Mehmet Emre Atabek

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.

Oxidative stress in childhood obesity.

OBJECTIVE To measure products of free radical damage in childhood obesity. METHODS Plasma free radicals were assayed in 24 children with exogenous obesity and 24 non-obese healthy controls. A new colorimetric method was used that measures the generation of peroxy radicals (D-Roms), first products of the reaction between free radicals and oxygen. RESULTS D-Roms levels were higher in the obese children than in the non-obese group (33.3+/-10.1 mg% of H2O2 vs 22.8+/-2.8 mg% of H2O2; p <0.001). Moreover, D-Roms levels were higher in children with hyperlipidemia than in children with normolipidemia (49.6+/-3.1 mg% of H2O2 vs 27.8+/-3.2 mg% of H2O2; p <0.001). D-Roms level was positively correlated with waist-hip ratio, serum total cholesterol, serum triglycerides, serum low-density lipoprotein-cholesterol, systolic blood pressure, diastolic blood pressure and fasting blood glucose in obese children. In a multivariate regression model for obese children, the independent correlates for D-Roms level were systolic blood pressure (p <0.001) and serum total cholesterol (p <0.001), with the total variance explained being 82%. CONCLUSION Our study demonstrates for the first time that there was increased D-Roms levels in obese children and adolescents and suggests that increased systolic blood pressure associated with hyperlipidemia may independently contribute to increased oxidative stress in childhood obesity.

Assessment of insulin sensitivity from measurements in fasting state and during an oral glucose tolerance test in obese children.

BACKGROUND Few previous studies have examined the validity of the fasting glucose-to-insulin ratio (FGIR), homeostasis model assessment of insulin resistance (HOMA-IR) and quantitative insulin-sensitivity check index (QUICKI) in pediatric populations. OBJECTIVE To compare simple indices of insulin resistance calculated from fasting glucose and insulin levels with insulin sensitivity indices (area under the response curve [AUCinsulin], insulin sensitivity index [ISI-compositeL) determined by oral glucose tolerance testing (OGTT) in obese children. METHODS One hundred and forty-eight obese children and adolescents (86 girls and 62 boys, mean age: 10.86 +/- 3.08 years, mean body mass index (BMI): 27.7 +/- 4.2) participated in the study. OGTT was performed in all participants. After glucose and insulin measurements from OGTT, the children were divided into two groups according to the presence or absence of insulin resistance. Insulin sensitivity indices obtained from the OGTT were compared between the groups. The total plasma glucose response and insulin secretion were evaluated from the AUC estimated by the trapezoid rule. Cut-off points, and sensitivity and specificity calculations were based on insulin resistance with receiver operating characteristic curve (ROC) analysis. RESULTS The prevalence of insulin resistance, glucose intolerance and dyslipidemia was 37.1%, 24.3% and 54% in obese children, respectively. The groups consisted of 93 children without insulin resistance (54 girls and 39 boys; mean age: 10.5 +/- 3.3 years; mean BMI: 27.0 +/- 4.2) and 55 children with insulin resistance (32 girls and 23 boys; mean age: 11.4 +/- 2.5 years; mean BMI: 27.9 +/- 3.9). There were significant differences in mean FGIR (10.0 +/- 7.2 vs 5.6 +/- 2.8, p < 0.001), HOMA-IR (3.2 +/- 2.3 vs 4.9 +/- 2.3, p < 0.001) and QUICKI (0.33 +/- 0.03 vs 0.30 +/- 0.02, p < 0.001) between the groups. The cut-off points for diagnosis of insulin resistance were < 5.6 for FGIR (sensitivity 61.8, specificity 76.3), > 2.7 for HOMA-IR (sensitivity 80, specificity 59.1), and < 0.328 for QUICKI (sensitivity 80, specificity 60.2). CONCLUSIONS Indices derived from fasting samples for diagnosis of insulin sensitivity are reliable criteria in obese children and adolescents. HOMA-IR and QUICKI appeared to have similar sensitivity and specificity and to have higher sensitivity than FGIR.

