Anders Rosengren Group

Research Summary

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.

Specifically, we

1. test the effect of existing anti-diabetic drugs in patients with different disease characteristics;
2. determine the effect of a digital lifestyle tool on the progression and prevention of lifestyle diseases such as T2D; 
3. 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.