The effect of beta-glucan supplementation on glycemic control and variability in adolescents with type 1 diabetes mellitus.

AIMS: This study aimed to investigate whether supplemental soluble fiber, oat ß-glucan, has any effect on glycemic control and variability of adolescents with type 1 diabetes mellitus. METHODS: This study was conducted in 30 adolescents with type 1 diabetes mellitus and it consisted of three phases lasting one week. At Phase I, all subjects followed a standard diet program. For Phase II and Phase III, the subjects continued their standard diet program and added natural oat flakes containing 3 g/day and 6 g/day ß-glucan, respectively. Glucose levels were monitored by continuous glucose monitoring (CGM). The maximal, minimal, mean and daytime and night blood glucose levels, percentages of glucose values in a target range and below and above a target values were calculated for each of the phases. Premeal, postmeal, peak blood glucose values and peak times of meals were evaluated for each of the phases. Glycemic variability was measured via SD, CV, MAGE, IQR, MODD, LBGI, HBGI, and CONGA parameters. RESULTS: The maximal, mean and daytime and night blood glucose levels were the lowest at Phase III (p < 0.05). Minimal blood glucose levels were the highest at Phase III (p < 0.05). Phase I, II, and III showed similar durations elapsed for Level 2 and Level 1 hypoglycemia, euglycemia, Level 1 and Level 2 hyperglycemia (p > 0.05). Premeal and postmeal blood glucose levels were lowest at Phase III for breakfast, lunch, and overall (p < 0.05). The lowest peak blood glucose levels were detected at Phase III for breakfast, lunch, dinner and overall (p < 0.05). Phase III also showed delayed peaks for all time-points (p < 0.05 for each) compared to other phases. Phase III had significantly lower levels of SD, CV, LBGI, and CONGA levels than those in either Phase I or Phase II (p < 0.05 for each). CONCLUSION: 6 g/day oat ß-glucan have favorable outcomes in glycemic control and variability in adolescents with type 1 diabetes mellitus.

Diagnostic value of urinary luteinizing hormone levels in the monitoring of precocious puberty treatment.

Objective To determine whether first-voided urinary LH (FV-ULH) - level measurement can adequately assess pubertal suppression as much as standard tests can. Subjects and methods The study group included patients with central precocious puberty and rapidly progressing early puberty who received up to 3 - 4 doses of GnRHa therapy monthly and did not have adequate hormonal suppression after GnRH stimulation (90-minute LH level > 4 IU/L). Design: All of the participants underwent an LHRH test just after admission to the study. According to the stimulated peak LH levels, the patients were divided into 2 groups and followed until the end of the first year of treatment. The concordance between FV-ULH and stimulated LH levels was assessed. Results The FV-ULH levels in patients with inadequate hormonal suppression were significantly high compared to patients with adequate hormonal suppression. FV-ULH levels were very strongly correlated with stimulated LH levels (r = 0.91). Its correlation with basal LH levels was significant (r = 0.65). However, this positive correlation was modestly weakened after the first year of treatment. The cutoff value for FV-ULH of 1.01 mIU/mL had the highest sensitivity (92.3%) and specificity (100%). Conclusion FV-ULH levels, using more reliable and sensitive assay methods, can be used to monitor the adequacy of GnRHa therapy.

Diagnostic value of urinary luteinizing hormone levels in the monitoring of precocious puberty treatment

ABSTRACT Objective To determine whether first-voided urinary LH (FV-ULH) - level measurement can adequately assess pubertal suppression as much as standard tests can. Subjects and methods The study group included patients with central precocious puberty and rapidly progressing early puberty who received up to 3 - 4 doses of GnRHa therapy monthly and did not have adequate hormonal suppression after GnRH stimulation (90-minute LH level > 4 IU/L). Design: All of the participants underwent an LHRH test just after admission to the study. According to the stimulated peak LH levels, the patients were divided into 2 groups and followed until the end of the first year of treatment. The concordance between FV-ULH and stimulated LH levels was assessed. Results The FV-ULH levels in patients with inadequate hormonal suppression were significantly high compared to patients with adequate hormonal suppression. FV-ULH levels were very strongly correlated with stimulated LH levels (r = 0.91). Its correlation with basal LH levels was significant (r = 0.65). However, this positive correlation was modestly weakened after the first year of treatment. The cutoff value for FV-ULH of 1.01 mIU/mL had the highest sensitivity (92.3%) and specificity (100%). Conclusion FV-ULH levels, using more reliable and sensitive assay methods, can be used to monitor the adequacy of GnRHa therapy.

