Anna Majcher

Relation of Fat-Mass and Obesity-Associated Gene Polymorphism to Fat Mass Content and Body Mass Index in Obese Children

Fat mass content, fat distribution, and fat-mass and obesity associated (FTO) gene have been reported among a broad spectrum of genetic variation connected with body weight. The aim of our study was to investigate whether the T/A rs9939609 polymorphism of the FTO gene may influence obesity and metabolic indices in children. A 160 children were examined (136 obese and 24 non-obese). The anthropometric measurements and calculations included: height, weight, waist and hip circumference, sum of the thickness of 3 and 10 skin folds, % of fat content, % FAT- BIA , % LBM-BIA. BMI, SDS of BMI, WHR, and WHtR. Fasting plasma total cholesterol (TC), HDL and LDL-cholesterol, triglycerides (TG), oral glucose tolerance test (OGTT), and HOMA-IR were analyzed and the blood pressure were measured. The rs9939609 polymorphism of FTO gene was genotyped by allele-specific real-time polymerase chain- reaction (RT-PCR). We found that the mean concentrations of TC, TG, LDLC, and HOMA-IR were significantly higher, and HDL was lower in the obese than in non-obese children. The presence of TT, but not AA alleles, related to the percentage of fat content, BMI, and z-score of BMI. None of the other anthropometric indices did differ between the children with gene polymorphism and wild homozygous. In conclusion, rs9939609 polymorphism in the fat-mass and obesity-associated gene is associated with BMI and the percent of fat content in children.

Cardiovascular Risk Factors in Obese Children and Adolescents

The aim of the study was to analyze cardiometabolic risk factors andcarotid intima-media thickness (IMT) in obese children. We studied 122 obese children fulfilling the criteria of the International Obesity Task Force and 58 non-obese children. Anthropometric parameters, blood pressure, lipid profile, C-reactive protein, and adiponectin were assessed in all children. Glucose and insulin during the oral glucose tolerance test were assessed in obese children. The IMT was determined using ultrasound B-mode imaging in 81 obese and 32 non-obese children. We found that obese children had significantly higher levels of lipid andother non-lipid atherogenic indicators, but lower levels of adiponectin compared with non-obese children. The difference in the mean carotid IMT was insignificant in the two groups. Taking the combined groups, the level of adiponectin correlated negatively with body mass index and lipid atherogenic indicators. The IMT strongly correlated with systolic blood pressure in obese children. In the children fulfilling the criteria of metabolic syndrome, 17 out of the 84 obese children older than 10 years of age, IMT was greater than in those who did not fulfil these criteria. We conclude that the coexistence of abdominal obesity with abnormal lipid profile and hypertension leads to the early development of atherosclerosis accompanied by increased carotid intima-media thickness. Obesity initiates the atherosclerotic processes in early childhood.

Thyroid Function in Obese Children and Adolescents and Its Association with Anthropometric and Metabolic Parameters

Fat accumulation leads to dysfunction of hypothalamic-pituitary-thyroid axis and to changes in thyroid function. A higher serum level of thyroid stimulating hormone (TSH), with normal levels of thyroid hormones, suggesting subclinical hypothyroidism, is often found in obese individuals. The influence on lipid and glucose metabolism of thyroid dysfunction in obese patients remains unclear. This retrospective study encompassed 110 obese children and 38 healthy non-obese children aged 5-18. Anthropometric measurements, including bioelectrical impedance, were taken in all children. Fasting TSH, fT4, glucose, lipid profile, and a glucose tolerance test in case of the obese individuals, were evaluated. The obese children demonstrated a significantly higher mean concentration of TSH compared with their peers with proper body weight: 2.1 ± 1.0 μIU/ml vs. 1.5 ± 0.6 μIU/ml, p = 0.001. The fT4 was not different between the two groups. In the obese children, TSH correlated with body mass index (BMI) and waist circumference after controlling for age and gender. A multivariate regression analysis showed a relationship of TSH with total cholesterol, LDL cholesterol, triglycerides, and non-HDL after adjusting for BMI. None of these relationships were revealed for fT4. The level of TSH correlated with the degree of abdominal obesity. We conclude that the serum TSH concentration, even remaining within the norm, could adversely affect the lipid profile, irrespective of obesity.

