June 1, 2018, Dr Chee L Khoo
Have you noticed that your patients with type 2 diabetes (T2D) are a heterogeneous group? Some T2D patients are more insulin resistant than others. Some T2D patients are more insulin deficient than others. These tend to be the younger T2D. Some patients are obese and some are not. Some suffer from more retinopathy than others despite similar HbA1c. Yet, others have significant chronic kidney disease despite seemingly good HbA1c. Naturally, if we apply the same treatment algorithm to all T2D, the outcomes will be different. There must be a better way.
A group of Scandinavian researchers attempted to reclassify T2D patients into 5 different subgroups. This could be a first step towards individualise treatment regimen for different patients and help identify which patients are at increased risk of which complications. Patients with type 1 diabetes (T1D), latent autoimmune diabetes in adults (LADA) or secondary diabetes were excluded. 12,112 patients were considered to have T2D. Based on glutamic acid decarboxylase antibodies (GADA), age at diagnosis, HbA1c, insulin resistance levels and beta cell function, patients were divided into 5 clusters. Insulin resistance and beta-cell function were assess using Homeostasis Model Assessment (HOMA2-IR & HOMA2-B).
Cluster 1 – Severe autoimmune diabetes (SAID)
Characterised by early onset disease, relatively low BMI, poor metabolic control, insulin deficiency and GADA positive
Cluster 2 – Severe insulin deficient diabetes (SIDD)
Characterised by early onset disease, relatively low BMI, poor metabolic control, insulin deficiency and GADA negative
Cluster 3 – Severe insulin resistance diabetes (SIRD)
Characterised by significant insulin resistance and high BMI
Cluster 4 – Mild obesity-related diabetes (MOD)
Characterised by obesity but no insulin resistance
Cluster 5 – Mild age-related diabetes (MARD)
Characterised by older patients but modest metabolic derangements
Are these just fancy names or do they have practical implications for management? The researchers compared disease progression, treatment and complication rates between the clusters.
Clusters 1 and 2 have insulin deficiency and as such had higher HbA1c than the rest. They are also more likely to have ketoacidosis.
Cluster 2 had the highest incidence of early retinopathy. Insulin deficiency and/or hyperglycaemia appears to be important triggers of retinopathy.
Cluster 3 appears to be our typical insulin resistant diabetic and have more fatty liver and have a higher risk of developing chronic kidney disease. This reinforces the association between insulin resistance and chronic kidney disease irrespective of HbA1c. Therefore, glycaemic control may not be enough to prevent the development of diabetic kidney disease.
Cluster 5 also identify a subgroup of older T2D patients. Their risks seems to be between those of cluster 1-2 and cluster 3 in chronic kidney disease, retinopathy and coronary disease.
Cluster 4, the mild obesity related group, seems to par lower than the other groups generally.
This is but the first attempt to further delineate the different subcategories in our T2D. This allows us to treat them more specifically and watch out for different complications in different groups. We already seeing this differentiation in our practice and this seeks to formalise what we see.
Ahlqvist E et al. Novel subgroups of adult onset diabetes and their association with outcomes: a data driven analysis of 6 variables. Lancet Diabetes Endocrinol 2018; 6; 361-69