The Relationship Between Premature Adrenarche and Platelet Aggregation

Objective: Premature adrenarche (PA) has been associated with an increase in adrenal androgens, and the hyperandrogenic hormonal environment is known to lead to increased platelet (PLT) aggregation. Here, we evaluated the effects of PA on PLT aggregation in PLT-rich plasma samples from female patients. Methods: The study included 40 female patients diagnosed with PA between February, 2014 and June, 2018 and 30 healthy female individuals as a control group. Adenosine diphosphate (ADP) and collagen-induced PLT aggregation were studied via the photometric aggregometry method. Results: There were no significant differences in the PLT count or volume values between those participants with PA and the control group. Additionally, the ADP-induced maximum aggregation time, value, and slope values did not significantly differ between the patient and control groups (p>0.05). However, the collagen-induced maximum aggregation time, value, and slope values were significantly higher in the studygroup (p<0.001). Conclusion: Increased collagen-induced PLT aggregation was detected in female patients with PA. As PA is associated with a higher risk of cardiovascular events later in life, close follow-up of PA in this respect may be beneficial.

Relation of insulin resistance to neurocognitive function and electroencephalography in obese children.

BACKGROUND: Childhood obesity may lead to neuronal impairment in both the peripheral and the central nervous system. This study aimed to investigate the impact of obesity and insulin resistance (IR) on the central nervous system and neurocognitive functions in children. METHODS: Seventy-three obese children (38 male and 35 female) and 42 healthy children (21 male and 21 female) were recruited. Standard biochemical indices and IR were evaluated. The Wechsler Intelligence Scale for Children-Revised (WISC-R) and electroencephalography (EEG) were administered to all participants. The obese participants were divided into two groups based on the presence or absence of IR, and the data were compared between the subgroups. RESULTS: Only verbal scores on the WISC-R in the IR+ group were significantly lower than those of the control and IR- groups. There were no differences between the groups with respect to other parameters of the WISC-R or the EEG. Verbal scores of the WISC-R were negatively correlated with obesity duration and homeostatic model assessment-insulin resistance (HOMA-IR) values. EEGs showed significantly more frequent 'slowing during hyperventilation' (SDHs) in obese children than non-obese children. CONCLUSIONS: Neurocognitive functions, particularly verbal abilities, were impaired in obese children with IR. An early examination of cognitive functions may help identify and correct such abnormalities in obese children.

Association of nerve conduction impairment and insulin resistance in children with obesity.

AIM: The objective of our study was to investigate nerve conduction in normoglycemic obese children. METHODS: A total of 60 children with obesity (30 female and 30 male) and 30 healthy children (15 female and 15 male) were enrolled in the study. Insulin resistance (IR) and other metabolic disturbances were investigated and nerve conduction was measured in all participants. Obese children were divided into groups according to the presence of IR. All results were compared between these subgroups. RESULTS: The nerve conduction velocity (NCV) of motor median nerves in the IR+ group was significantly higher than that in the IR- group and lower than that in the control group. The NCV of the motor peroneal nerve in the IR+ group was significantly lower than that in the IR- group. The sensory nerve action potential (SNAP) of the sensory median nerve was significantly lower in the IR+ group compared to that in the IR- group. The sensory sural nerve's SNAP was significantly lower in the IR+ group than that in the control group. CONCLUSION: Nerve conduction tests may help to detect early pathologies in peripheral nerves and to decrease morbidities in obese children.

Visual and brainstem auditory evoked potentials in children with obesity.

