Sleep Disorders and Obesity in Childhood: A New Component in Solving Obesity.

Sleep disorders have been widely reported in obese individuals. Previous studies have shown that together with an increase in obesity prevalence, so does sleep duration in children and adolescents decrease. By contributing to energy imbalances, hormonal changes occurring with reduced sleep quality may cause weight gain and obesity. Current evidence shows that short sleep duration has effects on body weight and weight gain. Compared to individuals sleeping for a normal duration, insulin sensitivity is lower in those who sleep less. Lack of sleep increases the desire for food and has a direct effect on physical activity. Further studies are required to determine the contribution of sufficient sleep to obesity treatment.

Correlation of P-wave dispersion with insulin sensitivity in obese adolescents.

BACKGROUND: P-wave dispersion is a new and simple electrocardiographic marker that has been reported to be associated with inhomogeneous and discontinuous propagation of sinus impulses. In the present study, we evaluated P-wave dispersion in obese adolescents and investigated the relationship between P-wave dispersion, cardiovascular risk factors, and echocardiographic parameters. METHODS: We carried out a case-control study comparing 150 obese adolescents and 50 healthy controls. Maximum and minimum P-wave durations were measured using a 12-lead surface electrocardiogram, and P-wave dispersion was calculated as the difference between these two measures. Echocardiographic examination was also performed for each subject. Multivariate linear regression analysis with stepwise variable selection was used to evaluate parameters associated with increased P-wave dispersion in obese subjects. RESULTS: Maximum P-wave duration and P-wave dispersion were significantly higher in obese adolescents than control subjects (143±19 ms versus 117±20 ms and 49±15 ms versus 29±9 ms, p<0.0001 for both). P-wave dispersion was positively correlated with body mass index, waist and hip circumferences, systolic and diastolic blood pressures, total cholesterol, serum levels of low-density lipoprotein cholesterol, triglycerides, glucose, and insulin, homoeostasis model assessment for insulin resistance score, left ventricular mass, and left atrial dimension. P-wave dispersion was negatively correlated with high-density lipoprotein cholesterol levels. By multiple stepwise regression analysis, left atrial dimension (ß: 0.252, p=0.008) and homoeostasis model assessment for insulin resistance (ß: 0.205; p=0.009) were independently associated with increased P-wave dispersion in obese adolescents. CONCLUSIONS: Insulin resistance is a significant, independent predictor of P-wave dispersion in obese adolescents.

Assessment of ovarian reserve in euthyroid adolescents with Hashimoto thyroiditis.

AIM: We aimed to investigate the ovarian function and reserve in euthyroid adolescents (TSH < 2.5 mIU/L) diagnosed with Hashimoto thyroiditis (HT). METHODS: This case-control study included 30 adolescent girls (mean age 15.1 ± 1.4 years) newly diagnosed as HT with presence of high thyroid antibodies with gland heterogeneity in ultrasound and age-matched 30 healthy female subjects. Anti-ovarian antibody (AOAb), LH/FSH ratio, estradiol, anti-mullerian hormone (AMH), inhibin-B, total testosterone, antral follicle count, ovarian volumes and uterine length were measured. The clinical, laboratory, and ultrasound data of the HT and control groups were compared. RESULTS: There were no significant differences between the girls with HT and healthy controls in relation to LH/FSH ratio, estradiol and inhibin-B levels. AOAb (p = 0.02), AMH (p = 0.007) and total testosterone levels were higher in HT group than the control group (p = 0.03). AOAb level was found to be positively correlated with LH/FSH ratio (p = 0.03), AMH (p = 0.01) and inhibin-B (p < 0.001) in HT group. CONCLUSION: This study demonstrated that the adolescent girls diagnosed with autoimmune thyroiditis had normal ovarian reserve based on measurements of AMH, inhibin B, FSH, LH/FSH ratio, estradiol and antral follicle counts.

Effects of Inhaled Corticosteroids on the Growth Plates of Infant Rats.

The most significant adverse effect of inhaled steroid administration in children is suppression of hypothalamic-pituitary-adrenal axis responsiveness and suppression of growth. This study evaluates the effects of inhaled corticosteroids on the growth plates in infant rats. Rats aged 10 days were divided into five groups. Low and high doses of budesonide and fluticasone propionate (50-200-250 mcg/day) were applied with a modified spacer for 10 days. The rat's tibias were then removed and the effects of the steroids on the growth plates were compared. Growth cartilage chondrocyte proliferation and apoptosis rates; IGF-1 and glucocorticoid receptor levels; and resting, proliferative, hypertrophic, and total zone (TZ) measurements were compared using immunohistochemical-staining methods. With high doses of fluticasone, growth plates were affected much more than with high doses of budesonide (p = 0.01). Fluticasone, particularly at a dose of 250 mcg, inhibited the growth plate with an intensive negative impact on all parameters.

