Chromium levels in healthy and newly diagnosed type 1 diabetic children.

BACKGROUND: The aim of this study was to compare the chromium levels of plasma (PCL), erythrocyte (ECL) and urine (UCL) in type 1 diabetics and healthy subjects and to review the relation between metabolic parameters. METHODS: We evaluated 165 subjects who were: newly diagnosed type 1 diabetics (group 1 [n= 29]); previously diagnosed type 1 diabetics (group 2 [n= 18]); non-diabetic control subjects who were admitted and treated for any reason in hospital (group 3 [n= 21]); and two other groups of control subjects from two schools that have different socioeconomic levels (group 4 [n= 48] and group 5 [n= 49]). RESULTS: PCL in group 1 and group 2 subjects (7.21 ± 4.78 and 10.94 ± 3.04 mcg/L, respectively) was significantly lower than in all control groups (21.84 ± 7.87, 16.11 ± 7.44, 17.25 ± 8.58 mcg/L, respectively) (P < 0.05). A significant difference in PCL between the group 1 and group 2 subjects was present (7.21 ± 4.78 and 10.94 ± 3.04, respectively) (P= 0.021). ECL (as tissue chromium) in group 1 and group 2 subjects (13.99 ± 11.37 and 19.64 ± 12.58, respectively) was significantly lower than in all control groups (28.20 ± 7.34.25, 49 ± 12.47, 26.37 ± 9.77 mcg/L, respectively) (P= 0.05). UCL in group 1 and group 2 subjects (11.44 ± 6.88 and 15.68 ± 6.75 mcg/L, respectively) was significantly lower than in group 3 subjects (28.83 ± 9.37 mcg/L) (P < 0.05). There were significant correlations between length, bodyweight and PCL in the group 1 subjects (r = 0.42, P= 0.22 and r = 0.53, P= 0.03, respectively). There was a negative correlation between plasma glucose and UCL, which was not statistically significant in group 2 subjects (r =-0.4, P= 0.061). CONCLUSION: There was a negative chromium balance in type 1 diabetics. This negative balance may affect the insulin function badly. If this negative balance should be confirmed by recent studies we suggest that chromium supplementation with insulin is necessary for type 1 diabetes.

Ambulatory blood pressure monitoring and serum nitric oxide concentration in type 1 diabetic children.

Blood pressure can be determined more precisely with the use of 24 hours ambulatory measurement in type 1 diabetics. Nitric oxide (NO) has been suggested to be responsible for the vascular changes described in early diabetic nephropathy. We aimed to investigate serum NO concentration along with ambulatory blood pressure monitoring (ABPM) parameters in type 1 diabetic patients and to find out whether there are correlation between serum NO level and ABPM parameters. Forty type 1 diabetic subjects and 35 controls were enrolled. Diabetic subjects were grouped as microalbuminuric (n=16) and normalbuminuric (n=24). Casual and ambulatory blood pressure parameters and serum NO concentrations were measured in all study population. Microalbuminuric subjects had higher nighttime systolic blood pressure (SBP), 24 hours diastolic blood pressure (DBP) and 24 hours mean arterial pressure (MAP) than controls. Both microalbuminuric and normalbuminuric subjects had also significantly higher nighttime DBP and nighttime MAP than controls. Serum NO concentrations were higher in normalbuminuric and microalbuminuric subjects than controls. Serum NO concentrations were positively correlated with daytime DBP and MAP, nighttime SBP, DBP and MAP, and 24 hours DBP and MAP in microalbuminuric subjects. Serum NO concentrations were also positively correlated with nighttime DBP in normalbuminuric subjects. Multiple linear regression analysis revealed that serum NO(2)- + NO(3)- concentrations and 24 hours DBP were independently associated with the development of microalbuminuria. Albuminuria seems to be closely associated with serum NO concentrations and ABPM parameters in type 1 DM patients. A prospective follow-up study on diabetic patients with normo- and micro- albuminuria is needed to confirm the predictive values of increased NO concentrations and ABPM parameters on the development of albuminuria.

The importance of arginine mutation for the evolutionary structure and function of phenylalanine hydroxylase gene.

