Anthropometric findings from birth to adulthood and their relation with karyotpye distribution in Turkish girls with Turner syndrome.

To evaluate the anthropometric features of girls with Turner syndrome (TS) at birth and presentation and the effect of karyotype on these parameters. Data were collected from 842 patients with TS from 35 different centers, who were followed-up between 1984 and 2014 and whose diagnosis age ranged from birth to 18 years. Of the 842 patients, 122 girls who received growth hormone, estrogen or oxandrolone were excluded, and 720 girls were included in the study. In this cohort, the frequency of small for gestational age (SGA) birth was 33%. The frequency of SGA birth was 4.2% (2/48) in preterm and 36% (174/483) in term neonates (P < 0.001). The mean birth length was 1.3 cm shorter and mean birth weight was 0.36 kg lower than that of the normal population. The mean age at diagnosis was 10.1 ± 4.4 years. Mean height, weight and body mass index standard deviation scores at presentation were -3.1 ± 1.7, -1.4 ± 1.5, and 0.4 ± 1.7, respectively. Patients with isochromosome Xq were significantly heavier than those with other karyotype groups (P = 0.007). Age at presentation was negatively correlated and mid-parental height was positively correlated with height at presentation. Mid-parental height and age at presentation were the only parameters that were associated with height of children with TS. The frequency of SGA birth was found higher in preterm than term neonates but the mechanism could not be clarified. We found no effect of karyotype on height of girls with TS, whereas weight was greater in 46,X,i(Xq) and 45,X/46,X,i(Xq) karyotype groups.

The relationship of periaortic fat thickness and cardiovascular risk factors in children with Turner syndrome.

Children with Turner syndrome (TS) have a broad range of later health problems, including an increased risk of cardiovascular morbidity and mortality. The aim of this study was to evaluate the relationship between periaortic fat thickness (PAFT) and metabolic and cardiovascular profiles in children with TS. Twenty-nine TS and 29 healthy children and adolescents were enrolled in the study. Anthropometric measurements, pubertal staging, and blood pressure measurements were performed. Fasting serum glucose, insulin, and lipid profile were measured. Periaortic fat thickness was measured using an echocardiography method, which has not previously been applied in children with TS. No difference was found between TS and control subject (CS) in age, weight, waist/hip ratio, HDL cholesterol and LDL cholesterol levels. However, in TS subjects, total cholesterol (p = 0.045) was greater than that in controls. It was determined that 13.7 % (N: 4) of TS subjects had dyslipidemia. Mean fasting glucose, fasting insulin, QUICK-I, HOMA, and FGIR index were similar in TS and in CS, whereas 17.2 % (N: 5) of TS subjects had insulin resistance (IR) and 13.7 % (N: 4) had impaired glucose tolerance. Six subjects (20.6 %) were diagnosed as hypertensive. Periaortic fat thickness was significantly higher in the TS group (p < 0.001) (0.1694 ± 0.025 mm in the TS group and 0.1416 ± 0.014 mm in the CS group) In children with TS, PAFT was positively correlated with fasting insulin, body mass index, and diastolic blood pressure. Our results provide additional evidence for the presence of subclinical cardiovascular disease in TS. In addition to existing methods, we recommend the measurement of periaortic fat thickness in children with TS to reveal the presence of early atherosclerosis.

Ambulatory blood pressure and subclinical cardiovascular disease in children with turner syndrome.

