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Syndromes of ketosis-prone diabetes mellitus

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

INTRODUCTION

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".)

CLASSIFICATION OF KPD

Ketosis-prone diabetes (KPD) comprises a group of diabetes syndromes characterized by severe beta cell dysfunction (manifested by presentation with diabetic ketoacidosis [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. The goal of new classification schemes is to enable clinicians to predict which patients with DKA require temporary insulin treatment versus life-long insulin therapy. They also highlight subgroups for genetic and pathogenetic studies.

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].

ADA system — In the ADA classification, type 1 diabetes is characterized by autoimmune destruction of the pancreatic beta cells, leading to absolute insulin deficiency. Markers of immune-mediated diabetes include antibodies to glutamic acid decarboxylase (GAD) and to the tyrosine phosphatase IA-2. Among patients presenting with DKA (absolute insulin deficiency), those who lack autoantibodies are referred to as "idiopathic type 1" or "type 1b"; the latter includes patients with the clinical appearance of type 2 diabetes, with some becoming insulin-independent. (See "Classification of diabetes mellitus and genetic diabetic syndromes", section on 'Type 1 diabetes'.)

                      

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Literature review current through: Nov 2016. | This topic last updated: Wed Jun 03 00:00:00 GMT+00:00 2015.
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