AIMS: The aim of our study is to investigate alterations in visual evoked potentials (VEP) and brainstem auditory evoked potentials (BAEP) in children with obesity. METHODS: A total of 96 children, with a mean age of 12.1±2.0 years (range 9-17 years, 63 obese and 33 age and sex-matched control subjects) were included in the study. Laboratory tests were performed to detect insulin resistance (IR) and dyslipidemia. The latencies and amplitudes of VEP and BAEP were measured in healthy and obese subjects. RESULTS: The VEP P100, BAEP interpeak latency (IPL) I-III and IPL I-V averages of obese children were significantly longer than the control subjects. When the obese group was divided into two subgroups, those with IR and without IR, BAEP wave I, wave III and P100 wave latencies were found to be longer in the group with IR. A statistically significant correlation was observed between BAEP wave I latency, IPL I-V, IPL I-III and the homeostatic model assessment insulin resistance (HOMA IR) index and fasting insulin level. CONCLUSIONS: Our findings suggest that VEP and BAEP can be used to determine early subclinical on auditory and visual functions of obese children with insulin resistance.

Oxidative stress in obese children and its relation with insulin resistance.

BACKGROUND: In obese populations, oxidative stress plays a major role in the pathogenesis of serious diseases such as diabetes, coronary heart disease, and atherosclerosis. In this study, we investigated the status of oxidative stress in obese children as to nitrite/nitrate and glutathione peroxidase levels, and their relation with insulin resistance (IR). METHODS: A total of 63 obese children were enrolled in the study. Each was relegated to one of three groups: 20 obese children without IR (11 adolescents, 9 prepubertal; mean age 10.27 +/- 2.36 years; 10 males, 10 females), 22 obese children with IR (13 adolescents, 9 prepubertal; mean age 11.26 +/- 2.52 years; 10 males, 12 females), and a control group of 21 children (14 adolescents, 7 prepubertal; mean age 11.41 +/- 2.00 years; 10 males, 11 females). RESULTS: Glutathione peroxidase levels were lower in the obese group with IR than in either the control group or the obese group without IR (0.032 +/- 0.01 vs. 0.048 +/- 0.01 and 0.042 +/- 0.01, respectively). Nitrite/nitrate levels were higher in the obese group with IR than in the control group or the obese group without IR (89.83 +/- 25.00 vs. 66.00 +/- 21.75, and 68.65 +/- 28.98, respectively) and compared by pubertal status, adolescents' results were similar. However, in prepubertal children, nitrite/nitrate and glutathione peroxidase levels were not significantly different between groups. Multiple regression analysis revealed that nitrite/nitrate levels were positively correlated with the homeostasis model assessment of IR (HOMA-IR) independent of body mass index, age, gender, serum lipids, and pubertal stages, and that glutathione peroxidase levels were negatively correlated with body mass index and HOMA-IR independent of age, gender, pubertal status, and serum lipids. CONCLUSION: This study demonstrates that oxidative stress exists even in populations of obese children, and that oxidative stress markers have a relation with the HOMA-IR, which was used as a surrogate marker of IR.

Serum chitotriosidase activity: is it a new inflammatory marker in obese children?

Chitotriosidase (ChT) is an enzyme secreted by activated macrophages and involved in defense against, and in degradation of chitin-containing pathogens, such as fungi, nematodes, and insects. In addition, it plays an important role in the development of atherosclerosis related with systemic low-grade inflammation. To this effect of activity of ChT, we aimed to investigate serum ChT activity in obese subjects and to determine to relation with insulin resistance and high-sensitive C-reactive protein (hsCRP). A total of 73 obese subjects (10.9 +/- 2.6 years of age, 44 male patients) and 41 age and gender-matched healthy lean subjects (11.6 +/- 2.9 years of age, 18 male patients) were included in this study, between 2007 and 2008. The criterion for diagnosing obesity was defined as the body mass index (BMI) being over 97th percentile of the same gender and age. Fasting serum glucose, insulin, hsCRP and ChT levels were measured. We compared the differences in variables between obese and lean subjects with Student's t-test compared after ascertaining that the data were normally distributed. All data were expressed as mean +/- standard deviation. There was statistically significant increase in serum ChT activity of obese subjects, while there was statistically significant difference in serum hsCRP levels when compared to healthy lean subjects (30.0 +/- 17.9 and 23.0 +/- 17.8, p=0.045; 2.3 +/- 3.1 and 0.7 +/- 1.2, p=0.001). Obese subjects had significantly higher BMI-SDS, TG and HOMA-IR and lower HDL-C levels when compared with the healthy lean subjects (p<0.05). Correlation analysis showed no significant correlation between serum ChT activity and hsCRP, HOMA-IR and BMI-SDS (p>0.05). Although the data need to be validated by further investigation, the observations made in this study seem to indicate that serum ChT activity may not be a useful marker for monitoring systemic low-grade inflammation and insulin resistance in obese subjects.