Effect of Telehealth System on Glycemic Control in Children and Adolescents with Type 1 Diabetes

Objective: A close diabetes team-patient relationship is required for establishing satisfactory metabolic control. The purpose of this study was to investigate the effect of a telehealth system on diabetes control. Methods: The study was carried out between June 2015 and January 2016 at the Gazi University Faculty of Medicine, Pediatric Endocrinology Department. The telehealth system was developed by the diabetes team. The demographic characteristics, frequency of use and hemoglobin A1c (HbA1c) changes of type 1 diabetic (T1DM) patients using this communication network were analysed. Results: Eighty two patients [43 (52.4%) females, mean (±standard deviation) age 10.89±4 years] used the telehealth system. Fourteen (17.1%) of the cases were on pump therapy and 59 (72.0%) were counting carbohydrates. The individuals with diabetes or their families preferred WhatsApp communication. Whatsapp provided a means for instant messaging in most instances (57.3%), contact with diabetes education nurse (32.9%) and consultation with the diabetes team about insulin doses and blood glucose regulation (42.7%). HbA1c values after six months were significantly lower in patients/parents calling frequently (p<0.001) compared with HbA1c values recorded at the beginning of the study. Conclusion: Increase in frequency of counselling by the diabetes team led to improved blood glucose control in T1DM patients. A telehealth system is useful for early detection of the need for changes in treatment and for intervention. It also promoted better self care.

Vitamin D status and premature adrenarche.

BACKGROUND: Vitamin D, an important factor in calcium-phosphate homeostasis, has recently been suggested to play an important role in the pathogenesis of numerous chronic conditions such as hyperandrogenism. The aim of this study was to investigate the relationship between vitamin D status and premature adrenarche (PA). METHODS: A total of 71 girls with PA and 52 healthy girls, as the control group, were recruited. Axillary and/or pubic hair development before the age of 8 years was defined as PA. Bone age and anthropometric measures including height, weight, and body mass index (BMI) were obtained. 25-Hydroxyvitamin D (25(OH)D), fasting plasma glucose and insulin were measured. Vitamin D insufficiency was defined as <20 ng/mL. RESULTS: The PA patients had older bone age, higher BMI standard deviation score, homeostasis model of assessment-insulin resistance (HOMA-IR), and androgen but lower 25(OH)D than the control group. HOMA-IR and dehydroepiandrosterone sulfate were also higher in PA patients with vitamin D insufficiency compared with those with normal vitamin D. There was a negative correlation between 25(OH)D and HOMA-IR. CONCLUSION: Low vitamin D is associated with PA; and insulin resistance may be a factor in this association.

Anxiety and depression states of adolescents with polycystic ovary syndrome

Background/aim: Various studies have shown that adult patients with polycystic ovary syndrome (PCOS) have higher levels of anxiety and depression compared to their normal counterparts. However, it is still unclear whether these mood disorders already exist in adolescents affected by PCOS. The aim of the present study is to assess differences in anxiety and depression levels between adolescents with PCOS and age- and body mass index (BMI)-matched controls and to determine the possible factor(s) impacting these psychological parameters in adolescents with PCOS. Materials and methods: The study included 80 adolescents with PCOS and 50 age- and BMI-matched controls. All participants completed standardized questionnaires assessing anxiety and depression. A multiple linear regression model was used to analyze the impact of potential variables on anxiety and depression scores of the adolescents with PCOS. Results: Significantly higher levels of anxiety, specifically generalized and social anxieties, as well as depression were found in adolescents with PCOS compared to controls. Higher BMI was found to be associated with higher levels of depression and generalized anxiety, and higher modified Ferriman-Gallwey score with higher level of panic disorder in adolescents affected by PCOS. Conclusion: Adolescents with PCOS experience significantly more emotional distress compared to adolescents without PCOS. This emotional distress may be related, at least in part, to certain clinical features of PCOS including obesity and hirsutism. PCOS in adolescents should be assessed not only for the gynecological and metabolic aspects but also for the emotional aspects of the disease.