Patients with Turner syndrome (TS) have an increased risk of cardiovascular morbidity. 29 TS and 25 healthy control subjects (CS) were included in the study. We investigated body mass index, waist circumference, fasting glucose and insulin, homeostatic model assessment (HOMA) index, serum lipids, oral glucose tolerance test, 24-h ambulatory blood pressure (BP) monitoring, and carotid intima-media thickness (CIMT) and compared them with CS. 28 % (N = 7) of TS had insulin resistance (IR), and 36 % (N = 9) had IGT. Mean systolic BP and diastolic BP (DBP) dip were 7.24 ± 3.97 % and 11.84 ± 6.2 %, respectively. CIMT was greater in TS than in CS (p = 0.00). CIMT was correlated positively with fasting insulin, HOMA index, and insulin-sensitivity check index (r = 0.563, p = 0.015; r = 0.603, p = 0.008; and r = 0.623, p = 0.006, respectively) and negatively with fasting glucose-to-insulin ratio and DBP dipping (r = -0.534, p = 0.022; r = -0.534, p = 0.00, respectively) in the two groups combined. These results provide additional evidence for the presence of subclinical cardiovascular disease and its relation to hypertension in TS. They also indicate a significant relation between DBP dipping and increased arterial stiffness. It is also important to note that our findings show significant relationships between insulin sensitivity and cardiovascular changes and underline the importance of insulin resistance for predicting cardiovascular disease.

Serum ischemia-modified albumin levels in children with epileptic seizures.

OBJECTIVES: The aim of the present study was to determine the level of ischemia-modified albumin (IMA) in children with epileptic seizures (ESs) and its relation with the seizure duration. METHODS: The study was performed with 88 children as a prospective case-control study. Blood samples for IMA were obtained from 57 patients (mean age [SD], 50.86 [51.15] months) within 3 hours after ES and 31 healthy control subjects (mean age [SD], 53.13 [40.87] months). Ischemia-modified albumin was measured by the albumin cobalt binding test. RESULTS: Although the mean (SD) of serum IMA level of the patients with seizure was 13.66 (13.16) U/mL, the mean (SD) of serum IMA level for the control group was 3.73 (1.93) U/mL. Ischemia-modified albumin levels were significantly higher in patients with seizure, compared with that in the control group (P < 0.01). When patients were grouped in itself according to the duration of ESs, the levels of IMA were detected to be increased in patients as the duration of seizures was lengthened. CONCLUSIONS: Increased IMA levels after seizures suggest that IMA assay during seizure may be useful for predicting the diagnosis and severity of convulsion.

Which metabolic syndrome criteria best predict non-alcoholic fatty liver disease in children?

OBJECTIVE: The aim of this study was to identify which metabolic syndrome criteria (WHO or IDF) better reflect the presence of non-alcoholic fatty liver disease (NAFLD) and to determine the prevalence of metabolic syndrome (MS) and NAFLD. METHODS: Two hundred and seventeen obese children and adolescents, 8-15 years of age (body mass index >95 p), were included in the study. Anthropometric measurements, blood pressure measurements, an oral glucose tolerance test and lipid profile were measured. MS was diagnosed according to WHO and IDF criteria. NAFLD risk ratio was assessed according to the two MS criteria. RESULTS: The prevalence of MS according to the IDF criteria was 43.3 %, and according to WHO criteria it was 55.2 %. NAFLD prevalence in the metabolic syndrome group according to IDF criteria was 25.5 % and this was statistically significant (p = 0.007). The prevalence of NAFLD was 20.8 % in the group with MS according to WHO criteria and this was not a statistically significant difference (p = 0.15). NAFLD hazard ratios were 7.06 (95 % CI 1.29-5.50) in the MS group according to IDF criteria and 2.02 (95 % CI 0.81-3.53) in the group with metabolic syndrome according to WHO criteria. IDF criteria were found to have a higher odds ratio. CONCLUSION: The prevalence of MS depends on the diagnostic criteria used. IDF criteria give the best measure for the presence of NAFLD. NAFLD might be important as diagnostic criterion for MS.

Pentoxifylline treatment for protecting diabetic retinopaty in children with type 1 diabetes.