Phenylalanine hydroxylase (PAH) gene mutations were investigated in 23 (46 alleles) unrelated phenylketonuria (PKU) patients in Cukurova region. First, all exons of PAH gene were screened by denaturing high performance liquid chromatography (DHPLC), and then, the suspicious samples were analyzed by direct sequencing technique. Consequently, the following results were obtained: IVS10-11g-->a splicing mutation in 27/46 (58.7%), R261Q mutation in 7/46 (15.2%) and E178G, R243X, R243Q, P281L, Y386C, R408W mutations, each found in the frequency of 2/46 (4.3%). In many countries, Arginine mutations have the highest frequency among PAH gene mutations in PKU patients. Although, CpG dinucleotids are effective in mutations resulting in arginine changes, this finding originated from the studies on the causes of mutations rather than the studies on the importance of arginine amino acid. In our analyses, we have detected that a majority of mutations causing a change in arginine and other amino acids concentrated in exon 7 comprising the catalytic domain (residues 143-410) of PAH gene. Several studies has emphasized the role of arginine amino acid; with the following outcomes; arginine repetition is significant for RNA binding proteins, and for histon proteins in eukaryotic gene expression, and also arginine repetition occurring in the structure of signal recognition particle's (SRPs) as a consequence of post-translational processes is very important in terms of gene expression. Therefore, the role of arginine amino acid in PAH gene is rather remarkable in that it shows the role of amino acids in the protein/RNA interaction that has started in the evolutionary process and is still preserved and maintained in the motif formation of active domain structure due to its strong binding properties. Thus, such properties imply that both arginine amino acid and exon 7 is of great significance with regards to the structure and function of the PheOH enzyme.

Bone calcium changes during diabetic ketoacidosis: a comparison with lactic acidosis due to volume depletion.

In this study, we aimed to compare bone calcium system changes from children with diabetic ketoacidosis or acute metabolic acidosis due to dehydration to find out the relative contribution of metabolic acidosis and diabetes-related factors on expected negative calcium balance. We studied a set of non-invasive parameters of bone remodeling in 16 children with diabetic ketoacidosis due to new onset type 1 diabetes and 25 children with acute metabolic acidosis due to dehydration complicating acute gastroenteritis before and after the correction of acidosis. The two groups of subjects were matched for age, sex, pubertal status, and degree of metabolic acidosis and dehydration. A group of 18 age and sex-matched healthy children served as the control group. Plasma ionized calcium levels were increased in both groups, significantly more so in diabetic ketoacidosis. While osteoblastic markers, osteocalcin and alkaline phosphatase, were depressed to a comparable degree in both groups, urinary calcium/creatinine ratio and hydroxyproline excretion were significantly greater in diabetic ketoacidosis. No significant changes in calcitrophic hormone (intact PTH, calcitonin, 25-hydroxy vitamin D3) levels were observed. All study parameters except for serum phosphate levels behaved in parallel in both clinical conditions, and abnormalities disappeared with the correction of acidosis except for IGF-1, which remained low in diabetic subjects. In conclusion, our results suggest that, in diabetic ketoacidosis, the observed severe negative calcium balance occurred through diminished bone formation mediated by metabolic acidosis per se and increased bone mineral dissolution and bone resorption because of severe insulin deficiency and secondarily via metabolic acidosis. Observed changes appear to be independent of calcitrophic hormones.

Urinary neopterin levels in the different stages of pregnancy.

BACKGROUND/AIMS: Neopterin is a biochemical marker of activated cell-mediated immune response which increases in pathological conditions associated with cellular immune activation as well as in pregnancy where cellular immune response is predominant. The aim of this study was to determine the urinary neopterin level in each trimester of pregnancy and to determine if it can be used as a marker. METHODS: 104 healthy pregnant women (mean age 22.10 +/- 4.39 years; 36 in the first, 30 in the second and 38 in the third trimester) and 16 non-pregnant healthy women (mean age 20.94 +/- 4.48 year) were included. RESULTS: The mean urinary neopterin concentration of all pregnant women was higher than that of non-pregnant women (166.4 +/- 31.7 and 103.1 +/- 27.5 micromol/mol creatinine respectively, p < 0.01). The mean urinary neopterin levels in each trimester and non-pregnant women were 139.8 +/- 49.6, 131 +/- 40.2, 227.9 +/- 86.5 and 103.1 +/- 27.5 micromol/mol creatinine, respectively. Urinary neopterin levels were not significantly different between non-pregnant, first and second trimester groups, but were significantly higher in the third trimester than each of these groups (p < 0.05, p < 0.01 and p < 0.01 respectively). CONCLUSION: Urinary neopterin levels increase significantly in the third trimester probably due to more predominated cellular immunity. The pathologies causing cellular immune activation, especially in the first two trimesters can be predicted with urinary neopterin levels.

