Ozgur Pirgon

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.

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.

Vaspin and its correlation with insulin sensitivity indices in obese children

AIM The aim of this study was to assess the vaspin and adiponectin concentrations on markers of insulin sensitivity and obesity in pubertal obese children and adolescents. MATERIAL AND METHODS Plasma vaspin and adiponectin level and its relationships with body mass index standard deviation score (BMI-SDS), insulin sensitivity and lipids were analyzed in 33 pubertal obese children (19 girls and 14 boys) and 36 healthy control children (18 girls and 18 boys) aged 11-16 years. Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR) and fasting glucose-to-insulin ratio (FGIR). Plasma vaspin and adiponectin concentrations were determined with radioimmunoassay. RESULTS Mean vaspin levels were found significantly higher and inversely, adiponectin levels were found significantly lower in obese pubertal group than control subjects. Vaspin levels were positively correlated with BMI-SDS, triglycerides, fasting insulin and HOMA-IR and negatively correlated with adiponectin levels and FGIR. Adiponectin levels were positively correlated with high density lipoprotein-chloesterol, FGIR and negatively correlated with vaspin, BMI-SDS, fasting insulin and HOMA-IR. CONCLUSION We found higher vaspin and lower adiponectin levels in obese children and these adipokines were significantly correlated with insulin sensitivity indices in this age.

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.

Prevalence of Metabolic Syndrome in Obese Children and Adolescents using Three Different Criteria and Evaluation of Risk Factors

Objective: To compare the prevalence of the metabolic syndrome (MS) in Turkish obese children and adolescents by using three different definitions and to assess the risk factors through a retrospective evaluation of anthropometric and laboratory parameters. Methods: Sixty hundred and fourteen obese patients (307 male, 307 female; mean age: 11.3±2.5 years) were included in the study. Medical history, physical examination, anthropometric measurements, results of biochemical and hormonal assays were obtained from the hospital records. MS was diagnosed according to the modified World Health Organization (WHO), Cook and the International Diabetes Federation (IDF) consensus criteria. Results: The prevalence of MS was found to be 39%, 34% and 33% according to the modified WHO, Cook and the IDF consensus criteria, respectively. MS prevalence in patients aged 12-18 years was significantly higher than that in patients between 7 and 11 years of age (p<0.05). Pubertal patients had a significantly higher MS prevalence than the non-pubertal cases (p<0.05). MS prevalence was also significantly higher in children who had a family history of heart disease, diabetes, obesity and hypertension as well as in those who had not been breast-fed (p<0.05). Conclusion: The use of the modified WHO criteria was found to result in a slightly higher prevalence rate for MS as compared to the other criteria. The prevalence of MS in our study population was higher than that reported in most previous studies in Turkey. A positive family history, puberty and not being breastfed in infancy were shown to be significant risk factors for MS in childhood. The prevalence of MS was found to be 39%, 34% and 33% according to the modified WHO, Cook and the IDF consensus criteria, respectively. MS prevalence in patients aged 12-18 years was significantly higher than that in patients between 7 and 11 years of age (p<0.05). Pubertal patients had a significantly higher MS prevalence than the non-pubertal cases (p<0.05). MS prevalence was also significantly higher in children who had a family history of heart disease, diabetes, obesity and hypertension as well as in those who had not been breast-fed (p<0.05). Conclusion: The use of the modified WHO criteria was found to result in a slightly higher prevalence rate for MS as compared to the other criteria. The prevalence of MS in our study population was higher than that reported in most previous studies in Turkey. A positive family history, puberty and not being breastfed in infancy were shown to be significant risk factors for MS in childhood. Conflict of interest:None declared.

Evaluation of new adipocytokines and insulin resistance in adolescents with polycystic ovary syndrome

