Metabolic monitoring of obese children born small for gestational age.

INTRODUCTION: The "catch-up growth" phenomenon in children born small for gestational age (SGA) has been linked to early onset obesity with the subsequent emergence of metabolic syndrome (MetS) or its components. It has been postulated that the prevalence of MetS and its components increases strongly with age. MATERIALS AND METHODS: A retrospective study was carried out over a 5 year period (2007-2011) to determine long-term metabolic complications in obese children born with normal weight for gestational age (appropriate for gestational age: AGA) and SGA. 517 patients were qualified into the study. According to birth weight and gestational age they were first divided into SGA (107 patients--20%) and AGA (410 patients--80%) and then by age into three subgroups: prepubertary group, pubertary group and adolescents. Blood pressure, lipids and glucose were measured. Oral glucose tolerance tests (oGTT) were performed in all subjects. RESULTS: Prepubertary patients showed no significant differences between SGA and AGA; 4.8% met the framing criteria (according to Weiss) for MetS. Pubertary patients showed a slightly increased prevalence of MetS among SGA patients 10.8%, compared to AGA patients 7.3%. MetS prevalence was significantly higher in obese adolescents born SGA 26.3% compared to AGA 15.7%. CONCLUSION: MetS or its components develop progressively with age. Increased prevalence of MetS in SGA patients indicates that being born SGA appears to be an additional risk factor in the development of MetS starting with puberty.

Is small for gestational age status associated with an increased risk of atherogenesis?

ABSTRACT: The "catch-up growth" phenomenon in children born small for gestational age (SGA) has been linked to early onset obesity with the subsequent emergence of metabolic syndrome (MetS). The intima media thickness of the common carotid artery (CIMT) is a well-known marker of subclinical atherosclerosis. AIM: to determine the association between being born SGA and CIMT, a measure of atherogenesis and to investigate metabolic risk factors which impact on CIMT in obese children. MATERIAL AND METHODS: A prospective study was carried out over a 1 year period (July 2012-June 2013). We analyzed 122 obese patients, 96 patients appropriate for gestational age (AGA) and 26 patients SGA. Both groups were matched for age, sex and BMI. Blood pressure, lipids and glucose were determined. Oral glucose tolerance tests (oGTT) were performed. Insulin resistance (IR) was assessed by homeostasis model assessment (HOMA). CIMT was measured in all the patients. RESULTS: CIMT in obese children born SGA was significantly increased as compared with obese children born AGA similar age, sex and BMI (p=0.0035). We demonstrated a strong correlation between CIMT and all other metabolic factors (r=0.98). In both groups, mean CIMT of was significantly related to diastolic blood pressure, triglycerides and HOMA. CIMT was not significantly related to systolic blood pressure and baseline glucose. CONCLUSION: High triglycerides levels and low HDL-cholesterol levels, IR and diastolic blood pressure, which are all components of MetS are strong predictors of increased CIMT in obese children. Being born SGA increases the atherogenic risk.

Biosimilars: controversies as illustrated by rhGH.

UNLABELLED: Abstract Background and scope: Similar biological medicinal products, also called 'biosimilars', are copies of biopharmaceutical products whose patent has expired. Whether biosimilars are truly comparable and interchangeable with their reference biopharmaceutical products in terms of quality, efficacy and tolerability, is still a matter of debate. This review discusses the controversies related to the criteria for regulatory approval of biosimilars. These concerns are illustrated using recombinant human growth hormone (rhGH) biosimilars as an example. METHODS: Publications on the regulatory approval of biosimilars in general and rhGH biosimilars in particular were searched in MEDLINE by exploding and combining the medical subject heading terms 'human growth hormone', 'efficacy' or 'safety' and the free-text words 'biosimilar', 'biopharmaceutical', 'similar biological medicinal product', 'follow-up biologic' or 'biogeneric'. Searches were limited to full-text English-language articles. The websites from the European Medicines Agency (EMA) and from the American Food and Drug Administration were also consulted. Regulatory status: To obtain regulatory approval of a biosimilar product by EMA, demonstration of comparability with an approved reference biopharmaceutical product in terms of quality, efficacy and tolerability is needed. Thus, comparative quality studies, non-clinical and clinical efficacy and tolerability studies are required. However, in contrast to the reference product, comparative non-clinical pharmacokinetics, safety pharmacology, reproduction toxicology, mutagenicity and carcinogenicity studies are not mandatory to obtain approval of a biosimilar. In addition, comparable efficacy and tolerability only needs to be established by one study in a single population during a limited time interval (12 months) and often allows extrapolation to all other approved indications of the reference product. Consequently, for the currently approved rhGH biosimilars, long-term efficacy and tolerability in all indications has not been proven to the same degree as for the reference products. CONCLUSIONS: The validity of the current criteria for comparability and interchangeability of biosimilars and their reference products remains controversial. The authors conclude that long-term clinical investigations and systematic monitoring of the efficacy and tolerability of rhGH biosimilars in all indications are needed. In addition, the medico-economical environment should allow physicians to take a free and informed decision about the type of rhGH to be prescribed.