Department of Metabolic Diseases, Jagiellonian University Medical College, Kraków, Poland
University Hospital in Krakow, Kraków, Poland
Pol Arch Intern Med. 2022 Feb 28;132(2). doi: 10.20452/pamw.16143. Epub 2021 Nov 26.
Some patients with type 1 diabetes (T1DM) are free from advanced complications despite long‑standing disease. These patients may be carriers of gene mutations responsible for maturity‑onset diabetes of the young and may have been misdiagnosed with T1DM.
We aimed to determine the clinical characteristics of patients with long‑term T1DM, without advanced microvascular complications, and with well‑preserved kidney function. A search for mutations in monogenic diabetes genes was performed.
Patients were recruited at 2 Polish university centers based on the following criteria: T1DM duration of 40 years or longer and absence of advanced complications defined as chronic kidney disease (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2 ), overt proteinuria, blindness, and diabetic foot syndrome. Mutations in the 7 most frequent monogenic diabetes genes were identified using next‑generation sequencing.
We enrolled 45 patients with T1DM (mean [SD] age at examination, 59.2 [8.0] years; mean [SD] age at T1DM diagnosis, 14.6 [6.7] years). Mean (SD) hemoglobin A1c levels were 7.6% (1.4%); daily insulin dose, 0.48 (0.17) U/kg; high‑density lipoprotein (HDL) cholesterol levels, 1.9 (0.6) mmol/l; body mass index (BMI), 26.4 (5.0) kg/m2 ; and eGFR, 82.2 (12.1) ml/min/1.73 m2 . Albuminuria and retinopathy were reported in 7 and 39 patients, respectively. We were not able to assign a causative role to any of 10 genetic variants identified by next‑generation sequencing in this cohort.
Patients with long‑term T1DM and preserved kidney function have good glycemic control, elevated HDL cholesterol levels, low insulin requirements, near ‑normal BMI, and a rare occurrence of mutations in monogenic diabetes genes.
一些 1 型糖尿病（T1DM）患者尽管患病时间较长，但没有出现晚期并发症。这些患者可能是年轻起病的成人型糖尿病相关基因突变的携带者，并且可能被误诊为 T1DM。
我们旨在确定长期 T1DM 患者的临床特征，这些患者没有晚期微血管并发症，且肾功能良好。我们对单基因糖尿病基因的突变进行了研究。
我们在 2 个波兰大学中心招募了患者，入选标准为：T1DM 病程 40 年或以上，且无晚期并发症，定义为慢性肾脏病（估算肾小球滤过率[eGFR]＜60ml/min/1.73m2）、显性蛋白尿、失明和糖尿病足综合征。使用下一代测序技术鉴定 7 种最常见的单基因糖尿病基因中的突变。
我们共纳入了 45 例 T1DM 患者（检查时的平均[标准差]年龄为 59.2[8.0]岁；T1DM 诊断时的平均[标准差]年龄为 14.6[6.7]岁）。平均（标准差）血红蛋白 A1c 水平为 7.6%（1.4%）；每日胰岛素剂量为 0.48（0.17）U/kg；高密度脂蛋白（HDL）胆固醇水平为 1.9（0.6）mmol/L；体重指数（BMI）为 26.4（5.0）kg/m2；估算肾小球滤过率（eGFR）为 82.2（12.1）ml/min/1.73m2。分别有 7 例和 39 例患者报告存在白蛋白尿和视网膜病变。我们未能确定下一代测序鉴定的该队列中 10 种遗传变异的致病作用。
长期 T1DM 且肾功能良好的患者血糖控制良好，HDL 胆固醇水平升高，胰岛素需求低，BMI 接近正常，且单基因糖尿病基因突变罕见。