OBJECTIVE: The purpose of this study was to determine whether oral pentoxifylline (PTX) would improve retinal microvascular hemodynamics in children with type 1 diabetes mellitus (DM). PATIENTS AND METHODS: Non-invasive ultrasonographic measurements were made in 56 type 1 diabetic patients. The diabetic patients were matched first in terms of age, diabetes duration, then one individual within each pair was randomized into a pentoxifylline group and a control group. Pentoxifylline was administered for 6 months. We investigated the change of peak systolic velocity (PSV), end diastolic velocity (EDV), pulsatility index (PI), and resistivity index (RI) of central retinal artery (CRA) at 6 months after pentoxifylline. We investigated the relationship between PI, RI and carotide cross-sectional compliance (C-CSC). RESULTS: In comparison to changes in CRA measurements between the two groups, the pentoxifylline treatment group had significantly lower PI values (p=0.01). The RI, PSV and EDV were lower in pentoxifylline group but not statistically different. There was a positive correlation between CRA PSV and carotid Vmax (cm/s) (r=0.29, p=0.02) and also C-CSC (r=0.27, p=0.03). In addition, there was a positive correlation between PI and C-CSC (r=0.3, p=0.02). In the pentoxifylline group there was a significant reduction in systolic blood pressure, diastolic blood pressure, microalbuminuria and an increase in HDL level. CONCLUSION: Our results suggest that pentoxifylline may have a protective action for diabetic retinopathy and might modulate risk factors for atherosclerosis in type 1 diabetes.

Serum ischemia-modified albumin level and its association with cardiovascular risk factors in obese children and adolescents.

BACKGROUND: Serum ischemia modified albumin (IMA) levels have been previously studied and found to correlate with some anthropometric and laboratory measurements in adult obesity. IMA had not been studied in obese children and adolescents. OBJECTIVE: The aim of the study is to analyze serum IMA levels and to evaluate their correlation with cardiovascular risk factors in obese children and adolescents with and without metabolic syndrome (MS). SUBJECTS AND METHODS: Sixty-one obese children/adolescents and 33 healthy children were included in the study. The obese group was divided into four subgroups, including MS (n=25), non-MS (n=36), liver steatosis (n=19) and non-liver steatosis (n=42) groups. Blood was collected to analyze biochemical parameters and IMA. Epicardial adipose tissue thickness was measured with echocardiography, and liver steotosis was determined with ultrasonography for each subject. RESULTS: Body mass index (BMI), waist circumferences (WC), left ventricular mass (LVM) and epicardial adipose tissue (EAT) thickness were significantly higher in obese subjects. Serum IMA levels were significantly higher in the metabolic syndrome (MS) and hepatosteotosis groups. Additionally, LVM and EAT thickness were found to be correlated with serum IMA levels in these groups. CONCLUSIONS: Our study suggests that serum IMA levels may be used to predict cardiovascular risk in obese children with MS and hepatosteotosis. This may be related to the duration of obesity in childhood ending in adulthood.

First Evaluation of P Dispersion and Tp-e Parameters in Electrocardiograms of Children with Diabetic Ketoacidosis

Objective: Diabetic ketoacidosis (DKA) is an important complication of type 1 diabetes mellitus. We aimed to evaluate the effect of metabolic disorders of DKA on electrocardiography (ECG) parameters in children. Methods: This study was performed between December 2018 and March 2020 and included 39 children with DKA and 40 healthy children. Three ECGs (one before and two after treatment) were obtained from the patient group. P-wave dispersion (Pd), QT dispersion (QTd), QTc dispersion (QTcd), Tp-e intervals, and the ratios of Tp-e/QT and Tp-e/QTc were measured electrocardiographically. ECG parameters from children with DKA and healthy controls were compared statistically. Results: The mean age of the patient group was 10.50±4.12 years. There was no significant difference in terms of age, gender, weight, height and body mass index between patients and controls. In the patient group, a statistically significant increase was found in Pd, QTd and QTcd in the initial ECG compared to the second and third ECGs. Also, when the first and third ECGs were compared, a significant increase in Tp-e and Tp-e/QT was evident in the first ECG. There was a significant difference in the values of Pd, QTd, QTcd, Tp-e and Tp-e/QT in the first ECGs, obtained before DKA treatment, and those values obtained from the control group. Conclusion: This is the first article evaluating Pd and Tp-e parameters in children with DKA. Cardiac arrhythmia risk markers were increased in children with DKA compared to controls. Therefore, clinicians should be aware of the possibility of developing new arrhythmias during DKA treatment.