AIM The aim of this study was to investigate the relationship between four circulating adipocytokines (apelin, vaspin, visfatin, adiponectin) and markers of insulin sensitivity, in the context of polycystic ovary syndrome (PCOS) in adolescents. SUBJECTS AND METHODS 48, obese, adolescent girls (mean age: 15.6±3.4 years, mean body mass index standard deviation score (BMI-SDS): 2.31±0.1), and 37 control subjects (mean age: 16.2±3 years, mean BMI-SDS: 2.17±0.05) were enrolled the study. The diagnosis of PCOS was established according to the Rotterdam criteria. Hyperinsulinism and insulin resistance was evaluated using the homeostasis model assessment (HOMA-IR) 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 (4.9±2 versus 1.4±0.7, p<0.001; 2.2±1.1 versus 0.58±0.16, p<0.001; 31.3±11.1 versus 18.5±10.7, p<0.001; respectively) were significantly elevated, and adiponectin levels (2.01±1.02 versus 12.5±6.2, p<0.001) were significantly lower in the PCOS group. Vaspin levels were higher in the PCOS group than in the control group, but the differences were not significant. Apelin and visfatin correlated positively and adiponectin correlated negatively with BMI-SDS and HOMA-IR. CONCLUSION Based on the findings of this study, apelin, visfatin and adiponectin levels can be used as specific markers for insulin sensitivity, and these adipocytokines might play a part in the pathogenesis of PCOS.

Association between insulin resistance and oxidative stress parameters in obese adolescents with non-alcoholic fatty liver disease.

Objective: Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases in children. The aim of this study was to investigate the associations of oxidative stress with insulin resistance and metabolic risk factors in obese adolescents with NAFLD. Methods: Forty-six obese adolescents (23 girls and 23 boys, mean age: 12.8±2.2 years) and 29 control subjects (15 girls and 14 boys, mean age: 12.7±2.7 years) were enrolled in the study. The obese subjects were divided into two groups (NAFLD group and non-NAFLD group) based on the elevated alanine aminotransferase levels (>30 IU/L) and the presence or absence of liver steatosis detected by ultrasonography. Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR) from fasting samples. Plasma total antioxidant status (TAS) and total oxidant status (TOS) level measurements (REL Assay Diagnostics) were done in all participants. The ratio of TOS to TAS was regarded as an oxidative stress index (OSI), an indicator of the degree of OS. Results: Fasting insulin levels and HOMA-IR values in the NAFLD group were significantly higher than in the non-NAFLD and control groups. TAS measurements were decreased in both obese groups (NAFLD and non-NAFLD) in comparison with the control group. TOS and OSI measurements were higher in the NAFLD group than in the non-NAFLD and control groups. OSI was positively correlated with fasting insulin (r=0.67, p=0.01) and HOMA-IR (r=0.71, p=0.02) in the NAFLD obese group. Conclusions: In this cross-sectional study, elevated OS markers in obese adolescents with NAFLD were associated with insulin resistance. This data suggest that an antioxidant therapy might have a potential for treating NAFLD associated with insulin resistance. Conflict of interest:None declared.

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.

Left Ventricular Function by Echocardiography, Tissue Doppler Imaging, and Carotid Intima-Media Thickness in Obese Adolescents With Nonalcoholic Fatty Liver Disease

The aims of this study were to evaluate left ventricular (LV) systolic and diastolic function in obese adolescents with nonalcoholic fatty liver disease (NAFLD) using conventional echocardiography and pulsed-wave tissue Doppler imaging and to investigate the relations between LV function and carotid intima-media thickness (CIMT). LV remodeling, tissue Doppler-derived LV velocities, and cardiovascular risk profiles in obese adolescents with NAFLD were also studied. One hundred eighty obese adolescents and 68 healthy controls were enrolled in the study. LV end-diastolic and end-systolic and left atrial diameters and LV mass were higher in the 2 obese groups compared with controls. By pulsed-wave Doppler echocardiography and pulsed-wave tissue Doppler imaging, the NAFLD group had normal LV systolic function, impaired diastolic function, and altered global systolic and diastolic myocardial performance. In patients with NAFLD, LV mass was positively correlated with homeostasis model assessment of insulin resistance and serum alanine aminotransferase. CIMT was positively correlated with homeostasis model assessment of insulin resistance, alanine aminotransferase, and LV mass. By multiple stepwise regression analysis, alanine aminotransferase (β = 0.124, p = 0.026), homeostasis model assessment of insulin resistance (β = 0.243, p = 0.0001), LV mass (β = 0.874, p = 0.0001) were independent parameters associated with increased CIMT. In conclusion, insulin resistance has a significant independent impact on CIMT and LV remodeling in the absence of diabetes in patients with NAFLD. Pulsed-wave tissue Doppler imaging is suggested to detect LV dysfunction at an earlier stage in obese adolescents with NAFLD for careful monitoring of cardiovascular risk.

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.