Bone mineral changes in acute metabolic acidosis due to acute gastroenteritis.

We studied bone mineral metabolism changes complicated by acute gastroenteritis in a clinical acute metabolic acidosis milieu where we observed hypercalcemia, hypercalciuria, and elevated urinary hydroxyproline excretion. Serum magnesium and plasma osteocalcin, alkaline phosphatase, and IGF-1 levels were decreased. No significant changes in serum inorganic phosphate and plasma PTH, calcitonin, or 25-hydroxy vitamin D3 levels were detected. All abnormalities disappeared with the correction of acidosis. Observed hypercalcemia seems to be the result of increased calcium efflux from bone due to metabolic acidosis-induced catabolism of type 1 collagen and decreased osteoblastic activity. This study provides data regarding acute metabolic acidosis-induced changes in noninvasive parameters of bone modeling, assessed for the first time in humans.

The detection of urinal neopterin concentration increases the efficiency of cervical smear in the diagnosis of cervical cancer.

OBJECTIVE: To investigate the importance of urinal neopterin detection carried out together with cervical smear test, in the diagnosis of cervical cancer. METHODS: In this study, urine samples were collected from randomly selected vulvovaginitis' women who attended hospital and an independent control group. The participants were classified into two representative sample groups and a control group; 1st Group: 35 women with vulvovaginitis, whose ages varied from 21 to 42 and who had no viral infections, and chronic inflammatory diseases and no smoking habit, but had complaints of vaginal discharge. 2nd Group: 25 women aged between 38-52 with no smoking habit, who applied to hospital with complaints of vaginal discharge, and cervical cancer was diagnosed for them as the result of biopsy, but no associated treatment of cancer had been carried out yet. 3rd Group: A control group with 30 women who aged between 20 and 28, with no smoking habit, and who had not taken part in sexual activities yet. They had no complaints from any type of tumors, and viral infections or chronic inflammatory diseases. Urinalysis was carried out for each group member's urine sample in order to measure the level of neopterin. Neopterin was estimated by HPLC. Some statistical analyses were done by SPSS Windows 10.0 and were analyzed by Oneway Annova test. (p=0.000) Meaningful differences between the groups were determined by Post Hoc Tukey Test. RESULTS: The mathematical results of neopterin levels for the groups revealed that the level of Group 1 was significantly higher than the level of Group 3 (p= 0.0001). When the levels of Group 1 and 2 were compared with each other, a significant difference was determined (p=0.004). Also, the difference in the levels of Group 2 and 3 was found to be significant (p=0.0001). CONCLUSIONS: If the results of this study were not confounded by another factor, then we can deduce that an increment in the level of neopterin may be considered as a risk factor that should warrant further investigation of cervical cancer. Then, the detection of urinal neopterin level as a noninvasive test done together with cervical smear can increase the sensitivity of smear test.

Four new cases of congenital secondary hypothyroidism due to a splice site mutation in the thyrotropin-beta gene: phenotypic variability and founder effect.

Isolated TSH deficiency is a rare cause of congenital hypothyroidism. We here report four children from two consanguineous Turkish families with isolated TSH deficiency. Affected children who were screened at newborn age had an unremarkable TSH result and a low serum TSH level at diagnosis. Age at diagnosis and clinical phenotype were variable. All affected children carried an identical homozygous splice site mutation (IVS2 + 5 G--> A) in the TSHbeta gene. This mutation leads to skipping of exon 2 and a loss of the translational start codon without ability to produce a TSH-like protein. However, using specific monoclonal antibodies, we detected a very low concentration of authentic, heterodimeric TSH in serum, indicating the production of a small amount of correctly spliced TSH mRNA. By genotyping all family members with polymorphic markers at the TSHbeta locus, we show that the mutation arose on a common ancestral haplotype in three unrelated Turkish families indicating a founder mutation in the Turkish population. These results suggest that this TSHbeta mutation is among the more common TSHbeta gene mutations and stress the need for a biochemical and molecular genetic workup in children with symptoms suggestive of congenital hypothyroidism, even when the neonatal TSH screening is normal.

