Research collaborations

Research collaborations

WORKPACKAGE

Click On each Work Package for a description and contact information

  1. Pathophysiology of type 1 diabetes
    Principal Investigator: Nils Billestrup, Professor
    Department of Biomedical Sciences, University of Copenhagen

  2. Beta cell biology
    Principal Investigator: Susanne Mandrup, Professor
    Department of Biochemistry and Molecular Biology, University of Southern Denmark

  3. Stem cells
    Principal Investigator: Palle Serup, Professor
    DanStem, Human Stem Cell Biology, Univsersity of Copenhagen

  4. Diabetes in childhood and adolescence
    Principal Investigator: Jesper Johannesen, MD, DMSc
    Department of Pediatrics, Herlev Hospital

  5. Insulin resistance
    Principal Investigator: Kurt Højlund, MD, Associate Professor
    Department of Endocrinology, Odense University Hospital

  6. Diabetes genetics
    Principal Investigator: Niels Grarup, Assistant Professor
    The Novo Nordisk Foundation Centre for Basic Metabolic Research, University of Copenhagen

  7. Molecular pharmacotherapy and pharmacogenetics
    Principal Investigator: Niels Jessen, Associate Professor
    Department of Molecular Medicine (MOMA), Aarhus University

  8. Macrovascular complications
    Principal Investigator: Esben Laugesen, Post Doc

    Department of Endocrinology and Internal Medicine, Aarhus University Hospital

  9. Microvascular complications
    Principal Investigator: Jakob Grauslund, MD, PhD, DMSc
    Department of Ophthalmology, Odense University Hospital

  10. Fat cells and obesity
    Principal Investigator: Susanne Mandrup, Professor
    Department of Biochemistry and Molecular Biology, University of Southern Denmark

  11. Pregnancy and diabetes
    Principal Investigator: Dorte Møller Jensen, MD
    Department of Endocrinology, Odense University Hospital

  12. Incretin (patho)physiology and treatment
    Principal Investigators: Tina Vilsbøl, Professor and Filip Knop, Associate Professor
    Diabetes Research Division, University of Copenhagen

  13. Diabetes technology
    Principal Investigator: Kirsten Nørgaard, MD, DMSc
    Department of Endocrinology, Copenhagen University Hospital, Hvidovre

  14. Diabetes epidemiology
    Principal Investigator: Marit Eika Jørgensen, MD, PhD
    Steno Diabetes Center, Gentofte

  15. Hypertension and diabetes
    Principal Investigator: Michael Hecht Olsen, Professor
    Department of Endocrinology, Odense University Hospital

  16. Quality of life and prevention of diabetes
    Principal Investigator: Annelli Sandbæk, MD, PhD
    Institute of Public Health, Aarhus University

  17. Exercise in prevention and treatment of diabetes
    Principal Investigator: Jørgen Wojtaszewski, Professor
    Department of Nutrition, Exercise and Sports, University of Copenhagen

  18. Developmental programming of diabetes
    Principal Investigator: Allan Vaag, MD, DMSc
    Department of Endocrinology, Copenhagen University Hospital

  19. Epigenetic control of insulin sensitivity
    Principal Investigator: Roman Barrés, Associate Professor
    The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen

  20. Diabetes, obesity and gastric bypass
    Principal Investigator: Dorte Worm, Chief Consultant
    Department of Endocrinology, Hvidovre Hospital

  21. Molecular and cellular enteroendocrine biology
    Principal Investigator: Birgitte Holst, Associate Professor
    The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen

  22. Inflammatory beta cell destruction
    Principal Investigator: Thomas Mandrup-Poulsen, Professor
    Department of Biomedical Sciences, Endocrinology Research Section, University of Copenhagen
     

Pathophysiology of type 1 diabetes (WP 1)

In this workpackage we focus on identifying processes and factors involved in activation of endogenous beta cell regeneration or reprogramming of other cell types into functional beta cells. In addition, factors that promote the survival and function of transplanted islets are being investigated. We used a combination of in vitro culture system using islets from both rodent and humans to study islet cell growth and function at the molecular and cellular level. The goal of our projects is to develop novel strategies for restoring functional beta cells mass by inducing regeneration of endogenous beta cells or by preserving viability and function of transplanted islets.

