Anders Rosengren Group
Anders Rosengren, MD, PhD, Professor in Molecular Medicine.
About Anders Rosengren Group
Anders Rosengren integrates clinical investigations, bioinformatics and experimental studies and aims to better understand the pathophysiology of lifestyle diseases such as type 2 diabetes and to identify more specific treatment targeted at the underlying disease mechanisms. He is also leading the research endeavour on Livsstilsverktyget (www.livsstilsverktyget.se) that aims to better prevent and manage lifestyle diseases.
He received his PhD in cellular and molecular physiology in 2007 at Lund University, followed by clinical internship in 2007-2009 at Skåne University hospital. In 2010 and 2011 he worked at Sage Bionetworks, Seattle, on bioinformatics. Through several national and international grants as a PI he started an independent research group at Lund University in 2011. In 2016 he was recruited to the University of Gothenburg. Since 2019 he also serves on the faculty board of the Sahlgrenska Academy.
He has received several grants at highest international and national level, including a Consolidator grant from the European Research Council as well as from the European Foundation for the study of diabetes, the Swedish Research Council, the Ragnar Söderberg foundation and the Swedish Foundation for Strategic Research.
His combined experience of cellular physiology, bioinformatics and clinical medicine has enabled his group to address important research questions from new and multi-disciplinary viewpoints. This includes the identification of SFRP4 as a link between inflammation and type 2 diabetes (Mahdi et al., Cell Metabolism 2012), the first application of optogenetics to measure beta-cell activity (Reinbothe et al., Islets 2015) and the identification of SOX5 as a regulator of beta-cell dedifferentiation in type 2 diabetes (Axelsson et al., Nature Communications 2017).
Since 2012 his research group has established an infrastructure to effectively translate their basic science to patient investigations. This is exemplified by the demonstration that ADRA2A antagonists improve insulin secretion in carriers of a genetic risk variant for ADRA2A (Axelsson et al., Science Translational Medicine 2014), which builds further on the identification of ADRA2A as a molecular link between the adrenergic system and type 2 diabetes (Rosengren et al., Science 2010). His group has also identified sulforaphane as a new anti-diabetic compound (Axelsson et al., Science Translational Medicine 2017). He is clinical Principal Investigator for the All New Diabetics In Scania (ANDIS) cohort with 20,000 diabetic patients. He combines research with clinical work.
Since 2016 he leads the development and evaluation of Livsstilsverktyget. Livsstilsverktyget is a digital tool that was developed in a systematic manner, with longitudinal analyses of biological and lifestyle factors, repeated interviews and patient co-participation. His team is currently conducting a large prevention study involving Livsstilsverktyget that includes people from all over Sweden.
Anders Rosengren’s group has extensive international collaborations, which includes e.g. Sage Bionetworks in Seattle and the University of Oxford.
Department of Physiology
405 30 Göteborg
413 90 Gothenburg
An alarming 500,000 people in Sweden and 300 million worldwide have type 2 diabetes (T2D). Current treatment strategies fail to both prevent and stop the progressive course of the disease. The disease causes severe complications in the kidneys, eyes and the cardiovascular system, making T2D one of the greatest threats to human health.
Clinical guidelines recommend metformin as initial therapy to all patients but emphasise the need for subsequent personalized treatment with additional drugs. Although this sounds attractive, it is currently implemented on trial-and-error fashion and the concept as such has in fact not been examined systematically and with scientific rigour. Recent guidelines from the European Association for the Study of Diabetes also recommend enhanced focus on lifestyle management in addition to glucose-lowering drugs. Individual or group-based diabetes education programs are, however, resource-intense and long-term outcomes are variable.2
We have recently analysed 9,000 diabetic patients, which highlighted different clusters of T2D patients, each with various characteristics and risk of complications (Ahlqvist et al., Lancet Diabetes & Endocrinology). Two of these clusters are particularly aggressive: one has been coined SIDD (Severe Insulin-Deficient Diabetes) and features low age at onset, low BMI and poor insulin secretion; the other, termed SIRD (Severe Insulin-Resistant Diabetes), presents at higher age and associates with high insulin resistance. There is also a third cluster, Mild Obesity-related Diabetes (MOD), which represents obese patients with relatively well-preserved insulin secretion and less severe disease progression.
This sheds new light on the mounting problem of T2D by emphasising the high variability of the pathophysiology and providing a new tool to distinguish individuals at different ends of the pathophysiological spectrum. Importantly, it leads us to propose that anti-diabetic treatment should ideally target the underlying pathophysiology of each individual patient.
The overarching goal of our current research is to test this proposition, by the use of existing drugs, by a new digital lifestyle tool and by a recently identified glucose-lowering compound to enable more precise interventions guided by the disease mechanisms.