Cardiac autonomic regulation is disturbed in children with euthyroid Hashimoto thyroiditis.

Hashimoto thyroiditis (chronic autoimmune thyroiditis) is the most common form of thyroiditis in childhood. Previous studies have found autonomic dysfunction of varying magnitude in patients with autoimmune diseases, which is considered a cardiovascular risk factor. We aimed to evaluate the heart rate variability (HRV), a measure of cardiac autonomic modulation, in children with euthyroid Hashimoto thyroiditis (eHT). The study included 32 patients with eHT (27 girls and 5 boys; mean age 11 ± 4.1 years, range 8-16; body mass index 0.47 ± 0.69 kg/m(2)), as judged by normal or minimally elevated serum TSH levels (normal range: 0.34-5.6 mIU/l) and normal levels of free thyroid hormones (FT4 and FT3) and 38 euthyroid age-matched controls. Patients with eHT and control subjects underwent physical examination and 24-hour ambulatory ECG monitoring. Time-domain parameters of HRV were evaluated for cardiac autonomic functions. Children with eHT displayed significantly lower values of time-domain parameters of SDANN (standard deviation of the averages of NN intervals), RMSSD (square root of the mean of the sum of the squares of differences between adjacent NN intervals), NN50 counts (number of pairs of adjacent NN intervals differing by more than 50 ms) and PNN50 (NN50 count divided by the total number of all NN intervals) for each 5-min interval, compared to healthy controls (p < 0.05 for each), indicating the decreased beat-to-beat variation of heart rate. In conclusion, eHT is associated with disturbed autonomic regulation of heart rate. Hence, the children with eHT are at higher risk for developing cardiovascular diseases.

Evaluation of adipocytokines in obese children with insulin resistance.

Obesity and overweight are among the most serious health problems in western societies and an increasing problem in developing countries. Recent studies indicate an important role of adipose tissue hormones, or "adipokines", in obesity-associated complications. To investigate the relation of two circulating adipokines (visfatin, adiponectin) with markers of insulin sensitivity and obesity in children, 40 obese children and 40 control children were recruited. Homeostasis model assessment for insulin resistance (HOMA-IR) and visfatin levels (4.99 +/- 2.08 vs. 1.47 vs. 0.7, p < 0.001; 31.3 +/- 11.1 vs. 18.5 +/- 10.7, p < 0.001, respectively) were significantly elevated and adiponectin levels (2.01 +/- 1.02 vs. 12.5 +/- 6.2, p < 0.001) were significantly lower in the obese group. Comparisons of the clinical and metabolic characteristics between insulin-resistant and noninsulin-resistant groups in obese children are summarized. The insulin-resistant group had higher visfatin levels (36 +/- 9.7 vs. 22.9 +/- 7.6, p < 0.001) and lower adiponectin levels (1.7 +/- 1.05 vs. 2.5 +/- 0.77, p: 0.016). Visfatin was correlated positively and adiponectin was correlated negatively with body mass index standard deviation score (BMI-SDS) and HOMA-IR. The role of various adipokines as connectors between obesity and diabetes mellitus has been better elucidated in recent years. Based on the findings of this study, visfatin and adiponectin levels can be used as specific markers for insulin sensitivity.