Association of adiponectin gene G276T polymorphism with atherogenic indicators in obese children.

Adiponectin plays a protective role against atherosclerosis. Genetic investigation has revealed that G276T adiponectin gene polymorphism is related to adiponectin concentration and metabolic disturbances. The aim of the present study was to investigate the association of adiponectin gene G276T polymorphism with indices of atherosclerosis in obese children. We examined 159 children (125 obese and 34 non-obese). G276T of adiponectin gene polymorphism was identified using a PCR-RFLP method. The intima media thickness (IMT) was evaluated in 82 patients. In all children, the anthropometric indices, fasting plasma total cholesterol (TC), HDL and LDL cholesterol, triglycerydes (TG), C-reactive protein (CRP), and adiponectin were measured. Oral glucose tolerance test (OGTT) also was performed. We found that the obese patients presented with higher values of atherogenic indicators than the non-obese patients. The indicators positively correlated with CRP and lipid concentrations. Ninety one percent of obese children presented with elevated IMT which correlated with CRP. The children with GG genotype (GG + GT allele) had lower values of BMI, TC, and TG but higher adiponectin concentrations. The mean level of adiponectin was statistically decreased in the compared with the homozygous TT children. The other anthropometric and atherogenic indicators did not differ between these two sets of obese children. We conclude that adiponectin concentrations were decreased in children with polymorphism G276T in adiponectin gene. The study, however, failed to show significant associations between carotid IMT, lipid markers, blood pressure, or HOMA-IR in obese children.

Body Mass Disorders in Healthy Short Children and in Children with Growth Hormone Deficiency

The aim of the study was to determine the degree of adiposity and the incidence of body mass disorders, including abdominal obesity, in healthy short children and children with growth hormone deficiency. The study included 134 short children (height < 10th percentile) aged 7-15. In this cohort there were 63 (31 boys and 32 girls) children without diagnosed hormonal disorders and 71 patients (35 boys and 36 girls) with growth hormone deficiency. Basic somatic features were assessed and the study participants were categorized according to the percentage of body fat (%FAT), body mass index (BMI), and waist-to-height ratio (WHtR). We found that there were no significant differences in %FAT and the incidence of body weight disorders depending on gender or diagnosis. %FAT deficit was observed in 12-21% of the participants and underweight in almost every fourth child. Overweight involved 3-14% of the participants and obesity was diagnosed in isolated cases (0-3%); both were considerably lower compared to the estimates based on %FAT. Using the cut-off points of WHtR, abdominal adiposity was observed in 3-15% of the participants. In conclusion, quite a large number of short children (between 25 and 50%) are characterized by abnormal body fat or body mass index values. The results indicate a limited usefulness of BMI in evaluating the incidence of overweight and obesity in children characterized by a height deficit.

The relationship between alkaline phosphatase and bone alkaline phosphatase activity and the growth hormone/insulin-like growth factor-1 axis and vitamin D status in children with growth hormone deficiency

