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The Relationship Between the Levels of Circulating Obestatin,Ghrelin and Insulin Resistance in Obese Children

Author: LiJianXu
Tutor: DongGuoQing
School: Southern Medical University,
Course: Pediatrics
Keywords: Obestatin Ghrelin Ghrelin/obestatin Obesity Children Insulinresistance
CLC: R723.14
Type: Master's thesis
Year: 2013
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Abstract


BackgroundObesity is a kind of chronic nutrition obstacle disease, that is, a condition where the body’s energy input exceeds its consumption for a long-term, the redundant energy being stored in tissues as fat, consequently leading to excessive internal fat and overweight status. Obesity have been becoming increasingly prevalent around the world. The tendency for the young to be inflicted by such diseases has clearly been increasing. The worldwide prevalence of obesity and overweight in preschool children increased from4.2%in1990to6.7%in2010. In China, there is an increasing prevalence rate of obesity in children. In2000, the prevalence rate of obese children of7to22-year-old in urban boys, rural boys, urban girls and rural girls were respectively4.37%,1.46%,2.32%and0.92%, whereas the prevalence rates had increased to13.33%,5.64%,7.83%and3.78%respectively in2010. Ninety-five to ninety-seven percent of cases of childhood obesity were simple obesity, related to a complex combination of hyperphagia, physical inactivity, genetic, environmental, birth weight, sex factors etc. Childhood obesity not only affects children’s heart and lungs function, but also closely relates to the incidence of serious psychological disorder, mental pressure and abnormal behavior. Childhood obesity is likely to persist into adulthood if it is untreated. Obesity is closely associated with cardiovascular and endocrine abnormalities(eg, dyslipidemia, insulin resistance and type Ⅱ diabetes),orthopedic problems, pulmonary complications(eg, obstructive sleep apnea),and mental health problems. The earlier age and higher degree of obesity, the greater risk of diseases occurs. Early childhood which is the key for the occurrence of obesity and prevention isn’t only the active phase of adipose cell growth, but also the way of lifestyle first format. It has already been confirmed that obese children exhibit the phenomenon of IR and hyperinsulinemia which effectively promote glucose uptake, intake, glycogen protein and fat synthesis, inhibit the fat decomposition. At the same time, insulin resistance burdens islet beta cells, Therefore, obese children are predisposed to type Ⅱ diabetes.Insulin Resistance is defined as an impaired ability for normal insulin in the blood to effectively promote peripheral glucose uptake, inhibit hepatic glucose output and very low density lipoprotein (VLDL) output. It is determined by insulin and glucose level, the commonest method is the homeostasis model assessment (HOMA)-IR index. It has already been confirmed that obese children exhibit the phenomenon of IR, which manifests mainly as hyperinsulinemia. As the study on IR had progressed further and further, the exploration of obesity and IR-related factors had been greatly concerned. Current research shows that more and more fat cell factors such as leptin, adiponectin, resistin, interleukin6, etc play an important role in obesity and insulin resistance, while the relationship between the gastrointestinal peptide like obestatin, ghrelin and obesity, insulin resistance is one of the hot topics.Ghrelin was first found in gastric endocrine cells and arcuate nucleus in hypothalamus of mice and human by Japanese scientists Kojima et al in1999. Subsequent considerable and unequivocal evidence shew that it played critical roles in the short-and long-term regulation of appetite and body weight. Ghrelin affected appetite and food intake as well as a diverse array of Processes involved in energy expenditure and fuel utilization, all of which Promote weight gain and fat accumulation. Exogenous ghrelin administration caused hyperphagia and obesity in rodents. Asakawa et al found that in a high-fat diet condition, the level of insulin increased significantly in the mice which was given ghrelin compared with control group, cholesterol level strikingly raised as well. It suggested that ghrelin which could lead to obesity may by means of causing or worsen insulin resistance and lipid metabolism disorders.Epidemiological studies demonstrated that low concentration of ghrelin was closely related with insulin resistance, hypertension, type Ⅱ diabetes.Obestatin is a kind of active peptide which was first separated and purified from rat gastric tissue by zhang et al in2005and it was found to present