Ketosis-Prone Atypical Diabetes: Glucagon Is There, Too

Abstract

As stated by Zimmet et al. (1) in the initial chapter of a classical textbook on diabetes, the major requirement for orderly epidemiologic, genetic, and clinical research on diabetes and glucose intolerance, and indeed for their clinical management, is an appropriate classification. Furthermore, a hallmark in the process of understanding the etiology of a disease and studying its natural history is the ability to identify and differentiate its various forms and place them into a rational etio-pathologic framework. In 1984, Ahren and Corrigan (2) reported the existence of a subgroup of diabetic patients observed in Tanzania where the need for insulin replacement therapy fluctuates with time, waxes and wanes, and transient ketoacidosis develops. This subtype of diabetes is not unusual in African Americans and sub-Saharan Africans and currently recognized under the term of ketosis-prone atypical diabetes (KPD) (review in ref. 3). Classifying KPD in relation with the other more frequent forms of diabetes is not easy. At the onset, KPD often appears as type 1 diabetes with acute hyperglycemia and ketosis or ketoacidosis and the obvious need for insulin therapy but the signs of autoimmunity against islet β-cells are absent. In contrast, during near-normoglycemic remission, patients with KPD usually display multisite insulin resistance similar to that seen in type 2 diabetes (4,5). In 2008, Sobngwi et al. (6) hypothesized that KPD is a subtype of type 2 diabetes with acute onset at diagnosis as the result of an environmental factor such as a human herpes virus infection that would severely impair glucose-stimulated insulin secretion and favor ketogenesis. In this issue of Diabetes Care , Choukem et al. (7) present original data on the islet dysfunction present in KPD during remission. Previous studies have shown severe insulin secretory deficiency during the acute ketotic phase of KPD while during …