Precision Medicine in Diabetes: Is It Time?

Diabetes is a heterogenous disease. Its very definition, anchored by thresholds for hyperglycemia, rests on the final common event on which disparate pathological processes converge. Although the traditional classification into type 1 and type 2 diabetes has proven useful in differentiating distinct pathophysiological mechanisms with clear therapeutic implications, it remains insufficient in explaining the wide variety of clinical manifestations of this disease. For example, we see lean members of specific ethnic groups with antibody-negative, nonketotic diabetes; we treat patients with childhood-onset, antibody-positive diabetes who become insulin resistant as they age; we do not fully understand why some patients progress rapidly to microvascular and/or macrovascular complications or require aggressive escalation of therapy; and we cannot predict the rate of β-cell failure, the degree of weight loss required to normalize glycemia, or the type of medication best suited for a given patient. Attempts at capturing greater granularity have resulted in the creation of new entities, such as latent autoimmune diabetes in the adult to describe autoimmune diabetes with onset after age 30 (1), and ketosis-prone diabetes to describe antibody-negative diabetes with a ketotic onset but only transient insulin requirements (2,3); however, absent a full understanding of the mechanism and its implications, these subtypes emerge mired in controversy or fail to penetrate clinical care (4,5). Evidently, despite extensive epidemiological and physiological characterization, we have fallen short in cataloging risk factors, identifying triggering events, elucidating pathophysiological pathways, outlining prognostic course, selecting effective therapies, and predicting complications. Specific patients continue to represent diagnostic challenges, and our approach to therapy continues to be based on population averages. Recent thoughtful attempts at tailoring type 2 diabetes therapy to individual patients have focused on personal, social, and economic considerations rather than on a lucid molecular understanding of the underlying disease process (6). …