Type-2 Diabetes Has Four Subtypes, Reveals Study; Expert Decodes Different Types

While everybody has probably heard of diabetes as a condition where the blood sugar levels are very high, very few people know that there are different types of diabetes. Today there are different types of diabetes which include type-1 diabetes which is insulin dependent and occurs usually in children, type-2 diabetes which comprises the vast majority of all forms of diabetes in the world (upto 90 - 95%) and several other forms like Gestational diabetes, Maturity Onset Diabetes of the Young (MODY), Neonatal diabetes and genetic forms of diabetes. However the 'common garden variety' of diabetes is what is called as 'type-2 diabetes'. By default, whenever when one talks about diabetes, one is referring to type-2 diabetes. All guidelines for treatment of diabetes mention a common method of treating type-2 diabetes. In 2018, Dr. Leif Groop (Professor in Endocrinology at Lund University and Director of Lund University Diabetes Centre) and colleagues from Scandinavia showed that even among type-2 diabetes, there are several sub-types of diabetes. In India type-2 diabetes, presents several differences from that seen in the West. For example-

1. Type 2 diabetes occurs 10 -15 years younger than in the West

2. One need not have obesity or overweight to develop type 2 diabetes in India. It is also seen among lean people

3. Insulin deficiency, rather than insulin resistance, seems to be the main defect

4. There is an excess of fat especially in the abdominal area

5. HDL (good cholesterol) levels are among the lowest in Indians

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According to a study published in the BMJ Open Diabetes Research and Care. The study entitled 'Novel subgroups of type-2 diabetes and their association with microvascular outcomes in an Asian Indian population: a data-driven cluster analysis - The Inspired Study'

What are the novel findings from this study?

For the first time, that type-2 diabetes in Indians can be classified into four distinct phenotypic clusters and this has important implications for prognosis and management of diabetes.

Cluster 1 is referred to as Severe Insulin Deficient Diabetes (SIDD), which was present in 26.2% of patients and is characterised by the lowest body weight and waist circumference, as well as the lowest insulin reserve as measured by C-peptide levels. Both insulin secretion and insulin resistance are low in this cluster. These individuals also have the most severe forms of diabetes as shown by the highest HbA1c values and thus are more likely to need insulin compared to the other clusters. This group was also more prone to diabetic eye disease.

Cluster 2 is a novel cluster described for first time and is referred to as Insulin Resistant Obese Diabetes (IROD). This comprised 25.9 % of patients. These individuals had the highest body weight and waist circumference and insulin secretion and insulin resistance were also the highest for this cluster. This group was most prone to diabetic kidney disease.

Cluster 3, was another novel group identified for the first time and is referred to as CIRDD (Combined Insulin Resistant and Deficient Diabetes) and constituted 12.1% of study population. This group was characterised by the lowest age at onset of diabetes. Body weight and waist circumference were intermediate between SIDD and IROD. CIRDD had the lowest HDL cholesterol levels of all the four clusters. Insulin secretion and insulin resistance were also intermediate between SIDD and IROD, indicating coexistence of both insulin deficiency and insulin resistance. This group was prone to both diabetic eye and kidney disease.

Cluster 4 referred to as Mild Age-Related Diabetes (MARD), represented the most frequent cluster in this population (35.8%) and was characterised by older age at onset (after 50 years). MARD was characterised by the highest HDL cholesterol, well preserved insulin secretion and they had the mildest form of diabetes of all the 4 groups. This group had the least use of insulin and was much less prone to develop complications of diabetes.

Also read: How To Prevent Prediabetes From Turning Into Diabetes

What is the significance of this study?

Classifying Indians with type-2 diabetes into different phenotypic clusters provides insights into the pathophysiological processes driving diabetes in this ethnic group which could help in focusing more attention on individuals with the highest risk of developing complications of diabetes. The paper is of great interest to all health care professionals and also to people with diabetes. These sub groups of type-2 diabetes have implications as far as treatment is concerned and the choice of anti-diabetic drugs used. For example the severely dependent diabetes (SIDD) variety would probably respond better to insulin secretagogues or indeed even to insulin, whereas the insulin resistant variety would respond better to an insulin sensitiser.

(This was based on 'INSPIRED' is a collaborative research study between the Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialities Centre, Chennai and the Division of Population, Health and Genomics, and the Division of Cardiovascular and Diabetes Medicine, University of Dundee, School of Medicine, Dundee, Scotland, UK.)

(Dr.V. Mohan is Head of MDRF-Hinduja Foundation T1D program and also Chairman & Chief of Diabetology, Dr. Mohan's Diabetes Specialities Centre & President, Madras Diabetes Research Foundation, Chennai, India)

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