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Background Diabetic neuropathy(DN) is the least recognized complication of diabetes mellitus and may start early in the course of disease. Aldose reductase(AKR1B1) gene promoter Z-2/Z-2 polymorphism increases the expression of AKR1B1enzyme and may contribute to DN. Subjects 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). Methods 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 AKR1B1gene were evaluated using microsatellite(AC)n sequence Z. Results 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, BMI, 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. Conclusions 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. This article is protected by copyright. All rights reserved.

Diabetic neuropathy (DN) is a common long-term complication of type 1 (T1D) and type 2 (T2D) diabetes mellitus, with significant morbidity and mortality. DN is defined as impaired function of the autonomic and/or peripheral nervous system, often subclinical, particularly in children and adolescents with T1D. Nerve conduction studies (NCS) and skin biopsies are considered gold-standard methods in the assessment of DN. Multiple environmental and genetic factors are involved in the pathogenesis of DN. Specifically, the role of metabolic control and glycemic variability is of paramount importance. A number of recently identified genes, including the AKR1B1, VEGF, MTHFR, APOE, and ACE genes, contribute significantly in the pathogenesis of DN. These genes may serve as biomarkers to predict future DN development or treatment response. In addition, they may serve as the basis for the development of new medications or gene therapy. In this review, the diagnostic evaluation, pathogenesis, and associated genetic markers of DN in children and adolescents with T1D are presented and discussed.

Aim To evaluate the prevalence of early somatic neuropathy in children and adolescents with Type 1 diabetes mellitus (Type 1 DM) and its association with the presence of glutamic acid decarboxylase and islet antigen-2 autoantibodies (GADA and IA-2A). Methods A cross-sectional study was conducted in a hospital-based cohort of pediatric Type 1 DM patients ( n = 85, mean(±SD) age: 13.5 ± 3.4 years, mean(±SD) disease duration 5.5 ± 3.4 years). Peripheral neuropathy was assessed with nerve conduction studies (NCS). GADA and IA-2A titers were measured with radioligand assays. Results Among the study population, 34.1% had at least one abnormal electrophysiological parameter, although predominantly asymptomatic. The highest rates of abnormality were detected in sensory peroneal nerve (25.9%) followed by sural nerve (15.3%). Affected patients were not different in terms of age, diabetes duration or glycaemic control. Among the participants, 62.4% had positive GADA, 58.8% positive IA-2A and 42.4% double antibody positivity. Abnormal NCS correlated neither with GADA nor with IA-2A levels or positivity. However lower sensory nerve action potential in the peroneal nerve, indicative of early axonal dysfunction, was observed in patients with GADA or IA-2A positivity. Absence of both antibodies was associated with better action potentials in all the examined nerves of the lower limbs. Conclusions Impaired indices of subclinical peripheral primarily sensory neuropathy were present among one third of Type 1 DM children and adolescents, with no impact of diabetes duration or glycaemic control. GADA and IA-2A seem to be involved in the development of axonal degeneration, in a pathway which remains to be identified.

Aims To define the reproducibility of vibration perception thresholds (VPTs) and the possible associated factors, as an early index of peripheral diabetic neuropathy (PDN) in type 1 diabetes mellitus (T1DM) children and adolescents. Methods A single examiner studied 118 T1DM subjects (aged 13.5±3.4 years) and 79 controls (aged 12.0±3.07 years). Glycaemic control was assessed with HbA1c levels. VPT was measured twice on upper and lower limbs, using a Biothesiometer. Concordance between the two VPT measurements was evaluated using the Cohen's Weighted Kappa statistic (Kappa=0.41–0.60→moderate concordance, Kappa=0.61–0.80→substantial concordance). Results T1DM children had significantly higher VPTs than controls at all sites ( p =0.001), but with lower Kappa values (0.64–0.70). VPT values increased in parallel with HbA1c ( a . b . 8–9.5%, c .>9.5%) and T1DM duration ( a . b .5.1–10, c .>10 years). However, Kappa values were lower in the groups with the poorest control (HbA1c>9.5%) (Kappa=0.54–0.76) or the longest T1DM duration (>10 years) (Kappa=0.49–0.71). Although VPTs increased with stature and male gender, no effect on VPT reproducibility was observed. However, obesity was associated with lower VPT values and poorer concordance. Conclusions These findings suggest that the reproducibility of VPTs is lower in the high-risk patients for early subclinical PDN development, who need a regular follow-up.

Type 1 diabetes mellitus (T1DM) is characterized by selective autoimmune destruction of pancreatic b-cells, resulting in insulin deficiency. Associated autoimmune disorders, such as celiac disease, autoimmune thyroiditis, and gastritis, can coexist in patients with T1DM. These disorders are characterized by the presence of antibodies against tissue transglutaminase (anti-tTG-IgA), thyroglobulin, and thyroid peroxidase (anti-TG, anti-TPO), as well as antibodies against gastric parietal cells. Children with T1DM may also develop organ-specific multiple autoimmunity, with the coexistence of one or more autoimmune disorders. Furthermore, there is a lot of controversy regarding the role of thyroid autoimmunity in the pathogenesis of thyroid cancer. We present a child with T1DM and multiple autoimmunity including autoimmune Hashimoto's thyroiditis (HT), who developed thyroid cancer. The literature on the prevalence of associated autoimmunity in children with T1DM and the prevalence, pathogenesis, and timely diagnosis of thyroid cancer among patients with HT is also reviewed.

Materials The boy was referred to our department with right retrobulbal pain and bilateral papilledema, while brain MRI was normal. Physical examination revealed faint left radial pulse, non palpable left femoral artery, and hypertension, with right hand blood pressure 162/64 mmHg, in a difference with left hand blood pressure 128/70 mmHg. Bruits were auscultated all over the chest (precordium, supraclavicular, axillary and scapular area).