There were no correlations between serum leptin and CRP, ESR, albumin, or PCDAI in the children with IBD (data not shown: P > 0.05 in all cases).
The present study investigated the nutritional status of a group of children with IBD, with detailed anthropometry and serum leptin levels collected and then compared with values obtained from age- and sex-matched control children without IBD. The children with IBD were markedly undernourished and had low leptin levels that correlated positively with BMI. In this group of children with IBD, leptin levels did not correlate with the degree of inflammation, as defined by serum markers of inflammation.
This cohort of children diagnosed with IBD in the present study was similar to several previous reports of pediatric IBD and is likely representative of children with IBD. The mean age of the children in the present study was 9.4 years with a median of 10 years, similar to 2 previous series from Western Europe (22) and North America (23). Many children diagnosed with IBD present at prepubertal or peripubertal ages. This is a vulnerable age because the pubertal growth spurt is about to occur and the effect of the disease on the final growth of the individual is most marked. The effect of IBD on final height is most marked in children at Tanner stage 1 and 2 (24–26). There was also a male predominance in the present cohort, again similar to other reports (23). This is also relevant to a consideration of the nutritional effect of IBD because boys have later and longer puberty; hence, the effect of IBD on nutrition can be greater and more concerning.
The present study highlights the high rates of undernutrition in the children with IBD, in agreement with previous reports (27,28). Moreover, our results indicate that children with IBD were more wasted than stunted. This is in agreement with the findings of Azcue et al (28), who reported children with IBD to have significantly lower weight and ideal body weight compared with controls, but found no difference in height between IBD and controls. A further study, which included 104 patients with CD ages 4 to 25 years and compared with 233 controls, found that key anthropometric measurements (weight, height, and BMI) were significantly lower in CD compared with controls (29). In addition, several cross-sectional studies show that weight is affected more than height in children with IBD (22,27). Interestingly, it is pertinent to note that up to 5% of children diagnosed with IBD may present solely with growth failure (without other typical symptoms) (30). The markedly undernourished state in children with IBD favors reduced FM. A report of adolescent patients in apparent remission demonstrated significantly lower BMI than healthy controls, demonstrating lower body fat in children with IBD (31).
Corresponding to decreased BMI in IBD, serum leptin levels were also significantly lower in IBD than in matched controls. Further analysis by covariance analysis also showed that after adjusting for BMI percentiles, the serum leptin levels remained high in controls. In contrast, Hoppin et al (15) found no difference in serum leptin levels between children with IBD and controls and concluded that serum leptin levels depend on BMI and sex and not on disease activity or severity. Serum leptin levels are reflective of the body fat stores (32–34) and are lower in children with severe protein energy malnutrition (35). However, lower concentrations of serum leptin have been reported in several chronic diseases (32,36–39) and in other illnesses causing undernutrition, such as intrauterine growth retardation, untreated anorexia nervosa, and malnourishment in chronically ill elderly patients (37,40–42).
Serum leptin levels were also assessed in different age groups and the different sexes. In healthy children, leptin levels increase with age until 10 years (43,44). After this age, levels fall in boys until the onset of puberty and then rise again. Children older than 12 years with IBD had significantly reduced leptin compared with controls. Furthermore, for this age group, mean BMI percentile scores were significantly lower in children with IBD compared with controls, yet there were no significant differences in either serum leptin levels or BMI percentile in lower age groups. In addition, the serum leptin level was assessed in detail for both sexes. The mean serum leptin level in boys with IBD was significantly lower compared with male controls; however, there was no difference between girls with IBD and female controls. This can be explained by a significant difference in the mean weight for age and BMI for boys with IBD compared with controls, whereas there was no difference in these measures for the girls. In a further study, girls with CD had higher serum leptin levels compared with boys, which could not be explained by BMI alone (15). It has been suggested that boys are affected by the disease process more than girls, despite the same stage of puberty, age at diagnosis, duration, and activity of disease (45). Similarly, other researchers have reported that the FM of men with IBD is affected more than in women with IBD (46). Thus, the nutritional status and leptin levels of male children of pubertal age are affected the most by IBD.
Several studies in adults have shown that serum leptin concentrations strongly correlate with FM and body weight in both normal and obese people (47–51). Furthermore, serum leptin concentrations correlate with adipose tissue in children (44,52–55). Additionally, our results show a correlation between serum leptin levels and BMI percentile both in controls and in children with IBD. However, contrary to these findings, Tuzun et al (14) reported that serum leptin levels did not correlate with BMI in adults with UC. This is the only study to our knowledge that has reported high serum leptin levels in patients with UC as compared with controls. However, in extremely malnourished children with fluid retention, BMI does not correlate with serum leptin levels because in this situation BMI does not adequately represent the body fat stores (56). Thus, serum leptin levels are a marker of body fat stores except in extremely undernourished states.
The strengths of the study are the detailed and focused assessment of the nutritional status of the children with newly diagnosed IBD presenting at an Australian tertiary hospital, in comparison with age- and sex-matched controls. In addition, serum leptin level in these children with IBD was evaluated in comparison with this control group. There are, however, potential limitations of the present study. First, Tanner staging was not completed, and therefore the pubertal and prepubertal stages were based solely on the age of the child. Having said this, the majority of the children in the present study were in a prepubertal age group. Second, the serum leptin level was analyzed and considered from the nutritional perspective. A detailed examination of correlations between serum leptin level and key inflammatory markers elevated in IBD would further enhance our understanding of the patterns of serum leptin level production in IBD. Lastly, the control group included in the present study did not comprise normal healthy individuals from the general population. The use of such a control group may have aided the interpretation of the data arising.
In conclusion, these children with IBD were significantly undernourished and had significantly lower serum leptin levels than controls. BMI correlated positively with serum leptin levels in children with IBD as well as in controls. Serum leptin levels are markedly reduced in boys with IBD in the prepubertal and pubertal period as compared with control boys. Detailed and focused nutritional assessment should be an integral part of the management of all of the children with IBD. Children with IBD at prepubertal and pubertal ages deserve particular attention to aspects of their nutritional status at and following their diagnosis.
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