Pancreatic Endocrine Function Research Articles

Perceptions of genetic testing in patients with hereditary chronic pancreatitis and their families: a qualitative triangulation

Hereditary chronic pancreatitis (HCP) is a genetically determined condition characterized by intermittent acute episodes of pancreatitis and long-term impairment of the exocrine and endocrine pancreatic functions. Genetic test results can have substantial psychological and social consequences for the individuals tested and their families. Nevertheless, little is known so far about the subjective experience of individuals genetically tested for HCP. This qualitative study examines the viewpoints of HCP patients and their relatives in order to identify the psychosocial and ethical implications related to genetic testing within families. Semi-structured qualitative individual interviews and a focus group with HCP patients and their family members were conducted. Data were audio-recorded, transcribed verbatim and analysed using qualitative content analysis. A total of 28 individuals were enrolled in the study: 24 individuals (17 patients, 7 relatives) were interviewed in semi-structured one-on-one interviews and 4 individuals (2 patients, 2 life partners) participated in the focus group. Emerging topics covered (1) genetic testing in childhood, (2) genetic testing within the family and (3) family planning. The study reveals that genetic testing for HCP has a wide influence in familial contexts and is accompanied by normative issues, such as autonomy, reproductive decisions and sharing of information within the family. The results raise the awareness of the complexity of family contexts: familial relationships and dynamics can have great influence on the individual decisions related to genetic testing. Increased understanding of these relational contexts can help health professionals, for example, in counselling, to discuss genetic testing better with patients and families.

Open modified puestow procedure in an advanced endoscopic era for chronic pancreatitis with dilated pancreatic duct and stones

Background: Chronic pancreatitis has been defined as a continuing inflammatory disease of the pancreas characterized by irreversible morphological changes. These changes typically cause pain and loss of exocrine and endocrine pancreatic function. The most common symptom of chronic pancreatitis is pain, which can be severe and intractable in some patients. Although it is itself benign, chronic pancreatitis can significantly affect quality of life and can cause significant distress with its complications [1]. The initial treatment for pain in most cases is to start of enzyme replacement, control of diabetes with insulin, and administration of oral analgesics. Surgical intervention is required in patients with intractable pain that is resistant to conventional nonsurgical therapy, in patients with associated or suspected malignancy, and in patients who have developed complications such as biliary or duodenal obstruction, pancreatic fistulae, pancreatic ascites/pleural effusion, pseudocyst, or rare hemosuccus pancreaticus [2]. The aetiology of pain in chronic pancreatitis is unclear. Some evidence has suggested that perineural inflammation may be the cause of pain. A dilated pancreatic duct, secondary to obstruction, may cause increased intraductal pressures, resulting in pain [3]. The primary aim of therapy is the achievement of primary pain relief and an improvement in quality of life. This could be achieved by means of endoscopic, open or laparoscopic /robotic lateral pancreaticojejunostomy [4, 13]. Methods: We selected 41 cases of chronic pancreatitis of both genders with moderate to intractable pain hampering routine life. All patients tried conservative treatment for more than 6 months. All selected patients underwent haematological and radiological work up. MRCP of all patients showing dilated pancreatic duct more than 7mm. in size. All of these patients operated for longitudinal pancreaticojejunostomy (Modified Puestow’s). Follow up done for one year to ten years Results: All 41 patients in long term follow up were recovered well from pain and abdominal discomfort. Appetite were improved and weight gain noted in the patients after surgery. Conclusions: Longitudinal pancreaticojejunostomy is still safe, simple and timely approved procedure for pain associated with chronic pancreatitis.

Pancreatic necrosis and severity are independent risk factors for pancreatic endocrine insufficiency after acute pancreatitis: A long-term follow-up study.

BACKGROUNDPancreatic endocrine insufficiency after acute pancreatitis (AP) has drawn increasing attention in recent years.AIMTo assess the impact of risk factors on the development of pancreatic endocrine insufficiency after AP.METHODSThis retrospective observational long-term follow-up study was conducted in a tertiary hospital. Endocrine function was evaluated by the oral glucose tolerance test. The data, including age, sex, body mass index, APACHE II score, history of smoking and drinking, organ failure, pancreatic necrosis, debridement of necrosis (minimally invasive and/or open surgery), and time interval, were collected from the record database.RESULTSA total of 361 patients were included in the study from January 1, 2012 to December 30, 2018. A total of 150 (41.6%) patients were diagnosed with dysglycemia (including diabetes mellitus and impaired glucose tolerance), while 211 (58.4%) patients had normal endocrine function. The time intervals (mo) of the above two groups were 18.73 ± 19.10 mo and 31.53 ± 27.27 mo, respectively (P = 0.001). The morbidity rates of pancreatic endocrine insufficiency were 46.7%, 28.0%, and 25.3%, respectively, in the groups with different follow-up times. The risk factors for pancreatic endocrine insufficiency after AP were severity (odds ratio [OR] = 3.489; 95% confidence interval [CI]: 1.501-8.111; P = 0.004) and pancreatic necrosis (OR = 4.152; 95%CI: 2.580-6.684; P = 0.001).CONCLUSIONPancreatic necrosis and severity are independent risk factors for pancreatic endocrine insufficiency after AP. The area of pancreatic necrosis can affect pancreatic endocrine function.

