Diabetes is really five different diseases, a study looking at nearly 9,000 people with diabetes in Sweden and Finland suggests.
Based on their results, they came up with 5 sub-types or clusters of diabetes. Cluster 1 corresponds to what could be called classic type 1 diabetes, while clusters 4 and 5 correspond to type 2 diabetes. Clusters 3 and 4 can be thought of as falling between the two extremes.
5 Clusters Of Symptoms
The study has value for improving our understanding of diabetes. For example, the researchers found that people who had cluster 3 or 4 diabetes had a higher risk of kidney disease or vision problems (retinopathy) than people in the other clusters.
But the diagnosis and management of diabetes isn’t going to change overnight. Further research is needed to see whether these 5 clusters hold true for non-Scandinavian populations.
The study, conducted by researchers from Lund University, Uppsala University and the University of Gothenburg in Sweden; and Vaasa Health Centre and the University of Helsinki in Finland, analysed several cohorts and registries of people with diabetes from Sweden and Finland to look at the characteristics of people newly diagnosed with the disease.
Traditionally, diabetes has been understood to have two main forms. In type 1, the body’s immune cells attack the insulin-producing cells in the pancreas. The person is completely unable to produce insulin and relies on lifelong insulin.
Type 2, however, has always been a bit more of a mixed condition. People either don’t produce enough insulin or their body’s cells don’t respond to it, with varying degrees of severity. Management ranges from dietary control or medication through to daily insulin injections.
The researchers felt refining the classification to recognise other types of diabetes could help to personalise treatment and identify those who may be at higher risk of specific complications.
5 Cohort Studies
The researchers looked at data from 5 cohort studies.
The first study – All New Diabetics in Scania (ANDIS) – recruited 14,625 people newly diagnosed with diabetes from across 177 general practices in Scania County, Sweden, between 2008 and 2016. They were followed up after an average of 4 years.
The Scania Diabetes Registry (SDR) study recruited 7,400 people with diabetes from Scania County between 1996 and 2009, following them up after an average of 12 years.
All New Diabetics in Uppsala (ANDIU) was a similar project to ANDIS but was carried out in the Uppsala region of Sweden. It included 844 people.
Diabetes Registry Vaasa (DIREVA) included 5,107 people with diabetes recruited in western Finland between 2009 and 2014.
Finally, the Malmö Diet and Cancer CardioVascular Arm (MDC-CVA) study included 3,330 people randomly selected from the larger Malmö Diet and Cancer study.
In the ANDIS study, blood samples were taken from people at registration, allowing the researchers to analyse their DNA and blood chemistry.
They also looked at various patient characteristics, complication rates – such as kidney and diabetic eye problems – and use of medications. People were clustered according to 6 main characteristics:
age at diagnosis
body mass index (BMI)
glycated haemoglobin (HbA1c) – a long-term indication of blood sugar control
function of the insulin-producing cells of the pancreas
level of insulin resistance – a measurement of how effectively, if at all, cells respond to insulin
presence of glutamate decarboxylase antibodies (GADA)
GADAs are antibodies linked with what is known as late-onset autoimmune diabetes (LADA). LADA is often mistaken for type 2 diabetes because of its similar symptoms, but it needs to be treated in the same way as type 1 diabetes.
The other cohorts were analysed in a similar way, but the researchers did not have the additional information on DNA and blood chemistry that they did for ANDIS.
Researchers identified 5 main disease clusters.
Severe autoimmune diabetes (SAID): this tended to start at a younger age, in people with a relatively low BMI, poor blood sugar control, insulin deficiency and GADA. About 6% of the people in the ANDIS study had SAID.
Severe insulin-deficient diabetes (SIDD): GADA-negative but otherwise similar to SAID. Identified in 18% of the people in ANDIS.
Severe insulin-resistant diabetes (SIRD): characterised by insulin resistance and high BMI. Identified in 15% of the people in ANDIS.
Mild obesity-related diabetes (MOD): characterised by obesity but not insulin resistance. Identified in 22% of the people in ANDIS.
Mild age-related diabetes (MARD): people were generally older than those in other clusters and had only mild problems with glucose control, similar to MOD. Identified in 39% of the people in ANDIS.
The researchers observed that people in cluster 3 had a higher risk of kidney disease, while those in cluster 2 had higher risk of diabetic eye disease than people in other clusters.
“This new sub-stratification might eventually help to tailor and target early treatment to patients who would benefit most, thereby representing a first step towards precision medicine in diabetes,"
the study concludes.
This is a worthwhile study that suggests the diagnosis of diabetes may not be as simple as just types 1 and 2. It’s already come to light that some people with late-developing diabetes, who are often presumed to have type 2 diabetes, may actually have LADA.
Improved understanding may allow necessarily treatment to be tailored and help us recognise which patients are more likely to develop complications.
However, this study alone is not sufficient to lead to changes in diabetes treatment guidelines, as it was only based on groups of diabetes patients in Scandinavia. The clusters and associated complications will need to be verified in other populations, including other ethnicities that may have a different risk of diabetes, such as Asian populations.
Funding for the work was provided by the Swedish Research Council, European Research Council, Vinnova, the Academy of Finland, Novo Nordisk Foundation, Scania University Hospital, Sigrid Jusélius Foundation, the European Union Innovative Medicines Initiative 2 Joint Undertaking, Vaasa Hospital, Jakobstadsnejden Heart Foundation, Folkhälsan Research Foundation, the Ollqvist Foundation and the Swedish Foundation for Strategic Research.
Ahlqvist, Emma et al. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables The Lancet Diabetes & Endocrinology, DOI: https://doi.org/10.1016/S2213-8587(18)30051-2