I am a Diabetologist and Endocrinologist, and will be discussing the shift in treating type 2 diabetes and the new research on the subtypes within what we used to consider one single disease. 

For decades, type 2 diabetes was treated as a one-size-fits-all condition and was mainly focused on controlling blood sugar levels. In my years of clinical practice, I have observed how patients with identical diabetes diagnoses responded differently to the same treatments. What works for one patient may not work for others. 

With the recent research, we can understand that type 2 diabetes isn’t one disease but it is at least 5 distinct subtypes, each with unique pathophysiological mechanisms and treatment responses. 

Let me break down the subtypes:

These subtypes were identified using cluster analysis, that is, grouping patients based on age of onset, BMI, insulin resistance, insulin secretion and presence of autoantibodies. 

The Subtypes are

Severe autoimmune diabetes

It is defined by the presence of glutamate decarboxylase autoantibodies. This subtype has some features of type 1 Diabetes, such as autoimmune β-cell destruction. Patients with SAID often exhibit insulin deficiency and may require early initiation of insulin therapy. It is similar to type 1 DM and is often misclassified. These patients have autoantibodies and need insulin early on.  

Severe insulin-deficient diabetes

Patients with Severe Insulin-deficient diabetes have moderate BMI but significantly impaired beta-cell function. It is present at a younger age with high blood sugar levels and high HbA1c levels. These patients benefit from the early use of insulin therapy and GLP-1 receptor agonists that preserve remaining beta-cell function. They are more prone to develop complications like diabetic retinopathy. 

Severe Insulin-Resistant Diabetes

Patients with severe insulin-resistant diabetes have high insulin resistance, obesity and elevated liver fat. Their insulin production may be relatively preserved, but their tissues don’t respond effectively to the insulin they produce. 

Treatment is usually focused on insulin sensitisers like metformin and thiazolidinediones. Weight management interventions have shown benefits, and with bariatric surgery, remission rates have been higher. 

Mild Obesity-Related Diabetes 

The fourth subtype is the Mild Obesity-related diabetes, which is common in people with obesity but relatively preserved beta-cell function and milder metabolic abnormalities compared to SIRD patients. Main treatment is weight management; GLP-1 receptor agonists have shown remarkable results.

Mild Age-Related Diabetes 

The fifth and last subtype is the Mild age-related diabetes, the most common subtype and the onset is late and seen in older adults. The patient shows moderate metabolic derangements and more gradual disease progression. The pathophysiology involves mild beta-cell dysfunction combined with age-related insulin resistance. The treatment starts with lifestyle modification, and metformin and DPP-4 inhibitors have shown beneficial results with minimal risk of hypoglycaemia. 

Do these subtypes matter?

Yes, they do as we focus on personalised treatment. 

We can utilise this knowledge by assessing biomarkers, such as measuring C-peptide levels to evaluate beta-cell function, calculating HOMA-IR to quantify insulin resistance, assessing body composition instead of relying on BMI, and evaluating novel biomarkers like adiponectin and proinsulin ratios. 

The era of one-size-fits-all diabetes management is behind us. By recognising these distinct diabetes subtypes, we should offer more personalised treatment targeting the specific pathophysiology.