| BackgroundBariatric&metabolic surgery is currently one effective treatment of type 2 diabetes mellitus(T2D)with obesity.With Roux-en-Y gastric bypass(RYGB)the most significant effect.However,the current middle and long-term efficacy of patients in China remained unclear,the predictor of postoperative remission of T2D need to be further explored.ObjectivesOur aim was to explore the middle-term effect of RYGB on T2D with obesity.By exploring the predictors of postoperative remission of T2D,and screening different genes.These works lay an experimental base for the future research for the mechanism of metabolic surgery treatment of type 2 diabetes.MethodsPart ?,clinical researchA retrospective analysis was performed on 170 patients with T2D and obesity who underwent RYGB,and the mid-term efficacy of RYGB and predictors of postoperative remission of T2D was analyzed.Part ?,animal researchEstablish the T2D with obesity SD rat model with a high-fat diet combined with low-dose streptozotocin,then operated and compare the effects of different metabolic surgery type.Visceral fat was analyzed by RNA-seq to screening different genes,and verify the relationship between the expression of specific different genes,surgical efficacy and islet function by qPCR.ResultsPart ?,clinical researchA total of 167 patients(98.2%)completed the study.The female rate was 53.9%with an average T2D duration of 7.1 ± 4.9 years.The hypertension and/or dyslipidemia accounted for 48.5%and 44.9%in patients,respectively.The baseline average BMI was 31.43 ± 3.56 kg/m2.The amount of medication related to metabolic disorders decreased significantly after surgery,and the curative effect of diabetes was the best in the first year after surgery.Remission rate of T2D at 3-year follow-up was 67.7%(113 patients).The T2D duration,fasting C peptide level,and visceral fat area are predictors of postoperative remission of T2D.Patients were more likely to get T2D remission as T2D duration<5.5 years,fasting C peptide level>2.54 ng/ml,and the visceral fat area>110.25 cm2.Serum Nrg4 levels in clinical patients at 3 years after RYGB showed that the Nrg4 level in remission group was significantly higher than in no remission group,which was significantly related to Hemoglobin Alc,postprandial blood glucose,rGT and glycated serum albumin.Part ?,animal researchThe overall success rate of the rat model was 77.2%(44/57).RYGB has significant effects on weight loss,improving blood glucose and insulin secretion.By RNA-seq of visceral fat,RYGB group showed many differences in the expression of glucose-lipid metabolism,endocrine and metabolic disease-related genes compared with control group,while in the expression of signal molecular interactions,signal transduction,and genes related to the endocrine system compared with sham group.The qPCR results in different gene showed that Nrg4(Neuroregulin 4)was highly expressed in the RYGB group,and was positively correlated with the expression of adiponectin and PDX-1(Pancreatic Duodenal Homeobox-1).ConclusionMetabolic surgery can improve T2D and obesity-related metabolic disorders.The T2D duration,fasting C peptide level,and visceral fat area are predictors of postoperative remission of T2D.Nrg4 was highly expressed in visceral fat after RYGB.Pancreatic PDX-1 highly expression after RYGB with islet ? cell function improved,and positively correlated with Nrg4 expression.Nrg4 might be an important gene involved in the mechanism of metabolic surgery in treatment of T2D. |
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