The NeuroCardioMetabol Group – Thomas Nyström and Cesare Patrone

Our research focus is on the pathophysiological mechanisms at the basis of the complications of diabetes and obesity, with main emphasis on stroke. We also work on the identification of both life-style and pharmacological strategies to improve neurological recovery after stroke.

Part of the:
The NeuroCardioMetabol group

The Group

Our research focus is on the pathophysiological mechanisms at the basis of the complications of diabetes and obesity, with main emphasis on stroke. We also work on the identification of both life-style and pharmacological strategies to improve neurological recovery after stroke in diabetes. Our team currently includes one senior researcher, one assistant professor, one postdoctoral fellow, and two PhD students. In addition, several researchers from the Department of Internal Medicine at Södersjukhuset are scientifically affiliated with the group with their research lines, contributing to a strong translational and collaborative framework.

News from the group

International Journal of Molecular Sciences - Special edition
Enhancing Neurological Recovery after Stroke: Potential Therapies and Mechanisms

Collaboration in Science 2022, October 6-7th

Diet-induced weight loss in obese/diabetic mice normalizes glucose metabolism and promotes functional recovery after stroke.

Collaborations

The group has ongoing partnerships with Professors Claes-Göran Östensson, Henrik Druid, Tomas Hökfelt, Helena Erlandsson Harris (KI); with Associate Professors Sergiu-Bogdan Catrina, André Fisahn, Jan Kehr, Camilla Krizhanovskii, Martin Holzman, Ulrik Sartipy, Anna-Norhammar (KI); with Professor Jan Eriksson (Uppsala University); with Professors Milos Pekny and Carina Mallard and with Dr. Maria E Johansson (University of Gothenburg); with Professors Gesine Paul and Joao Duarte (Lund University); with Dr. Stefania Ceruti and Giulia Magni (University of Milan), Professor Massimo Collino (Turin University) and with Professor Mariagrazia Grilli (Novara University). We also have an ongoing collaboration with Boehringer Ingelheim Pharma GmbH & Co. KG, Germany, since 2011.

Our research project

We were the first to demonstrate (Nyström et al. AJP 2004) that the incretin hormone glucagon-like peptide 1 (GLP-1) improves endothelial function in type 2 diabetic (T2D) patients.

We were the first group to show the acute neuroprotection mediated by GLP-1 receptor agonists (Darsalia et al., Clinical Science 2012) by dipeptidyl peptidase-4 inhibitors (Darsalia et al. 2013 Diabetes) and by SGLT2 inhibitors (Vercalsteren et al. 2024 Cardiovascular Diabetology) in animal models of diabates, as well as effects of these drugs to also enhance post-stroke neurological recovery (Augestad et al., 2021, Diabetes; Augestad et al., 2022, British Journal of Pharmacology)

In recent publications we provided the first experimental evidence that weight loss induced pharmacologically or by a diet change enhances neurological recovery after stroke (Vercalsteren et al Diabetologia 2026; Karampatsi et al., 2022, Cardiovascular Diabetology). These effects are mediated by the normalization of insulin resistance (Vercalsteren et al., Diabetes 2026).

We also showed that T1D patients have a dire prognosis after coronary artery bypass grafting (CABG) than non-diabetics (Holzmann et al. JACC 2015) and that glycemic control is a key predictor for mortality in T1D after CABG (Nyström et al. JACC 2015) as for T2D (Kuhl et al. Int J Cardiol 2015). Moreover we are participating in population based studies evaluating prevalence, incidence and life expectancy of pharmacologically treated T2D patients (Norhammar et al., Diabetologia 2016) and effects of novel oral glucose lowering drugs (Nyström et al., Diabetes obesity and metabolism, 2017).

Preclinically, we showed that the anti-stroke efficacy by DPP-4 inhibitors is not mediated via GLP-1 (Darsalia et al. Diabetes Obes Metab 2016) but SDF1a (Chiazza et al. Cardiovasc Diabetol 2017). We also provided new insights on how T2D impairs neuroplasticity and neurogenesis during aging (Lietzau et al. Psychoneuroendocrinol. 2017 and Acta Neuropathol Commun 2018, Mansouri et al. PLOS One 2016, Hussain S et al. J Alzheimer's Dis. 2014); observations that could be at the basis of decreased olfaction and cognitive decline in T2D.