The relationships between bone turnover, the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and vitamin D are complex, but still not fully explained. The GH/IGF-1 axis and vitamin D can mutually modulate each others metabolism and influence the activation of cell proliferation, maturation, and mineralization as well as bone resorption. The aim of this study was to evaluate the reciprocal associations between bone formation markers [alkaline phosphatase (ALP), bone alkaline phosphatase (BALP)], the GH/IGF-1 axis and 25-hydroxyvitamin D [25(OH)D] in children with growth hormone deficiency at baseline and during recombinant human growth hormone (rhGH) therapy. ALP, BALP, 25(OH)D and IGF-1 levels were evaluated in 53 patients included in this prospective three-year study. ALP, BALP and IGF-1 increased during rhGH therapy. Baseline ALP activity correlated positively with baseline height velocity (HV). ALP and BALP activity at 12 months correlated positively with HV in the first year of therapy. We found positive correlations between ALP and IGF-1 at baseline and during the first year of therapy, between BALP activity at 12 months and rhGH dose in the first year of therapy, and between doses of cholecalciferol in the first year of rhGH therapy and early changes in BALP activity during rhGH therapy. Our results indicate that vitamin D supplementation enhances the effect of rhGH on bone formation process, which could improve the effects of rhGH therapy. ALP and BALP activity are useful in the early prediction of the effects of rhGH therapy, but their utility as long-term predictors seemed insufficient.

Ocena użyteczności wskaźnika nie-HDL w otyłości brzusznej u dzieci i młodzieży ☆ ☆☆

Streszczenie Wstep Wskaźnik nie-HDL jest rekomendowany przez NCEP ATP III (2005), jego wartośc ściśle koreluje ze stezeniem apo B i odzwierciedla stezenie wszystkich aterogennych lipoprotein. Wylicza sie go odejmując od cholesterolu calkowitego cholesterol lipoproteiny HDL. Jest on lepszym wskaźnikiem aterogenności niz cholesterol lipoproteiny LDL. Cel pracy Ocena uzyteczności wskaźnika nie-HDL w zaburzeniach gospodarki lipidowej u dzieci i mlodziezy z otylością prostą. Material i metody Badaniem objeto 306 dzieci i mlodziezy (♀ = 162; ♂ = 144) w wieku 7–18 lat (13,1 ± 2,7) z otylością prostą (SDS BMI ≥2). Oceniono wskaźniki antropometryczne, parametry gospodarki lipidowej i weglowodanowej. Dzieci podzielono na 2 grupy: 1) 182 (60%) pacjentow (♀ = 47%; ♂ = 53%) z podwyzszoną wartością nie-HDL (≥123 mg/dl); 2) 124 (40%) pacjentow (♀ = 62%; ♂ = 38%) z prawidlową wartością nie-HDL ( Wyniki U dzieci z nie-HDL ≥123 mg/dl stwierdzono: istotnie wyzsze średnie wartości obwodu talii (91,2 cm vs. 94,1 cm; p = 0,04), stezenia TC, LDL – Ch, TG, TC/HDL, TG/HDL oraz nizsze średnie stezenia HDL-Ch. W badaniach korelacyjnych wykazano, ze w miare wzrostu obwodu talii wzrastalo stezenie TG (r = 0,22; p = 0,001) i nie-HDL (r = 0,11; p = 0,07), a obnizalo sie stezenie HDL-Ch (r = –0,11; p = 0,09). Wzrost nie-HDL byl proporcjonalny do % naleznej masy ciala (r = 0,16; p = 0,01) i % FAT (r = 0,11; p = 0,08). Wnioski 1. W ocenie zaburzen gospodarki lipidowej obwod talii jest czulszym wskaźnikiem niz SDS BMI. 2. Wskaźnik nie-HDL jest przydatnym wskaźnikiem oceny stopnia aterogenności u dzieci otylych.

Gender-Dependent Growth and Insulin-Like Growth Factor-1 Responses to Growth Hormone Therapy in Prepubertal Growth Hormone-Deficient Children

Gender seems to be an important factor influencing the response to recombinant human growth hormone (rhGH) therapy in GH-deficient adolescents and adults. The results of studies evaluating gender-specific response to rhGH therapy in prepubertal GH-deficient children are divergent. The aim of this study was to determine the effect of gender on the growth and insulin-like growth factor-1 (IGF-1) responses in 75 prepubertal GH-deficient children during the first 2 years of rhGH therapy. There were no baseline gender differences in age, bone age, anthropometrical parameters, and IGF-1 SDS for bone age. After the initiation of rhGH therapy, there were no gender-specific differences concerning the reduction of height deficit. Serum IGF-1 levels were higher in the prepubertal GH-deficient girls than in the age-matched boys, but the difference was not significant when expressed as IGF-1 SDS for bone age. The increase in IGF-1 SDS for bone age was significantly greater in girls versus boys after the first 6 months of therapy, comparable between girls and boys after the first year of therapy, and tended to be higher in boys after the second year of therapy. In conclusion, prepubertal GH-deficient girls and boys do not differ significantly in growth response in the first 2 years of rhGH therapy.

