A Study Proposes 5 New Distinct Types of Adult-Onset Diabetes

Emma Ahlqvist, PhD, Associate Professor, Lund University

Emma Ahlqvist, PhD

A new analysis published in The Lancet Diabetes and Endocrinology indicates researchers were able to distinguish 5 new subgroups of patients with adult-onset diabetes, representing a first step toward precision medicine for the roughly 415 million patients with the chronic condition.

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, authors wrote.

The results indicate a major difference in the 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.

“Implementing this clustering in the clinic could both guide the choice of therapy and help identify patients with a high risk of diabetic complications,” lead author, Emma Ahlqvist, PhD, Lund University, told MD Magazine. “Patients in the severe insulin-deficient diabetes (SIDD) and severe insulin-resistant diabetes (SIRD) clusters start developing complications (retinopathy and nephropathy respectively) at a very early stage of disease and identifying these patients already at diagnosis and giving them the most appropriate treatment could therefore help prevent complications.”

Researchers in this study used 4 cohort studies since 2008 to monitor 14,775 newly diagnosed patients across Sweden and Finland over the age of 18 who had been recently diagnosed with diabetes.

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.

“It is likely that patients in the severe insulin-deficient diabetes cluster would benefit from early treatment with insulin whereas patients in the severe-insulin resistant diabetes cluster need treatment focusing on increasing insulin sensitivity,” Ahlqvist added. “Importantly, patients in the insulin-resistant diabetes cluster would likely benefit from an early more intensified treatment. In our cohort the insulin-resistant cluster patients received similar diabetes treatment as the age-related diabetes cluster patients in spite of significant differences in risk of complications, likely because current treatment goals are too focused on HbA1c levels, which are similar in the 2 clusters.”

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 March 1, 2018.