RT Journal Article
SR Electronic
T1 Systematic Genetic Study of Youth With Diabetes in a Single Country Reveals the Prevalence of Diabetes Subtypes, Novel Candidate Genes, and Response to Precision Therapy
JF Diabetes
JO Diabetes
FD American Diabetes Association
SP 1065
OP 1071
DO 10.2337/db19-0974
VO 69
IS 5
A1 Stankute, Ingrida
A1 Verkauskiene, Rasa
A1 Blouin, Jean-Louis
A1 Klee, Philippe
A1 Dobrovolskiene, Rimante
A1 Danyte, Evalda
A1 Dirlewanger, Mirjam
A1 Santoni, Federico
A1 Razanskaite-Virbickiene, Dovile
A1 Marciulionyte, Dale
A1 Jasinskiene, Edita
A1 Mockeviciene, Giedre
A1 Schwitzgebel, Valerie M.
YR 2020
UL http://diabetes.diabetesjournals.org/content/69/5/1065.abstract
AB Identifying gene variants causing monogenic diabetes (MD) increases understanding of disease etiology and allows for implementation of precision therapy to improve metabolic control and quality of life. Here, we aimed to assess the prevalence of MD in youth with diabetes in Lithuania, uncover potential diabetes-related gene variants, and prospectively introduce precision treatment. First, we assessed all pediatric and most young-adult patients with diabetes in Lithuania (n = 1,209) for diabetes-related autoimmune antibodies. We then screened all antibody-negative patients (n = 153) using targeted high-throughput sequencing of >300 potential candidate genes. In this group, 40.7% had MD, with the highest percentage (100%) in infants (diagnosis at ages 0–12 months), followed by those diagnosed at ages >1–18 years (40.3%) and >18–25 years (22.2%). The overall prevalence of MD in youth with diabetes in Lithuania was 3.5% (1.9% for GCK diabetes, 0.7% for HNF1A, 0.2% for HNF4A and ABCC8, 0.3% for KCNJ11, and 0.1% for INS). Furthermore, we identified likely pathogenic variants in 11 additional genes. Microvascular complications were present in 26% of those with MD. Prospective treatment change was successful in >50% of eligible candidates, with C-peptide >252 pmol/L emerging as the best prognostic factor.