Diabetes mellitus reclassified into 5 subtypes

Diabetes classification has been typically restricted to three types until now – types 1 and 2 and gestational diabetes. Type 1 was a result of autoimmune conditions wherein insulin hormones would be necessary to correct its deficiency while type 2 diabetes was associated with an imbalance of insulin need and supply and utilization within the body.

Image Credit: Africa Studio
Image Credit: Africa Studio

Gestational diabetes was diabetes associated with pregnancy. Now researchers have come up with a five subgroup classification for diabetes to differentiate between their risks and related complications. The report comes from Emma Ahlqvist, PhD, of Lund University in Sweden, and her team and is published in the latest issue of the Lancet Diabetes & Endocrinology.

According to this new classification, diabetes can be classified as;

  • Cluster 1: Severe autoimmune diabetes (SAID)
  • Cluster 2: Severe insulin-deficient diabetes (SIDD)
  • Cluster 3: Severe insulin-resistant diabetes (SIRD)
  • Cluster 4: Mild obesity-related diabetes (MOD)
  • Cluster 5: Mild age-related diabetes (MARD)

According to the authors of the report, the results of their study show that there are distinct clusters of patients with diabetes – especially adult onset diabetes. This new classification can help identify patients who would be at higher risk of complications, they write. These clusters can also understand the disease mechanism better they write adding that they used the key parameters that are used to monitor diabetes. They explain that this method of classification could also be used in clinical trials for drugs used in diabetics for better results and deeper understanding of the mechanism of action of the drugs.

For this study, the team looked at All New Diabetics in Scania (ANDIS) cohort comprising of 8,980 newly diagnosed Swedish patients of diabetes. They were hierarchically classified. The study included only those who had adult-onset diabetes and those diagnosed before they were 18 were thus excluded from the study. Next the patients were classified based on their clinical characteristics such as –

  • age at diagnosis of diabetes
  • BMI or body mass index
  • hemoglobin A1c
  • glutamate decarboxylase antibodies (GADA)
  • homeostasis model assessment 2 (HOMA2) that measures beta-cell function and insulin resistance

Based on these parameters the participants were classified into 5 groups.

Cluster 1: Severe autoimmune diabetes (SAID)

Severe autoimmune diabetes or SAID or Cluster one was least common with only 6.4 percent affected. Autoimmune diabetes is generally diabetes that is classified traditionally as type 1 diabetes where the body’s immune system attacks the pancreatic beta cells and stops the production and release of insulin hormone. These patients had an early onset of the disease and were positive for GADA. Their BMI was low and they had poor metabolic control and deficiency of insulin. They had to be prescribed insulin injections for treatment (in 42 percent patients).

Cluster 2: Severe insulin-deficient diabetes (SIDD)

The second cluster was patients who showed insulin deficiency and were GADA negative. These patients benefitted most from Metformin and had lower usage of insulin compared to cluster 1 despite being clinically similar to them in many ways. This group was at greatest risk of diabetic eye damage or retinopathy.

Cluster 3: Severe insulin-resistant diabetes (SIRD)

The third cluster made up 15.3 percent of the whole cohort of participants. These patients had a high degree of insulin resistance and a high HOMA2-IR index. They were likely to have higher BMIs and were overweight or obese. The authors speculated that these patients would benefit most from Metformin. However their Metformin use was relatively low. This group showed kidney damage more frequently than other groups. They also had a higher risk of nonalcoholic fatty liver disease.

Cluster 4: Mild obesity-related diabetes (MOD)

Around a fifth of all participants were classified in cluster 4. These patients typically had high BMIs meaning they were obese or overweight but they did not show insulin resistance.

Cluster 5: Mild age-related diabetes (MARD)

Most of the patients (nearly 40 percent) in the cohort belonged to the cluster 5. They were usually older adults and their metabolic profiles were not as bad as the others.

Some of the overlapping features include the fact that clusters 3, 4 and 5 were prescribed similar anti-diabetic treatment and they responded well.  TCF7L2 gene mutation further was seen in clusters 2, 4, and 5 and was not seen in cluster 3. Clusters 1 and 2 had a greater risk of diabetic ketoacidosis and had a higher HbA1c at diagnosis.

Leif Groop, PhD, professor in the department of clinical sciences at Lund University Diabetes Centre, Sweden, and the Institute for Molecular Medicine Finland and one of the main investigators in this study, explained that this study provides insights into development and progression of diabetes. He said that this would lead to more precise diagnosis and treatment of diabetes tailored to individual needs.

Rob Sladek, MD, of McGill University, Montral, wrote an accompanying editorial with this landmark paper. He wrote that one of the most important messages from this study is that the cluster SIRD is most vulnerable to “end-organ damage”. He also added that future studies should investigate the effects of age on diabetes in patients. He mentioned a caveat saying that this study cohort was a uniform Scandinavian population and thus all races and ethnicities were not adequately represented. Further larger studies with diverse populations may be necessary before these results can be generalized. He concluded that these results still are “compelling” and provide a baseline for genetic and molecular investigations to look at the different presentations of diabetes in adult populations.

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