Éva Erhardt

Safety and efficacy of treatment with an ephedrine=caffeine mixture. The first double-blind placebo-controlled pilot study in adolescents

OBJECTIVE: The present study was performed to investigate the efficacy and safety of a caffeine/ephedrine (CE) mixture in obese adolescents.SUBJECTS: Thirty-two (m/f=16/16) obese children were included into the study. They were treated by diet (calculated daily energy requirement minus 500 kcal) and either CE or placebo (PL) for 20 weeks in a randomized double-blind placebo-controlled trial. Those weighing less than 80 kg took one tablet three times (100 mg/10 mg), whereas those weighing more than 80 kg took two tablets three times per day. There were three dropouts (girls) from the PL group. The age, weight body mass index (BMI) values (mean (range)) of the PL and CE groups were 16.0 (14.3–17.6) and 16.0 (14.2–17.7) y, 103.0 (77.2–126.4) and 104.8 (69.8–150.2) kg, 35.2 (28.3–42.3) and 36.5 (31.3–51.8) kg/m2, respectively.RESULTS: The decrease in relative body weight, BMI and body fat (measured by bioelectric impedance) was significantly (P<0.05) greater in the CE group (mean±s.d.; 14.4±10.5%, 2.9±1.9 kg/m2, 6.6±6.0 kg) than in the PL group (2.2±5.8%, 0.5±1.6 kg/m2, 0.5±2.7 kg). Relative body weight decreased by more than 5% in 81% of the CE group, out only in 31% of the PL group. Adverse events were negligible and did not differ between the CE and PL groups. Withdrawal symptoms were mild, transient and their frequency and severity were not different between the placebo and active groups.CONCLUSION: According to the present pilot study, CE can be a safe and effective compound for the treatment of obesity in adolescents.

Polyunsaturated fatty acids in plasma lipids of obese children with and without metabolic cardiovascular syndrome.

Previously we reported significantly higher values of γ-linolenic acid (GLA, 18∶3n−6), dihomo-γ-linolenic acid (DHGLA, 20∶3n−6), and arachidonic acid (20∶4n−6) in plasma lipid classes in obese children than in nonobese controls. In the present study, fatty acid composition of plasma phospholipids (PL) and sterol esters (STE) was determined by high-resolution capillary gas-liquid chromatography in obese children with an without metabolic cardiovascular syndrome [MCS: defined as simultaneous presence of (i) dyslipidemia, (ii) hyperinsulinemia, (iii) hypertension, and (iv) impaired glucose tolerance] and in nonobese controls. Fatty acid composition of PL and STE lipids did not differ between obese children without MCS and controls. Obese children with MCS exhibited significantly lower linoleic acid (LA, 18∶2n−6) values in PL (17.43 [2.36], %wt/wt, median [range from the first to the third quartile]) than obese children without MCS (19.14 [3.49]) and controls (20.28 [3.80]). In contrast, PL GLA values were significantly higher in obese children with (0.13 [0.08]) than in those without MCS (0.08 [0.04]), whereas STE GLA values were higher in obese children with MCS (1.04 [0.72]) than in controls (0.62 [0.48]). DHGLA values in PL were significantly higher in obese children with MCS (4.06 [0.74]) than in controls (2.69 [1.60]). The GLA/LA ratio was significantly higher, whereas the AA/DHGLA ratio was significantly lower in obese children with MCS than in obese children without MCS and in controls. In this study, LA metabolism was affected only in obese children with but not in those without MCS. In obese children with MCS, δ6-desaturase activity appeared to be stimulated, whereas δ5-desaturase activity appeared to be inhibited. Disturbances in LA metabolism may represent an additional health hazard within the multifaceted clinical picture of MCS.

Type 2 diabetes mellitus in European children and adolescents

AIM The aim of the study was to review the published and unpublished data on type 2 diabetes in European children in order to determine how common this problem is in the dominantly Caucasian population. METHODS The MEDLINE database was searched and a questionnaire was distributed among European Childhood Obesity Group (ECOG) representatives from 16 countries. RESULTS One hundred and eighty-four children with type 2 diabetes were diagnosed in Europe, 144 of them of Caucasian origin. The majority of them were overweight females and, had positive family history for type 2 diabetes mellitus. CONCLUSION Because of the significant rates of type 2 diabetes in Europe, screening for it in obese children and adolescents is highly recommended.