Subclinical hypothyroidism as a risk factor for the development of cardiovascular disease in obese adolescents with nonalcoholic fatty liver disease.

No data are available on the relationship between subclinical hypothyroidism and risk factors for the development of cardiovascular disease in obese adolescents with nonalcoholic fatty liver disease (NAFLD). This study aimed to determine whether an association exists between subclinical hypothyroidism and risk factors for the development of cardiovascular disease in obese adolescents with NAFLD. The study enrolled 111 obese adolescents and 42 lean subjects. The obese subjects were divided into two subgroups based on the presence or absence of fatty liver with high transaminases: a NAFLD group and a non-NAFLD group. Subclinical hypothyroidism was defined as a thyroid-stimulating hormone (TSH) level higher than 4 mIU/l and a normal free-thyroxine level (0.6-1.8 ng/dl). Insulin resistance was calculated by the homeostasis model assessment (HOMA-IR). Left ventricular mass (LVM), LVM index measurements, carotid intima media thickness (IMT), and HOMA-IR values were higher in the NAFLD obese group with TSH levels higher than 4 mIU/l than in the NAFLD obese group with TSH levels lower than 4 mIU/l. Elevated TSH values in the NAFLD obese group were positively correlated with most of the metabolic and cardiovascular risk parameters such as total cholesterol (r = 0.606, p = 0.001), triglycerides (r = 0.476, p = 0.016), low-density lipoprotein cholesterol (r = 0.461, p = 0.004), insulin (r = 0.607, p = 0.001), HOMA-IR (r = 0.596, p = 0.002), carotid IMT (r = 0.894, p < 0.0001), and LVM (r = 0.563, p = 0.003). The findings demonstrated that the obese adolescents with NAFLD and subclinical hypothyroidism had a more adverse cardiovascular risk profile and a higher carotid IMT and LVM.

Low 25-hydroxyvitamin D level and adiponectin is associated with insulin sensitivity in large gestational age infants.

OBJECTIVE: To investigate the relationship between adipokines (visfatin, adiponectin) and 25-hydroxyvitamin D (25(OH)D), and markers of insulin sensitivity in large for gestational age (LGA) infants. PATIENTS AND METHODS: Forty LGA infants (25 LGA born to diabetic mothers and 15 LGA born to non-diabetic mothers) and 34 appropriate for gestational age (AGA) infants were recruited. RESULTS: FGIR, QUICK-I, adiponectin and 25(OH)D levels were significantly lower in LGA with diabetic mother group than AGA and LGA with non-diabetic mother group. HOMA-IR, fasting insulin, visfatin and parathormone (PTH) levels were significantly higher in LGA with diabetic mother group than AGA and LGA with non-diabetic mother group. CONCLUSION: Based on the findings of this study, visfatin, adiponectin and 25(OH)D levels can be used as specific markers for insulin sensitivity and may help advance new therapies for glucose intolerance spectrum.

Relationship between left ventricular mass and carotid intima media thickness in obese adolescents with non-alcoholic fatty liver disease.

BACKGROUND/AIMS: No data are available examining the relationship between carotid intima media thickness (IMT) and left ventricular mass (LVM) in obese adolescents with non-alcoholic fatty liver disease (NAFLD). Therefore, we investigated LVM and carotid IMT in obese adolescents with NAFLD. METHODS: Eighty obese adolescents and 37 lean subjects were enrolled in the study. The obese subjects were divided into two subgroups based on the presence or absence of fatty liver with high transaminases (NAFLD group and non-NAFLD group). Fasting blood samples were assayed for serum transaminases, glucose and insulin levels. Insulin resistance was calculated by the homeostasis model assessment (HOMA-IR). RESULTS: LVM measurements were higher in both NAFLD and non-NAFLD obese patients in comparison with the lean children. The NAFLD group had significantly higher LVM measurements than the non-NAFLD and lean groups. Carotid IMT was higher in both the NAFLD and non-NAFLD obese patients in comparison with the lean group. The NAFLD group had significantly higher carotid IMT measurements than the non-NAFLD and lean groups. LVM was positively correlated with HOMA-IR and serum alanine aminotransferase levels in the NAFLD obese group. Carotid IMT was positively correlated with HOMA-IR, serum alanine aminotransferase levels and LVM in the NAFLD obese group. CONCLUSIONS: We demonstrated that obese adolescents with NAFLD have increased LVM and carotid IMT and low insulin sensitivity. Obese adolescents with NAFLD and increased carotid IMT may demonstrate a more adverse cardiovascular risk profile and higher LVM. Therefore, assessment of carotid IMT, in addition to echocardiography, may assist in risk stratification in obese adolescents with NAFLD with elevated cardiovascular risk factor levels.