A research on the level of urine neopterin to see if it may provide a vital clue for a provisional diagnosis of breast cancer in menopausal women.

OBJECTIVES: To search the relation between the level of neopterin in urine and breast cancer developed in menopause. METHODS: In this study, urine samples were collected from randomly selected menopausal and post-menopausal women who attended hospital, and from a control group. The participants were classified into two representative sample groups and a control group; 1st group: 30 menopausal and post-menopausal women whose ages varied from 45 to 80 and who suffered from breast cancer but had no viral infections, chronic inflammatory diseases and smoking habit; 2nd group: 30 menopausal and post-menopausal women aged between 48 and 63 with no complaint of any type of tumors, viral infections or chronic inflammatory diseases and with no smoking habit; 3rd group: A control group with 20 women aged between 20 and 28, who did not take part in sexual activities yet, and had no complaint of any type of tumors, viral infections or chronic inflammatory diseases and had no smoking habit. Urinalysis was carried out for each sample in order to measure the level of neopterin. RESULTS: The mathematical results of neopterin levels for the groups showed that group I was significantly higher than group II and III (P = 0.0001 ); group II was significantly higher than group III (P = 0.003 ). CONCLUSIONS: If the results of this study were not confounded by another factor, then can we deduce that this relationship can be used as a risk factor that should warrent further investigation of breast cancer during the care and treatment of menopausal women.

Fucosidosis with hypothyroidism: a case report.

Fucosidosis is a rare, autosomal recessive lysosomal storage disorder caused by a severe deficiency of alpha-L-fucosidase. Here we present a 27-month-old male who was referred to us for evaluation of developmental delay, which was first detected at age six months. His past medical history was also remarkable for recurrent pulmonary infections and myoclonic seiures. His family history revealed that he was the first living child from a consanguineous marriage. He had a younger sister who died at five months of age from pneumonia who had facial resemblance to the proband, developmental delay and a congenital heart defect. Physical examination revealed length: 81 cm (25-50p), weight: 10.2 kg (25-50p), and head circumference: 49 cm (50-75p). He had a coarse face, hepatomegaly and generalized spasticity. His initial laboratory examination revealed negative urine screening column chromatography for mucopolysaccharidosis. His X-ray findings were consistent with mild form of dysostosis multiplex. Based on clinical and laboratory features, fucosidosis was suspected. Fucosidase enzyme activity was zero. In addition to fucosidosis, thyroid function tests indicated primary hypothyroidism. This is, to the best of our knowledge, the fourth case of fucosidosis diagnosed in Turkey.

Type II hyperprolinemia: a case report.

Hyperprolinemia type II (HP II) is a rare inherited metabolic disease due to the deficiency of pyroline-5-carboxylate dehydrogenase. It is generally believed to be a benign condition although some patients have neurological problems such as refractory convulsions. Here we report a six-year-old girl with HP II who admitted to our hospital with recurrent seizure refractory to multiple antiepileptic drugs. She was the third child of healthy, consanguineous parents. The family history was negative for neurological and renal disorders. On physical examination, she had no facial dysmorphy; the anthropometric measurements, and systemic and neurological examinations were normal. Mental and motor development was appropriate for her age. Laboratory findings revealed elevated levels of proline, glycine, and ornithine in serum and pyrroline-5-carboxylate and hydroxyproline in urine. Cerebral computerized tomography and magnetic resonance imaging were both normal. Electroencephalogram showed a very active epileptic abnormality; partial control of seizures was achieved by two antiepileptics. Increased plasma glycine and ornithine levels are the unique features of our case when compared to the other HP II cases reported in the literature.

Familial thyroxin-binding globulin excess with ichthyosis: a case report.

Thyroxin (T4) binding globulin (TBG) the major thyroid hormone transport protein in humans. Congenital or acquired problems lead to TBG excess. Inheritance of TBG excess follows an X-linked pattern. A 21-month-old boy with ichthyosis was referred to the Pediatric Endocrinology Clinic with high levels of thyroid hormones (TT3 = 325 ng/dl, TT4 23 microg/dl, FT3 = 3.49 pg/dl, FT4 = 1.44 ng/dl, TSH = 2.48 microIU/ml). He was clinically euthyroidic. Thyroid gland was normal in size and homogeneous. Thyroid autoantibodies were negative. TSH responded normally to thyroid releasing hormone (TRH) stimulus. TBG was elevated (56 microg/ml). Family investigation revealed high levels of TBG in mother grandfather, and an uncle. To our knowledge, no other TBG excess with ichthyosis has been reported in the literature.

