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Diabetes affects about one in 11 adults worldwide and increases the risk of heart attack, stroke, blindness, kidney failure and limb amputation.
The older classification divided diabetes into Type 1 and 2. Type 1 has been considered a disease of the immune system, which affects around 10% of people. It errantly attacks the body's insulin factories (beta-cells) so there is not enough of the hormone to control blood sugar levels. Type 2 diabetes is largely seen as a disease of poor lifestyle as body fat can affect the way the insulin works.
The results from the study indicate a major difference in the old classification, and suggest that type 2 diabetes actually consists of several subgroups.
The 5 types of the disease are associated with different characteristics and complications, illustrating a variety of treatment methods needed.
Cluster 1 - severe autoimmune diabetes is broadly the same as the classical type 1 - it hit people when they were young, seemingly healthy and an immune disease left them unable to produce insulin
Cluster 2 - severe insulin-deficient diabetes patients initially looked very similar to those in cluster 1 - they were young, had a healthy weight and struggled to make insulin, but the immune system was not at fault
Cluster 3 - severe insulin-resistant diabetes patients were generally overweight and making insulin but their body was no longer responding to it
Cluster 4 - mild obesity-related diabetes was mainly seen in people who were very overweight but metabolically much closer to normal than those in cluster 3
Cluster 5 - mild age-related diabetes patients developed symptoms when they were significantly older than in other groups and their disease tended to be milder
The new clustering of patients is superior to the standard diabetes classification because it identifies patients at high risk of diabetic complications at diagnosis, providing information about underlying disease mechanisms and ultimately guiding choice of therapy. The three severe forms could be treated more aggressively than the two milder ones.
Cluster 2 patients would currently be classified as type 2 as they do not have an autoimmune disease. However, the study suggests their disease is probably caused by a defect in their beta-cells rather than being too fat. And perhaps their treatment should more closely mirror patients who are currently classed as type 1. Cluster 2 had a higher risk of blindness while cluster 3 had the greatest risk of kidney disease, so some clusters may benefit from enhanced screening.
There were 6 measurements analyzed that are used to monitor those with diabetes: age at onset of illness, body mass index, long-term glycemic control, insulin resistance, insulin secretion and presence of auto-antibodies associated with autoimmune diseases. Genetic analyses and disease progression, treatment and development of diabetic complications were also conducted for each type of diabetes.
After analyzing the measures in a cohort of 8980 adults at first, researchers identified 1 autoimmune type of diabetes and 4 distinct subtypes of type 2 diabetes, which were then tests across 3 more cohorts of 5795 people: the Scania Diabetes Registry (n=1466), All New Diabetics in Uppsala (n=844) and Diabetes Registry Vaasa (n=3485).
Researchers then distinguished 5 distinct clusters that differ from today’s classification: 3 severe and 2 mild forms of the disease.
Additionally, the findings concluded that the different subgroups are more or less at risk of developing various secondary disease.
Diabetes is currently divided into type 1 diabetes (approximately 10%), type 2 diabetes (85–90%) and several less common diseases like latent autoimmune diabetes in adults (LADA), maturity onset diabetes of the young (MODY) and secondary diabetes.
Among the 3 new severe classifications, there was 1 group with severe insulin resistance that had the highest incidence of kidney damage than the other types and is characterized by obesity and severe insulin resistance (cluster 3/severe insulin-resistant diabetes (SIRD), affecting 11–17% of patients), another group is characterized by relatively young, insulin-deficient individuals with poor metabolic control high HbA1C impaired insulin secretion and has the highest incidence of retinopathy (cluster 2/severe insulin-deficient diabetes (SIDD), affecting 9–20%), while the last severe group were insulin-deficient patients who had auto-antibodies associated with autoimmune diabetes (cluster 1/severe autoimmune diabetes (SAID), affecting around 6–15%), a form of diabetes formerly called type 1 diabetes or LADA.
The largest group of the disease was one of the more moderate forms and was seen in elderly people, affecting 39–47% of patients (cluster 5/ mild age-related diabetes (MARD)). The other mild form (cluster 4/ mild obesity-related diabetes (MOD)), was seen mainly in obese patients who fall ill at a young age and affected 18–23% of patients.
The 5 subtypes are genetically distinct with no mutations, concluding that the types are not different stages of the same disease. The new substratification might help to tailor and target early treatment to those who would benefit most.
Some limitations were noted including that the study cannot confirm that the 5 types have different causes, nor whether patients’ type of disease changes over time. Researchers also did not have data on known risk factors for diabetic complications like blood pressure and blood lipids.
While the study had limited non-Scandinavian involvement, similar studies are in the works in China and India with people of different ethnic backgrounds.
Future research is also needed to test and refine the 5 types to include biomarkers, genotypes, genetic risk scores, blood pressure and blood lipids.
The study, “Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables” was published in The Lancet Diabetes and Endocrinology. To read the article, click here.
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