Change Of The Level Of Blood Ghrelin, Leptin And NPY In The Children With Anorexia And Their Associated Clinical Significance

Anorexia is long-term decrease or loss of appetite, as well as the decrease of foodintake. The etiologic factors are diverse, general diseases, improper feeding,deficiency of trace element, change in living environment, mental stress and medicinemay all be involved. Anorexia should be corrected timely, or it could lead tomalnutrition, growth retardation;deficiency in immunity which makes the childrensusceptible to respiratory diseases and gastrointestinal diseases;sexual hypoevolutismand hypofunction in pubescence. The morbility of anorexia is comparatively high inchildren, and so far the pathology of it is not clear, no effective therapy is available forit.Recent studies have focused on the influence of gastrointestinal function statuson appetite, rare is known about the effect of "brain-gut peptide-appestat" to anorexia.Disorder of the secretion of peripheral or central brain-gut peptide can influencefunctional activity of appestat, then affect food intake behavior, which is an importantstep in occurrence and development of anorexia.Appetite regulation network regulates appetite of mammalian through the signaltransmission of appetite regulators. Any problem in the transmission pathway wouldinfluence appetite, and induce anorexia. Ghrelin is a polypeptide newly found ingastric cell and hypothalamus ARC, it is a kind of brain-gut peptide secreted instomach and then acts on central nervous system. So far Ghrelin is the only peripheralappetite stimulator that has been found. The study of Ghrelin once emphasized itseffect on release of somatotropic hormone, but now the focus has shifted to itsregulation for energy balance. Leptin, which is mainly from fat cell, is proteinencoded by obesity gene. Among all the appetite regulators, Leptin is the mostimportant appetite inhibitory factor. Ghrelin and Leptin are complementary factors ofcentral energy balance imput system. NPY is the strongest appetite promotion factor,Ghrelin and Leptin take their biological effects through NPY.Many studies have been done on the effects of Ghrelin, Leptin and NPY in Chinaand abroad. However, few are related to anorexia, and there is no study targeted onchildren.ObjectiveThe aim of the study is firstly to observe the change of level of blood Ghrelin,Leptin and NPY in children with anorexia, then to elucidate their interrelation withanorexia and their associated clinical significance, which subsequently provideexperimental data for children appetite regulation disorder and work foundation forfurther study.Study Object and Methods1. Study ObjectAnorexia group: Children in Liwan district of Guangzhou City and Shunde district ofFushan City who were randomly selected for food intake behavior investigation in theperiod of April 2005 and March 2006 were recruited in our study if they measure upthe criteria for anorexia. There were 40 children in anorexia group, whose age range isbetween 3 to 6 years old. Children with lower height or weight than 2SD wereexcluded.Control group: Twenty healthy children at the age of 3 to 6 with matched age andgender proportion were chosen for control group.2. Study methods2.1 clinical indices3) Appetite, the amount of food intake, time of meal.4) Height, weight, body mass index(BMI), thickness of skin fold(SF).2.2 experimental indices4) The level of blood Ghrelin, Leptin, NPY, insulin and blood glucose.5) Calculate insulin sensitivity index ISI=1/(FBG×FINS).6) The level of red blood cell, hemoglobin, total protein, albumin, globulin wererecorded.Enzyme linked immunosorbent assay was used to assay the level of bloodGhrelin. Radioimmunoassay was used to assay the level of blood Leptin, NPY,insulin. The level of blood glucose was assayed by glucose oxidase method.Corresponding commercial kits are available for assay of these indices.Statistical AnalysisSPSS13.0 was used. Mean ± standard deviation was used to show the data withnormal distribution;the data of insulin and ISI were transformed to normaldistribution through logarithmic transformation. Independent-samples T test, ranksum test, Pearson correlation and rank correlation were used. P<0.05 was thought tobe statistically significant.Results1. General clinical data: Forty children with anorexia, including 18 males and 22females were recruited in this study. The age ranged from 3 years 1 month to 6years, and the median age