Diabetes and Metabolism Clinic, 2nd Department of Paediatrics, National and Kapodistrian University of Athens "P&A Kyriakou" Children's Hospital, Athens, Greece.
Laboratory of Medical Genetics, Medical School, National and Kapodistrian University of Athens, "Aghia Sophia" Children's Hospital, Athens, Greece.
Pediatr Diabetes. 2022 Feb;23(1):104-114. doi: 10.1111/pedi.13285. Epub 2021 Nov 24.
Diabetic neuropathy (DN) is the least recognized complication of diabetes mellitus and may start early in the course of the disease. Aldose reductase (AKR1B1) gene promoter Z-2/Z-2 polymorphism increases the expression of AKR1B1 enzyme and may contribute to DN.
We evaluated 108 Type 1 diabetes (T1D) children and adolescents (mean ± SD age: 13.5 ± 3.46 years, disease duration: 5.3 ± 3.4 years) and 150 healthy controls (age: 11.9 ± 2.7 years).
In both groups, pupillary dilation (PD) in darkness, postural blood pressure test (PBPT), and vibration sensation thresholds (VST) in upper and lower limbs were estimated as indices of autonomic and peripheral neuropathy, respectively. Nerve conduction studies (NCS) were performed in patients as peripheral neuropathy index. The polymorphisms of AKR1B1 gene were evaluated using microsatellite (AC)n sequence Z.
PBPT, PD, and VST impairments were more frequent in patient group compared with controls, while 38.6% of patients exhibited NCS abnormality. Gender, age, pubertal status, height, body mass index, diabetes duration, HbA1c, and anti-GAD titers were associated with neuropathy indices in patients. There was a strong correlation between PD and NCS in patients, while homozygous patients for Z-2 AKR1B1 gene polymorphism had higher prevalence of abnormal NCS (83.3% vs. 34.6%), PD (62.5% vs. 31.5%), and PBPT values compared with heterozygous or negative patients. Homozygous AKR1B1 status predicted PD, NCS, and PBPT variance, while PD, VST, NCS, and PBPT parameters accurately discriminated homozygous AKR1B1 patients.
Impaired indices of peripheral and autonomic DN were present in a significant proportion of young T1D patients. PD, VST, NCS, and PBPT parameters were simultaneously associated with homozygous state of AKR1B1 Z-2 gene polymorphism, implicating polyol metabolism with both autonomic and peripheral neuropathies.
糖尿病神经病变（DN）是糖尿病最容易被忽视的并发症之一，并且可能在疾病早期就开始出现。醛糖还原酶（AKR1B1）基因启动子 Z-2/Z-2 多态性增加了 AKR1B1 酶的表达，可能导致 DN。
我们评估了 108 名 1 型糖尿病（T1D）儿童和青少年（平均年龄 ± 标准差为 13.5 ± 3.46 岁，病程：5.3 ± 3.4 年）和 150 名健康对照者（年龄：11.9 ± 2.7 岁）。
在两组中，瞳孔扩张（PD）在黑暗中、体位血压试验（PBPT）和上下肢振动感觉阈值（VST）分别估计为自主神经和周围神经病变的指标。神经传导研究（NCS）在患者中作为周围神经病变指标进行。使用微卫星（AC）n 序列 Z 评估 AKR1B1 基因的多态性。
与对照组相比，患者组的 PBPT、PD 和 VST 损害更为频繁，而 38.6%的患者存在 NCS 异常。性别、年龄、青春期状态、身高、体重指数、病程、HbA1c 和抗 GAD 滴度与患者的神经病变指标相关。患者中 PD 与 NCS 之间存在很强的相关性，而 AKR1B1 基因 Z-2 多态性纯合子患者的异常 NCS（83.3%比 34.6%）、PD（62.5%比 31.5%）和 PBPT 值的发生率更高。AKR1B1 纯合状态预测 PD、NCS 和 PBPT 变异性，而 PD、VST、NCS 和 PBPT 参数可准确区分 AKR1B1 纯合子患者。
在相当一部分年轻的 T1D 患者中存在外周和自主 DN 的受损指标。PD、VST、NCS 和 PBPT 等参数与 AKR1B1 Z-2 基因多态性纯合状态同时相关，提示多元醇代谢与自主和周围神经病变均有关。