AIMS

  • To explore and elucidate the molecular mechanisms and biochemical pathways involved in beta cell neogenesis, growth and survival
  • To identify and validate potential key pathways in the process of beta cell regeneration and survival
  • To perform proof of principle studies in relevant animal models based on regeneration of endogenous beta cells or by transplantation

CONTACT INFORMATON

Professor Nils Billestrup (Principal Investigator)
Dept of Biomedical Sciences
University of Copenhagen
Blegdamsvej 3, DK-2200 Copenhagen

billestrup@sund.ku.dk  

Beta cell biology (WP 2)

In this work package we use cell culture and animal models combined with advanced high throughput technologies such as mass spectrometry and genomics to investigate the molecular mechanisms of the responses of beta-cells to nutrients and incretins. This will be combined with targeted approaches investigating the role of specific factors by loss- and gain-of-function experiments and detailed molecular studies. We will instigate how nutrients lead to proliferative as well as detrimental effects in the β-cells. Our long term goal is to understand how the detrimental nutrient-induced effects can be avoided while maintaining the beneficial effects.
 

AIMS

  • To obtain in-depth mechanistic insight into the signaling pathways (in particular GPRs) and transcriptional programmes regulating beta cell function and capacity in response to nutrients such as glucose and fatty acids
  • To obtain a detailed and comprehensive mechanistic understanding of the effects of GLP-1 and other incretins on the beta cell gene programme and function
  • To determine the function and regulation of novel G protein-coupled receptor (GPCR) in pancreatic beta cells

CONTACT INFORMATION

Professor Susanne Mandrup (Principal Investigator)
Department of Biochemistry and Molecular Biology
University of Southern Denmark
Campusvej 55, DK-5230 Odense M

s.mandrup@bmb.sdu.dk
+45 6550 2340
http://www.sdu.dk/mandrupgroup  

Stem cells (WP 3)

In this work package we use mouse genetics and cultures of human pluripotent stem cells to investigate the signalling mechanisms that govern development of beta cells during embryonic development and in stem cell cultures. We use fluorescent signalling reporters and conditional loss- and gain-of-function experiments to investigate the role of specific signalling pathways in beta cell development. We will investigate how a particular signalling pathway (Notch) regulates dynamic changes in chromatin structure and eventually leads to the expansion and differentiation of the different pancreatic cell types incl. beta cells. Our long-term goal is to translate knowledge of these signalling events into efficient protocols for generation of beta cells from human pluripotent stem cells in vitro.

AIMS

  • To obtain detailed mechanistic insight into the cell biology of different signalling pathways (in particular Notch) that regulate beta cell development
  • To understand the transcriptional mechanism of Notch signalling, and it’s downstream effector Hes1 on a genome-wide scale
  • To use knowledge of pancreatic signalling events to generate beta cells from human pluripotent stem cells in vitro

CONTACT INFORMATION

Professor Palle Serup (Principal Investigator)
Danish Stem Cell Center (DanStem)
University of Copenhagen
Blegdamsvej 3B, DK-2200 Copenhagen N

palle.serup@sund.ku.dk
+45 4022 0026
http://danstem.ku.dk/research1/serup_laboratory/  

Diabetes in childhood and adolescence (WP 4)

The paediatric diabetes research environment cover various aspects ranging from clinical research focusing at i.e. (i) epidemiology, a) describing the rate of incidence increase of childhood diabetes, and b) identifying risk factors for metabolic outcome and diabetic complications; (ii) clinical, biochemical and genetic characterisation of the remission phase.

AIMS

With basis in the nationwide Danish Childhood Diabetes Registry combined with a Biological Bank, The International Hvidoere Cohort and The Danish remissionphase cohort the following aims have been pursued:

  1. Prolong the life-time free of diabetes in children by halting the increasing trend of type 1 diabetes by identifying modifiable environmental risk factors contributing to the increased incidence
  2. Develop treatment modalities to ensure that young people achieve as low HbA1c as possible without acute complications
  3. Launch intervention therapies to prolong the remission period, by preventing the autoimmune process and enhance beta-cell replication and identify modifiable biomarkers responsible for the length of the remission period

Thus the focus of our research is to conduct patient-oriented scientific research and promote the advancement of technology to improve the understanding of disease mechanisms and to translate this into optimized treatment (bench to bedside).