The pre-treatment characteristics and evaluation of the effects of recombinant human growth hormone therapy in children with growth hormone deficiency and celiac disease or inflammatory bowel disease

The aim of the study was to investigate the coincidence of growth hormone deficiency (GHD) and celiac disease (CD) or inflammatory bowel disease (IBD) in patients referred for short stature, and to evaluate the baseline anthropometric parameters and the effectiveness of recombinant human growth hormone (rhGH) therapy in the first year in those patients (GHD+CD/IBD subgroup) in comparison to patients with GHD without CD or IBD (GHD-CD/IBD subgroup). Material and methods The study was retrospective and included 2196 short patients (height SDS [Standard Deviation Score] ≤ –1.2). 1454 patients had height SDS ≤ –2. Twenty-nine patients suffered from CD or IBD. GHD was confirmed in 419 patients with height SDS ≤ –2. The coexistence of GHD and CD or IBD was found in seven patients (GHD+CD/IBD subgroup). Results At baseline the GHD-CD/IBD subgroup did not differ significantly in chronological age, height SDS, height velocity (HV) before rhGH therapy, body weight SDS, and body mass index SDS from the GHD+CD/IBD subgroup. The improvement in height SDS within the first year of rhGH therapy was higher in the GHD+CD/IBD subgroup than in the GHD-CD/IBD subgroup and the difference was statistically significant (p<0.05). HV in the first year of rhGH therapy was also significantly higher in the GHD+CD/IBD subgroup than in the GHD-CD/IBD subgroup (p < 0.05). Conclusions In patients with chronic inflammatory disorders of the gastrointestinal tract, especially celiac disease, coexisting with GHD, rhGH therapy could be effective and should be administered together with therapy of primary gastrointestinal disease.

The associations between the growth hormone/insulin-like growth factor-1 axis, adiponectin, resistin and metabolic profile in children with growth hormone deficiency before and during growth hormone treatment

This study investigated associations between the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis, adiponectin, resistin and metabolic profile in 47 GH-deficient children before and during 12 months of GH treatment. 23 short age-matched children without growth hormone deficiency (GHD) or any genetic or chronic disorders were recruited as controls at baseline. Metabolic evaluation included measurements of adiponectin, resistin, IGF-1, total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), glucose, insulin, glycated haemoglobin (HbA1c), thyroid stimulating hormone (TSH) and free thyroxine (free T4) concentrations. The GH-deficient children had significantly higher adiponectin (p<0.05) and total cholesterol (p<0.05) levels, and a significantly lower level of resistin (p<0.05) than the controls. Resistin at 6 months of GH treatment significantly correlated with changes in height SDS in that period (r=0.35) and with the level of fasting insulin (r=0.50), the HOMA-IR (r=0.56) and the QUICKI (r=-0.53) at 12 months of therapy. Adiponectin level at 12 months of GH treatment was significantly associated with changes in HDL-C within the first 6 (r=0.73) and within 12 (r=0.56) months of therapy, while resistin significantly correlated with an increment in IGF-1 within 12 months of treatment (r=0.49) and with total-C at 12 months (r=0.56). Untreated GH-deficient children had higher adiponectin and lower resistin levels than healthy short children without GHD. Adiponectin and resistin levels did not change significantly during the first 12 months of GH therapy. Good responders to GH treatment had a tendency for higher resistin level during GH therapy, which positively correlates with the insulin resistance parameters.