshuler, David ; Ardlie,
Kristin ; Barroso, Inês ; Boehnke, Michael ; Cornelis, Marilyn C ;
Frayling, Timothy M ; Grallert, Harald ; Grarup, Niels ; Groop, Leif
; Hansen, Torben ; Hattersley, Andrew T ; Hu, Frank B ; Hveem,
Kristian ; Illig, Thomas ; Kuusisto, Johanna ; Laakso, Markku ; Lan
genberg, Claudia ; Lyssenko, Valeriya ; McCarthy, Mark I ; Morris,
Andrew ; Morris, Andrew D ; Palmer, Colin N A ; Payne, Felicity
; Platou, Carl G P ; Scott, Laura J ; Voight, Benjamin F ; Wareham,
Nicholas J ; Zeggini, Eleftheria ; Ioannidis, John P A. I: American
Journal of Epidemiology. 2009 ; vol. 170, nr. 5, 2009-Sep-1. United
States. s. 537-45 / Underlying genetic models of inheritance in
established type 2 diabetes associations.
96. Scheller, Rudolf Albert ; Bygum, Anette ; Brixen, Kim ; Brøndum
Nielsen, Karen. I: Investigative Ophthalmology & Visual Science.
2009 ; vol. 50, nr. 3, 03-2009. s. 1058-1064 / Birth prevalence and
mutation spectrum in danish patients with autosomal recessive albi
nism.
97. Sparsø, T ; Grarup, N ; Andreasen, C ; Albrechtsen, A ; Holmkvist,
J ; Andersen, G ; Jørgensen, T ; Borch-Johnsen, K ; Sandbaek, A ;
Lauritzen, T ; Madsbad, S ; Hansen, Torben ; Pedersen, O. I: Dia
betologia. 2009 ; vol. 52, nr. 7, 2009-Jul. Germany. s. 1308-14 /
Combined analysis of 19 common validated type 2 diabetes su
sceptibility gene variants shows moderate discriminative value and
no evidence of gene-gene interaction.
98. Sparsø, Thomas ; Bonnefond, Amélie ; Andersson, Ehm ; Bouatia
Naji, Nabila ; Holmkvist, Johan ; Wegner, Lise ; Grarup, Niels ;
Gjesing, Anette P ; Banasik, Karina ; Cavalcanti-Proença, Christi
ne ; Marchand, Marion ; Vaxillaire, Martine ; Charpentier, Guil
laume ; Jarvelin, Marjo-Riitta ; Tichet, Jean ; Balkau, Beverley ;
Marre, Michel ; Lévy-Marchal, Claire ; Faerch, Kristine ; Borch
Johnsen, Knut ; Jørgensen, Torben ; Madsbad, Sten ; Poulsen, Per
nille ; Vaag, Allan ; Dina, Christian ; Hansen, Torben ; Pedersen,
Oluf ; Froguel, Philippe. I: Diabetes. 2009 ; vol. 58, nr. 6, 2009-Jun.
United States. s. 1450-6 / G-allele of intronic rs10830963 in MT
NR1B confers increased risk of impaired fasting glycemia and type
2 diabetes through an impaired glucose-stimulated insulin release:
studies involving 19,605 Europeans.
99. Thingholm, Tine E ; Jensen, Ole N ; Larsen, Martin R. I: Proteo
mics. 2009 ; vol. 9, nr. 6, 2009-Mar. Germany. s. 1451-1468 / Ana
lytical strategies for phosphoproteomics.
100.Thingholm, Tine E ; Larsen, Martin R. I: Methods in Molecular
Biology. 2009 ; vol. 527, 2009-null. United States. s. 57-66 / The
use of titanium dioxide micro-columns to selectively isolate phos
phopeptides from proteolytic digests.
101.Vad Winkler, Laura ; Andersen, Marianne ; Hørder, Kirsten ; Schu
mann, Thorsten ; Støving, René Klinkby. I: International Journal of
Eating Disorders. 2009 ; vol. 42, nr. 5, July. s. 475-478 / Slow-gro
wing craniopharyngioma masquarading as early-onset eating disor
der: Two cases.
102.Wang, Bijue ; Chen, Pingping ; Jensen, Anne-Christine Bay ; Kars
dal, Morten A ; Madsen, Suzi H ; Sondergaard, Bodil-Cecilie ;
Zheng, Qinlong ; Qvist, Per. I: B M C Research Notes. 2009 ; vol.
2, 2009-null. England. s. 259 / Suppression of MMP activity in bo
vine cartilage explants cultures has little if any effect on the release
of aggrecanase-derived aggrecan fragments.
103.Wedderkopp, Niels ; Kjaer, P ; Hestbaek, L ; Korsholm, L ; Leboeuf
Yde, C. I: Spine Journal. 2009 ; vol. 9, nr. 2, s. 134-141 / High-level
physical activity in childhood seems to protect against low back
pain in early adolescence.
104.Watt, Torquil ; Bjorner, Jakob Bue ; Groenvold, Mogens ; Rasmus
sen, Ase Krogh ; Bonnema, Steen Joop ; Hegedüs, Laszlo ; Feldt
Rasmussen, Ulla. I: Quality of Life Research. 2009 ; vol. 18, nr. 4,
2009-May. Netherlands. s. 483-96 / Establishing construct validity
for the thyroid-specific patient reported outcome measure (Thy
PRO) : an initial examination.
105.Watt, Torquil ; Hegedüs, Laszlo ; Groenvold, Mogens ; Bjorner,
Jakob Bue ; Rasmussen, Ase Krogh ; Bonnema, Steen Joop ; Feldt
Rasmussen, Ulla. I: European Journal of Endocrinology. 2009 ; vol.
162, nr. 1, 2010-Jan. England. s. 161-7 / Validity and reliability of
the novel thyroid-specific quality of life questionnaire, ThyPRO.
106.Xiao, X ; Wang, T ; Li, W ; Song, H ; Gong, C ; Diao, C ; Yu, M ;
Yuan, T ; Zhang, Y ; Sun, X ; Zhang, Q ; Lu, K ; Wang, H ; Schmitz,
O ; Hansen, Torben. I: Hormone and Metabolic Research. 2009 ;
vol. 41, nr. 7, 2009-Jul. Germany. s. 580-2 / Transfer from insulin
to sulfonylurea treatment in a chinese patient with permanent neo
natal diabetes mellitus due to a KCNJ11 R201H mutation.
107.Yderstraede, Knud Bonnet ; Clemmensen, Ole ; Nielsen, Anna Ma
rie ; Marckmann, Peter ; Bygum, Anette. I: Ugeskrift for læger.
2009 ; vol. 171, nr. 22, 2009-May-25. Denmark. s. 1860-4 / Kalci
fylaksi.
108.Zimmermann, Esther ; Kring, Sofia I I ; Berentzen, Tina L ; Holst,
Claus ; Pers, Tune H ; Hansen, Torben ; Pedersen, Oluf ; Sørensen,
Thorkild I A ; Jess, Tine. I: PLoS ONE. 2009 ; vol. 4, nr. 2, 2009
null. United States. s. e4428 / Fatness-associated FTO gene variant
increases mortality independent of fatness--in cohorts of Danish
men.
In the lab
29
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The Bone and Calcium Research Unit
Kim Brixen, Professor, Consultant, DMSc
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Research, Consultant
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University of Southern Denmark
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DK- 5000 Odense C
[email protected]
Tel.: +45 6550 3018
Layout: Anne Christrup
Odense University Hospital
All units are situated at Kløvervænget 6
DK- 5000 Odense C