Miriam Čiljaková

The association between glutathione S-transferase T1 and M1 gene polymorphisms and cardiovascular autonomic neuropathy in Slovak adolescents with type 1 diabetes mellitus ☆ ☆☆

Glutathione S-transferase (GST), as antioxidant enzyme, protects tissue from oxidative damage typical for many pathologic conditions as type 1 diabetes (T1D) and its chronic complications. The aim of the study was to compare the prevalence of GST T1/M1 gene polymorphisms between diabetic adolescents with (CAN+) and without (CAN-) cardiovascular autonomic neuropathy. Forty-six subjects with T1D at the age 15-19 years were enrolled. CAN was diagnosed in 19 patients (41.3%) based on standard cardiovascular tests. GST M1 null genotype was more prevalent in CAN+subjects but this was not statistically significant (OR=1.889, 0.61-6.55, p>0.05). GST T1 wild genotype nearly 5-fold increased the risk of CAN (OR=4.952, 1.13-21.739, p<0.05). Regarding genotype combination, GST T1/M1 wild/null genotype was significantly more frequent in CAN+compared to the CAN- subjects (OR=3.96, 1.024-15.302, p<0.05). No significant difference was found in any biochemical parameters between CAN+and CAN- subgroups. Multivariable logistic regression showed that none of the biochemical parameters estimated was considered a risk factor for CAN, however GST T1 wild and GST T1/M1 wild/null represented a risk factor for CAN development (OR=2.227, 1.079-4.587, p<0.05 and OR=1.990, 1.026-3.859, p<0.05, respectively). GST T1 wild allele and GST T1/M1 wild/null genotype can be considered as risk factors for CAN in Slovak adolescents with T1D.

Hypovitaminosis D in children with type 1 diabetes mellitus and its influence on biochemical and densitometric parameters.

The aim of the study was to establish the frequency of hypovitaminosis D in children with type 1 diabetes mellitus (T1D), its influence on biochemical and densitometric parameters and the relation to diabetic nephropathy. 58 children with T1D at the age 9-19 years were enrolled to the study. Vitamin D concentration less than 30 ng/ml was considered as insufficient. 37 children (63.79%) had vitamin D level under 30 ng/ml, from these 19 subjects (32.7%) had vitamin D level under 20 ng/ml and 2 subjects (3.44%) under 10 ng/ml. Children with vitamin D deficiency had significantly lower magnesium concentration and lower Z score of lumbar spine (-1.34 +/- 1.24 vs. -.030 +/- 1.21, p = 0.01) compared to diabetics with sufficient vitamin D concentration. No significant difference was found in parameters calcium, phosphorus or glycosylated hemoglobin. Patients with diabetic nephropathy (n = 18) showed no significant difference in vitamin D, glycosylated hemoglobin or Z score of lumbar spine compared to the patients without nephropathy (n = 40). Subjects with nephropathy had significantly longer diabetes duration, significantly higher cholesterol and triacylglycerol concentration. In our cohort of patients nearly two thirds of children had insufficient vitamin D concentration what supports the need to monitor and eventually supplement vitamin D in T1D subjects.

Recurrent Respiratory Infections in Children – Definition, Diagnostic Approach, Treatment and Prevention

Paediatric respiratory tract infections are one of the most common reasons for physician visits and hospitalisation, and are associated with significant morbidity and mortality. Respiratory infections are common and frequent diseases and present one of the major complaints in children and adolescents. The role of physicians and other healthcare providers has expanded from merely treating disease to implementing measures aimed at health maintenance and disease prevention (Bellanti, 1997). Respiratory infections (RI), mainly involving the upper airways, are common in children and their recurrence constitutes a demanding challenge for the paediatricians. There are many children suffering from so-called recurrent respiratory infections (RRI). The child with recurrent respiratory infections presents a difficult diagnostic challenge. It is necessary to discriminate between those with simply-managed cause for their symptoms such as recurrent viral infections or asthma, from the children with more serious underlying pathology such as bronchiectasis or immune dysfunction. Many different disorders present this way, including cystic fibrosis, various immunodeficiency syndromes, congenital anomalies of respiratory tract, but in some children lung damage could follow a single severe pneumonia or can be the consequence of the inhalation of food or foreign body (Couriel, 2002). According to the epidemiological studies it was estimated that around 6% of the children younger than 6 years of age present RRI. In developed countries, up to 25% of children aged < 1 year and 18% of children aged 1-4 years experience RRI (Bellanti, 1997). Moreover, ENT infections represent the most frequent pathologies in children aged from 6 months to 6 years. Although the etiologic agents responsible for RRI are not always readily identifiable, viral agents are typically the main cause. The real task for the paediatricians is to discriminate the normal children with high respiratory infections frequency related to an augmented exposure to environmental risk factors from the children affected by other underlying pathological conditions (immunological or not), predisposing to infectious respiratory