Evidence for association between insulin resistance and premature carotid atherosclerosis in childhood obesity

The present study was undertaken to determine the presence and predictors of the subclinical atherosclerosis in obese children. Fifty obese children [mean age: 11.7 ± 2.5 y, mean body mass index (BMI): 28.2 ± 4.0 kg/m2] and 50 age- and sex-matched healthy nonobese controls (mean age: 11.4 ± 3.73 y, mean BMI: 17.6 ± 3.0 kg/m2) were enrolled in the present study. Oral glucose tolerance test was performed to all obese subjects. Common carotid artery intima-media thickness (IMT) was measured by high-resolution B-mode ultrasonography. Carotid artery IMT was significantly increased (0.0476 ± 0.007 versus 0.033 ± 0.011 cm; p < 0.001) in the obese group. There were significant relations between carotid artery IMT and insulin sensitivity indexes derived from fasting samples (fasting glucose to insulin ratio (FGIR; p = 0.004, r = –0.404), quantitative insulin-sensitivity check index (QUICK-I; p = 0.002, r = –0.401) and homeostasis model assessment of insulin resistance (HOMA-IR; p = 0.034, r = 0.300) in the obese group. In a multivariate regression model, QUICK-I emerged as independent correlates for mean IMT in obese children with the total variance explained being 20.7% (β = –0.58, p < 0.001). We concluded that insulin resistance is an independent risk factor for increased carotid artery IMT in obese children.

Association Between Nonalcoholic Fatty Liver Disease and Cardiovascular Risk in Obese Children and Adolescents

BACKGROUND The recent rise in the prevalence of obesity likely explains nonalcoholic fatty liver disease (NAFLD) epidemic worldwide. We evaluated cardiac functions, cardiovascular risk, and associated parameters with grades of NAFLD in obese children. METHODS Four hundred obese children were enrolled in the study. Obese children with NAFLD were classified in 2 subgroups according to ultrasonographic visualizing. Ninety-three obese children with NAFLD (mean age 11.73 ± 2.72 years in group 2 and 12.69 ± 2.61 years in group 3) were compared with 307 age- and sex-matched non-NAFLD obese children and 150 control subjects. Laboratory parameters were measured during the fasting state. Pulsed and tissue Doppler echocardiography were performed. Intima-media (IMT) and epicardial adipose tissue (EAT) thicknesses were measured. RESULTS NAFLD groups had a significantly higher body mass index (29.15 ± 3.42 and 30.46 ± 4.60; P < 0.001), total adipose tissue mass (37.95 ± 4.46% and 46.57 ± 6.45%; P < 0.001), higher insulin, alanine aminotransferase, and aspartate aminotransferase levels. Increased end-systolic thickness of the interventricular septum (P < 0.001), larger left ventricular mass (P < 0.003) and index (P < 0.003) were found in NAFLD groups. Children with NAFLD had higher Tei index values. Also, carotid artery IMT and EAT thickness were significantly higher in obese children. Waist and hip circumference, total cholesterol level, total adipose tissue mass, and interventricular septum were statistically different in NAFLD groups. CONCLUSIONS Children with NAFLD had mildly altered left and right ventricular functions and all obese children had increased IMT and EAT thickness. Also, grade of liver steatosis was positively correlated with total adipose tissue mass and interventricular septum systolic thickness.

The association of plasma homocysteine levels with serum leptin and apolipoprotein B levels in childhood obesity.

BACKGROUND An elevated plasma total homocysteine (tHcy) level has recently been established as an independent risk factor for thrombosis and vascular disease. However, the relationship between hyperhomocysteinemia and cardiovascular disease and obesity remains controversial. The aim of the study was to investigate a possible relationship between plasma tHcy levels and measures of childhood obesity. SUBJECTS AND METHODS Forty children and adolescents with exogenous obesity and 20 non-obese subjects in an age-and sex-matched control group were investigated. Fasting samples were collected for plasma tHcy, serum insulin, leptin, vitamin B12, folate, creatinine and lipid parameters. Anthropometric characteristics and body compositions were assessed in both groups. RESULTS The obese patients had significantly higher tHcy levels than the non-obese controls (14.3±11.8 μmol/L vs 8.7±5.9 μmol/L; P=0.017). In both groups, plasma tHcy was positively related to serum leptin, but serum apolipoprotein B (apo B) levels were positively related to plasma tHcy levels only in obese patients. CONCLUSIONS Our study demonstrates for the first time that leptin and apo B are main correlates of tHcy in obese children and adolescents and suggests that hyperleptinemia and increased apo B may contribute to impairment of tHcy metabolism in childhood obesity.