CONTACT INFORMATION

Dr Jesper Johannesen, MD, DMSc (Principal Investigator)
Clinical Associate Professor 
Paediatric Endocrinologist 
Herlev University Hospital, Copenhagen, DK 

jesper.johannesen@regionh.dk

Dr Henrik Bindesbøl Mortensen, MD, DMSc
Professor in Paediatrics
Paediatric Endocrinologist
Herlev University Hospital, Copenhagen, DK

henrik.bindelboel.mortensen@regionh.dk  

Insulin resistance: pathophysiology of T2D (WP 5)

Insulin resistance plays a major role for the increased risk of cardiovascular disease in obesity and type 2 diabetes (T2D). While the precise molecular mechanisms remains elusive, defects in insulin signalling, accumulation of lipid metabolites and mitochondrial dysfunction in skeletal muscle have all been linked to insulin resistance. Novel pathways such as autophagy, the unfolded protein response, and lipid droplet formation have emerged as possible co-players in the pathogenesis of insulin resistance.
 
This work package will focus on translational research with extensive metabolic characterisation of insulin resistant individuals in response to different interventions in vivo. Muscle and fat biopsies will provide the basis for subsequent studies of molecular mechanism using global and targeted transcriptional profiling and mass-spectrometry-based proteomics as first line approaches, and classical protein technologies and genetic manipulation of cell cultures and animals to validate findings and get mechanistic insight. The ultimate goal is to identify novel targets of treatment for insulin resistance, which are currently missing in the treatment and prevention of T2D and cardiovascular disease.
 
AIMS
  • To further investigate the role of novel components in insulin signalling to glucose transport and glycogen synthesis in the pathogenesis of insulin resistance
  • To further dissect the molecular mechanisms of mitochondrial dysfunction in muscle and fat of insulin resistant individuals
  • To characterise abnormalities in autophagy, unfolded protein response and lipid droplet formation and their possible involvement in the pathogenesis of mitochondrial dysfunction and insulin resistance 

CONTACT INFORMATION

Professor, MD Kurt Højlund (Principal Investigator)
Department of Endocrinology, Odense University Hospital
Sdr. Boulevard 29, Entrance 93, DK-5000 Odense C

Section of Molecular Diabetes & Metabolism
University of Southern Denmark
Winsløwparken 25, DK-5000 Odense C

kurt.hoejlund@rsyd.dk
+45 2532 0648  

Diabetes genetics (WP 6)

Type 2 diabetes is a disorder caused by a subtle combination of heritable factors and environmental and lifestyle risk factors. Also intermediary diabetes-related physiological traits such as obesity, insulin resistance and disturbed insulin secretion have been shown to be partly modulated by genetic factors. In this work package we apply state-of-the art methodology to detect genetic variation associated with type 2 diabetes (diabetes genomics discovery) and to perform detailed physiological characterization of these variants in relation to diabetes phenotype (genetic-epidemiology and genetic-physiology studies).
 
Genetic variation is explored by both next generation nucleotide sequencing of entire exomes (all coding regions) or targeted regions of interest and by large-scale genotyping array-based genotyping. Our goals are to gain a deeper understanding of the genetic architecture of type 2 diabetes, to expand our insights into diabetes pathogenesis and pathophysiology and possibly thereby derive novel drug targets for diabetes and in the longer term cause advances in clinical diabetes management and prevention.
 
AIMS
 

The overall aims of this WP are:

  • To explore genetic variation in relation to type 2 diabetes – both sporadic and familial forms
  • To characterize common, low-frequency and rare diabetes-related genomic risk elements in population-based genetic epidemiological studies to elucidate intermediate phenotypes and by targeted detailed physiological investigations in risk allele carriers and non-carriers
  • To combine diabetes-related risk variation in pathway and tissue specific analyses including gene expression studies in target tissues to assess the vulnerability of multiple risk alleles
  • To assess the clinical impact of genetic variation in relation to development of diabetes and diabetes-related complications 

CONTACT INFORMATION

Assistant Professor Niels Grarup (Principal Investigator)
Section of Metabolic Genetics
The Novo Nordisk Foundation Center for Basic Metabolic Research
Faculty of Health and Medical Sciences
University of Copenhagen
Universitetsparken 1, 1., DK-2100 Copenhagen Ø

niels.grarup@sund.ku.dk
+45 3533 7126
http://metabol.ku.dk/  

Molecular pharmacotherapy and pharmacogenetics (WP 7)

Over the last decades the pharmacological treatment of diabetes and its associated complications has become increasingly more aggressive (1). The progressive use of multiple drugs is common and is recommended by international guidelines (2) and is considered cost-effective (3). However, polypharmacy is associated with an increased morbidity and costs as the use of multiple medications often leads to inappropriate drug use, underprescription, low adherence and side effects (4). Individual tailoring of drug prescriptions to the patient is a strategy to overcome these challenges, but this demands detailed knowledge of the drug response in the diabetic patients.
 

