Figure 2.

Application of the “continuum model” to define diabetes endotypes. Spectrum of diabetes endotypes ranging from “autoimmune beta cell targeting” (red) to “insulin-resistant” diabetes forms (blue). Color intensity indicates the magnitude of islet autoimmunity and insulin-resistance components, red and blue respectively. The impact of diet/environment on diabetes endotypes is shown by the gray arrow (the larger and darker the arrow, the stronger the effect). Each individual represents a specific endotype, whose position is the result of a cumulative overlay of multiple factors (islet autoimmunity, insulin-resistance, diet/environment). The shades of green of each individual indicate the weight of genetics in determining the endotype, dark green refers to a stronger effect than light green. We used the clusters identified by Ahlqvist et al. (63) as endotypes that may fit our model, i.e., the Severe Autoimmune Diabetes (SAID) endotype, Severe Insulin-Resistance Diabetes (SIRD), Severe Insulin-Deficient Diabetes (SIDD), and Obesity-related diabetes (ORD). This cluster analysis approach may be enriched by other disease variants, such as the “LADA-like” endotype, that lies in the middle and shows intermediate traits