Publications

Selected publications

All publications from group members

Funding

Grants

  • Weight Loss by Glucagon-like peptide 1 receptor activation to improve Stroke Outcome in Diabetes: a Translational Project
    Swedish Stroke Association
    1 March 2026 - 31 December 2026
  • SRP Diabetes
    1 March 2026 - 28 February 2026
  • Weight Loss by Glucagon-like peptide 1 and Glucagon receptors activation to improve Stroke Outcome in Diabetes: a Translational Project
    Diabetesfonden
    1 January 2026 - 31 December 2027
  • Towards novel stroke therapies: targeting post-stroke obesity in diabetes to improve stroke
    Ulla Hamberg Angeby and Lennart Angeby Foundation
    1 October 2025 - 30 September 2026
  • Medel för kompetenshöjande insatser
    Region Stockholm
    1 September 2025 - 31 December 2025
  • The prevention of obesity and diabetes by dietary nitrate: a novel strategy to improve stroke recovery
    Ulla Hamberg Angeby and Lennart Angeby Foundation 2023
    1 January 2024 - 31 December 2025
  • The pre-stroke targeting of obesity in diabetes: a novel approach to improve stroke recovery
    Swedish Stroke Foundation
    1 January 2024 - 31 December 2025
  • Swedish Cancer Society
    1 January 2024
    The applicant has been a treating physician for the last 23 years for patients with myeloma, the median survival has increased from 3 to >10 years. The project is a direct consequence of the questions from everyday life with the patients. The key question in our research over the years has been and still is to identify why some patients have a quiescent disease with good long-term survival after standard treatment, while others have a more aggressive disease that does not respond to treatment and has a very dismal survival. Better understanding can be achieved through a better mapping of the biology of the disease and resistance mechanisms of the cancer cell in the individual patient. Multiple myeloma is the second most common blood cancer, despite advances in treatment, most patients suffer from relapse. We investigate new treatment methods that may be effective where conventional therapy fails, try to understand the mechanisms of action and identify the group of patients who would benefit most from the drug or treatment method with no or minimal side effects. We are establishing new prognostic markers predicting which patients will relapse and introducing new treatments. Our research has direct clinical implications both for prognosis and choice of treatment. Our optimal goal is a cure, which is achievable in the near future, through the introduction of new treatments/combinations. We also aim to better understand action/resistance mechanisms and correlate them with cancer cells' DNA changes, which can differ from patient to patient, even within the same disease. New markers of relapse aimed at
    on the one hand shortening the treatment time thus fewer side effects if negative and on the other hand changing/extending the treatment in those with positive markers for a better survival.
  • Typ 2 diabetes och stroke: Antidiabetisk behandling och återhämtning
    ALF
    1 January 2024
  • Swedish Heart-Lung Foundation
    1 January 2024 - 31 December 2026
  • Swedish Research Council
    1 January 2023 - 31 December 2025
  • Sodium Glucose Cotransporter 2-Inhibitors to Improve Recovery after Stroke in Diabetes
    Ulla Hamberg Angeby and Lennart Angeby Foundation 2022
    1 January 2023 - 31 December 2024
  • Sodium Glucose Cotransporter 2-Inhibitors to Improve Post-Stroke Recovery in Diabetes
    Swedish Stroke Association
    1 January 2023 - 31 December 2024
  • The treatment of insulin resistance to improve stroke recovery in pre-diabetes and type 2 diabetes
    Foundation for Geriatric diseases at Karolinska Institutet 2022
    1 January 2023 - 31 December 2023
  • Sodium Glucose Cotransporter 2-Inhibitors to Improve Recovery after Stroke in Diabetes
    Ulla Hamberg Angeby and Lennart Angeby Foundation
    1 January 2023 - 31 December 2023
  • Swedish Research Council
    1 December 2022 - 30 November 2025
  • Behandling av insulinresistens för förbättrad återhämtning efter stroke
    The Swedish Brain foundation
    1 October 2022
  • Stroke och typ 2 diabetes: Riskmarkörer - återhämtning - reparation
    ALF
    1 January 2022
  • Impaired Stroke Recovery in Type 2 Diabetes: Identification of Causes and new Therapies
    Ulla Hamberg Angeby and Lennart Angeby Foundation
    1 January 2021 - 31 December 2021
  • Inkretinbaserad läkemedelsbehandling mot hjärtsjukdom och stroke
    ALF
    1 January 2021
  • The interplay between obesity, type 2 diabetes (T2D) and weight loss on stroke outcome
    Diabetesfonden
    1 March 2020 - 31 December 2022
  • Swedish Heart-Lung Foundation
    1 January 2020 - 31 December 2022
  • Swedish Cancer Society
    1 January 2020