Effectiveness of pentoxifylline on the cross-sectional area of intima media thickness and functions of the common carotid artery in adolescents with type 1 diabetes.

OBJECTIVE: The aim of the present study was to evaluate the effect of oral pentoxifylline on the cross-sectional area of intima media thickness (CSA-IMT) and functions of the common carotid artery, a marker of early atherosclerosis, in adolescents with type 1 diabetes. PATIENTS AND METHODS: Non-invasive ultrasonographic measurements were made in 56 type 1 diabetic patients. The diabetic patients were matched first in terms of age, diabetes duration, major cardiovascular risk factors, including anthropometric and metabolic parameters as well as ultrasonographic measurements, then one individual within each pair randomized into a pentoxifylline group and a placebo (control) group (i.e., 32 on pentoxifylline group and 24 on placebo). Pentoxifylline was administered for 6 months. We investigated the change of CSA-IMT, compliance, distensibility, diastolic wall stress (DWS), and incremental elastic modulus of the common carotid artery at 6 months after pentoxifylline. RESULTS: In comparison of changes in common carotid artery measurements between the two groups, the pentoxifylline treatment group had significantly higher values than the controls for CSA-IMT (-2.6 +/- 0.1 vs. 0.7 +/- 0.4 mm2, p = 0.001) and for DWS (-0.38 +/- 0.02 vs. -0.05 +/- 0.05 mm Hg x 10(2), p < 0.001). In a multivariate regression model for all patients, being in pentoxifylline group was the best predictor of the change DWS (beta = -0.52, p < 0.001). CONCLUSION: Our preliminary results suggest that pentoxifylline has an antiatherogenic action and might modulate risk factors for atherosclerosis in type 1 diabetes.

Relationship of acanthosis nigricans with metabolic syndrome in obese children.

OBJECTIVES: Acanthosis nigricans is a skin symptom in obesity that helps to identify patients at high risk for dyslipidemia, hypertension, insulin resistance, and diabetes. It is the most important complication of obesity in metabolic syndrome. Studies investigating the relationship between acanthosis nigricans and metabolic syndrome in obese children are insufficient. In our study, the relationship of acanthosis nigricans and metabolic syndrome was evaluated in children. METHODS: Obese children aged between 6 and 18 years old, who were examined in the pediatric endocrinology outpatient clinic, were included. The patients' anthropometric measurements and laboratory results were recorded. Modified IDF (International Diabetes Federation) criteria for children were used in metabolic syndrome classification. RESULTS: A hundred and forty-eight obese children were evaluated. The mean age of the cases was 11.91 ± 2.94 years old. Of the cases, 56.1% were female (n=83) 43.9% (n=65) were male. In 39.9% (n=59) of cases, acanthosis nigricans was determined. Acanthosis nigricans was mostly located in the axillary area (27.1%) and the neck (16.9%). In 55.9% of the cases, it was located in more than one area. The relation of regionally detected acanthosis nigricans and metabolic syndrome was not significant (p=0.291). Metabolic syndrome was detected in 14% of 136 patients according to IDF criteria. Acanthosis nigricans and metabolic syndrome combination was present in 27.7%; however, 6.7% of the metabolic syndrome patients did not have acanthosis nigricans. There was a strong relation between metabolic syndrome and the presence of acanthosis nigricans (p=0.003). CONCLUSIONS: In our study, a correlation between acanthosis nigricans and metabolic syndrome was detected. Acanthosis nigricans is a skin sign that can be easily detected by clinician. It is an important and easy-to-detect dermatosis that helps determine patients at risk of metabolic syndrome in obese children.

