Unraveling A-β+ ketosis-prone diabetes: An evolving diagnosis with an elusive pathogenesis

Since the discovery of insulin over a century ago, how we conceptualize, describe and treat diabetes has evolved, paving the way for the identification of distinct diabetes subgroups and individualized treatment options. Historically, the term ketosis-prone diabetes (KPD) has comprised a group of diabetes syndromes characterized by severe pancreatic β-cell dysfunction, but lacking the autoimmunity and irreversibility that underlies type 1 diabetes (T1D). Similarly, the defining feature of KPD-diabetic ketoacidosis-is uncharacteristic of type 2 diabetes (T2D). Initially, it was thought to be unique to Black populations, which led to early etiologic investigations narrowly focused on monogenic causes. However, it is now recognized that KPD occurs in diverse racial and ethnic groups and may be provoked by infection, leading to an expanded view of its pathogenesis. Here, we review these updated mechanistic views, highlight novel research tools being deployed to advance our understanding of KPD, and discuss implications of these data to inform our views on β-cell biology.