Diabetes Management And Gut Microbiota In Patients Undergoing Total Pancreatectomy

BackgroundIn recent years,with the advances in surgical techniques and postoperative management,total pancreatectomy(TP)has been increasingly performed in diffuse pancreatic diseases.The pancreatic endocrine and exocrine functions are completely lost after TP.Diabetes management is important to improve the quality of life and prognosis of these patients.However,studies on diabetes management after TP during different postoperative periods are still limited.Pancreatic diabetes mellitus has its special characteristics of gut microbiota,but studies on the gut microbiota of patients undergoing TP are also lacking.Objectives(1)To evaluate the glycemic control and diabetic treatment of patients undergoing TP during the perioperative and long-term follow-up period.(2)To explore the characteristics of gut microbiota in patients undergoing TP.MethodsA total of 104 patients undergoing TP for pancreatic tumors from a single center were included in the cohort.Based on preoperative glycemic status,patients were divided into three groups:nondiabetic group(NDG,n=46),short-duration diabetic group(SDG,preoperative diabetes duration ≤12 months,n=25),and long-duration diabetic group(LDG,preoperative diabetes duration>12 months,n=33).Perioperative and long-term follow-up data,including the overall survival,glycemic control,and treatment,were evaluated.Comparative analysis with complete insulin-deficient type 1 diabetes mellitus(T1DM)was conducted.The gut microbiota of 9 patients underwent TP without preoperative history of diabetes was compared with that of 9 sex-,age-,body mass index-,and glycated hemoglobin A1c(HbA1c)-matched patients with type 2 diabetes mellitus(T2DM)and 9 healthy controls by 16S rDNA V3-V4 sequencing.Results(1)The patients were recruited with a mean age at operation of 59.6±10.7 years,of which 50%were male.The most common pathological types were pancreatic ductal adenocarcinoma,intraductal papillary mucinous neoplasm,and pancreatic neuroendocrine tumor.(2)During hospitalization after TP,glucose values within the target(4.4-10.0 mmol/L)and 4.4-13.9 mmol/L accounted for 43.6%and 75.2%of the total data,respectively.During this period,45.2%of the patients experienced hypoglycemic events,and the majority were level 1 hypoglycemia(3.0-3.8 mmol/L).Patients received continuous intravenous insulin infusion during parenteral nutrition at a daily insulin dose of 1.22±0.47 units/kg/day.After the combination of basal insulin,glycemic control was improved,and the total daily insulin dose decreased.With the recovery of enteral nutrition,the daily insulin dose was significantly reduced(0.35±0.14 vs 1.22±0.47 U/kg/day,P<0.001).(3)In the long-term follow-up period,the HbA1c level was 7.37±0.77%.The daily insulin dose increased significantly in comparison with one month after surgery(0.49±0.18 vs.0.37±0.12 U/kg/day,P<0.001),and 14 patients were treated with insulin pumps at a daily insulin dose of 0.44±0.14 U/kg/day.HbA1c,as well as time in range and coefficient of variation assessed by continuous glucose monitoring,were similar to those in patients with T1DM.However,patients after TP had lower daily insulin dose(0.49±0.18 vs 0.64± 0.19 U/kg/day,P<0.001)and basal insulin percentage(38.3±16.3 vs 43.6±10.0%,P=0.01)than patients with T1DM.Whether in the perioperative or long-term follow-up period,daily insulin dose was significantly higher in LDG patients than in NDG and SDG patients.(4)The gut microbiota of TP patients showed different characteristics from that of healthy controls and patients with T2DM.Alpha diversity index,like Chaol index and observed species in patients undergoing TP showed a decreasing trend than in healthy controls,but there was no statistical significance.Beta diversity analysis suggested that the gut microbiota of TP patients was significantly different from that of healthy controls.The abundance of p＿Proteobacteria increased significantly in patients after TP.At the genus level,opportunistic pathogen such as g＿Klebsiella,g＿Veillonella,g＿Streptococcus and g Haemophilus were enriched in patients after TP.The abundance of short-chain fatty acid(SCFA)producing bacteria or bile acid metabolizing bacteria like g＿Parabacteroides and g＿parabcolarctobacterium decreased.ConclusionsThe glycemic control and insulin dose in patients undergoing TP varied according to different postoperative periods.During long-term follow-up,glycemic control and variability following TP were comparable to complete insulin-deficient T1DM but with fewer insulin requirements.As the postoperative insulin needs were higher in patients with long-duration preoperative diabetes,it was recommended to evaluate preoperative glycemic status for the guidance of insulin therapy after TP.The gut microbiota of patients undergoing TP showed increased abundance of opportunistic pathogen and decreased abundance of SCFAs producing bacteria,which might be related to pancreatic exocrine insufficiency or the underlying disease,so adequate pancreatic enzyme replacement therapy should be given to these patients.