Reference values for leptin and adiponectin in children below the age of 10 based on the IDEFICS cohort

Objective:To establish age- and sex-specific reference values for serum leptin and adiponectin in normal-weight 3.0–8.9-year old European children.Subjects and methods:Blood samples for hormone analysis were taken from 1338 children of the IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health Effects in Children and infantS) study cohort. Only normal-weight children aged 3.0–8.9 years were included (n=539) in our analysis. Using the General Additive Model for Location Scale and Shape, age- and sex-specific percentiles were derived. The influence of under/overweight and obesity on the proposed reference curves based on normal-weight children was investigated in several sensitivity analyses using the sample without obese children (n=1015) and the whole study sample (n=1338).Results:There was a negative age trend of adiponectin blood levels and a positive trend of leptin levels in boys and girls. Percentiles derived for girls were generally higher than those obtained for boys. The corresponding age-specific differences of the 97th percentile ranged from −2.2 to 4.6 μg ml−1 and from 2.2 to 4.8 ng ml−1 for adiponectin and leptin, respectively.Conclusions:According to our knowledge, these are the first reference values of leptin and adiponectin in prepubertal, normal-weight children. The presented adiponectin and leptin reference curves may allow for a more differentiated interpretation of children’s hormone levels in epidemiological and clinical studies.

Plasma levels of acylated ghrelin during an oral glucose tolerance test in obese children

Objective: Ghrelin is an acylated peptide with octanoyl modification, which is essential for its GH-releasing ability. Coexpression of GH secretagogue receptor (GHS-R) and ghrelin in the pancreas suggests that this peptide is involved in glucose metabolism. The other form of the molecule, the non-acylated ghrelin, has been reported to be devoid of any pituitaric endocrine activities. Previous reports demonstrated that plasma total ghrelin levels decrease after oral glucose administration in obese children, but no data are available about the plasma levels of acylated ghrelin. Therefore, in the present study the plasma levels of acylated ghrelin were measured in obese and control children during oral glucose tolerance test (OGTT). Materials and methods: Acylated ghrelin response to OGTT was evaluated in 11 obese and 9 age-matched control children. All subjects received 0.75 g/kg (maximum 75 g) glucose solution orally after an overnight fast. Acylated ghrelin, insulin, glucose, and GH were determined at 0, 30, 60 and 120 min, and leptin at 0 min of the OGTT. Results: Plasma basal levels of acylated ghrelin were significantly lower in the obese children than in the controls (66.3±6.7 vs 97.2±14.4 pg/ml, p<0.05). The plasma acylated ghrelin concentration decreased significantly at 30 and 60 min in the control group (53.3±9.9 and 57.4±7.0 pg/ml, p<0.05), but not in the obese group (64.7±9.6 and 49.3±4.6 pg/ml) as compared to the basal value. In the obese group the acylated ghrelin level was significantly higher at 120 min, than at 0 min (91.6±9.8 vs 66.3±6.7 pg/ml, p<0.05). Conclusions: There was no rapid fall in plasma levels of acylated ghrelin in obese children after OGTT at 30 min, but there was an increase at 120 min, suggesting that the dynamic of the response to OGTT is slower and there is an upregulation of active ghrelin in the second half of OGTT in obese children.

Plasma lipids, phospholipid fatty acids and indices of glycaemia in 10-year-old children born as small-for-gestational-age or preterm infants

Low birthweight has been epidemiologically associated with unfavourable plasma lipid profiles and enhanced risk of cardiovascular morbidity in adulthood. Plasma lipids, lipoprotein cholesterols, apolipoproteins, fatty acid composition of plasma phospholipids and basic indices of glycaemia were investigated in 10‐y‐old children born with similarly low birthweights as small‐for‐gestational‐age (SGA; n = 16) or preterm infants (n = 16). Plasma total cholesterol (4.32 ± 0.57 vs 4.60 ± 0.52, mmol l_1, mean ± SD, SGA vs preterm subjects), low‐density lipoprotein cholesterol (2.54 ± 0.51 vs 2. 65 ± 0.51) and high‐density lipoprotein cholesterol (1.61 ± 0.25 vs 1.76 ± 0.18) concentrations did not differ between the 2 groups. There was no difference in plasma tri‐acylglycerol, apolipoprotein A‐I and B, insulin and glucose concentrations or phospholipid fatty acid values. There was no correlation between indices of lipid and carbohydrate metabolism. In conclusion, plasma lipid profiles and basic indices of glycaemia are not different in 10‐y‐old children born with similarly low birthweights as SGA or preterm infants. □Apolipoprotein, cholesterol, insulin, lipoprotein cholesterol, low birthweight, phospholipid fatty acid, 10‐y‐old children

Polyunsaturated fatty acids in plasma lipids of diabetic children during and after diabetic ketoacidosis

