Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Institute of Endocrinology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Diabetes. 2020 May;69(5):1065-1071. doi: 10.2337/db19-0974. Epub 2020 Feb 21.
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 ( = 1,209) for diabetes-related autoimmune antibodies. We then screened all antibody-negative patients ( = 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 diabetes, 0.7% for , 0.2% for and , 0.3% for , and 0.1% for ). 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.
鉴定导致单基因糖尿病 (MD) 的基因变异可加深对疾病病因的理解，并有助于实施精准治疗，以改善代谢控制和生活质量。在此，我们旨在评估立陶宛青少年糖尿病患者中 MD 的患病率，发现潜在的与糖尿病相关的基因变异，并前瞻性地引入精准治疗。首先，我们评估了立陶宛所有儿科和大多数青年期糖尿病患者（=1209 例）的糖尿病相关自身抗体。然后，我们使用 >300 个潜在候选基因的靶向高通量测序对所有抗体阴性患者（=153 例）进行了筛查。在该组中，40.7%的患者患有 MD，其中婴儿的比例最高（100%，诊断年龄为 0-12 个月），其次是年龄>1-18 岁（40.3%）和>18-25 岁（22.2%）。立陶宛青少年糖尿病患者中 MD 的总体患病率为 3.5%（1.9%为 ，0.7%为 ，0.2%为 ，0.3%为 ，0.1%为 ）。此外，我们在另外 11 个基因中发现了可能的致病性变异。MD 患者中有 26%存在微血管并发症。在符合条件的候选者中，超过 50%的患者治疗改变成功，C 肽 >252 pmol/L 是最佳预后因素。
