Analysis Of Pathogenic Genes In 2 Children With Diabetes Mellitus And Observation Of Their Efficacy And Literature Review

Objective To investigate molecular mechanism of neonatal diabetes mellitus by analysising the pathogenic genotypes in 2 kids with diabetes mellitus.Take glibenclamide in experimental treatment on neonatal diabetes.Mellitus patients who,diagnosed by molecular genetics,get KCNJ11 or ABCC8 mutation.Investigate the dose of oral sulfonylureas in children with NDM and evaluate the efficacy of the drug by observing the effect of clinical medication and provide reference for individualized treatment.The aim is to raise the awareness of physician in endocrinology department and pediatricians about this disease and provide new ideas for clinical treatment.Methods Two children with diabetes who were treated in Linyi People's Hospital of Shandong Province from May 2014 to December 2016 were diagnosed in line with the standards of medical diagnosis and treatment of diabetes issued by the American Diabetes Association in 2015.The diagnosis of iatrogenic hyperglycemia and stress hyperglycemia.Take peripheral blood from the two patience and then isolate and extract the DNA from it.Detect the two genes KCNJ11 and ABCC8 in method of Sanger(dideoxy chain termination method)and then get an clear image on situation of the gene mutation by nucleotide sequencing.According to the results of genetic testing,apply glibenclamide in experimental treatment on patients.Do research on reports of such case,in Wanfang Database,VIP Database,CNKI,and pubmed from 2004 to the present,which related to the treatment with sulfonylurea drugs for NDM patients who result from KCNJ11 mutation and review relevant literature.Retrieval words are in English and Chinese,Chinese retireval words include??????;KCNJ11;?????;????.English retireval words were neonatal diabetes mellitus;NDM;KCNJ11;sulfonylurea;SU;glybenclamide.Those releated paper issued from year of 2004 up to now.Results In the case of 1 KCNJ11 gene,one mutation locus c.602G>A was detected,which is a common known site of pathogenic gene mutation in permanent neonatal diabetes mellitus(PNDM).Case 2 KCNJ11 detected 2 heterozygous mutation c.67A>G and c.1009G>A,ABCC8 gene detected c.4106G>T 1 heterozygous mutations,all of which are nonpathogenic single nucleotide polymorphisms(Single Nucleotide Polymorphisms,SNP).Case 1 was given glibenclamide experimental treatment,the initial dose of 0.25mg/d,gradual withdrawal of insulin,glyburide dose was maintained at 0.20mg/kg/d,stable blood glucose control,no obvious hypoglycemia reaction.No obvious growth retardation,no mental abnormalities,followed up for 3 years to observe the growth of the same age children;Case 2 because found KCNJ11 and ABCC8 gene mutations,did not give glyburide conversion treatment,the application of insulin control blood sugar,repeated hypoglycemia,Poor blood glucose control,follow-up observation 1 year height and weight significantly behind their peers.During retrieving and reading the titles and abstracts of the literature,76 articles were selected,including 8 Chinese and 68 English texts.We carefully go through the full text of the literature,4 Chinese literatures and 43 English documents abandoned.Finally,a total of 29 articles were considered to be valuable,involving a total of 32 NDM children.Conclusion NDM is a rare disease,the pathogenesis of complex molecular mechanisms,the relative clinical manifestations of nonspecific,in our country KCNJ11 gene mutation may lead to the occurrence of NDM,genetic testing is an important method of diagnosis and NDM,oral glyburide for the presence of KCNJ11 genetic mutations in children with NDM significant effect.So for children born within 6 months after the occurrence of hyperglycemia should be related to the screening of pathogenic genes,which not only contribute to the diagnosis of etiology,to help clinicians according to different types of pathogenic genes for precise treatment,but also to enable children get rid of the pain caused by insulin injection,to achieve better control of blood sugar purposes,greatly improving children's quality of life and clinical prognosis.