ESPE Abstracts (2018) 89 P-P1-061

The Prevalence of Autonomic and Peripheral Neuropathy in Children and Adolescents with Type 1 Diabetic Mellitus (T1D) and Its Association with the Homozygous Status of Z-2/Z-2 Polymorphism of the Aldose Reductase Gene (AKR1B1) in the Polyol Pathway

Dimitra Kallinikoua, Charalampos Tsentidisa, Kyriaki Kekoub, Maria Lourakia, Christina Kanaka-Gantenbeinc, Emmanouil Kanavakisb & Kyriaki Karavanakia


aDiabetes Clinic, 2nd Department of Paediatrics, Medical School, University of Athens, ‘P&A Kyriakou’ Children’s Hospital, Athens, Greece; bDepartment of Medical Genetics, Choremeio Research Laboratory, Medical School, University of Athens, Athens, Greece; cDiabetes Center, Division of Endocrinology, Metabolism and Diabetes, First Department of Paediatrics, Medical School, University of Athens, ‘Aghia Sophia’ Children’s Hospital, Athens, Greece


Introduction: Diabetic neuropathy (DN) significantly reduces patients’ quality of life and increases cardiovascular death risk. However, it is the least recognized complication of diabetes. Z-2/Z-2 polymorphism of the aldose reductase (AKP1B1) gene increases the expression of the relative enzyme and is likely to contribute to DN expression.

Purpose: To study the prevalence of DN in T1D children and adolescents and its associations with the homozygous state of Z-2/Z-2 polymorphism of the AKR1B1 gene.

Methods: We evaluated 106 T1D children and adolescents (mean±S.D. age: 13.5±3.46 years, T1D duration: 5.3±3.4 years) and 100 healthy controls (age: 11.9±2.7 years). Pupillary dilation (PD) in darkness was assessed as an index of autonomic neuropathy. Abnormal cut-off values (<5%) were calculated from control values distribution. Nerve conduction studies (NCS) were performed with a standard technique using surface electrodes. The polymorphisms of AKR1B1 gene were evaluated using microsatellite sequence Z.

Results: PD impairment was more frequent in the T1D group (31.6% vs 3.3%, P<0.001). PD was associated with age (r=0.16, P=0.038), HbA1c (r=0.23, P=0.048) and T1D duration (r=0.20, P=0.022). There was a strong correlation between PD and NCS in T1D patients (r=0.34, P=0.008). In T1D patients, NCS was neither associated with age (r=0.01, P=0.91), nor with HbA1c (r=0.14, P=0.27), or disease duration (r=−0.2, P=0.12). Patients homozygous for Z-2 polymorphism of the AKR1B1 gene had higher prevalence of NCS abnormality (21.74% vs 2.86%, P=0.032) and also PD abnormality (62.5% vs 37.5%, P=0.023) compared to controls.

Conclusions: Impaired indices of peripheral and autonomic DN were present in a significant proportion of young T1D patients, although asymptomatic. Indices of DAN were associated with age, diabetes duration and glycemic control, while NCS were not. PD and NCS abnormalities were related to the homozygosity of Z-2/Z-2 polymorphism of AKR1B1gene in the polyol pathway.