in blood circulation. Abdominal or intracerebroventricular injection of obestatin could inhibit appetite and weight gain, prolonged the mice gastric emptying time, reduced intestinal contraction frequency, counteracted the promoting actions of ghrelin in rodent animal experiments. Studies had found that fasting obestatin concentration which was relevant to insulin resistance was significantly lower in obese、Impaired glucose tolerance and non-obese type Ⅱ diabetes group, and there was no gender difference. The level of fasting obestatin was negatively correlated with BMI and basic insulin.To the best of our knowledge, there was little knowledge about the changes of the levels of obestatin and ghrelin in obese children as well as the relationship between obestatin、ghrelin and insulin resistance, so further research is needed. The study of the pathophysiological significance of obestatin and ghrelin will help to know the prevention and control mechanism and explore the new measures of diabetes, insulin resistance, obesity and so on.Objective To observe BMI,WC,WHR,serum lipid concentration,IR, ghrelin、obestatin、 ghrelin/obestatin concentration in children with simple obesity,and analyse their correlations and stepwise multiple regression.Meanwhile, the relationship between BMI, WC, WHR, serum lipid concentration.IR and ghrelin, obestatin, ghrelin/obe-statinconcentration was investigated.MethodFifty children suffering from simple obesity were selected, who had seen a doctor between January,2011and December,2012at the pediatric endocrine clinic of Shenzhen Maternal and Child Health care Hospital. There were31boys and19girls aged2.25-13.00years, averaging (8.10±3.13) years old. They had undergone a physical examination, abdominal ultrasound and endocrine, hepatic, renal function examinations. Secondary obesity caused by other endocrine diseases, hereditary metabolic disease and central nervous system disease were excluded. Their height was in the normal range for the same age and sex. The diagnostic criteria for obesity was body mass index(BMI) cut-off point method for screening of overweight and obesity in the Chinese children aged2-18, which was concordant with the BMI cut off point for screening of overweight and obesity in adults.In addition, we chose another30children who had visited this hospital in the same period, and were found to be healthy in the physical examination as the healthy control group. Their body weight, liver and renal functions were all normal and they had no chronic diseases. Of which, there were14boys and16girls, aged2.50~12.83years, averaging (7.22±2.83) years old. There was no significant difference of age and sex between the two groups.Physical indicators measurementAll the ages and genders were recorded. Between8AM and9AM before meals, all the children took off their shoes and hats and wore unlined garments. Height, weight, blood pressure, waist circumference, hip circumference, etc. of each child were measured, and BMI=weight(kg)/height2(m2), WHR=waist circumference (cm)/hip circumference (cm) were calculated.Specimen collection and laboratory testsBetween8AM and9AM before meals,4millilitre (ml) venous blood was exsanguinated. Fasting insulin(FINS), fasting blood glucose(FBG), total cholesterol (TC), triglycerides(TG), high density lipoprotein cholesterol(HDL-C), low density lipoprotein cholesterol(LDL-C),alanine aminotransferase(ALT)and aspartate aminotransferase(AST), etc. were measured immediately after the serum was separated. FINS was measured via an automatic fluorescence immunoassay analysis system; FBG, TC, TG, HDL-C, LDL-C, ALT and AST was measured by an automatic biochemical analyzer. HOMA-IR (=FINS×FBG/22.5) was calculated. The serum left was saved in-70℃refrigerator. Serum obestatin and ghrelin levels were measured by radioimmunoassay. Kit was provided by millipore companies in the United States.The instrument is XH6020full-automatic y counter which was produced by xi’an nuclear instrument factory.The serum concentration of obestatin and ghrelin was test by designated persons.Statistical processingAll of the statistical analyses were performed with SPSS13.0software:data was tested to see if it was normally distributed. Skew distributed data were expressed as a median (P25,P75), normal distributions were expressed as X±S;HOMA-IR data which was not normal distribution, was translated as natural logarithm and then treated as a normal distribution. In comparing the two groups, two independent samples t test was applied to normal distributions (most medical physiology data is a normal distribution, this study’s sample was small, and although FBG and serum lipid were not normally distribution, we still treated them as normal