| Background and objectiveOverweight and obesity of children has become an important public health problem that affects the physical and mental health of children and adolescents in China and even in the world.Overweight or obesity in children essentially increases the risk of other diseases,such as abnormal glucose and lipid metabolism,and it is easy to lead to many chronic diseases such as obesity,diabetes and cardiovascular and cerebrovascular diseases in adults.Studies have shown that the common metabolic change of childhood obesity(CO)is Insulin resistance(IR),which has been considered as the main factor of abnormal glucose metabolism,Type 2 diabetes mellitus(T2DM)and various cardiovascular diseases in children and adults.Obesity and T2 DM are mainly caused by multiple factors such as environment and heredity,and genetic factors play an important role.Scholars at home and abroad,through a large number of Genome-Wide Association Studies(GWAS),point out that there is a significant correlation between GNPDA2 and early childhood obesity,insulin resistance(IR)and type 2 diabetes mellitus(T2DM)in obese individuals.Therefore,this study provides a theoretical basis for early diagnosis and intervention of obesity,IR and T2 DM in children by exploring the role of this gene in glucose metabolism in obese children.Methods112 children,aged from 7 to 14 years,were selected from the Department of child care of the Affiliated Hospital of Affiliated Hospital of Nantong University from January 2022 to December 2022.According to the diagnostic criteria of obesity and insulin resistance in children,they were divided into 34 cases of simple obesity group(OB group),34 cases of insulin resistance group(IR group)and 44 cases of normal control group(Control group).The three groups of children were investigated by clinical data,laboratory data and venous blood collection.The expression levels of GNPDA2,PDE3 B and PDE4 D in children’s blood were detected by real-time fluorescence quantitative PCR.The level of IL-6 in serum in the subjects was measured by enzyme-linked immunosorbent assay.IBM SPSS Statistics 26 statistical software for statistical analysis,Graphpad Prism9.3 software for draft.SPSS 22.0 statistical software for statistical analysis.The measurement data conform to the normal distribution,The measurement data conform to the normal distribution,expressed by mean ± standard deviation,and the non normal distribution is expressed by median and interquartile spacing.The variance of normal distribution was homogeneous,and the comparison between groups was analyzed by analysis of variance;Kruskal-Wallis H test was used to compare the data of uneven variance and non normal distribution.The counting data are expressed by constituent ratio and chi square test is used.Pearson correlation analysis was used for correlation analysis.P < 0.05 was statistically significant.Results1.The BMI of obese children(including IR group and OB group)was significantly higher than that of healthy children,and the BMI of children in insulin resistance group was significantly higher than that of children in simple obesity group,with statistical significance(P < 0.05).2.The levels of FINS,HOMA-IR,C-peptide and TG in obese children(including IR group and OB group)were higher than those in healthy children,and the difference was statistically significant(P < 0.01).The levels of HDL and Apo A1 were lower than those of healthy children,and the difference was statistically significant(P < 0.05).However,there was no significant difference in FPG,Hb Alc%,TC,LDL,Apo B,lipoprotein A and FFA among the three groups(P > 0.05).Comparing the three groups,the levels of FINS,HOMA-IR and C-peptide in children with insulin resistance were higher than those in children with simple obesity,and the levels of FINS,HOMA-IR and C-peptide in children with simple obesity were higher than those in healthy controls,with statistical significance(P < 0.05).3.WBC,monocyte,IL-6,monocyte/high density lipoprotein ratios(MHR)and monocyte/apolipoprotein A1 ratios(MAR)of obese children(including OB group and IR group)were higher than those of healthy children,and the difference was statistically significant(P < 0 However,there was no significant difference in the levels of hypersensitivity CRP among the three groups(P > 0.05).Among them,the level of IL-6in the insulin resistance group was higher than that in the other two groups,and the level of IL-6 in the simple obesity group was also higher than that in the healthy control group,with statistical significance(P < 0.05).The MHR and MAR values in insulin resistance group were higher than those in the other two groups(P < 0.05).However,there was no significant difference between the results of MHR and MAR between simple obesity group and healthy control group(P > 0.05).4.The levels of LH and uric acid in obese children(including OB group and IR group)were higher than those in healthy children,and the difference was statistically significant(P < 0.01).However,there was no significant difference in FSH level(P >0.05).The LH level of children in insulin resistance group was higher than that in simple obesity group and healthy control group(P < 0.05),but there was no statistical difference between simple obesity group and healthy control group(P > 0.05).The uric acid of obese children was higher than that of healthy children,but there was no significant difference between simple obesity group and insulin resistance group(P >0.05).5.The expression level of GNPDA2 gene in children with insulin resistance was higher than that in healthy children(P < 0.05);However,the expression levels of PDE3 B and PDE4 D genes were lower than those of healthy children,and the difference was statistically significant(P < 0.05).GNPDA2 was negatively correlated with the expression levels of PDE3 B and PDE4D(the correlation coefficients were: r =-0.275;r=-0.276;P<0.05)。 There was a positive correlation between PDE3 B and PDE4 D gene expression level(correlation coefficient r = 0.285;P<0.05)6.The expression level of 6)GNPDA2 gene was positively correlated with glucose and lipid metabolism indexes BMI,FINS,HOMA-IR,C-peptide,Hb Alc% and FFA(the correlation coefficients were r = 0.372;r=0.306;r=0.328;r=0.350;r=0.285;r=0.208,P<0.05)。7.The expression level of 7)GNPDA2 was positively correlated with WBC count,MHR,MAR,IL-6,serum uric acid and LH(the correlation coefficients were r = 0.277;r=0.355;r=0.365;r=0.349;r=0.236;r=0.265;P<0.05)。Conclusion1.GNPDA2 is closely related to childhood obesity and insulin resistance.2.GNPDA2 may regulate blood sugar through PDE3B/PDE4 D pathway.3.GNPDA2 may affect glucose metabolism in obese children through the related pathway of inflammatory factor IL-6. |
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