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Five distinct types of diabetes, not just two, suggests study

Findings could inform more tailored treatment of the disease, say researchers

Caroline White

Friday, 02 March 2018

There are five distinct types of diabetes rather than two, suggests Scandinavian research* published today in The Lancet Diabetes & Endocrinology journal.

The findings might help to better tailor early treatment for patients, and might be a first step towards precision medicine, say the researchers.

The five types of diabetes each had different characteristics and were associated with different complications, illustrating the varied treatment needs of patients with diabetes, they add.

Rates of diabetes are increasing worldwide, and faster than for any other disorder, yet the medical classification of diabetes hasn’t been updated for 20 years and largely relies on measuring blood glucose.

While type 1diabetes is generally diagnosed in childhood, type 2 disease typically occurs later in life. Most diagnoses are type 2 (75-85%), and while it’s known that type 2 disease is highly variable, few attempts have been made to explore these distinctions.

Existing treatment guidelines focus on the response to poor metabolic control when it has already developed, but it doesn’t give us the means to predict which patients will need intensive treatment, explains lead study author Professor Leif Groop, Lund University Diabetes Centre, Sweden, and Institute for Molecular Medicine Finland.

“Evidence suggests that early treatment for diabetes is crucial to prevent life-shortening complications. More accurately diagnosing diabetes could give us valuable insights into how it will develop over time, allowing us to predict and treat complications before they develop,” he suggests.

“This study moves us towards a more clinically useful diagnosis, and represents an important step towards precision medicine in diabetes.”

The study involved four cohort studies of 14775 adults who had been recently diagnosed with diabetes across Sweden and Finland.

The researchers analysed six measurements that reflect key aspects of the disease: age at diagnosis; body mass index; long-term glycaemic control [HbA1c], functioning insulin-producing cells in the pancreas; insulin resistance; and presence of auto-antibodies associated with autoimmune diabetes.

They also did genetic analyses, and compared disease progression, treatment, and development of diabetic complications for each type of diabetes.

Initial analysis of the six measures in a cohort of 8980 patient identified one autoimmune type of diabetes and four distinct subtypes of type 2 diabetes, which they then tested across three more cohorts of patients (5795 people). They found that the five different disease profiles were also present in these patients.

These types of diabetes were distinct, and included three severe and two mild forms of the disease.

Among the severe forms, there was one group with severe insulin resistance and a significantly higher risk of kidney disease than the other types (cluster 3: severe insulin-resistant diabetes, affecting 11-17% of patients), and a group of relatively young, insulin-deficient individuals with poor metabolic control but no auto-antibodies (cluster 2: severe insulin-deficient diabetes, affecting 9-20%).

Insulin-deficient patients who had auto-antibodies associated with autoimmune diabetes (cluster 1: severe autoimmune diabetes, affecting around 6-15%), a form of diabetes formerly called type 1 diabetes, or latent autoimmune diabetes in adults (LADA) comprised the other severe group.

The most common form of the disease was one of the more moderate forms, which was seen in elderly people and affected 39-47% of patients (cluster 5, or mild age-related diabetes). The other mild form (cluster 4, or mild obesity-related diabetes) was mainly seen in obese people and affected 18-23% of patients.

All five types of diabetes were also genetically distinct, with no mutations associated with all types of the disease. This lends credence to the idea that the five types of diabetes are not simply different stages of the same disease.

Lastly, the authors looked at treatment and found that many were not being treated appropriately.

The study cannot confirm that the five types of adult-onset diabetes have different causes, nor whether patients’ disease type changes over time. And it only involved Scandinavian patients, so will need to be confirmed in other populations.

Writing in a linked comment**, Dr Rob Sladek, McGill University and Génome Québec Innovation Centre, Canada, says: “Diabetes is a group of chronic metabolic disorders that share the common feature of hyperglycaemia, meaning that, in principle, diabetes can be diagnosed via measurement of a single blood component.

“However, elevations in blood glucose can be caused by a number of genetic and acquired factors that reduce the circulating concentrations of insulin or decrease its effectiveness, leading to heterogeneity in the clinical presentation and progression of the disease.”

*Ahlqvist E, Storm P, Käräjämäki A. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. The Lancet Diabetes and Endocrinology, March 2018. Doi:10.1016/S2213-8587(18)30051-2.
**Saldek R. The many faces of diabetes: addressing heterogeneity of a complex disease. The Lancet Diabetes and Endocrinology, March 2018. Doi:10.1016/S2213-8587(18)30070-6.

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