Cardiac autonomic functions in obese children.

OBJECTIVE: The autonomic nervous system is assumed to have a role in the pathophysiology of obesity. In this study, we evaluated the autonomic system by measuring heart rate variability (HRV) in obese children. METHODS: Thirty-two obese and 30 healthy children (mean ages: 11.6±2.0 years and 11.0±2.9 years, respectively) were enrolled in the study. Obesity was defined as a body mass index higher than 97th percentile for age- and gender-specific reference values. All participants were free of any disease and none of them was receiving any medication. Twenty-four-hour ambulatory electrocardiographic recordings were obtained and the time-domain and frequency-domain indices of HRV were analyzed. The study group was evaluated with respect to insulin resistance by HOMA-IR values. RESULTS: A significant decrease in calculated HRV variables was observed in obese children as compared to controls. The HRV alteration was found in both time-domain and frequency-domain parameters. The subgroup analysis of the study group revealed a significant decrease in all investigated HRV parameters in the insulin-resistant obese children compared to the non-insulin-resistant obese ones. CONCLUSIONS: Our results indicate that HRV is decreased in obese children, which implies parasympathetic withdrawal and sympathetic predominance. A marked decrease in HRV was observed in insulin-resistant obese children compared to their non-insulin-resistant counterparts. We propose that autonomic imbalance pertaining especially to insulin resistance may be involved in the pathogenesis of obesity in pediatric patients.

The effect of gonadotropin-releasing hormone analog treatment (leuprolide) on body fat distribution in idiopathic central precocious puberty.

Gonadotropin-releasing hormone analog (GnRHa) therapy is used in idiopathic central precocious puberty (ICPP) worldwide. It has also been shown that during this therapy, body mass index (BMI) increases slightly as a side effect. We investigated the side effects of GnRHa treatment in ICPP on body composition and insulin resistance (IR). Twenty girls (7.55 +/- 1.02 y) with ICPP were treated with GnRHa (leuprolide) for an average of 20.83 +/- 4.8 months. Bioelectrical Impedance Analysis (BIA) was used to measure the body's fat balance. Nine patients out of 20 (45%) had significant gain weight. We showed a significant elevation in trunk fat mass compare to baseline values (p < 0.01). These nine patients had high homeostasis model assessment (HOMA)-IR and low glucose/insulin (G/I) index. This study showed a slight increase in BMI, moderate increase in total body fat, and exaggerated elevation in trunk fat mass and IR in GnRHa-treated ICPP children.

P300 auditory event-related potentials in children with obesity: is childhood obesity related to impairment in cognitive functions?

OBJECTIVE: To investigate alterations in P300 auditory event-related potentials in children with obesity to detect changes in cognitive functions. METHOD: A total of 50 children with obesity and 23 age- and sex-matched healthy control subjects were included in the study. Laboratory tests were performed to detect dislipidemia and insulin resistance (IR). The latencies and amplitudes of P300 waves were measured in healthy and obese subjects with or without IR. The oddball paradigm was used in recordings of P300 auditory event-related potentials. RESULTS: A significant difference was observed between groups regarding latency and amplitude of P300 component obtained from central (Cz) electrode. The grand means of P300 latency were longer, and amplitude decreased significantly in obese group compared to that of healthy controls. When the obese group was divided into two different subgroups, those with IR and without IR, the grand means of P300 latency were longer and the amplitude decreased significantly in subjects with IR compared to those without IR. CONCLUSION: Both decreased amplitude and prolonged latency of P300 are associated with IR in children with obesity, which shows the impairment of neural activity associated with sensory and cognitive information processing in these children. Further studies are necessary to strengthen the current findings and to determine the exact mechanism of cognitive impairment in obese children.

Trace elements in obese Turkish children.

