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Aim: To determine the influence of Type 1 diabetes mellitus on circulating adipocytokines in children., Methods: The circulating concentrations of leptin, adiponectin, resistin and tumour necrosis factor (TNF)-alpha were measured in 91 children, aged 11.1 +/- 2.7 years, with Type 1 diabetes mellitus (T1DM). Ninety-one healthy children were selected as control subjects., Results: Body mass index-adjusted leptin concentrations were higher in the pubertal diabetic children compared with the control children. There was a significant positive correlation between leptin and daily insulin dose in the diabetic group. Circulating adiponectin concentrations were higher in the prepubertal diabetic children and were positively associated with HbA(1c). Resistin concentrations were lower in the prepubertal non-diabetic subjects compared with the pubertal non-diabetic children, whose values were higher than those of the diabetic children. TNF-alpha concentrations were similar in non-diabetic and diabetic children., Conclusions: Circulating concentrations of adipocytokines are abnormal in Type 1 diabetic children, although the direction of change differs by cytokine. Pubertal development, in addition to insulin treatment and glycaemic control, also influences the concentrations.

Objective: To evaluate the dependence of body mass index (BMI) values on pubertal stage in subjects similar in age., Design, Subjects and Measurements: Height and weight were recorded cross-sectionally in school subjects from three provinces in central Italy. The subjects were subdivided into three groups: (1) 4271 school subjects (2125 males and 2146 females; 8.5-15.5 y old), in whom the pubertal development was also recorded, were selected to subdivide BMI values according to pubertal stage and age; (2) 6345 females (10.5-14.5 y old), who were asked whether or not they had had their first menstrual period, were selected to subdivide BMI values according to age in pre-menarche and post-menarche girls, separately; and (3) 1919 females (10.5-14.5 y old), who had presented their menarche within the previous 6 months, were selected to subdivide short-term post-menarche BMI values according to age., Results: The medians and interquartile ranges of BMI varied according to age and pubertal stage. Kruskall-Wallis test performed in subjects similar in age demonstrated that significant differences existed among the medians of BMI values of subjects at different pubertal stages in 12-14-y-old males (P<0.05), and in 11-14-y- old females (P<0.001). The difference also proved to be significant between stage I and stage II (P<0.05) in 10-y-old females, but not in 10-11-y-old males. The Kruskal-Wallis test performed in subjects similar in pubertal stage demonstrated that significant differences among the medians of BMI at different ages existed only in females at stages II and III. A significant positive trend was observed in both genders according to pubertal stage for BMI values of subjects similar in age (z-test for trend, P<0.01). On the contrary, a negative age trend proved to be significant in females at stages I (P<0.01), II (P<0.01) and III (P<0.001), but not in males when the subdivision of BMI was made according to age in subjects similar in pubertal stage. BMI values were significantly higher in post-menarche girls as compared to pre-menarche girls similar in age (P<0.001). However, at partial regression analysis BMI values were influenced by pubertal stage and, to a lesser extent, by age, but not by menarcheal status. An inverse association between short-term post-menarche BMI and age was observed, with the highest values in girls presenting menarche at 11 y of age (P<0.05). The negative trend was demonstrated at the z-test for trend (P<0.001)., Conclusions: BMI values depend on pubertal degree of maturation, especially in girls. This influence should be taken into account when BMI is evaluated in adolescents., Sponsor: University of Perugia, Region of Umbria.

Objective: Leptin, the product of the ob gene, is present in higher concentrations in blood of obese subjects than of lean subjects. There is scarce information on the role of leptin in the pathogenesis of human obesity and little is known about leptin serum levels in obese children., Design, Subjects and Measurements: To evaluate the influences of age, sex, pubertal development and weight excess on serum leptin levels, we have studied 390 obese subjects (OS) and 320 normal weight subjects (NWS) aged 5-16 y. Fasting insulin concentrations were assayed in NWS, and an oral glucose tolerance test was carried out in OS and total insulin area under the curve (TIA) was calculated., Results: Log-transformed values of leptin serum concentrations appeared to be distributed according to an acceptable Gaussian pattern. As observed in adults, serum leptin concentrations in children and adolescents were also increased (4-5 times) in OS as compared to NWS. In both males and females, subdivided according to pubertal stages, serum leptin varied significantly in stage IV-V as compared to the lower stages, with a reduction in males and an increase in females. On comparing the two sexes, greater serum leptin concentrations were observed in females of both NWS and OS. A significant linear correlation was found in both groups, subdivided according to sex and pubertal stage, between log values of serum leptin and standard deviation scores (SDS) of body mass index (BMI), and log-transformed relative body weight (RBW). Using partial correlation analysis in subjects subdivided according to sex and pubertal stages, log values of serum leptin and fasting insulin values, adjusted by age and SDS of BMI, correlated significantly with a weaker correlation in males than in females. In OS, the leptin concentrations correlated better with TIA than with fasting insulin. A weight reduction program (WRP) was carried out in 141 OS and significant reductions of serum leptin and fasting insulin were observed, showing a reduction of RBW. There was a correlation between the reduction of RBW and of serum leptin, but not of fasting insulin. No variation was found in non-responsive OS. RBW reduction correlated with leptin, but not with insulin (fasting and TIA), evaluated before the therapeutic program started., Conclusion: As observed in adults, obese children and adolescents have higher serum leptin concentrations. However, several conditions should be taken into account when evaluating leptin concentrations in children. There are differences, independent of BMI, relative to pubertal stage and sex, females having greater leptin concentrations than males. There is evidence of a possible role for leptin in the effectiveness of a weight reduction program in OS.

To study the circulating levels of two gut-derived peptides in children with type 1 (insulin-dependent) diabetes mellitus (IDDM). Plasma levels of ghrelin, both total ghrelin (TG) and the acylated form (AG), and galanin and their relationships with insulin dosage, metabolic control, IGFBP-1, body mass and pubertal development were evaluated in 91 children, aged 11·1 ± 2·7 years, affected by IDDM and treated with insulin. Ninety-one healthy children were selected as controls. Body mass index (BMI)-adjusted levels of both forms of ghrelin were reduced in IDDM compared with healthy subjects, with greater values in prepubertal than pubertal IDDM subjects. A negative association was found between AG and fasting insulin serum levels and insulin resistance [measured by using the homeostasis model assessment of insulin resistance (HOMA IR)] among the healthy children. IDDM children showed a negative association of their plasma ghrelin (both acylated and total) with daily insulin dosage, and the three adiposity indices (BMI, skinfold thickness and percentage fat mass). IGFBP-1 levels were higher among the IDDM children without any association with ghrelin serum values. BMI-adjusted plasma levels of galanin were higher among IDDM compared to healthy subjects, irrespective of sex or pubertal development. Greater values for galanin were found among pubertal than prepubertal subjects in both groups without any significant differences between the genders. A positive association was found between galanin and BMI in both groups and between galanin and haemoglobin A1c (HbA1c) among the IDDM children. No relationship existed between either galanin and fasting serum insulin among the healthy subjects or galanin and both insulin dosage or duration of treatment among the IDDM subjects. The associations found between both ghrelin and galanin with adiposity indices could be considered as an indirect signal of involvement of the two peptides in the development of the nutritional status of the IDDM adolescents. The reduction in both forms of ghrelin could be involved in the development of the body mass increase of IDDM subjects with opposite effects, either influencing insulin sensitivity or exerting a compensatory restraint of feeding. [ABSTRACT FROM AUTHOR]