Microdeletion and mutation analysis of the SHOX gene in patients with idiopathic short stature with FISH and sequencing

Background/aim: The aim of this study was to investigate the prevalence of the microdeletions and mutations of the SHOX gene in children with idiopathic short stature (ISS) by the usage of fluorescence in situ hybridization (FISH) and direct sequencing technique. Materials and methods: Thirty-seven children referred to our clinic because of short stature were classified as having ISS after clinical examination. Chromosome analyses, FISH analysis of the SHOX gene, and direct sequencing of the coding exons of SHOX , through the second to the sixth exon, in 24 of the 37 patients were also performed. Results: All children had normal karyotypes and the SHOX gene region was found to be intact in all. No mutation was detected in the exonic sequences and exon/intron boundaries of the SHOX gene in 24 children analyzed. Conclusion: No mutation was detected in the exonic sequences and exon/intron boundaries of the SHOX gene and this indicated that the prevalence of the SHOX mutations can differ according to the selection criteria, used methods, sample size, and population.

Relationship between obesity and iron deficiency anemia: is there a role of hepcidin?

OBJECTIVES: Iron deficiency is common in obese children although the underlying mechanism is unclear. The aim of this study was to investigate the associations between iron parameters, leptin, hepcidin and adiponectin levels in obese children. METHODS: A total of 237 children, ranging in age from 5 to 18 years, 180 with primary obesity and 57 healthy children and adolescents, were enrolled. Complete blood count, serum iron levels, iron-binding capacity, ferritin levels, leptin, hepcidin and adiponectin levels were studied. RESULTS: White blood cell and platelet count, iron-binding capacity, high-sensitive C-reactive protein, leptin and hepcidin values in the obese group were higher than those of the control group (p < 0.001, p = 0.002, p < 0.001, p < 0.001, p < 0.001 and p < 0.001, respectively). However, mean corpuscular volume, adiponectin and transferrin saturation values in the obese group were lower than in the control group (p = 0.026, p = 0.003, and p < 0.001, respectively). No significant differences were found in terms of hemoglobin, serum ferritin, iron and IL-6 levels. CONCLUSIONS: Our study suggests that hepcidin levels do not contribute to the development of iron deficiency anemia in pediatric obese individuals.

Retinal Neural and Vascular Structure in Isolated Growth Hormone Deficiency Children and Evaluation of Growth Hormone Treatment Effect

OBJECTIVE: To evaluate neural and vascular retinal morphology of children with isolated growth hormone deficiency (GHD) and to determine any retinal changes due to GH treatment. METHODS: Twenty-eight children with isolated GHD and 53 age-, gender- and body mass index-matched healthy volunteers were enrolled in this prospective study. The retinal nerve fibre layer (RNFL) and macular thickness (MT) were measured, as well as intraocular pressure (IOP). The number of retinal vascular branching points were calculated. Effect of GH treatment on the retina and IOP was evaluated after one year of treatment. Measurements were also made in the control group at baseline and following the initial examination. Pre- and post-treatment changes were compared. The findings were also compared with those of the controls. The correlation between ocular dimensions and insulin-like growth factor-I (IGF-1) levels were also analysed. RESULTS: The number of branching points was significantly lower in GHD patients as compared with control subjects (15.11±2.67 and 19.70±3.37, respectively, p=0.05 for all comparisons). No statistically significant differences were found in mean RNFL, MT and IOP values between GHD patients and control subjects. GH treatment did not create any significant changes in the retinal vascularization or other retinal neural parameters and IOP either within the patient group or when compared with the control group. No correlations were observed between ocular dimensions and IGF-1 levels. CONCLUSION: Our findings suggest that isolated GHD may lead to decreased retinal vascularization. However, retinal neural growth and differentiation were not affected by GHD. These findings may be related to the fetal development process of pituitary somatotropic cells and the retina. Additionally, GH treatment did not cause any changes in retinal neural and vascular tissues.