Correlation of insulin sensitivity with bone mineral status in obese adolescents with nonalcoholic fatty liver disease.

AIM: The aim of this study was to investigate the relationships between bone mineral density (BMD) vs insulin resistance and metabolic risk factors in obese adolescents with nonalcoholic fatty liver disease (NAFLD). PATIENTS AND METHODS: Eighty-two obese adolescents [45 girls and 37 boys, mean age: 12·3 ± 1·7 years, mean body mass index-standard deviation score (BMI-SDS): 1·9 ± 0·2] and 30 control subjects (15 girls and 15 boys, mean age: 12·3 ± 1·45 years, mean BMI-SDS: 0·5 ± 0·7) were enrolled the study. The obese subjects were divided into two groups based on the presence or absence of liver steatosis with high transaminases (NAFLD group and non-NAFLD group). Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR) from fasting samples. BMD was determined by dual-energy X-ray absorptiometry. RESULTS: Fasting insulin levels in the NAFLD group were significantly higher than in the non-NAFLD obese (32·3 ± 24·0 vs 11·02 ± 2·95 mU/l, P < 0·001) and control groups (8·4 ± 2·4 mU/l, P< 0·001). The NAFLD group had higher values of HOMA-IR than the non-NAFLD obese (7·3 ± 0·1 vs 2·3 ± 0·7, P < 0·001) and control groups (1·8 ± 0·5, P < 0·001). BMD-SDS measurements were lower in the NAFLD group than in the non-NAFLD (0·56 ± 0·3 vs 1·02 ± 0·9, P < 0·001) and control groups (0·56 ± 0·3 vs 1·37 ± 1·04, P < 0·001). BMD-SDS was positively correlated with BMI-SDS (r = 0·530, P = 0·004) and negatively correlated with HOMA-IR (r = -0·628, P = 0·017) in the NAFLD obese group. CONCLUSION: This study reports the association between BMD-SDS and insulin resistance in obese adolescents both with and without NAFLD, although the NAFLD group had a lower BMD-SDS than the non-NAFLD group. We suggest that NAFLD has a detrimental effect on bone health in adolescents, and it is correlated with increased insulin resistance.

Apelin, vaspin, visfatin and adiponectin in large for gestational age infants with insulin resistance.

OBJECTIVE: To investigate the relation of circulating four adipokines (apelin, vaspin, visfatin, adiponectin) with markers of insulin sensitivity in large for gestational age (LGA) infants. PATIENTS AND METHODS: Forty LGA infants (20 LGA born from diabetic mothers and 20 LGA born from non-diabetic mothers) and 34 appropriate for gestational age (AGA) infants were recruited. Hyperinsulinism and insulin resistance was evaluated using the homeostasis model assessment (HOMA-IR), fasting glucose-to-insulin ratio (FGIR), quantitative insulin-sensitivity check index (QUICK-I) from fasting samples. Plasma adiponectin and vaspin levels were determined by radioimmunoassay. Determination of visfatin and apelin levels was performed by enzyme immunoassay. RESULTS: HOMA-IR, apelin and visfatin levels (p<0.001, p<0.001, p<0.001, respectively) were significantly elevated and adiponectin levels, FGIR and QUICK-I values. (p<0.001, p<0.001, p<0.05, respectively) were significantly lower in the LGA group. Vaspin levels were higher in the LGA group than AGA neonates without a significance. The LGA infants with diabetic mother had significantly higher visfatin, apelin, HOMA-IR values, fasting insulin levels and significantly lower adiponectin, FGIR, QUICK-I values. Apelin and visfatin were correlated positively, and adiponectin was correlated negatively with birthweight, HOMA-IR values and fasting insulin levels. CONCLUSION: Based on the findings of this study, it is too difficult to explain relation between birthweight and these adipocytokines, but findings of high insulin, HOMA-IR, visfatin, apelin and low adiponectin levels in the LGA neonates showed that these adipocytokines can be used as a good predictor for metabolic syndrome.