AIM

To develop methods that will personalize treatment strategies for diabetic patients based on measurements of known and putative factors regulators of drug responses, and thereby optimize treatment efficiency and minimize inappropriate use of medicine.

REFERENCES

  1. Stolar,MW: Defining and achieving treatment success in patients with type 2 diabetes mellitus. Mayo Clin Proc 85:S50-S59, 2010
  2. Nathan,DM, Buse,JB, Davidson,MB, Heine,RJ, Holman,RR, Sherwin,R, Zinman,B: Management of hyperglycaemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 49:1711-1721, 2006
  3. Cost-effectiveness of intensive glycemic control, intensified hypertension control, and serum cholesterol level reduction for type 2 diabetes. JAMA 287:2542-2551, 2002
  4. Osterberg,L, Blaschke,T: Adherence to medication. N Engl J Med 353:487-497, 2005

CONTACT INFORMATION

Associate Professor, MD, PhD Niels Jessen (Principal Investigator)
Department of Molecular Medicine
Aarhus University Hospital
Brendstrupgårdsvej 100, DK-8200 Aarhus N

niels.jessen@ki.au.dk  

Macrovascular complications (WP 8)

Despite major advances in primary and secondary preventive measures, patients with diabetes still suffer from a high incidence of cardiovascular disease, and fatal cardiovascular events are responsible for the majority of the 54% increased age-standardized mortality rate seen in diabetes patients. Thus, the prevention of premature cardiovascular disease (CVD) remains of outmost importance in the treatment of diabetic patients and further research in this area is of profound importance.

Patients with type 2 diabetes are generally characterized by a clustering of conventional cardiovascular risk factors e.g. hypertension and hyperlipidemia. However, these risk factors cannot alone explain the increased incidence of cardiovascular disease found in diabetes patients. Accordingly, an improved understanding of the pathophysiological causes of the increased risk, and identification of new cardiovascular risk markers, which add prognostic information to established risk factors, are essential in diabetic patients in order to develop new treatments and to improve cardiovascular risk stratification.

CONTACT INFORMATION

Post Doc Esben Laugesen (Principal Investigator)
Department of Endocrinology and Internal Medicine
Aarhus University Hospital
Nørrebrogade 44, DK-8000 Aarhus C

esben.laugesen@ki.au.dk  

Microvascular complications: retinopathy, nephropathy and neuropathy (WP 9)

Diabetic retinopathy, nephropathy, and neuropathy constitute leading causes of visual impairment, end-stage renal disease, and amputations world-wide, despite intensive treatment of hyperglycaemia, elevated arterial blood pressure, and other preventive measures.

 

 

 

 

The aim of this WP is to enable earlier diagnosis of microvascular complications and their precursor conditions, to identify mechanisms of pathophysiology, and to develop and test new interventions in relevant clinical test populations. The investigators will collaborate and coordinate basic and clinical studies of pathogenesis, diagnosis, screening, prevention, and treatment of microvascular complications of diabetes in large study populations.

Basic, epidemiologic, and clinical studies are being carried out in order to enhance our understanding of microvascular complications like retinopathy, nephropathy and neuropathy, and not the least the intriguing interplay between these microvascular manifestations.

CONTACT INFORMATION

Diabetic retinopathy
Clinical Associate Professor Jakob Grauslund (Principal Investigator)
Department of Ophthalmology
Odense University Hospital
Sdr. Boulevard 29, DK-5000 Odense C

jakob.grauslund@rsyd.dk

Diabetic nephropathy
Consultant Søren Tang Knudsen (Principal Investigator)
Medical Department MEA (Diabetes and Endocrinology)
Nørrebrogade 44, DK-8000 Aarhus C

soerknud@rm.dk

Diabetic neuropathy
DMSc, PhD Niels Ejskjaer 
Toldbodgade 4, DK-5000 Odense

Mobil 3123 9910
d270946@dadlnet.dk  

Fat cells and obesity (WP 10)

In this work package we use cell culture, animal models and human tissue biopsies combined with advanced technologies such as mass spectrometry and genomics to investigate the molecular mechanisms of the development of white and brown adipocytes. This will be combined with targeted approaches investigating the role of specific factors by loss- and gain-of-function experiments and detailed molecular studies. Furthermore, we use these systems to gain insight into the crosstalk between adipocytes and immune cells and to understand how obesity and lifestyle impact the intercellular crosstalk.
 