distributions), while the rank sum test was applied to skew distribution data. Count data comparisons between groups were tested by chi-square test. Partial correlation analysis was performed, controlling for age. The correlation analysis of multiple factors was investigated in stepwise multiple regression. P<0.05was statistical difference.Results1、Gender and age of both the simple obesity group and the healthy control group showed no significant difference, X2/t=1.250,1.623,P=0.264,0.210, respectively. In the simple obesity group, BMI, WHR and WC were respectively24.17±3.70kg/m2,78.29±12.24cm and0.94±0.05, significantly higher than that of healthy control group,whose were16.37±2.13kg/m2,57.83±7.99cm,0.87±0.06t=11.960,9.040,5.490, respectively,with P<0.001for all of them. The differences were statistically significant.2、Fasting blood glucose was4.91±0.49mmol/L in the simple obesity group,5.09±0.79mmol/L in the healthy control group,t=-1.122,P=0.268. There was no significant difference. Blood FINS in simple obesity group was116.24(61.57,150.66)pmol/L and Ln (IR) was3.08±0.66which were significantly higher than healthy control group, whose FINS was57.58(35.57,106.74)pmol/L and Ln (IR) was2.53±0.76,Z/t=-3.399,3.43, both P=0.001, there were obviously different. TC, TG and LDL-C in the simple obesity group were3.97±0.90mmol/L,1.34±0.91mmol/L,2.32±0.76mmol/L respectively, significantly higher than that of healthy control group, whose were3.50±1.08mmol/L,0.99±0.53mmol/L,1.83±0.69mmol/L, respectively,t=2.187,2.148,2.886,P=0.032,0.035,0.005.There were statistically different. HDL-C of both groups had no significant difference,t=1.131,P=0.265. HOMA-IR index was positively related to BMI,WC,WHR, serum TG, r=0.390,0.337,0.223,0.405respectively, with P=0.000,0.000,0.039,0.000. 3、The serum concentration of obestatin in the simple obesity group was414.234±117.876pg/L, lower than that of healthy control group sharply, whose was485.109±140.498pg/L,t=-2.421, P=0.018; There was a significant difference. There was no significant correlation between BMI, WC, WHR, TQ TC, HDL-C, LDL-C and obestatin.Obestatin was positively related to ghrelin.r=0.401,P<0.001,while negatively related to FINS,HOMA-IR, r=-0.365,-0.336respectively, P=0.001,0.002.4、The serum concentration of ghrelin in the simple obesity group was54.800(42.854,68.467) pg/L, significantly lower than that of healthy control group, whose was84.420(53.840,141.293)pg/L,Z=-2.772,P=0.006,the difference was statis-tically significant.There was no significant correlation between WC,FINS,TG, TC,LDL-C and ghrelin, while ghrelin was negatively related to BMI,WC,WHR, HDL-D,Ln(IR),r=-0.260,-0.259,-0.256,-0.233,-0.311,P=0.021,0.021,0.023,0.039,0.005respectively.5、The ratio of ghrelin/obestatin in the simple obesity group was0.140(0.104,0.200), while it was0.164(0.118,0.304) in the healthy control group, Z=-1.958, P=0.05, there was no significant difference between two groups. There was no significant correlation between WC,WHR,TG,TC,LDL-C,Ln(IR) and ghrelin/obe-statin ratio.Ghrelin/Obestatin ratio were negatively related to BMI, WHR, r=-0.292,-0.237,P=0.009,0.036respectively.6、Multiple stepwise regression analysis indicated that BMI was the most dominant influencing factor of ghrelin. Standardized regression coefficient is0.351, adjusted R2=0.112. The regression equation was ghrelin=178.586-4.561BMI.Conclusion1、Children with simple obesity had such phenomena as IR, and increased BMI, WC, WHR, and dyslipidemia, mainly indicated that the levels of TC, TQLDL-C were higher than normal. 2、The serum concentration of obestatin and ghrelin were significantly lower in the simple obesity group. Both of them were positively correlated with each other. obestatin was in relation to FINS,Ln(IR),which ghrelin was significant association with BMI,FINS,HDL-D,Ln(IR). These evidence suggested that they were concerned with insulin level and insulin resistance in obese children. Obestatin and ghrelin may play an important role in insulin level and insulin resistance of obese children and the development of obesity.3、The insulin resistance of simple obese children was positively correlated to BMI,WC and TG. Keeping BMI,WC,blood fat,obestatin,ghrelin is beneficial to reduce the occurrence, delay the development of obesity and insulin resistance.4、There was significant correlation between ghrelin/obestatin and BMI、 WHR.It indicated that ghrelin/obestatin had some relationship with obesity of children, especially with abdominal obesity of children.

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CLC: > Medicine, health > Pediatrics > Infant nutrition disorders > Digestion and nutrition disorders > Obesity
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