Syndromes of Ketosis-Prone Diabetes Mellitus

Abstract

Ketosis-prone diabetes (KPD) is a widespread, emerging, heterogeneous syndrome characterized by patients who present with diabetic ketoacidosis or unprovoked ketosis but do not necessarily have the typical phenotype of autoimmune type 1 diabetes. Multiple, severe forms of beta-cell dysfunction appear to underlie the pathophysiology of KPD. Until recently, the syndrome has lacked an accurate, clinically relevant and etiologically useful classification scheme. We have utilized a large, longitudinally followed, heterogeneous, multiethnic cohort of KPD patients to identify four clinically and pathophysiologically distinct subgroups that are separable by the presence or absence of beta-cell autoimmunity and the presence or absence of beta-cell functional reserve. The resulting "Abeta" classification system of KPD has proven to be highly accurate and predictive of such clinically important outcomes as glycemic control and insulin dependence, as well as an aid to biochemical and molecular investigations into novel causes of beta-cell dysfunction. In this review, we describe the current state of knowledge in regard to the natural history, pathophysiology, and treatment of the subgroups of KPD, with an emphasis on recent advances in understanding their immunological and genetic bases.

Short-Term Case Fatality Rate and Associated Factors among Inpatients with Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State: A Hospital-Based Analysis over a 15-Year Period

“…De t e r mi n a n t s o f 2 8 -d a y Ca s e -f a t a l i t y a mo n g Di a b e t i c P a t i e n t s wi t h a S e c o n d a r y Di a g n os (3,22). Additionally, in the study of Ko et al (4) (24). In Taiwan, Yan et al (2000) (25) …”

Japanese cases of acute onset diabetic ketosis without acidosis in the absence of glutamic acid decarboxylase autoantibody

“…However, it has been suggested that there is a subgroup of type 2 diabetes characterized by acute onset diabetic ketosis, and subsequent normoglycemic remission without insulin therapy [1]. Ketosis-prone type 2 diabetes (KPD) belongs to this subgroup, which has mainly been reported in AfricanAmericans [1,2].…”

On the origin of the β cell

“…More recently, autoimmunity has been detected in a subset of patients with type 2 diabetes, which has led to a revision of the classification to include LADA, latent autoimmune diabetes of adulthood, underscoring the continuum between type 1 and type 2 diabetes, and raising questions as to the role of immunity and inflammation in ␤-cell dysfunction and death in type 2 diabetes (Syed et al 2002; Pozzilli and Buzzetti 2007). Conversely, forms of ketosis prone diabetes due to severe ␤-cell dysfunction but without evidence of autoimmunity are now recognized (Balasubramanyam et al 2008). Decreased ␤-cell function also underlies early-onset monogenic forms of diabetes termed MODY (maturity-onset diabetes of the young) resulting from mutations in transcription factors that regulate ␤-cell development and differentiation.…”