Endoglin and obestatin levels, cardiometabolic risk factors and subclinical atherosclerosis in children aged 10-18 years.

BACKGROUND: The aim of this study was to investigate the early signs of atherosclerosis and to evaluate serum endoglin and obestatin levels as predictors of subclinical atherosclerosis in obese children. METHODS: A total of 95 children (60 obese and 35 controls) aged 10-18 years were included in the study. Their endoglin and obestatin levels and biochemical parameters were measured. The carotid intima media thickness (cIMT) and brachial artery flow-mediated dilatation (FMD) responses were evaluated. RESULTS: The cIMT values were higher (p < 0.001) and FMD responses were lower (p = 0.003) in the obese group than in the control group. A logistic regression multivariate analysis revealed that cIMT was independently associated with the body mass index (BMI) Z-score (ß = 0.323, p = 0.003) and low density lipoprotein (LDL) (ß = 0.29, p = 0.008), while FMD % was independently associated with waist circumference (ß = -0.36, p = 0.002). The obese and control groups were similar in endoglin (p = 0.67) and obestatin levels (p = 0.70). The endoglin level was inversely correlated with the cholesterol and LDL levels (r = -0.23, p = 0.032; rho = -0.25, p = 0.019). CONCLUSIONS: The cIMT and brachial artery FMD response in obese children are significantly different compared to healthy controls. Circulating endoglin and obestatin levels are not predictive markers for subclinical atherosclerosis in obese children aged 10-18 years old.

Effect of Cytokine Signaling 3 Gene Polymorphisms in Childhood Obesity.

OBJECTIVE: Although polymorphisms in suppressor of cytokine signaling 3 (SOCS3) was reported to be related to obesity, Metabolic syndrome (MS), and type 2 diabetes mellitus in various adult studies, there is a lack of data in children. In this study, we examined eight reported polymorphisms of SOCS3 in obese Turkish children and adolescent with and without MS and compared the results with that of controls. METHODS: One hundred and forty eight obese and 63 age- and sex-matched control subjects were enrolled in the study. Obesity classification was carried out according to body mass index. World Health Organization and National Cholesterol Education Program criteria were used for the diagnosis of MS. Genotyping procedure was carried out by polymerase chain reaction and Sanger sequencing protocol. RESULTS: The frequency of rs2280148 polymorphism was significantly higher in obese subjects with MS than in the control group, whereas the frequency of rs8064821 polymorphism was significantly higher in obese subjects with MS than in obese children without MS. CONCLUSION: The significant associations of certain SOCS3 polymorphisms with obesity parameters in both MS and MS -related insulin resistance, hypertension, and fatty liver suggest that polymorphisms in this gene may play a role in the pathogenesis of MS and also that they can be potentially used as a marker for attenuated or aggressive disease.

Soluble Endoglin Level Increase Occurs Prior to Development of Subclinical Structural Vascular Alterations in Diabetic Adolescents.

OBJECTIVE: Soluble endoglin (S-endoglin) has been implicated as a potential marker of endothelial dysfunction (ED) and was reported to be elevated in diabetic adults, correlating with the severity of diabetic vasculopathy. However, circulating S-endoglin and its association with other markers of ED have not been formerly analyzed in the first decade of diabetes onset in adolescents with type 1 diabetes mellitus (T1DM). METHODS: Fifty-eight adolescents with moderately/poorly controlled T1DM were included in this study and twenty-nine healthy adolescents served as controls. The diabetic group was divided into two groups based on the presence of microalbuminuria, as the microalbuminuria group (n=15) and the normoalbuminuria group (n=43). Functional vascular alterations were evaluated by measuring serum S-endoglin and plasma nitric oxide (NO) concentrations, the flow-mediated dilatation (FMD) of the brachial artery. Carotid intima media thickness (CIMT) was measured for evaluation of structural vascular alterations. RESULTS: The S-endoglin and NO levels of both microalbuminuria and normoalbuminuria groups were higher than those of the control group (for S-endoglin, p=0.047 and p<0.001; for NO, p=0.004 and p=0.006, respectively). The FMD percent was lower in the microalbuminuria group compared to the normoalbuminuria and control groups (p=0.036 and p=0.020, respectively). There were negative correlations between S-endoglin concentration and FMD percent (r=-0.213, p=0.051) and between serum S-endoglin concentration and albumin excretion rate (r=-0.361, p=0.005). No significant differences were found in CIMT among any of the groups (p=0.443). CONCLUSION: In adolescents with T1DM, S-endoglin concentrations might increase in parallel to the deterioration in endothelial function before subclinical structural vascular alterations become evident.