The quality of the diet of obese children is poor. Eating habits may alter micronutrient status in obese patients. In this study, we determined the serum levels of selenium, zinc, vanadium, molybdenum, iron, copper, beryllium, boron, chromium, manganese, cobalt, silver, barium, aluminum, nickel, cadmium, mercury, and lead in obese Turkish children. Thirty-four obese and 33 healthy control subjects were enrolled in the study. Serum vanadium and cobalt levels of obese children were significantly lower than those of the control group (0.244 ± 0.0179 vs. 0.261 ± 0.012 µg/l, p < 0.001, and 0.14 ± 0.13 vs. 0.24 ± 0.15 µg/l, p = 0.011, respectively). There was no significant difference between groups regarding the other serum trace element levels. In conclusion, there may be alterations in the serum levels of trace elements in obese children and these alterations may have a role in the pathogenesis of obesity.

Osteopetrosis and congenital hypothyroidism complicated by slipped capital femoral epiphysis.

OBJECTIVE: To describe a 13-year-old girl with unilateral slipped capital femoral epiphysis (SCFE), who presented with an acute onset limp during follow-up for congenital hypothyroidism and osteopetrosis. METHODS: We present a case report detailing the patient's history as well as clinical, laboratory, and imaging findings and discuss the related literature. RESULTS: The patient had been diagnosed elsewhere with congenital hypothyroidism, and levothyroxine therapy was initiated when she was 20 days of age; however, adherence to the treatment was irregular. Both her weight and her height were below the 5th percentile, her breast development and pubic hair were consistent with Tanner stage 1, and she had mental retardation and atypical facies. Her gait was antalgic; no muscle atrophy or shortness in the affected leg was present. On laboratory investigation, thyroid function tests were concordant with primary hypothyroidism. Her bone age was estimated as 8 years. Dual-energy x-ray absorptiometry revealed increased bone mineral density. Radiographic studies disclosed striking opacity of the bones of the pelvis and sclerosis at the skull base. Computed tomography of the affected left lower limb showed a fragmented appearance of the capital femoral epiphysis and thickening and irregularities of the physis line on the left, consistent with SCFE. CONCLUSION: We underscore the possible facilitator role of osteopetrosis in the pathogenesis of SCFE, suggest the need to consider SCFE in the differential diagnosis when a lower extremity abnormality is detected in patients with congenital hypothyroidism or delayed puberty (or both), and emphasize this association with osteopetrosis.

The effect of insulin resistance and obesity on low-density lipoprotein particle size in children.

OBJECTIVE: In adults, it was shown that obesity and insulin resistance affect low-density lipoprotein (LDL) particle size and small dense (sd) LDL is associated with cardiovascular diseases. In this study, we investigated the effect of obesity and insulin resistance on LDL particle size. METHODS: Twenty-six obese children (13 girls, 13 boys) with a median age of 10.5 years and 27 healthy control subjects (17 girls, 10 boys) with a median age of 11.5 were enrolled in the study. RESULTS: The number of patients with insulin resistance in the obese group was 15 out of 26. In the control group, there was no subject with insulin resistance. Serum triglyceride and very LDL (VLDL) levels were higher and serum high-density lipoprotein levels (HDL) were lower in the obese patients than in the controls. There was no statistical difference in the LDL particle size between the two groups (medians: 26.6 vs. 26.7 nm (p=0.575)). The size of LDL particle was not correlated with body mass index (BMI) standard deviation score (SDS), homeostasis model assessment of insulin resistance (HOMA-IR), or serum lipids. CONCLUSION: Measurement of LDL particle size as a routine procedure is not necessary in childhood obesity.

Nephrogenic diabetes insipidus due to a novel AVPR2 mutation.

Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited disease characterized by renal tubular unresponsiveness to the antidiuretic effect of arginine-vasopressin due to the mutations of two molecules, the vasopressin V2 receptor (AVPR2) and the aquasporin-2 water channel. We report a novel AVPR2 mutation in a Turkish 18 month-old boy with skeletal anomalies.