AIMS 

  • To obtain in-depth knowledge of the transcriptional networks, epigenetic modulators and specific signaling networks controlling differentiation of white and brown preadipocytes, respectively.
  • To understand how stromal stem cells in different adipose depots and bone marrow are preprogrammed and to understand whether this preprogramming is affected by obesity and lifestyle.
  • To gain insight into the inflammatory signals and obesity and lifestyle impact on adipocyte function.

CONTACT INFORMATION

Professor Susanne Mandrup (Principal Investigator)
Department of Biochemistry and Molecular Biology
University of Southern Denmark
Campusvej 55, DK-5230 Odense M

s.mandrup@bmb.sdu.dk
+45 6550 2340
http://www.sdu.dk/mandrupgroup  

Pregnancy and diabetes (WP 11)

Diabetes in pregnancy (both T1D and T2D), and to a lesser extent GDM and obesity, are associated with increased rates of maternal and fetal complications, and evidence clearly shows optimized metabolic control during all trimesters of pregnancy to significantly reduce the risk of these complications. Recent reports indicate intrauterine hyperglycaemia to dramatically increase the risk of diabetes, overweight, the metabolic syndrome and cardiovascular disease in the offspring. We will take advantage of a well-established collaboration between Danish Centres for Diabetes and Pregnancy to examine the long term consequences of a diabetic intrauterine environment in large cohorts of offspring of women with T1D.
 
In selected subgroups, we will study the specific molecular signature of intrauterine exposure to hyperglycaemia in human tissues and blood, including the role of epigenetics and transcriptional changes. The new international criteria for diagnosis, potential biomarkers for complications as well as effects of different treatment regimens in women with GDM will be evaluated. Finally, we will examine the effect of lifestyle interventions in obese pregnant women and their offspring.
 

AIMS 

The major aims of this WP are:

  • To examine long-term consequences of a hyperglycaemic intrauterine environment and address possible epigenetic mechanisms.
  • To study effects of lifestyle interventions in pregnancy on offspring metabolism and growth in childhood.
  • To improve diagnosis and treatment of hyperglycaemia and obesity in pregnancy.

CONTACT INFORMATION

Clinical Associate Professor Dorte Møller Jensen (Principal Investigator)
Department of Endocrinology
Odense University Hospital
Sdr. Bouldevard 29, DK-5000 Odense C

dorte.moeller.jensen@rsyd.dk  

Incretin (patho)physiology and treatment (WP 12)

During the past decades, it has become clear that the gastrointestinal tract plays a pivotal role in the regulation of glucose homeostasis. The description of the gut incretin hormones (GIP and GLP-1) - secreted from endocrine cells in the intestine in response to nutrient ingestion - and their pleiotropic effects in several organs of importance for glucose metabolism have paved the way for new and promising antidiabetic treatment modalities (incretin enhancers and incretin mimetics).

The so-called incretin effect is exerted by the incretin hormones and accounts for up to 70 % of the insulin response following glucose ingestion. The incretin effect is severely reduced in patients with type 2 diabets (T2D). Our group has shown that the reduced incretin effect in patients with T2D is accompanied by a reduced postprandial GLP-1 response, a reduced potency of the insulinotropic effect of GLP-1 and an abolished effect of GIP.

Furthermore, recent results from our group point toward gut-derived glucagon and GIP as culprits in diabetic hypersecretion of glucagon. Additionally, our group is delineating the mechanisms behind the immediate remission of T2D occurring in most patients following the bariatric surgical procedure Roux-en-Y gastric bypass (RYGB); a phenomenon underscoring the significance of the small intestine as an endocrine organ of importance for the maintenance of normal glucose handling, the pathophysiology of T2D and the future treatment of T2D.

AIMS

The present WP encompasses studies with the overall aim to understand the role of the gastrointestinal tract and gut-derived hormones in human physiology and diabetic pathophysiology. Eight conglomerates of clinical studies form the basis of the WP.

CONTACT INFORMATION

Associate Professor Filip Knop (Principal Investigator)
Diabetes Research Division/ Department of Internal Medicine
Gentofte Hospital/ University of Copenhagen
Niels Andersens Vej 65, DK-2900 Hellerup

filipknop@dadlnet.dk

Professor Tina Vilsbøl (Principal Investigator)
Diabetes Research Division/ Department of Internal Medicine
Gentofte Hospital/ University of Copenhagen
Niels Andersens Vej 65, DK-2900 Hellerup

t.vilsboll@dadlnet.dk  

Diabetes technology (WP 13)

Patients with diabetes experience an overall shortening of life spans of about 10 years due to late complications of diabetes – and many suffer from diabetic complications for years with greatly reduced quality of life. This is in general attributable to early development of diabetic complications induced by suboptimal diabetes control. To obtain tight glycaemic control throughout a diabetes life is very difficult and almost impossible for most patients. With the current available tools, the task requires 24 hour attention and judgments from the diabetic patients on self-monitoring of blood glucose results, on food content of carbohydrate, effect of exercise and especially how much insulin to take in each situation. Despite their efforts many patients experience episodes with severe hypoglycaemia and inability to take care of themselves. Furthermore, all patients need regular support from health care providers in general practice or hospitals to make treatment decisions and contact with health care providers for advises on how to act with their disease in general.
 