Assessment of bone turnover markers and bone mineral density in normal short boys.

AIM: To investigate whether there is a change in bone turnover-related biochemical markers and bone mineral density of children with constitutional delay of growth and puberty (CDGP) in the prepubertal period. METHODS: We measured serum calcium, phosphorus, alkaline phosphatase, parathormone, 25-OH vitamin D, osteocalcin, osteoprotogerin and urinary deoxypyridinoline levels (D-pyd), and bone mineral density (BMD) in 31 prepubertal boys with CDGP. These children were compared with 22 prepubertal boys with familial short stature (FSS) and 27 normal prepubertal boys. RESULTS: Urinary D-pyd was significantly high in CDGP group as compared to control group (p=0.010). Volumetric BMD did not significantly differ between CDGP, FSS, and control groups (p=0.450). Volumetric BMD and urinary D-pyd levels of FSS and control groups were similar. Mean or median levels of calcium, phosphorus, alkaline phosphatase, parathormone, and osteoprotegerin did not significantly differ between CDGP, FSS, and control groups. CONCLUSIONS: Our data suggest that prepubertal boys with CDPG have normal bone turnover. However, their significantly higher urinary D-pyd levels relative to those of FSS and control groups might be an indicator of later development of osteoporosis. Therefore, long-term follow-up studies monitoring bone mineral status of prepubertal boys with CDPG from prepuberty to adulthood are needed to better understand bone metabolism of these patients.

Gonadoblastoma with Dysgerminoma in a Phenotypically Turner-Like Girl with 45,X/46,XY Karyotype.

Individuals with 45,X/46,XY karyotype are at increased risk for germ cell tumor development. We report a case with a diagnosis of 45,X/46,XY gonadal dysgenesis who presented with short stature, physical stigmata of Turner syndrome. Her pubertal development was at Tanner stage 3. At follow-up, bilateral prophylactic gonadectomy was performed when considering the risk factors. Pathological assessment was consistent with gonadoblastoma in the left gonad, and dysgerminoma and gonadoblastoma in neighboring areas in the right gonad. The karyotype analysis of the right and left gonadal tissues reveled 45,X[97,3]/46,XY[2,7] and 45,X[92,7]/46,XY[4,5]/47,XYY [2,8] mosaic, respectively. The clinical management of such patient should be individualized according to the present risk factors. Additionally, signs of estrogenization like advanced breast development always suggest the possible presence of germ cell tumor.

Extensive middle cranial fossa arachnoid cysts and different clinical presentation in two patients.

Arachnoid cysts (ACs), particularly suprasellar cysts, cause a wide spectrum of endocrine disorders. Herein, we report two patients diagnosed with an extensive AC in the middle cranial fossa while being investigated for etiologies of precocious puberty and short stature. One of them required surgery due to his pubertal disorders associated with compression effects of cyst. After surgery, his puberty progression was regressed within one year. On the other hand, surgery was not planned for the second patient considering of his cranial imaging findings and the extremely low incidence of growth hormone (GH) deficiency caused by middle fossa AC (MFAC). We started treatment with recombinant human GH and no complication was found during treatment follow-up. Endocrine disorders associated with MFACs are extremely rare. By presenting with these two cases, we aimed to remain our fellow physcians that ACs can be possibly cause of endocrine disorders. Clinicians should be careful evaluating endocrine disorders because real cause may not be cyst itself but masked by it.

Cardio-facio-cutaneous syndrome with precocious puberty, growth hormone deficiency and hyperprolactinemia.

