PERSPECTIVES WITH DR ALAN BARCLAY

DIABETES TIMES FIVE 
While we have known about diabetes for several thousand years, our knowledge and understanding of its causes, pathophysiology and management is constantly evolving. One of the more important areas of research that doesn’t receive the attention it deserves is how we classify the different types. It’s important because it affects how we manage the condition (e.g., with pharmaceuticals, dietary strategies, etc) and also how we pay for its management (Pharmaceutical benefits; Health Insurance rebates, etc).

The current diabetes classification system, with which most people are familiar, was developed back in 1979 and lists four types:

1. Insulin-dependent or type 1 diabetes 
2. Non-insulin-dependent or type 2 diabetes 
3. Gestational diabetes 
4. Diabetes associated with other syndromes or conditions (e.g., monogenic diabetes syndromes (such as neonatal diabetes and maturity-onset diabetes of the young [MODY]), diseases of the exocrine pancreas (such as cystic fibrosis), and drug- or chemical-induced diabetes (such as in the treatment of HIV/AIDS or after organ transplantation). 

Classifying diabetes into type 1 and type 2 relies primarily on the presence (type 1) or absence (type 2) of autoantibodies against pancreatic islet Beta (B)-cell antigens and age at diagnosis (younger for type 1 diabetes). With this approach, 75–85% of patients are classified as having type 2 diabetes. Of the fourth group, diabetes associated with other syndromes or conditions, latent autoimmune diabetes in adults (LADA) affects less than 10% of people with diabetes, is defined by the presence of glutamic acid decarboxylase antibodies (GADA), is phenotypically indistinguishable from type 2 diabetes at diagnosis, but becomes increasingly similar to type 1 diabetes over time.

Perhaps unsurprisingly, scientists and physicians have been thinking for some time that the current classification system presents challenges to the diagnosis and treatment of people with diabetes, in part due to its conflicting and confounding definitions of type 1, type 2, and LADA.

Back in 2016, a group of US scientists proposed a new B-cell-centric classification of diabetes, based on the presupposition that all diabetes originates from a common denominator – the abnormal pancreatic B-cell. It recognized that interactions between genetically predisposed B-cells with a number of factors, including insulin resistance, susceptibility to environmental influences, and immune dysregulation/inflammation, lead to the range of diabetes sub-types within the spectrum of diabetes. Individually or in concert, and often self-perpetuating, these factors contribute to B-cell stress, dysfunction, or loss through at least 11 distinct pathways. The authors concluded that this classification system enabled “Available, yet underutilized, treatments [to] provide rational choices for more personalized therapies that target the individual mediating pathways of hyperglycemia at work in any given person with diabetes, without the risk of pharmacologically-related hypoglycemia or weight gain or imposing further burden on the B-cells”. To-date, there is little evidence that the B-cell–centric classification of diabetes has been adopted.

The most recent (2018) diabetes classification system has been conceived by Swedish scientists. They developed a 5-cluster system based on the analysis of nearly 9000 people aged 0–96 years who developed diabetes between 2008 and 2016.

Modelling the new system in 500–3500 additional Swedish and Finnish people demonstrated that it was superior to the current diabetes classification system, because it identified people at high risk of diabetic complications (e.g., kidney and eye disease) at diagnosis and provided information about underlying disease mechanisms, thereby guiding choice of therapy.

This new analysis provides another important step towards a more precise, clinically useful stratification of diabetes, representing an important step towards precision medicine in diabetes. It is of course important to note that the new classification system was based on people primarily from northern Europe, with limited non-Scandinavian representation, and the applicability of this strategy to people of other ethnicities needs to be assessed before the model can be adopted globally.

Read more:

• History of diabetes 
• The Time Is Right for a New Classification System for Diabetes 
• Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables

 
Alan Barclay, PhD is a consultant dietitian. He worked for Diabetes Australia (NSW) from 1998–2014 . He is author/co-author of more than 30 scientific publications, and author/co-author of  The good Carbs Cookbook (Murdoch Books), Reversing Diabetes (Murdoch Books), The Low GI Diet: Managing Type 2 Diabetes (Hachette Australia) and The Ultimate Guide to Sugars and Sweeteners (The Experiment, New York).

Contact: You can follow him on Twitter or check out his website.