The Impacts Of Pancreatic Exocrine Diseases On Pancreatic Endocrine Function:Clinical Trials

Section 1: Clinical features and associated diseases of dorsal pancreas agenesis: a retrospective analysis of 91 cases.Objective: To analysis the clinical features of dorsal pancreas agenesis and describe associated diabetes,pancreatitis and other malformations.Methods: Chinese databases of Sinomed,CQVIP and CNKI,and English databases of Pubmed were systematically searched.All cases of dorsal pancreas agenesis so far were collected and fully analyzed.Results: A total of 91 patients with dorsal pancreas agenesis were included,of which 21 patients were reported in Chinese articles and the rest were reported in English literature.After removing cases with insufficient information,39 patients(61.9%)carried abnormal pancreatic head.Prevalence of diabetes or impaired glucose tolerance was 56.7% and the percentage of insulin-dependent diabetes was 47.3%.Otherwise,20 patients(26.7%)were associated with pancreatitis and 33 patients(36.2%)suffered other malformations,even multi-organs malformations.Conclusions: Dorsal pancreas agenesis is a rare congenital anormaly associated with diabetes,pancreatitis and other malformations.Diabetes is the most common complications and nearly half of the patients are insulin-dependent.The diagnosis of these patients should be considered as type 3c.In addition,some authors suggest the occurrence of pancreatitis may be associated with genetic predisposition.Finally,considering the high prevalence of other concurrent malformations,when a dorsal pancreas agenesis patient needs a surgery,a preoperative evaluation of anatomic structure of the operation area should be carried out thoroughly.Section 2: Pathogenesis and therapeutic strategy of chronic pancreatitis related diabetes: a primary clinical trial.Objective: to explore the role of insulin deficiency,insulin resistance and several pancreas-related endocrine hormones in the pathogenesis of chronic pancreatitis related pancreatogenous diabetes.Also,the clinical features of glycometabolism in chronic pancreatitis patients with different subtypes were compared to improve the therapeutic strategy of this subset of patients.Methods: Part 1: According to inclusion and exclusion criteria,consecutive patients with chronic pancreatitis from April 2016 to November 2016 in Department of Gastroenterology,Changhai Hospital,Second Military Medical University were included.Plasma insulin,C-peptide and index of homeostasis model assessment for insulin resistance between patients with dysfunctional glycometabolism and patients with normal glycometabolism was compared.Prevalence of dysfunctional glycometabolism,insulin,C-peptide,Hb A1 c,fasting blood glucose and index of homeostasis model assessment for insulin resistance were compared between groups of patients with alcoholic chronic pancreatitis and non-alcoholic chronic pancreatitis.Part 2: According to inclusion and exclusion criteria,consecutive patients from September 2016 to November 2016 in Department of Gastroenterology,Changhai Hospital,Second Military Medical University and ten healthy control(matched for age and gender)were included.Basal levels of glucagon-like peptide 1,pancreatic polypeptide,Secretin,glucagon,somatostatin between groups of CP vs healthy control,CP with abnormal glycometabolism vs CP with normal glycometabolism and alcoholic CP vs non-alcoholic CP were compared.Results: Part 1: A total of 121 patients with chronic pancreatitis were included in this study,including 41 alcoholic chronic pancreatitis and 80 non-alcoholic chronic pancreatitis.(1)Index of homeostasis model assessment for insulin resistance in patients with diabetes is statistically higher than that in patients with normal glycometabolism,whereas insulin and C-peptide were not statistically different among patients with diabetes,impaired glucose tolerance and normal glycometabolism.the level of secretin in healthy control patients is significant lower than that in CP patients;(2)Alcoholic chronic pancreatitis vs non-alcoholic chronic pancreatitis: the age,rates of male gender,prevalence of dysfunctional glycometabolism and Hb A1 c in patients with alcoholic chronic pancreatitis were significantly higher than that in non-alcoholic chronic pancreatitis,p<0.05;Part 2: A total of 53 patients with chronic pancreatitis and 8 healthy subjects were included in this study.(1)CP vs healthy controls: the level of secretin in healthy control patients is significant lower than that in CP patients;(2)CP with abnormal glycometabolism vs CP with normal glycometabolism: the level of triglyceride and somatostatin is significant lower than that in CP patients;the prevalence of patients with chronic alcohol consumption and the level of glucagon-like peptide 1 in CP with abnormal glycometabolism is significant higher than that in CP with normal glycometabolism,p<0.05;(3)the prevalence of abnormal glycometabolism in alcoholic CP group is significant higher than that in non-alcoholic CP.The results above are all of statistical significance,p<0.05.Conclusions: Patients with chronic pancreatitis related diabetes are frequently complicated with insulin resistance,progressive insulin deficiency and dysfunction of many kinds of pancreas-related hormones.We hypothesize that reversible hepatic insulin resistance combined with progressive insulin deficiency are likely to play an essential role in the pathogenesis of chronic pancreatitis related diabetes.When it comes to therapy,correct the deficiency of hepatic insulin resistance in patients with chronic pancreatitis may be helpful for interrupting the onset of pancreatogenous diabetes.Besides correcting hepatic insulin resistance,the methods to reduce deficiency of β-cells in patients with chronic pancreatitis related diabetes deserves further researches.