    Multiple myeloma (MM) is an incurable malignant disease. This disease accounts for about 2% of all cancer deaths and almost 20% of deaths caused by hematological malignancies. New drugs have improved the prospects for long-term survival, despite this improvement in survival in recent years, relapses affect almost all patients. Thus, new treatment modalities are needed for patients with MM. In recent years, immune and cellular therapies have rapidly evolved as exciting new cell-based therapies for many cancers, including MM. One mystery that remains to be solved is the serious side effects associated with such therapy. The purpose is to identify prognostic parameters, in particular genes on specific chromosomes, as well as perform a thorough analysis when the disease recurs and reduce side effects of immunotherapy. Specifically, we will A- Analyze prognostic parameters related to specific therapies and differences in outcomes B- Improving current immune / cell therapies in terms of effectiveness and reducing side effects C- Analyze the genetic characterization of MM at diagnosis and progressive disease, partly to better predict the prognosis, partly to provide any possible future therapies that target specific genes in recurrence The key issue in our research over the years has been and still is to identify why some patients with multiple myeloma have good long-term survival after standard treatment, while others have a more aggressive disease. Our hypothesis is that the right combination of available treatment methods and the addition of new therapies improves the results. We investigate new treatment methods that can have an effect where ordinary treatment fails, try to understand the mechanisms of action. Our goal is to achieve a cure in patients with myeloma and in cases where a cure cannot be achieved. We hope to achieve a significant extension of survival.
  • Swedish Research Council
    1 January 2019 - 31 December 2021
  • Improving prognosis marker, treatment strategies and minimizing the side effects in the treatment of Multiple Myeloma.
    Swedish Cancer Society
    1 January 2019
    Multiple myeloma (MM) is an incurable malignant disease. This disease accounts for about 2% of all cancer deaths and almost 20% of deaths caused by hematological malignancies. New drugs have improved the prospects for long-term survival, despite this improvement in survival in recent years, relapses affect almost all patients. Thus, new treatment modalities are needed for patients with MM. In recent years, immune and cellular therapies have rapidly evolved as exciting new cell-based therapies for many cancers, including MM. One mystery that remains to be solved is the serious side effects associated with such therapy. The purpose is to identify prognostic parameters, in particular genes on specific chromosomes, as well as perform a thorough analysis when the disease recurs and reduce side effects of immunotherapy. Specifically, we will A- Analyze prognostic parameters related to specific therapies and differences in outcomes B- Improving current immune / cell therapies in terms of effectiveness and reducing side effects C- Analyze the genetic characterization of MM at diagnosis and progressive disease, partly to better predict the prognosis, partly to provide any possible future therapies that target specific genes in recurrence The key issue in our research over the years has been and still is to identify why some patients with multiple myeloma have good long-term survival after standard treatment, while others have a more aggressive disease. Our hypothesis is that the right combination of available treatment methods and the addition of new therapies improves the results. We investigate new treatment methods that can have an effect where ordinary treatment fails, try to understand the mechanisms of action. Our goal is to achieve a cure in patients with myeloma and in cases where a cure cannot be achieved. We hope to achieve a significant extension of survival.
  • Achieving multiple myeloma cures by understanding the biology and introducing new treatment strategies
    Swedish Cancer Society
    1 January 2018
    Multiple myeloma (MM) is an incurable malignant tumor that accounts for about 2% of all cancer deaths and almost 20% of deaths caused by hematological malignancies. The presence of different chromosomal abnormalities among the malignant cells has been shown to have an effect on prognosis. Better understanding and classification of prognostic factors is needed to understand why different patients respond differently to treatment. By methodically analyzing both biological and clinical effects of different treatment strategists, we hope for better individual choice of treatment and the like. this better response in the individual. Analyze prognostic parameters, especially chromosome aberrations and genes on specific chromosomes. Specifically, we will: A-perform a retrospective analysis of forecasting parameters. B-identify and isolate specific genes in the chromosome region part (8) (p21) and to analyze their trivial importance for the development of MM. C-Implement a systematic effort to identify loci and avenues. D-Explore resistance and mechanism of action of different treatment strategists MM is still incurable. A better understanding of the effects of cytogenetic abnormalities and specific genes located in aberrant regions can help to understand pathogenetic mechanisms which, in turn, can contribute to the design of new and more effective drugs. Systematic work to identify genes that are associated with an increased risk of developing MM. The identification of such genes can lead to the development of tools to identify individuals-at-risk, and, in the longer term, to the development of new treatments. Together these methods can improve results and be a step towards the goal of curing MM.
  • Achieving multiple myeloma cures by understanding the biology and introducing new treatment strategies
    Swedish Cancer Society
    1 January 2017
    Multiple myeloma (MM) is an incurable malignant tumor that accounts for about 2% of all cancer deaths and almost 20% of deaths caused by hematological malignancies. The presence of different chromosomal abnormalities among the malignant cells has been shown to have an effect on prognosis. Better understanding and classification of prognostic factors is needed to understand why different patients respond differently to treatment. By methodically analyzing both biological and clinical effects of different treatment strategists, we hope for better individual choice of treatment and the like. this better response in the individual. Analyze prognostic parameters, especially chromosome aberrations and genes on specific chromosomes. Specifically, we will: A-perform a retrospective analysis of forecasting parameters. B-identify and isolate specific genes in the chromosome region part (8) (p21) and to analyze their trivial importance for the development of MM. C-Implement a systematic effort to identify loci and avenues. D-Explore resistance and mechanism of action of different treatment strategists MM is still incurable. A better understanding of the effects of cytogenetic abnormalities and specific genes located in aberrant regions can help to understand pathogenetic mechanisms which, in turn, can contribute to the design of new and more effective drugs. Systematic work to identify genes that are associated with an increased risk of developing MM. The identification of such genes can lead to the development of tools to identify individuals-at-risk, and, in the longer term, to the development of new treatments. Together these methods can improve results and be a step towards the goal of curing MM.
  • Swedish Research Council for Health Working Life and Welfare
    1 January 2017 - 31 December 2019
  • Achieving multiple myeloma cures by understanding the biology and introducing new treatment strategies
    Swedish Cancer Society
    1 January 2016
    Multiple myeloma (MM) is an incurable malignant tumor that accounts for about 2% of all cancer deaths and almost 20% of deaths caused by hematological malignancies. The presence of different chromosomal abnormalities among the malignant cells has been shown to have an effect on prognosis. Better understanding and classification of prognostic factors is needed to understand why different patients respond differently to treatment. By methodically analyzing both biological and clinical effects of different treatment strategists, we hope for better individual choice of treatment and the like. this better response in the individual. Analyze prognostic parameters, especially chromosome aberrations and genes on specific chromosomes. Specifically, we will: A-perform a retrospective analysis of forecasting parameters. B-identify and isolate specific genes in the chromosome region part (8) (p21) and to analyze their trivial importance for the development of MM. C-Implement a systematic effort to identify loci and avenues. D-Explore resistance and mechanism of action of different treatment strategists MM is still incurable. A better understanding of the effects of cytogenetic abnormalities and specific genes located in aberrant regions can help to understand pathogenetic mechanisms which, in turn, can contribute to the design of new and more effective drugs. Systematic work to identify genes that are associated with an increased risk of developing MM. The identification of such genes can lead to the development of tools to identify individuals-at-risk, and, in the longer term, to the development of new treatments. Together these methods can improve results and be a step towards the goal of curing MM.
  • Swedish Research Council
    1 January 2016 - 31 December 2018