General properties of autoimmune thyroid diseases and associated morbidities.

Background Autoimmune thyroid diseases (ATDs) can be classified into two basic diseases: Graves' disease (GD) and Hashimoto's thyroiditis (HT). Here, we review the effectiveness of laboratory and imaging methods used for the early diagnosis of ATD and draw attention to methods that may improve screening. Methods Retrospective data of 142 patients diagnosed with ATD between January 2010 and December 2015 at our paediatric endocrinology clinic were used. Sociodemographic characteristics, clinical findings, treatments and follow-up data of patients were statistically evaluated. Results Of the ATD cases, 81% (n = 115) were female. The median age was 12.5 ± 3.5 (range 1-17) years and 91% (n = 129) of patients were in puberty. There was a significant positive correlation between the height (standard deviation score) and follow-up time for patients with HT (r = 0.156, p < 0.01). Thyroglobulin antibody (TgAb) positivity was found in 75% (45/60) of females with a positive maternal ATD history (p = 0.045). Thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4) values were significantly altered during the treatment follow-up period in female patients with GD and HT, while only fT4 values were found to be significantly altered in boys with HT. Conclusion Although GD and HT have similar mechanisms, they differ in terms of treatment duration and remission and relapse frequencies. Ultrasonography (USG) screening is a non-invasive procedure that is suitable for all patients with ATD. Based on our results, TgAb could be useful in the screening of girls with a history of maternal ATD.

Investigation of the effect of epicardial adipose tissue thickness on cardiac conduction system in children with type 1 diabetes mellitus.

Objectives Investigation of the association between epicardial adipose tissue thickness (EATT) and P-wave dispersion (Pd), QT dispersion (QTd), corrected QT dispersion (QTcd) and Tp-e interval in children with Type 1 Diabetes Mellitus (T1DM) was aimed. Methods Forty-one children with T1DM and 41 age- and gender-matched healthy children were included in the study. Demographical characteristics of all cases were examined. In echocardiography; in addition to conventional echocardiographic measurements, end-systolic EATT was measured from right ventricular free wall. In electrocardiogram; Pd, QTd, QTcd and Tp-e interval durations, as well as Tp-e/QT and Tp-e/QTc ratios were calculated. Correlation values between EATT and electrocardiographic parameters were also noted. Results Mean age of the patient group was determined to be 12.43 ± 3.04 years and that of the control group was determined to be 12.08 ± 2.56 years. There was no significant difference between the groups in regard to age, gender, body weight, height and body mass index. In the patient group; EATT, Pd, QTd, QTcd and Tp-e interval were determined to be significantly higher compared to the control group. In the patient group, no significant correlation was determined between EATT and Pd, QTd, QTcd and Tp-e. However, when both patient and control groups were evaluated together, a statistically significant positive correlation was determined between EATT and Pd, QTd, QTcd and Tp-e. Conclusions In children with T1DM, an increase in epicardial adipose tissue thickness and in risk of cardiac arrhythmias has been demonstrated. To reveal the possible unfavorable effects of EATT on cardiac conduction system in T1DM patients needs further studies.

Insulin detemir improves glycemic control and reduces hypoglycemia in children with type 1 diabetes: findings from the Turkish cohort of the PREDICTIVE observational study.

