Arginine Metabolism Is Altered in Adults with A-β + Ketosis-Prone Diabetes.

Background: A-β + ketosis-prone diabetes (KPD) is a subset of type 2 diabetes in which patients have severe but reversible β cell dysfunction of unknown etiology. Plasma metabolomic analysis indicates that abnormal arginine metabolism may be involved.

Objective: The objective of this study was to determine the relation between gut microbiome and arginine metabolism and the relation between arginine availability and β cell function in KPD patients compared with control participants.

Presence or absence of a known diabetic ketoacidosis precipitant defines distinct syndromes of "A-β+" ketosis-prone diabetes based on long-term β-cell function, human leukocyte antigen class II alleles, and sex predilection.

Ketosis-prone diabetes (KPD) is heterogeneous. Longitudinal follow-up revealed that patients with "A-β+" KPD (absent autoantibodies and preserved β-cell function) segregated into 2 subgroups with distinct evolution of β-cell function and glycemic control. Generalized linear analysis demonstrated that the variable that most significantly differentiated them was presence of a clinically evident precipitating event for the index diabetic ketoacidosis (DKA).

A-beta-subtype of ketosis-prone diabetes is not predominantly a monogenic diabetic syndrome.

Objective: Ketosis-prone diabetes (KPD) is an emerging syndrome that encompasses several distinct phenotypic subgroups that share a predisposition to diabetic ketoacidosis. We investigated whether the A-beta- subgroup of KPD, characterized by complete insulin dependence, absent beta-cell functional reserve, lack of islet cell autoantibodies, and strong family history of type 2 diabetes, represents a monogenic form of diabetes.

Research Design And Methods: Over 8 years, 37 patients with an A-beta- phenotype were identified in our longitudinally followed cohort of KPD patients.