Cough reflex sensitivity in adolescents with diabetic autonomic neuropathy

ObjectiveDiabetic autonomic neuropathy (DAN) is one of the chronic complications of diabetes mellitus which can involve one or more organ systems. DAN without apparent symptoms is more often in childhood and adolescence. While heart rate variability (HRV) and Ewings battery of cardiovascular tests are regarded as a gold standard for the diagnosis of DAN, the examination of cough reflex sensitivity (CRS) is another possibility. The aim of this study was to compare HRV and CRS in children with diabetes mellitus.Materials and methodsSixty one patients (37 girls, 24 boys) aged 15-19 suffering from diabetes mellitus type 1 completed the study. Based on HRV, patients were divided into 2 groups - with DAN (n = 25) and without DAN (n = 32), 4 patients were excluded because of ambiguous results. CRS was studied in each patient by inhalation of gradually increasing concentration of capsaicin.ResultsSubjects with DAN required a significantly higher concentration of capsaicin needed to evoke 2 coughs (median 625 μmol/l, IQR 68.4-625.0 μmol/l vs. median 29.3 μmol/l, IQR 9.8-156.3 μmol/l, P < 0.001) and 5 coughs (median 2500.0 μmol/l, IQR 1250.0-2500.0 μmol/l vs. median 312.5 μmol/l, IQR 117.2-625.0 μmol/l, P < 0.001) compared with those without DAN. Moreover, a strong negative correlation between HRV and CRS was established.ConclusionDiabetes mellitus lowers the cough response. Cough reflex sensitivity appears to be another sensitive method for the evaluation of DAN in diabetes.

Exhaled carbon monoxide in adolescents with diabetic cardiovascular autonomic neuropathy.

Abstract The aim of the study was to determine if cardiovascular autonomic neuropathy (CAN) is associated with changed concentration of exhaled carbon monoxide (eCO) in adolescents with type 1 diabetes (T1D). A total of 46 T1D patients and 25 healthy controls (15–19 years) were enrolled. The parameters eCO and carboxyhemoglobin (HbCO) were established using a MICRO-4 Smokerlyser. CAN was examined by standard cardiovascular tests. Adolescents with T1D did not significantly differ in eCO compared to healthy subjects. eCO and HbCO were significantly lower in CAN-positive subjects (n=19) (1.36±1.65 ppm vs. 3.09±2.31, p=0.01 and 0.58±0.49% vs. 1.04±0.44, p<0.01, respectively) compared to CAN-negative subjects (n=27), whereas no significant difference was found in other measured parameters. By multivariate logistic regression, eCO and HbCO were associated with higher risk of CAN (OR=1.824, p<0.05 and OR=10.989, p<0.01). Our results indicate that eCO is decreased in CAN-positive diabetic subjects. Further studies are necessary to investigate the possible role of eCO as a marker for CAN.

Diabetic Microangiopathy - Etiopathogenesis, New Possibilities in Diagnostics and Management

Diabetic neuropathy affects peripheral nerves (sensory, motor, autonomic) so all organ systems can be affected. In childhood, subclinical forms are typical when no clinical symptoms are evident, however sensitive diagnostic methods can detect them. Later, autonomic and sensory-motor neuropathy is very common (see the classification in table 1). Some forms of diabetic neuropathy are presented in 40 – 90% of patients with diabetes duration ten years and more and even in 5% of patients after one year of diabetes diagnostics.

Pulmonary function tests in type 1 diabetes adolescents with diabetic cardiovascular autonomic neuropathy.