Therapeutic effect of metformin and vitamin E versus prescriptive diet in obese adolescents with fatty liver.

OBJECTIVE: The aim of the study was to determine whether metformin or vitamin E treatment for six months is effective in reducing body weight, blood pressure, and also ameliorating insulin resistance, adiponectin, and tumor necrosis factor (TNF)-alpha in obese adolescents with non-alcoholic fatty liver disease (NAFLD). METHODS: Sixty-seven obese adolescents with liver steatosis (age range, 9 - 17 years) were included in the study. The metformin group received an 850-mg dose of metformin daily and the vitamin E group received 400 U vitamin E /daily, in capsule form for 6 months, plus an individually tailored diet, exercise, and behavioral therapy. RESULTS: After 6 months later, there was a significant decline in body mass index, and fasting insulin and homeostatic model assessment (HOMA) values in all three groups. Moreover, in comparingson of changes in HOMA among the groups, the metformin- treated group showed significantly improved metabolic control and insulin sensitivity (HOMA) at the end of the study. There were no significant differences for changes of adiponectin, TNF-alpha, in all three groups after 6 months study. CONCLUSION: These data suggest that metformin treatment is more effective than dietary advice and vitamin E treatment in reducing insulin resistance, and also in ameliorating metabolic parameters such as fasting insulin and lipid levels, in obese adolescents having NAFLD.

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.

Investigation of quality of life in obese adolescents: the effect of psychiatric symptoms of obese adolescent and/or mother on quality of life.

OBJECTIVES: The present study assessed the obese adolescents' health-related quality of life (HRQoL) based on both adolescent-reported and maternal-reported questionnaires to clarify adolescent-related psychiatric factors, maternal psychiatric factors, and body mass index (BMI) percentile variables that independently affect the quality of life (QoL). METHODS: A total of 190 adolescents (120 females and 70 males) were included in the study. The impact of clinical and psychiatric factors on the Pediatric Quality of Life Inventory-Child Version (PedsQL-C) scores was analyzed using hierarchical linear regression methods. RESULTS: The final models showed that only the Revised Child Anxiety and Depression Scale-Child Version major depressive disorder scores negatively predicted the physical, psychosocial, and total health scores of the PedsQL-C. The psychosocial scores of the PedsQL-P were negatively predicted by the Strengths and Difficulties Questionnaire emotional, and Conners' Parent Rating Scale-Revised-Short Form (CPRS-R-S) attention-deficit/hyperactivity disorder (ADHD) index scores. The PedsQL-P total scores were negatively predicted by the CPRS-R-S ADHD index scores. CONCLUSIONS: The findings of this study indicate that the adolescents' psychiatric symptoms and BMI percentile played a significant role in the PedsQL subscale functioning of obese adolescents compared to maternal psychiatric symptoms.

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.

Pubertal Status and Gonadal Functions in Obese Boys with Fatty Liver.

BACKGROUND: In adult studies, obese subjects with nonalcoholic fatty liver disease (NAFLD) have been shown to have poor sperm quality, and lower testosterone and luteinizing hormone levels. The aim of this study was to investigate the pubertal status and gonadal functions in obese boys with NAFLD. MATERIALS AND METHODS: The study included 119 obese and 78 nonobese age-matched adolescents. The obese boys were separated into two groups based on the presence (NAFLD group) or absence of liver steatosis with high transaminases (non-NAFLD group). The levels of serum AMH (anti-Mullerian hormone), inhibin B, gonadotropins, total testosterone, lipids, high-sensitivity C-reactive protein, fasting glucose, insulin levels, and aortic intima media thickness were measured in all subjects. RESULTS: Of the total 197 children, 174 had reached puberty. There were no significant differences between the groups in respect of testicular sizes and the prevalence of pubertal status among the groups (84.3% of NAFLD vs. 70.6% of non-NAFLD vs. 98.7% of control subjects). No significant differences were found in respect of gonadotropins and AMH levels. Total testosterone levels in the NAFLD group were significantly lower than those of the non-NAFLD obese group (P < 0.001) and the control group (P < 0.001). Inhibin B levels were also significantly lower in all (NAFLD and non-NAFLD) obese groups compared to the control group (P = 0.008). CONCLUSIONS: The results of the study demonstrated that diminished testosterone and inhibin B levels occur in pubertal obese boys with NAFLD. No significant differences were detected according to pubertal status, AMH levels, and testicular volumes in the age-matched groups.

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.