was 4 years 5 months. The course of disease was3-36months, and the median was 12 months. The incipient manifestationsincluded 32 cases with loss of appetite(80%), 22 with decrease of food intake orearly satiety(55%), 20 with feeding difficulty(50%), 27 with emaciation(67.5%),18 with monophagism or choosy in food(45%), 9 with abdominal pain ordistention(22.5%), and 11 with constipation(27.5%). Twenty healthy children,including 9 males and 11 females were recruited in control group. The age rangedfrom 3 years 3 months to 6 years, and the median age was 4 years 6 months. Thereis no difference in sex constituent ratio and age between anorexia and controlgroups.2. The levels of height, weight, BMI and SF in anorexia group were significantlylower than that of control group (P=0.000). Compared with the mean of childrenwith the same gender and same age, there were 34 cases(85.00%) in anorexiagroup with lower weight level and 33 cases(82.50%) with lower height level.However, there were 4 cases(20.00%) and 7 cases(35.00%) respectively in controlgroup. In anorexia group, there were 24 cases(60.00%) with BMI level lower thannormal, the lowest was11.80(normal reference range 15-18). Meanwhile therewere 4 cases(20.00%) with lower BMI level in the control group, the lowest was14.05.3. The levels of albumin and A/G ratio in anorexia group were significantly lowerthan that in control group(P=0.000). No significant differences were found in RBC,HB, total protein and globulin levels between anorexia and control group(P>0.05).4. The serum level of NPY was 72.24±13.58pg/ml in anorexia group and 70.57±16.52pg/ml in control group. There was no significant difference beween twogroups(P>0.05). The Ghrelin and ISI levels in anorexia group were significantlyhigher than that in control group(P=0.000). But the serum Leptin, insulin andglucose levels were significantly lower in anorexia group than that in controlgroup(P<0.05).5. Ghrelin level showed positive correlation with appetite, the amount of food intakeand total score in anorexia group( rs =0.385, 0.570 and 0.445 respectively,P<0.05), no correlation with time of meal. Leptin level showed positivecorrelation with the amount of food intake( rs =0.400,P<0.05), no correlationwith appetite, time of meal and total score. No correlation was found betweenNPY and appetite, the amount of food intake, time of meal and total score.6. Ghrelin, Leptin, NPY levels showed no correlation with the sex, age, RBC, HB,total protein, albumin, globulin and A/G levels both in anorexia group and controlgroup. Positive correlation was found between serum insulin and glucoseconcentration in both groups(anorexia group r =0.588,P=0.000;control group r=0.585, P=0.009).6.1 There was negative correlation between Ghrelin and Leptin level in both groups( r=-0.680 and -0.757 respectively). Ghrelin level showed negative correlation withinsulin and blood glucose concentration in both groups, with r =-0.338, -0.687 and-0.373, -0.500 respectively, P<0.05;positive correlation with ISI level. Ghrelinlevel showed negative correlation with SF in control group with r =-0.622, andshowed r =-0.291, P=0.068 in anorexia group. Ghrelin level showed nocorrelation with weight, height, BMI and NPY levels.6.2 In anorexia group and control group, there was positive correlation betweenLeptin and blood glucose, insulin levels, with r =0.331, 0.766 and 0.396, 0.532respectively(P<0.05);negative correlation with ISI level, with r =-0.363 and-0.548 respectively(P<0.05). Leptin level showed positive correlation with weightand SF levels, with r = 0.391, 0.470 and 0.431, 0.884 respectively (P<0.05). Therewas no correlation between Leptin and height, BMI, NPY levels.6.3 NPY level showed no correlation with blood glucose, insulin, ISI, weight, height,BMI and SF in both groups.Conclusion1. The decrease of appetite in children with anorexia would not necessarily resultfrom the under-secretion of Ghrelin or the over-secretion of Leptin;the change ofGhrelin and Leptin levels are the organism compensation reaction for negativeenergy balance.2. The increase of Ghrelin in children with anorexia failed to induce enough respondof NPY, which indicated the existence of Ghrelin resistance. While the level ofblood NPY did not lower than the health children, which indicated the existence ofdysfunction of NPY transmission pathway.3. The increase of insulin sensitivity in children with anorexia may be a response tohigh level of Ghrelin secretion.