Chronic diabetic complications may afflict all organ tissues including cardiovascular and respiratory system. The aim of the study was to establish if the presence of cardiovascular autonomic neuropathy (CAN) was associated with impaired pulmonary function tests in adolescents with type 1 diabetes (T1D). 46 adolescents with T1D and 25 healthy subjects at the age 15-19years were enrolled to the study. Basic anthropometric data, diabetes onset and duration, plasma glucose and A1c were established. Pulmonary function tests were measured by spirometry and the presence of CAN was examined by heart rate variability. Adolescents with T1D had significantly lower pulmonary function test parameters - FVC (p<0.01), FEV1 (p<0.01), MMEF (p<0.05) and PEFR (p<0.05) compared to the control subjects. In diabetic group, patients with CAN (CAN+, n=19) had significantly lower FVC (p<0.05), FEV1 (p<0.05) and PEFR (p<0.05) compared to patients without CAN (CAN-, n=27). All spirometric parameters were significantly lower in CAN+ subjects compared to healthy controls; however, no significant difference was found in these parameters between CAN- subjects and healthy controls. Spirometric parameters (FVC, FEV1) significantly positively correlated with diabetes onset and body mass index; and negatively correlated with diabetes duration and resting heart rate. Our results indicate that CAN may be associated with reduced pulmonary functions in adolescents with T1D.

Bloom syndrome without typical sun-sensitive skin lesions in three Slovak siblings.

Bloom syndrome is an autosomal recessive disorder caused by mutation in the BLM gene (15q26.1), which results in chromosomal instability. It is rare in all populations but less rare among Ashkenazi Jews. It is characterized by growth deficiency of prenatal onset, telangiectasia, photosensitivity (typically seen as a butterfly distribution on the face), poikiloderma, immunodeficiency, and a high risk of cancer. Patients with Bloom syndrome usually have microcephaly, malar and mandibular hypoplasia, narrow facial features, a high-pitched voice, recurrent infections of the ears and the respiratory and gastrointestinal tracts, an increased risk of diabetes, learning disabilities, and reduced fertility. Other possible associated conditions are clinodactyly, syndactyly, ocular abnormalities, congenital heart disease, and an annular pancreas. The most serious feature is an increased risk of multiple malignancies at several sites and of different types at a young age. Most patients with Bloom syndrome have photosensitive skin lesions on the face, typically distributed in a butterfly formation; however, this is not a sine qua non sign of the disease. This case report aims to highlight the possibility that Bloom syndrome may present atypically, which could lead to delayed or incorrect diagnosis.

Management Approach to Hypoglycemia

Management of hypoglycemia in children and adults depends on many factors. The most important point of view is the level of hypoglycemia and the relevance of clinical symptoms. In the case of severe hypoglycemia, all effort must be used to maintain euglycemia as soon as possible. However, the appropriate therapeutic approach relies on correct diagnostic evaluation. In relation to the age of onset, different causes of hypoglycemia should be considered in neonates, infants, children and adults. The risk of hypoglycemia is declining during the life, low blood glucose level is the frequent problem, mainly in neonatal period. The majority of neonatal hypoglycemia are due to problems with the normal processes of metabolic adaptation after birth, and strategies enhance the physiologic transition should help prevent such episodes. Further investigation and specific intervention should be considered when hypoglycemia is unusual in severity, duration, or occurs in an otherwise low-risk infant (Desphande & Platt, 2005). Important factor for diagnosis is timing of hypoglycemia in relation to fasting. If hypoglycemia occured in a short period after meal (2-3 hours) and after overnight fasting, hyperinsulinism would be assumed. Low blood glucose level within 4-6 hours after ingestion is typical for defect in glycogenolysis. If hypoglycemia occurs more than 6 hours after feeding, disorders of fatty acid oxidation or defect in gluconeogenenesis are supposed (de Leon et al, 2008). In older patients, the fasting period inducing hypoglycemia is usually longer. Physical examination can also be helpful in diagnostic evaluation. The presence of central cleft lip (or palate), micropenis and undescended testes in male neonate strongly suggests the occurrence of hypoglycemia due to pituitary hormone deficiency. If TSH deficiency was associated, untreated infants would suffer from psychomotoric retardation, growth retardation is typical later at the age 2-3. Large for age newborns with recurrent hypoglycemia could be suspected of autosomal recessive form of hyperinsulinism, if mother did not suffer from diabetes in pregnancy. Short stature and hepatomegaly is a part of clinical picture of glycogen storage disease type 1 (Langdon et al, 2008). Hypoglycemia is expected in a risk group of neonates (e.g. premature, small for age) and in diabetic patients. If etiopathogenesis of low blood glucose level is unknown and unexpected, the sampling of blood and urine at the time of hypoglycemia is crucial (critical sample). In diagnostic algorithm, it is necessary to measure plasma substrates: ketones (aminoacetate and hydroxybutyrate acids), lactate, free fatty acids, ammonia level, and