Should the Negativity for Islet Cell Autoantibodies Be Used in a Prescreening for Genetic Testing in Maturity-Onset Diabetes of the Young? The Case of Autoimmunity-Associated Destruction of Pancreatic beta-Cells in a Family of HNF1A-MODY Subjects
Abstract
It was recently suggested that routine islet cell autoantibody testing should be performed to discriminate maturity-onset diabetes of the young (MODY) from type 1 diabetes mellitus (T1DM). This is the first report ever to describe the familial manifestation of T1DM autoimnnunity in nonobese HNF1A-MODY subjects and the presence of islet antigen-2 (IA-2) antibodies in MODY subjects.
Three nonobese subjects in an age range of 14-35 years were diagnosed with HNF1A-MODY (p.Arg159Gln mutation). All the tested subjects had detectable (but varying) levels of islet cell autoantibodies (i.e., antibodies against glutamate decarboxylase or IA-2) in the absence of other T1DM characteristics.
They displayed long-term expression of intermediate fasting C-peptide levels, ketoacidosis was absent even in periods of spontaneous insulin withdrawal, and full dependence on externally administered insulin was not detected in any of them although better glycemic control was achieved when insulin was supplemented. The course of the disease was similar to that of the autoantibody-negative HNF1A-MODY subjects.
The case questions the selectivity of autoantibodies as a marker of T1DM or late-onset autoimmune diabetes of adulthood (LADA) over MODY and challenges the use of autoantibodies as a universal negative marker of MODY in an effort to decrease the cost of health care, as it may eventually lead to the wrong diagnosis and thus to the incorrect treatment. Further research should involve examination of the autoantibody titers and prevalence in large and geographically diverse cohorts of MODY subjects selected for genetic testing (regardless of their autoantibody titers) as well as determination of the islet cell autoantibody kinetics in the course of MODY onset and progression.