AIMS 

The overall aims of this WP are:

  1. To develop a closed loop system for insulin delivery
  2. To optimise the patients’ and health care providers’ use of current technologies for support in diabetes treatment decisions
  3. To design and develop new technologies for treatment support purposes
  4. To develop information technology (telemedicine)

CONTACT INFORMATION

Associate Professor, MD, DMSc Kirsten Nørgaard (Principal Investigator)
Department of Endocrinology
Copenhagen University Hospital
Kettegård Allé 30, DK-2650 Hvidovre

kirsten.noergaard@hvh.regionh.dk  

Diabetes epidemiology (WP 14)

Demographic trends and lifestyle factors affecting prevalence of different types of diabetes are complex and further challenged by migration and globalisation. Ageing of the population and its effect on health care and the economy is especially relevant for diabetes research. While poly-pharmacological treatment has certainly improved the prognosis for individuals with diabetes, morbidity and increased mortality from micro- and macrovascular complications still remain. The availability of individually linked un-biased information on diabetes-related health based on clinically collected data and register-compiled information in Denmark provides a unique opportunity to bridge the two sources of information on a solid quantitative background
 

The overall aim will be to develop and apply novel methods to describe the burden of diabetes and to identify risk groups on a population level and to optimize the treatment of diabetic patients on an individual level.

AIMS

  • To describe prevalence, incidence, and mortality from diabetes 
  • To study the prognosis for patients with diabetes, including traditional micro- and macrovascular complications of diabetes, and non-traditional complications such as cancer, infectious diseases, dental health and mental illness with a specific focus on vulnerable patient-groups, e.g. migrants, elderly patients, patients with complex disease and patients with mental illness 
  • To describe trajectories of metabolic risk factors prior to diagnosis of complications, including the study of long term effects in type 1 diabetes on later health of metabolic exposures during childhood, adolescence and young adulthood. 
  • To integrate molecular methods derived from genetics, pathology and molecular biology in diabetes research into epidemiological studies
  • To integrate information from the established biobanks in the population-based registries that allow for improvement of causal inference in observational epidemiology

CONTACT INFORMATION

MD, PhD Marit Eika Jørgensen (Principal Investigator)
Steno Diabetes Center
Niels Steensens Vej 2, DK-2820 Gentofte

maej@steno.dk  

Hypertension and diabetes (WP 15)

Despite that Type 2 diabetes mellitus (T2D) and hypertension are well-known associated conditions with increasing prevalence and elevated cardiovascular risk many important issues are still unresolved. The reasons for the association between T2D and hypertension and for their additive detrimental cardiovascular effect remain unclear. The traditional concept of lower the antihypertensive treatment goals in patients with T2D has been challenged by the ACCORD study. The mechanism for and the prognostic importance of antihypertensive treatment-induced new onset diabetes remain also unclear.

 

 

AIMS

 

 

The aims are to investigate:

  1. The relationship between T2D and hypertension
  2. Whether the detrimental effect of T2D and hypertension is partly additive or supra-additive and what is the possible pathogenic mechanism
  3. Which factors are important for achieved BP and improved prognosis in patients with T2D and hypertension
  4. Which factors are important for the development of T2D during antihypertensive treatment and the prognostic importance of this type of new onset diabetes

CONTACT INFORMATION

Michael Hecht Olsen, MD, PhD, DMSc (Principal Investigator)
Professor in Hypertension
Cardiovascular and Metabolic Preventive Clinic
Department of Endocrinology
Odense University Hospital
Sdr. Boulevard 29, DK-5000 Odense C

mho@dadlnet.dk  

Health promotion, quality of life and prevention of diabetes (WP 16)

Diabetes is known to be associated with decreased quality of life due to co-morbidity, medicalization, social and psychological struggles. This complexity is far from understood, but studies have shown that people with diabetes have a higher risk of suffering from e.g. decreased cognitive function, depression and sexual dysfunction. These associations are not unambiguous with level of metabolic control (blood sugar levels), and other factors than pharmaceutical metabolic control are therefore important in diabetes care.
 