Short stature due to growth hormone neurosecretory dysfunction in a child with major depressive disorder.

Literature indicating clinical growth hormone deficiency due to depression is extremely limited, despite a well-known impaired basal and/or stimulated growth hormone secretion in depressive disorders. In this communication, we present a case of short stature due to growth hormone neurosecretory dysfunction in a nine year old girl with major depressive disorder.

Three children with triple A syndrome due to a mutation (R478X) in the AAAS gene.

OBJECTIVE: To investigate the phenotype and genotype of 3 unrelated children with triple A syndrome from southern Turkey. METHODS: The coding sequence of the AAAS gene was sequenced including exon-intron boundaries. Haplotype analysis using markers from AAAS region was performed in order to assess potential founder effects. RESULTS: In all 3 patients, the identical nonsense mutation (R478X) in exon 16 of the AAAS gene was identified. The patients who may be distantly related appeared phenotypically similar with the classical triad of the triple A syndrome (adrenal insufficiency, alacrima and achalasia) with dermatological manifestations while lacking neurological features except for mild mental retardation. CONCLUSION: The R478X mutation tends to result in a rather severe phenotype although genotype-phenotype relationships cannot be drawn due to the small number of patients.

Early onset of diabetic nephropathy in a child with type 1 diabetes mellitus.

An 11-year-old prepubertal girl with a history of metabolically poorly controlled type 1 diabetes for six years was diagnosed with diabetic nephropathy based on persistent overt proteinuria, hypertension, and renal biopsy findings typical of diabetic nephropathy. This case illustrates that diabetic nephropathy can develop even before puberty when metabolic control of the disease is not sufficient.

Serum IL-1, IL-2, TNFalpha and INFgamma levels of patients with type 1 diabetes mellitus and their siblings.

Type 1 diabetes mellitus (DM) develops as a result of autoimmune destruction of the pancreatic beta-cells. The aim of this study was to explore possible associations between serum levels of cytokines, IL-1, IL-2, TNFalpha and INFgamma and metabolic parameters in children with type 1 DM and their non-diabetic siblings to determine whether these cytokines could be indicators of disordered immune regulation. The study population consisted of 41 children with type 1 DM, 32 non-diabetic siblings, and 28 healthy controls. Children with DM were divided into three subgroups: 1) newly diagnosed patients with diabetic ketoacidosis (ND + DKA), 2) newly diagnosed patients without DKA (ND - DKA), and 3) previously diagnosed patients (PD). The highest serum IL-1alpha level was found in the ND - DKA group, which was significant compared to both the ND + DKA (p < 0.05) and the siblings (S) (p < 0.005). IL-2 levels were similar among all groups. The highest TNFalpha level was observed in the ND + DKA group, which was significant against the ND - DKA (p < 0.05), PD (p < 0.001), S (p < 0.05), and control (C) (p < 0.005) groups. TNFalpha concentration in the PD group was significantly lower than those of S (p< 0.005) and C (p < 0.001) groups. The ND - DKA group had the highest INFgamma and this was statistically significant when compared with the S (p < 0.005) and C (p < 0.05) groups. Both the newly diabetics and all diabetics as a group had statistically significantly higher INFgamma levels than both the S (p < 0.01 for both) and C (p < 0.05 for both) groups. In the diabetics as a whole group, TNFalpha showed correlations with INFgamma (r = 0.370, p < 0.05). IL-1 showed correlation with TNFalpha (r = 0.368, p < 0.05) INFgamma (r = 0.796, p < 0.001) and IL-2 (r = 0.862, p < 0.001) in the all diabetics group. IL-2 was correlated with TNFalpha (r = 0.320, p < 0.05) and INFgamma (r = 0.754, p < 0.01) in the all diabetics group. In conclusion, our results suggest that proinflammatory cytokines TNFalpha, INFgamma, IL-1alpha and IL-2 may play important roles alone or in combination in the pathogenesis of type 1 diabetes mellitus.