BACKGROUND: Insulin detemir is a basal insulin analog designed to produce a superior pharmacokinetic profile to basal formulations of human insulin. It has shown consistently improved tolerability in comparison to neutral protamine Hagedorn (NPH) insulin in adult cohorts, but there are relatively few publications involving pediatric cohorts. METHODS: The efficacy and safety of insulin detemir in children with type 1 diabetes was assessed using data from the Turkish cohort of PREDICTIVE (a large, multinational, observational) study. The children investigated were using basal-bolus therapy involving NPH insulin or insulin glargine at baseline but were switched to insulin detemir as part of routine clinical care by their physicians. RESULTS: Twelve weeks of treatment with insulin detemir significantly reduced mean hemoglobin A1c (9.7-8.9%, p < 0.001) and mean fasting glucose [185-162 mg/dL (10.3-9 mmol/L), p < 0.01]. Fasting glucose variability was also lower after treatment with insulin detemir than previously (on either NPH or glargine, p < 0.05). The frequencies of total, major and nocturnal hypoglycemic events were significantly reduced with insulin detemir relative to baseline, with an estimated mean of 6.89 fewer events/patient/yr overall (p < 0.001) and 2.6 fewer nocturnal events/patient/yr (p < 0.01). Weight and insulin dose remained relatively unchanged. CONCLUSIONS: Twelve weeks of treatment with insulin detemir improved glycemic control and reduced hypoglycemia in children with type 1 diabetes. This improved tolerability might allow further dose titration and therefore additional improvements in glucose control.

Treatment with human chorionic gonadotropin induces left ventricular mass in cryptorchid boys.

AIM: To examine the effects of human chorionic gonadotropin therapy on left ventricular mass index in boys with cryptorchidism. Cryptorchidism is the most frequent anomaly of male genitalia. PATIENTS AND METHOD: Thirty consecutive cryptorchid boys (mean age 4.8 +/- 3.2 years, range 1-8 years) undergoing human chorionic gonadotropin (hCG) therapy and 30 healthy controls were enrolled in the study. The patient group received hCG by intramuscular injection twice weekly for 5 weeks. At the end of the therapy, echocardiographic measures were reevaluated. The results of left ventricular mass were indexed to body surface area before and after therapy. RESULTS: Our results showed that cryptorchid boys undergoing hCG therapy had significantly higher left ventricular mass index than healthy controls at the end of therapy (p < 0.001). Serum total testosterone levels significantly increased in the patient group and positively correlated with left ventricular mass index (r = 0.48, p = 0.021). CONCLUSION: We demonstrated that hCG treatment for cryptorchidism caused a significant increase in left ventricular mass due to high testosterone levels. We conclude that hCG therapy may not be safe for the cardiovascular system in boys with cryptorchidism.

Clinical and Laboratory Characteristics of Hyperprolactinemia in Children and Adolescents: National Survey

Objective: We aimed to report the characteristics at admission, diagnosis, treatment, and follow-up of cases of pediatric hyperprolactinemia in a large multicenter study. Methods: We reviewed the records of 233 hyperprolactinemic patients, under 18 years of age, who were followed by different centers. The patients were divided as having microadenomas, macroadenomas, drug-induced hyperprolactinemia and idiopathic hyperprolactinemia. Complaints of the patients, their mode of treatment (medication and/or surgery) and outcomes were evaluated in detail. Results: The mean age of the patients with hyperprolactinemia was 14.5 years, and 88.4% were females. In terms of etiology, microadenomas were observed in 32.6%, macroadenomas in 27%, idiopathic hyperprolactinemia in 22.7% and drug-induced hyperprolactinemia in 6.4%. Other causes of hyperprolactinemia were defined in 11.3%. Common complaints in females (n=206) were sorted into menstrual irregularities, headaches, galactorrhea, primary or secondary amenorrhea and weight gain, whereas headache, gynecomastia, short stature and blurred vision were common in males (n=27). Median prolactin levels were 93.15 ng/mL, 241.8 ng/mL, 74.5 ng/mL, 93.2 ng/mL, and 69 ng/mL for microadenomas, macroadenomas, idiopathic hyperprolactinemia, drug-induced hyperprolactinemia, and other causes of hyperprolactinemia, respectively. Of 172 patients with hyperprolactinemia, 77.3% were treated with cabergoline and 13.4% with bromocriptine. 20.1% of the patients with pituitary adenomas underwent pituitary surgery. Conclusion: We present the largest cohort of children and adolescents with hyperprolactinemia in the literature to date. Hyperprolactinemia is more common in females and cabergoline is highly effective and practical to use in adolescents, due to its biweekly dosing. Indications for surgery in pediatric cases need to be revised.