Cardio-facio-cutaneous (CFC) syndrome is a rare disorder characterized by craniofacial dysmorphia, ectodermal abnormalities, cardiac malformations, as well as growth and developmental delay. Although some endocrine abnormalities have been reported in this syndrome, very little is known about CFC syndrome-related endocrine disorders. A 7.5-year-old boy was admitted to our endocrinology clinic with the complaint of short stature. He had a height of 103 cm [-4 standard deviation (SD)], a weight of 16 kg (<3(th) percentile, -1.7 SD), a facial appearance typical for the CFC syndrome, optic nerve hypoplasia and pulmonary stenosis. Genetic investigation revealed a heterozygous mutation in exon 3 of the MEK1 gene, c.389A>G (p. Y130C). During his long-term follow-up, the patient developed a variety of endocrine disorders including precocious puberty, growth hormone deficiency and hyperprolactinemia.

Octreotide-induced long QT syndrome in a child with congenital hyperinsulinemia and a novel missense mutation (p.Met115Val) in the ABCC8 gene.

BACKGROUND/AIMS: Congenital hyperinsulinism (CHI) denotes an inappropriate secretion of insulin from pancreatic ß-cells in the presence of a low blood glucose level due to various genetic causes. Diazoxide is the first-line medical treatment for CHI. In case of failure, a somatostatin analogue called octreotide is used. A prolonged QT interval is an unusual side effect of octreotide which can be lethal if unrecognized. CASE PRESENTATION: We report on a 35-day-old infant who was diagnosed with CHI on the 3rd day of his life and underwent pancreatectomy due to failure of medical treatment at 8 months. His genetic analysis revealed a compound heterozygosity for a novel missense mutation (p.Met115Val) and a nonsense mutation (p.Trp1339X) in the ABCC8 gene. Furthermore, at the 6th month of follow-up, a long QT (0.49 s) was determined by ECG examination, which was normalized following discontinuation of octreotide treatment after pancreatectomy. Thus, the long QT was considered to be secondary to octreotide medication. CONCLUSION: We recommend ECG monitoring before and during octreotide treatment in order to recognize a prolonged QT interval and to prevent related complications in cases with congenital hyperinsulinemia.

Serum adiponectin, leptin, resistin and RBP4 levels in obese and metabolic syndrome children with nonalcoholic fatty liver disease.

AIM: To investigate the relationship of adiponectin, leptin, resistin and RBP4 levels in obese and metabolic syndrome children with nonalcoholic fatty liver disease (NAFLD). PATIENTS & METHODS: Group I consisted of 63 obese children with liver steatosis, group II consisted of 12 obese children with elevated serum ALT activity from group I, and group III included 85 obese children without liver steatosis. RESULTS: Leptin levels were higher in the NAFLD children than in the control group. Serum RBP4 levels in obese children with NAFLD were higher than those in obese children without NAFLD and controls. Adiponectin and resistin levels were negatively correlated and RBP4 levels positively correlated with ALT activity and ultrasonographic grading. CONCLUSION: These data suggest that adiponectin, resistin and RBP4 may have a role in the pathogenesis of NAFLD in obese children. Adiponectin, leptin, resistin and RBP4 may be suitable markers for predicting metabolic syndrome and NAFLD.

Relationship of adipokines (adiponectin, resistin and RBP4) with metabolic syndrome components in pubertal obese children.

AIM: To investigate the relationship between serum adiponectin, resistin and RBP4 levels and the components of metabolic syndrome. PATIENTS & METHODS: Serum adiponectin, resistin and RBP4 levels were detected and analyzed in 148 8-18-year-old Turkish obese pubertal children with/without metabolic syndrome. RESULTS: Adiponectin and resistin concentrations were significantly inversely correlated with BMI standard deviation score, homeostatic model assessment insulin resistance, waist circumference, triglyceride levels and diastolic and systolic blood pressure, and were directly correlated with high-density lipoprotein cholesterol. RBP4 concentrations were directly correlated with homeostatic model assessment insulin resistance, waist circumference, triglyceride levels and diastolic and systolic blood pressure, and inversely correlated with high-density lipoprotein cholesterol. CONCLUSION: Adiponectin, RBP4 and, in particular, resistin levels may be used as suitable predictive biomarkers of metabolic syndrome.