This work package aims to produce research in better understanding of how to keep persons with diabetes healthy in a broad perspective, how to help them cope with their condition, and how to prevent development of diabetes in persons at high risk. Research projects focusing on high risk populations e.g. adolescents with diabetes and adults with known risky phenotypic characteristics such as obesity, physical inactivity, gestational diabetes and known cardiovascular disease will be conducted. Social inequality as a central component in understanding the mechanism of healthy behaviour will be investigated. Intervention studies with randomised controlled designs, clinical examinations and information obtained from registers, questionnaires and interviews are key methods used in this work package.

AIMS

  • To describe quality of life and self-reported health status in a population with screen detected diabetes over 10 years or more and to identify mechanisms affecting quality of life
  • To develop and evaluate a “care-strategy” for adolescents with type 1 diabetes
  • To develop and evaluate health promoting activities and treatments in primary care settings to prevent diabetes and diabetic complications, and to improve overall quality of life for people with diabetes and for people at risk of diabetes

CONTACT INFORMATION

Professor Annelli Sandbæk (Principal Investigator)
Institute of Public Health
University of Aarhus
Nordre Ringgade 1, DK-8000 Aarhus C

annelli.sandbaek@alm.au.dk  

Exercise in prevention and treatment of diabetes (WP 17)

In this work package our primary goal is to understand the beneficial effect of physical exercise in prevention and treatment of Diabetes, and to understand the adverse effects of physical inactivity. We explore this through the studies of both healthy and diseased human subjects and combine these with more mechanistic research mainly by the use of transgenic animal models and various advanced biochemical and molecular biological tools/analyses.
 

This WP provides a research environment focusing on integrative physiology in combination with molecular insight, thus offering postdocs a true translational environment (from molecule to human/patient and from human/patient to molecule). Understanding the mechanism by which exercise interventions may prevent diseases related to insulin resistance or may improve peripheral insulin sensitivity in subjects with insulin resistance may ultimately improve the basis for lifestyle recommendations. This knowledge may ultimately provide the basic insight needed in developing an effective pharmacologically based treatment or prevention regime.

AIMS

  • To explore the hypothesis that exercise resistance (non-responders) is a contributing factor causing IR by preventing the otherwise metabolic health promoting effects of exercise in various populations at risk of IR, T2D, PCOS, obesity and low birth weight
  • To explore whether maternal or paternal exercise can cause lasting changes in gene activity of importance for metabolic and cardiovascular health in offspring through epigenetic mechanisms
  • To elucidate the molecular mechanism for exercise and exercise training to improve insulin sensitivity, and use this information to indentify new drug targets “The Exercise pill” in the combat of IR and T2D
  • To explore the mechanism for the detrimental effects of energy and fuel surplus for cellular insulin action potentially involving sirtuin (SIRT), AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1a) signalling and lipotoxicity, and to explore the potential and the mechanism for exercise to improve insulin sensitivity in such conditions
  • To explore the influence of fatty acid transport, esterification and/or lipolysis in skeletal muscle to IR and the effect of physical activity hereon
  • To elucidate the importance of physical activity on microvascular perfusion on skeletal muscle metabolism and insulin sensitivity in T2D

CONTACT INFORMATION

Professor Jørgen Wojtaszewski (Principal Investigator)
Section of Molecular Physiology
The August Krogh Centre 
Department of Nutrition, Exercise and Sport 
University of Copenhagen
13 Universitetsparken, 2100 DK- Copenhagen

DIR +45 35321625
MOB +45 28751625
jwojtaszewski@ifi.ku.dk

NEXS: http://NEXS.ku.dk 
AKC: http://AKC.ku.dk  

Developmental programming of diabetes and metabolism (WP 18)

In this WP we want to address the impact and the underlying developmental programming of type 2 diabetes (T2D) and cardiovascular disease. More specifically, we aim to use and expand the current national cohorts and registries, in particular the Danish National Birth Cohort (DNBC) founded approximately 15 years ago. Our scope is to establish a life course-approach to expand ongoing and implement novel in-depth metabolic, integrative physiological and epigenetic studies of distinct and phenotypically extremely well characterized subgroups.
 
AIMS
 

We aim to identify novel mechanisms and molecular targets of developmental programming involved in the development of T2D with a focus on human muscle and adipose tissue biology, DNA methylation, miRNAs, as well as histone acetylations and their interactions with genetic and non-genetic factors.