BACKGROUND AND AIM Previously we reported significantly higher plasma values of the essential fatty acids but significantly lower values of their longer-chain metabolites in diabetic children than in healthy controls. Here, we report data on the acute effect of diabetic ketoacidosis (DKA) on the fatty acid composition of plasma lipids. METHODS Diabetic children (n=9; age: 16.1 [3.3] y; duration of diabetes: 5.0 [5.3.] y; daily insulin dose: 0.87 [0.66] unit/kg body weight/d; glycated haemoglobin: 13.4 [2.8] %; median [IQR]) were investigated at admission for DKA (during DKA) and at the end of the treatment of DKA (after DKA). Fatty acid composition of plasma lipid classes was determined by high-resolution capillary gas-liquid chromatography. RESULTS Blood glucose (27.0 [8.5] vs 6.5 [1.6] mmol/l), pH (7.28 [0.35] vs 7.36 [0.06]) and base excess (-8.9 [15.1] vs -2.2 [6.3] mmol/l) were grossly abnormal during but not after DKA. Values of linoleic acid were significantly lower after than during DKA (non-esterifed fatty acids (NEFA): 15.55 [1.47] vs 12.27 [5.74] % wt/wt; triacylglycerols (TG): 20.84 [9.23] vs 17.40 [5.78]; p<0.05). In contrast, values of gamma-linolenic acid (NEFA: 0.87 [0.54] vs 2.34 [1.85]; p<0.05) and arachidonic acid (TG: 1.37 [0.71] vs 1.74 [0.57]; p<0.05) were significantly lower during than after DKA. The product/substrate ratios for delta-6 desaturation were significantly lower during than after DKA. CONCLUSION Successful treatment of diabetic ketoacidosis is associated with a significant increase of long-chain polyunsaturated fatty acid values in blood plasma in diabetic children. This observation suggests that disturbances of essential fatty acid metabolism in diabetic children are related not only to diet but to hypoinsulinaemia as well.

Association of lean and fat body mass, bone biomarkers and gonadal steroids with bone mass during pre- and midpuberty.

Background/Aims: The association of bone mass with body composition, bone turnover markers and gonadal steroids was examined in Hungarian children during pre- and midpuberty. Methods: Two hundred and thirty-seven 7- to 16-year-old subjects (56% girls) were investigated. Bone mineral density (BMD), fat mass and total and appendicular lean mass were estimated with dual-energy X-ray absorptiometry (Lunar Prodigy). The fat mass index and appendicular lean mass index (LMI) were calculated. Serum bone markers, parathyroid hormone, estradiol and testosterone were analyzed. Associations between variables were evaluated by multiple regression analysis. Results: During prepuberty, bone biomarkers, gonadal steroids and appendicular LMI were associated with bone mass in both genders (p < 0.05). During midpuberty, girls’ bone turnover markers were negatively associated with bone mass (p < 0.001). In prepuberty, appendicular LMI and β-crosslaps were predictors of bone mass in both genders. During midpuberty, appendicular LMI and gonadal steroids positively contributed to bone mass in both genders, while osteocalcin exerted a negative influence on total and L1–L4 spine BMD in girls and on L1–L4 BMD in boys (all p < 0.001). Conclusions: Predictors for bone development varied according to Tanner stage and gender. The most significant determinants of bone mass were appendicular LMI and estradiol.

Uncoupling protein-2 gene polymorphisms are associated with obesity in Hungarian children

To determine the frequency of common polymorphisms of genes associated with energy metabolism among normal weight and overweight/obese children to look for effects on childhood obesity.

Is type 2 diabetes mellitus a significant problem in European adolescents

The rapidly rising incidence of type 2 diabetes mellitus in young patients is well known in North America, especially in some minorities. Population-based data suggest that the epidemic of paediatric obesity is being followed by an increase in type 2 diabetes mellitus, but for European countries there are such no population-based incidence and prevalence data. From the available data the magnitude of the problem in the European Caucasian population seems to be much less than in North America. Although type 2 diabetes mellitus is still rare in childhood, an increasing rate is expected paralleling the growing rates of obesity; therefore, children and adolescents with a substantial risk for the presence or development of type 2 diabetes should be screened. Among Hungarian obese adolescents impaired glucose tolerance was found in 17.3% and type 2 diabetes mellitus in 1.9% of children. Any feature or condition associated with insulin resistance or hyperinsulinaemia should alert health-care providers to screen young people at increased risk for type 2 diabetes mellitus. Keywords: adolescents; impaired glucose tolerance; type 2 diabetes mellitus