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Syndromes of ketosis-prone diabetes mellitus

Ashok Balasubramanyam, MD
Nalini Ram, MD
Section Editor
David M Nathan, MD
Deputy Editor
Jean E Mulder, MD


Since the mid-1990s, increasing attention has been focused on a heterogeneous condition characterized by presentation with diabetic ketoacidosis (DKA) in patients who do not necessarily fit the typical characteristics of autoimmune type 1 diabetes. Earlier reports used the terms "atypical diabetes," "Flatbush diabetes," "diabetes type 1B," and "ketosis-prone type 2 diabetes mellitus" to describe subsets of this condition, and it was noted that in some instances patients presented with DKA as the first manifestation of diabetes and evolved to insulin independence [1]. While initially these reports suggested that the condition, now termed ketosis-prone diabetes (KPD), might be limited to persons of non-Caucasian ethnicity, its prevalence appears to be increasing in a wide range of ethnic groups worldwide [2-5].

The classification, pathophysiology, natural history, and management of KPD will be reviewed here. Patients with islet autoantibodies who do not present with ketosis, including those termed "latent autoimmune diabetes in adults" (LADA), "type 1.5 diabetes" [6,7], and "slowly progressing type 1 diabetes" [8] are discussed elsewhere. (See "Classification of diabetes mellitus and genetic diabetic syndromes".)


The goal of new classification schemes is to enable clinicians to predict which patients with diabetic ketoacidosis (DKA) require temporary insulin treatment versus life-long insulin therapy. They also highlight subgroups for genetic and pathogenetic studies.

Ketosis-prone diabetes (KPD) comprises a group of diabetes syndromes characterized by severe beta cell dysfunction (manifested by presentation with DKA or unprovoked ketosis) and a variable clinical course. These syndromes do not fit the traditional categories of diabetes defined by the American Diabetes Association (ADA). To date, attempts to differentiate patients with KPD into clinically distinct subgroups have resulted in four different classification schemes: the ADA system, a modified ADA system, a body mass index (BMI)-based system, and the Aß system (based on the presence or absence of autoantibodies and the presence or absence of beta cell functional reserve).

In a longitudinal study comparing the four classification schemes for accuracy and predictive value, the Aß system was shown to be the most accurate in predicting long-term insulin dependence 12 months after the index DKA event, with 99 percent sensitivity and 96 percent specificity [9,10].

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Literature review current through: Nov 2017. | This topic last updated: Jun 20, 2017.
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