CONTACT INFORMATION

Professor, MD, DMSc Allan Vaag (Principal Investigator)
Department of Endocrinology, diabetes and metabolism
Copenhagen University Hospital
Blegdamsvej 9, DK-2100 Copenhagen Ø

allan.vaag@regionh.dk
www.diabetes-metabolism.dk  

Epigenetic control of insulin sensitivity in skeletal muscle (WP 19)

Physical exercise drives adaptive responses in skeletal muscle to improve metabolic efficiency, oxidative capacity and insulin sensitivity via remodeling of mRNA expression and protein level of a plethora of genes involved in insulin sensitivity and fuel usage. DNA methylation is a major epigenetic modification that under many conditions suppresses gene expression by modulating the access of the transcription machinery to the chromatin or by recruiting methyl-binding proteins.
 

Recently, we showed that in genes controlling lipid and glucose metabolism are hypomethylated after an acute exercise bout, suggesting DNA methylation participates in exercise-induced gene expression. In this work package, we further test the hypothesis that DNA methylation is involved in the adaptation to exercise training and the amelioration of insulin sensitivity. This work is of relevance for diabetes and obesity because regular physical activity is the first line of defense against the development of peripheral insulin resistance.

CONTACT INFORMATION

Associate Professor Roman Barrés (Principal Investigator)
The Novo Nordisk Foundation Center for Basic Metabolic Research
University of Copenhagen
Blegdamsvej 3, DK-2200 Copenhagen N

barres@sund.ku.dk  

Diabetes, obesity and gastric bypass (WP 20)

Gastric bypass is now an accepted operation in the treatment of severe obesity in the western world. The operation results in large and long lasting weight loss and metabolic changes including remission of type 2 diabetes or improvement of glycemic control together with improvement of other obesity related co-morbidities (sleep apnoe, hypertension, hyperlipidemia, arthrosis and PCOS) and reduction in cardiovascular events and cancer. The changes following the reorganisation of the gut are undergoing investigtion and much has been uncovered during the recent years. The neurohormonal signaling from the gastrointestinal tract to the brain and changes in liver and muscle sensitivity and improvement in insulin secretion in people with type 2 diabetes are central areas of interest.
 

However, better insight into the mechanisms of remission of Type 2 diabetes, of good and poor responders to weight loss, of post operative complications as postprandial hypoglycemia, of longterm results (weight, diabetes) and of the importance of the interaction between genes and microbiota is needed.

RYGB is one of the most interesting areas of research within diabetes and appetite regulation. RYGB remains an inspiration in the search of better understanding of the pathophysiology of type 2 diabetes and in the search for new drug targets. In particular possibilities for increasing endogenous release of GLP-1, which could perhaps lead to development of oral GLP-1 releasing agents for the treatment of diabetes and obesity.

CONTACT INFORMATION

Chief Consultant Dorte Worm (Principal Investigator)
Department of Endocrinology
Hvidovre Hospital
Kettegaard Alle 30, DK-2650 Hvidovre

Dorte.Worm@regionh.dk 

Molecular and cellular enteroendocrine biology

AIMS

To be announced ...

CONTACT INFORMATION

Associate Professor Birgitte Holst (Principal Investigator) 
The Novo Nordisk Foundation Center for Basic Metabolic Research
University of Copenhagen
Blegdamsvej 3, DK-2200 Copenhagen N

Inflammatory beta cell destruction (WP 22)

The research aim of the group is to contribute to the prevention and cure of type 1 and type 2 diabetes by therapeutic targeting of the causative molecular pathways leading to pancreatic β-cell failure. The research strategy of the group is to define the transcriptional, translational and posttranslational responses of the pancreatic β-cell to immune, inflammatory, metabolic and oxidative stress, with the aim of identifying novel therapeutic targets to be tested in preclinical models and clinical trials. We will achieve this goal by employing an interdisciplinary approach ranging from systems biology, bioinformatics, and in silico modelling, via cell-free and cell-based in vitro studies, ex vivo and in vivo studies in induced and genetic animal models, to clinical trials and biomarker studies.
 

CONTACT INFORMATION 

Professor Thomas Mandrup-Poulsen (Principal Investigator)
Department of Biomedical Sciences
Endocrinology Research Section
Panum Institute
Blegdamsvej 3, DK-2200 Copenhagen N

tmpo@sund.ku.dk
http://forskning.ku.dk/search/profil/?id=123515