Extensive brown tumors caused by parathyroid adenoma in an adolescent patient.

Primary hyperparathyroidism is a rare endocrine disease in children and young adults. The early detection and treatment of primary hyperparathyroidism led to a marked decrease in classical bone and renal manifestations of the disease. Osteitis fibrosa cystica and brown tumors have become extremely rare clinical entities. Moreover, the skeletal involvement in primary hyperparathyroidism secondary to parathyroid adenoma is extremely rare. We report on an adolescent girl with multiple brown tumors and a history of recurrent fractures as the manifestation of primary hyperparathyroidism associated with a parathyroid adenoma. The patient's clinical presentation mimicked parathyroid carcinoma. She had a large tumor associated with marked elevation in the parathyroid hormone and serum calcium levels. Skeletal manifestations were also atypical for benign primary hyperparathyroidism, with widespread brown tumors in the patient.

Hypokalemic rhabdomyolysis in a child with 11-hydroxylase deficiency.

Myopathy is a well-recognized complication of persistent hypokalemia. Although hypokalemic myopathy may be due to divers diseases or to drug administration, hypokalemic rhabdomyolysis as a complication of under-treated 11-hydroxylase deficiency has not previously been described in the literature. We describe a 10-year-old boy with under-treated 11-hydroxylase deficiency who developed rhabdomyolysis following severe hypokalemia. Patients with under-treated 11-hydroxylase deficiency may present with hypokalemia in association with muscle weakness; if serum potassium is markedly low, rhabdomyolysis may occur. Hypokalemia-induced rhabdomyolysis should be carefully followed.

Use of metformin in obese adolescents with hyperinsulinemia: a 6-month, randomized, double-blind, placebo-controlled clinical trial.

AIM: To determine whether metformin treatment for 6 months is effective in reducing body weight and hyperinsulinemia and also ameliorating insulin sensitivity indices in obese adolescents with hyperinsulinemia. METHODS: One hundred and twenty adolescents (age range 9-17 years) with BMI >95th percentile for age and sex were included (metformin group, n = 90 [45 females, 45 males]; placebo group, n = 30 [15 females, 15 males]). The groups received 500 mg metformin (n = 90) or placebo (n = 30) twice daily for 6 months, plus individually tailored diet, exercise and behavioral therapy. Hyperinsulinism and insulin sensitivity indices were defined from fasting samples. Oral glucose tolerance tests were performed before and after treatment. RESULTS: Before treatment, there were no significant differences between the metformin group and control group in terms of anthropometric data and metabolic parameters. After metformin, there was a significant decline in body mass index (from 28.5 +/- 3.4 to 26.7 +/- 4 kg/m2, p < 0.001), fasting insulin (from 19.2 +/- 10.4 to 11.1 +/- 6.1 microU/ml, p < 0.001) and 120 min insulin levels (from 103.7 +/- 73.8 to 49.8 +/- 30.9 microU/ml, p < 0.001). FGIR increased significantly from 6.26 +/- 3.0 to 12.5 +/- 10.6 (p < 0.001) and HOMA-IR was reduced from 4.95 +/- 3.34 to 2.6 +/- 1.6 (p < 0.001) after treatment. QUICKI significantly increased from 031 +/- 0.02 to 034 +/- 0.03 (p < 0.001) in the metformin group. Moreover, in comparison of changes in insulin sensitivity indices between the metformin treated and control groups, the metformin treated group showed significantly improved metabolic control at the end of the study. CONCLUSION: These data suggest that metformin treatment is effective in reducing insulin resistance and also ameliorating metabolic complications of insulin resistance syndrome in obese adolescents with hyperinsulinemia.