To reach this goal, we conduct a programme of research that combines tailored clinical studies with pathophysiological and metagenomic investigations. The programme represents the first attempt to date to systematically test the concept of ‘personalized medicine for T2D’, which is advocated by both the European and American diabetes associations but has – in fact – never been evaluated with scientific rigour and from a pathophysiological viewpoint. If successful, it will pave the way for new personalized strategies to prevent and treat T2D more effectively than today.
- test the effect of existing anti-diabetic drugs in patients with different disease characteristics;
- determine the effect of a digital lifestyle tool on the progression and prevention of lifestyle diseases such as T2D;
- investigate the effects and mechanisms of action of sulforaphane
The current studies have the potential to open up entirely new strategies for management and prevention based on the underlying pathophysiology. Importantly, the research programme takes both pharmacological and lifestyle interventions into account, which makes it unusually comprehensive.
The new clusters are not distinct disease entities but provide a useful tool to clinically distinguish patients with different pathophysiological characteristics to systematically test personalized treatment in a manner that has not previously been done. The digital tool can be provided either directly to individuals or via healthcare providers. It is an online tool and is easy to access via a web link. It has been shown to be cost-saving for healthcare and could become highly valuable in primary care, where discussions on lifestyle are often not possible because of time and resource constraints.
Finally, the proposed research will investigate how the gut microbiota contributes to the clinical phenotype of individuals with SIDD and SIRD characteristics, their response to treatment and their risk for complications, which has the potential to add a completely new facet to our understanding of T2D and our abilities to provide tailored treatment.
Grants and Awards
Grants as Principal Investigator
- ERC Consolidator grant
- Wallenberg Centre for Molecular and Translational Medicine
- Swedish Research Council
- European Foundation for the Study of Diabetes (EFSD)
- Crafoord Foundation
- Royal Physiographic Society
Rising Star Award 2013, the European Foundation for the Study of Diabetes
Ragnar Söderberg Foundation - Ragnar Söderberg Researcher in Medicine 2013
Swedish Foundation for Strategic Research - Future Research Leader 2013
Annika S Axelsson, Emily Tubbs, Brig Mecham, Shaji Chacko, Hannah A Nenonen, Yunzhao Tang, Jed W Fahey, Jonathan MJ Derry, Claes B Wollheim, Nils Wierup, Morey W Haymond, Stephen H Friend, Hindrik Mulder, AH Rosengren
Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes
Science Translational Medicine, 9, eaah4477, 2017 http://stm.sciencemag.org/content/9/394/eaah4477
Axelsson AS, Mahdi T, Nenonen HA, Hänzelmann S, Bagge A, Wendt A, Reinbothe TM, Millstein J, Yang X, Zhang B, Gusmao EG, Shu L, Tang Y, Wang J, Andersson SE, Eliasson L, Artner I, Wollheim CB, Derry JM, Mecham B, Spégel P, Mulder H, Gesteira Costa Filho I, Zhang E, Rosengren AH
Sox5 regulates adult beta-cell phenotype and is reduced in type 2 diabetes
Nature Communications, 15652, 2017. https://www.nature.com/articles/ncomms15652
Tang Y, Axelsson A, Spegel P, Andersson LE, Mulder H, Groop L, Renström E, Rosengren AH
Genotype-based treatment of type 2 diabetes with an alpha2A-adrenergic receptor antagonist
Science Translational Medicine Oct 2014.
Mahdi T, Hänzelmann S, Salehi A, Muhammed SJ, Reinbothe TM, Tang Y, Axelsson AS, Zhou Y, Jing X, Almgren P, Krus U, Taneera J, Blom AM, Lyssenko V, Esguerra JLS, Hansson O, Eliasson L, Derry J, Zhang E, Wollheim CB, Groop L, Renström E, Rosengren AH.
Secreted Frizzled-Related Protein 4 Reduces Insulin Secretion and Is Overexpressed in Type 2 Diabetes.
Cell Metabolism 3;16:625-33. 2012.
Rosengren AH, Braun M, Mahdi T, Andersson SA, Travers ME, Shigeto M, Zhang E, Almgren P, Ladenvall C, Axelsson AS, Edlund A, Gram Pedersen M, Jonsson A, Ramracheya R, Tang Y, Walker JN, Barrett A, Johnson PRV, Lyssenko V, McCarthy MI, Groop L, Salehi A, Gloyn AL, Renström E, Rorsman P and Eliasson L.
Reduced insulin exocytosis in human pancreatic beta-cells with gene variants linked to type-2 diabetes.
Diabetes 61(7):1726-33. 2012.
Rosengren AH, Jokubka R, Tojjar D, Granhall C, Hansson O, Li DQ, Nagaraj V, Reinbothe TM, Tuncel J, Eliasson L, Rorsman P, Salehi A, Groop L, Lyssenko V, Luthman H, Renström E.
Overexpression of alpha2A-adrenergic receptors contributes to type 2-diabetes.
Science 327:217. 2010.