  • Understanding the biology and introducing new treatment strategies for multiple myeloma
    Swedish Cancer Society
    1 January 2015
    Multiple myeloma (MM) is an incurable malignant tumor that accounts for about 2% of all cancer deaths and almost 20% of deaths caused by hematological malignancies. The presence of different chromosomal abnormalities among the malignant cells has been shown to have an effect on prognosis. Better understanding and classification of prognostic factors is needed to understand why different patients respond differently to treatment. The prevalence varies in MM globally from 1 per 100,000 in China, to about 10 per 100,000 in Africa and African Americans. Development of MM is preceded by gamma globulinopathy of unknown importance (MGUS), M protein without other signs of MM. Analyze prognostic parameters, especially chromosome aberrations and genes on specific chromosomes. Specifically, we will: A-perform a retrospective analysis of prognostic parameters, especially chromosome abnormalities, related to specific treatments in patients with MM. B-identify and isolate specific genes in the chromosome region part (8) (p21) and to analyze their trivial importance for the development of MM. C-Implement a systematic effort to identify loci and alleles (specific sites on a chromosome) risks associated with an increased risk of developing MM, both in unselected cases and in high-risk families-siblings / children with MM Myeloma is still incurable cancer. A better understanding of the effects of cytogenetic abnormalities and specific genes located in aberrant regions can help to understand pathogenetic mechanisms which, in turn, can contribute to the design of new and more effective drugs. Systematic work to identify genes that are associated with an increased risk of developing MM. The identification of such genes can lead to the development of tools to identify individuals-at-risk, and, in the longer term, to the development of new treatments. Together these methods can improve results and be a step towards the goal of curing MM.
  • GLUCAGON-LIKE PEPTIDE 1 ACTIVATION AGAINST STROKE IN DIABETES: FROM THE PRECLINICAL TO THE CLINICAL PHASE
    Novo Nordisk Foundation
    1 January 2014 - 1 January 2015
  • Understanding the biology and introducing new treatment strategies for multiple myeloma
    Swedish Cancer Society
    1 January 2014
    Multiple myeloma (MM) is an incurable malignant tumor that accounts for about 2% of all cancer deaths and almost 20% of deaths caused by hematological malignancies. The presence of different chromosomal abnormalities among the malignant cells has been shown to have an effect on prognosis. Better understanding and classification of prognostic factors is needed to understand why different patients respond differently to treatment. The prevalence varies in MM globally from 1 per 100,000 in China, to about 10 per 100,000 in Africa and African Americans. Development of MM is preceded by gamma globulinopathy of unknown importance (MGUS), M protein without other signs of MM. Analyze prognostic parameters, especially chromosome aberrations and genes on specific chromosomes. Specifically, we will: A-perform a retrospective analysis of prognostic parameters, especially chromosome abnormalities, related to specific treatments in patients with MM. B-identify and isolate specific genes in the chromosome region part (8) (p21) and to analyze their trivial importance for the development of MM. C-Implement a systematic effort to identify loci and alleles (specific sites on a chromosome) risks associated with an increased risk of developing MM, both in unselected cases and in high-risk families-siblings / children with MM Myeloma is still incurable cancer. A better understanding of the effects of cytogenetic abnormalities and specific genes located in aberrant regions can help to understand pathogenetic mechanisms which, in turn, can contribute to the design of new and more effective drugs. Systematic work to identify genes that are associated with an increased risk of developing MM. The identification of such genes can lead to the development of tools to identify individuals-at-risk, and, in the longer term, to the development of new treatments. Together these methods can improve results and be a step towards the goal of curing MM.
  • Swedish Research Council
    1 January 2013 - 31 December 2015
  • Swedish Research Council
    1 January 2012 - 31 December 2014
  • Swedish Research Council
    1 January 2010 - 31 December 2012
  • The Martin Rind Foundation
  • Identifying the Targets through which Glucagon-like Peptide 1 Receptor Activation improves Stroke Outcome in Diabetes
    Swedish Stroke Association

Staff and contact

Group leader

All members of the group

Visiting address

Karolinska Institutet, Department of Clinical Science and Education, Södersjukhuset, Sjukhusbacken 10, Stockholm, 11883, Sweden