Assessment of abnormal glucose homeostasis and insulin resistance in Turkish obese children and adolescents

Background:  The worldwide increase in the prevalence of childhood obesity is reaching epidemic proportions and is associated with a dramatic rise in cases of type 2 diabetes. We determined the prevalence of impaired glucose regulation and insulin resistance in obese children and adolescents.

Evidence for an Association Between Type 1 Diabetes and Premature Carotid Atherosclerosis in Childhood

Acute phase proteins have been suggested to be increased in patients with type 1 diabetes. The aim of this study was to evaluate the relationship between serum C-reactive protein (CRP) and intima-media thickness (IMT) and functions of the common carotid artery (CCA) in children and adolescents with type 1 diabetes. Serum CRP levels were measured in 65 children and adolescents with diabetes (33 girls and 32 boys; mean age, 12.7 ± 3.8 years; range, 7–18; duration of diabetes, 6.9 ± 3.6 years). Age and diabetes duration, as well as major cardiovascular risk factors including anthropometric and metabolic parameters, were matched between girls and boys. The relations of serum CRP levels to CCA structure and functions were measured by ultrasonography as IMT, cross-sectional compliance, cross-sectional distensibility, diastolic wall stress (DWS), and incremental elastic modulus (IEM). There was no significant difference for serum CRP levels between girls and boys (3.7 ± 1.3 vs 3.2 ± 0.4 mg/L; p > 0.05). CRP was positively correlated with IMT (r = 0.49, p = 0.001), IEM (r = 0.24, p = 0.05), DWS (r = 0.58, p < 0.001), and body mass index (BMI) (r = 0.28, p = 0.05). In a multivariate regression model, we included CRP and metabolic and anthropometric parameters such as duration of diabetes, HbA1c, BMI, waist:hip ratio, age, and systolic and diastolic blood pressure as independent variables in the model for CCA structure and functions. CRP emerged as an independent correlation for mean IMT (β = 0.51, p < 0.001) and DWS (β = 0.61, p < 0.001). According to our findings, CRP was associated with CCA structure and functions in children and adolescents with type 1 diabetes.

Oral alendronate therapy for severe vitamin D intoxication of the infant with nephrocalcinosis.

Vitamin D intoxication is a well-known cause of hypercalcemia in children. We report here the use of oral alendronate for the treatment of hypercalcemia due to vitamin D intoxication in a 7 month-old infant with nephrocalcinosis. The serum calcium levels were normalized without complications. Oral alendronate therapy may be safely used in hypercalcemia due to vitamin. D intoxication in pediatric patients with nephrocalcinosis resistant to hydration, diuretics or corticosteroids.

Relation of serum leptin and insulin-like growth factor-1 levels to intima-media thickness and functions of common carotid artery in children and adolescents with type 1 diabetes.

Background and aim: Leptin and insulin‐like growth factor‐1 (IGF‐1) have been suggested to be involved in the pathogenesis of atherosclerosis. The aim of this study was to evaluate the relationship between serum leptin, IGF‐1 and intima‐media thickness (IMT) and functions of common carotid artery (CCA) in children and adolescent patients with type 1 diabetes. Material and methods: Serum leptin and IGF‐1 levels were measured in 45 diabetic patients (23 girls and 22 boys). Age, diabetes duration as well as major cardiovascular risk factors, including anthropometric and metabolic parameters, were matched between girls and boys. The relation of serum leptin and IGF‐1 levels to CCA structure and functions were measured by ultrasonography as IMT, cross‐sectional compliance (CSC), cross‐sectional distensibility (CSD), diastolic wall stress (DWS) and incremental elastic modulus (IEM). Results: Serum leptin levels of diabetic girls were higher than those in the boys (21.8 ± 14.5 μg/1 vs 8.9 ± 10.6 μ.g/1, p= 0.002). However, the difference for serum IGF‐1 levels was not significant between diabetic girls and boys (240.7 ± 96.8 μg/ml vs 234.7 ± 93.2 ng/ml; p < 0.05). In all subjects, leptin levels were correlated with CSC (p= 0.04), CSD (p= 0.04) and IEM (p= 0.01), and IGF‐I levels were only correlated with CSC (p= 0.01). Leptin did not show any correlation with ultrasonographic measurements in both girls and boys separately. IGF‐1 was correlated with CSC (p= 0.001), CSD (p= 0.002) and IEM (p > 0.001) in boys but not in girls. In a multivariate regression model, IGF‐1 emerged as independent correlates for mean CSD and IEM in boys but not in girls.