Correlation of Pancreatic T1 Values Using Modified Look-Locker Inversion Recovery Sequence (MOLLI) with Pancreatic Exocrine and Endocrine Function.

Quantifying myocardial T1 values has been useful for detecting and characterizing fibrotic appearance in myocardial infarction, focal scars, and non-ischemic cardiomyopathies. Since pancreatic exocrine function decreases with chronic pancreatic fibrosis advancement, this study examined the correlation between pancreatic T1 values and pancreatic exocrine and endocrine insufficiency. Methods: Thirty-two patients underwent abdominal contrast-enhanced MRI in our department between October 2017 and February 2019. We evaluated the T1 values of the pancreas using a modified Look-Locker inversion recovery sequence (MOLLI), pancreatic exocrine insufficiency (PEI) by fecal elastase 1 (FE1) values, and pancreatic endocrine insufficiency using fasting insulin and blood glucose levels to calculate the HOMA-β. This trial is registered in the UMIN Clinical Trials Registry as UMIN 000030067. Results: The median cohort (9 males and 23 females) age was 71 (range: 49–84) years. Eighteen patients had pancreatic cysts, three had alcohol-induced chronic pancreatitis, three had pancreatic cancer, and eight possessed other pancreatic features (two patients each with autoimmune pancreatitis, acute pancreatitis, or a bile duct tumor, one with idiopathic chronic pancreatitis, and one healthy control with negative findings). The median pancreatic T1 value measured by the MOLLI was 857.5 ms (597–2569). A significant negative correlation was found between the T1 mapping and FE1 values (r = 0.69, p < 0.01), with none for the T1 with HOMA-β or serum albumin, triglycerides, or body mass index. Conclusions: the pancreatic T1 values correlated significantly with pancreatic exocrine function and might be useful in PEI diagnosis.

Comparative long-term outcomes for pancreatic volume change, nutritional status, and incidence of new-onset diabetes between pancreatogastrostomy and pancreatojejunostomy after pancreaticoduodenectomy.

The difference in volume change in a pancreatic remnant according to the type of pancreaticoenterostomy after pancreaticoduodenectomy (PD) for long-term follow-up is unknown. Also, there are few studies that evaluate the difference in general nutritional status and pancreatic endocrine function, including new-onset diabetes mellitus (NODM) depending on the type of pancreaticoenterostomy. This study aimed to compare serial pancreatic volume changes in pancreatic remnants between pancreatogastrostomy (PG) and pancreatojejunostomy (PJ) after PD and to evaluate the difference in general nutritional status and incidence of NODM between PG and PJ. This study enrolled 115 patients who had survived for more than 3 years after PD. They were divided into the PG group and the PJ group. Their clinicopathologic factors were collected and analyzed. We calculated serial pancreas volume and pancreatic duct size precisely from preoperative stage to 5 years after surgery by image-processing software specifically designed for navigation and visualization of multimodality and multidimensional images. Consecutive changes of albumin and body mass index (BMI) as related to general nutritional status were compared between the PG and PJ groups. To evaluate the incidence and risk factors of NODM following PD, subgroup analysis was performed in 88 patients who did not have diabetes preoperatively. Most patient demographics were not significantly different between the PG group (n=45) and PJ group (n=70). There was no significant difference in volume reduction between the groups from postoperative 1 month to 5 years (PG group -18.21±14.66 mL versus PJ group -14.43±13.05 mL, P=0.209). But there was a significant difference in increased pancreatic duct size between the groups from postoperative 1 month to 5 years (PG group 1.66±2.20 mm versus PJ group 0.54±1.54 mm, P=0.007). There was no significant difference in the increase of total serum albumin between the groups for 5 years after surgery (PG group 0.51±0.47 g/dL, 14.3% versus PJ group 0.42±0.60 g/dL, 11.3%, P=0.437). There was also no significant difference in BMI decrease between the groups (PG group -1.13±3.12, -4.9% versus PJ group -1.97±2.01, -8.7%, P=0.206). On the whole, NODM was diagnosed in 19 patients out of the 88 patients (21.6%) who did not have DM preoperatively. The incidence of NODM was not significantly different between the groups (PG group 21.6% versus PJ group 21.5%, P=0.995). In addition, pancreaticoenterostomy was not an independent risk factor for NODM by logistic regression analysis (odds ratio, 0.997, 95% CI: 0.356-0.2.788, P=0.995). No other risk factors for NODM were found. PG and PJ following PD induced similar pancreatic volume reduction during long-term follow-up. There was no difference in general nutritional status or incidence of NODM between the groups after PD.

147-OR: Long-Term Effect of GLP-1 on Pancreas Endocrine Function after Gastric Bypass in Individuals with and without Diabetes Remission

The contribution of GLP-1 on glucose control after gastric bypass (GBP) is not fully elucidated. Hypotheses: The improvement in β-cell glucose sensitivity (BCGS) to oral glucose after GBP is GLP-1 mediated, weight loss independent, and varies according to diabetes (T2D) remission status; The administration of exendin 9-39 (EX9), a GLP-1 receptor blocker, has minimal effect on blood glucose. Methods: Patients with T2D (n=29) underwent a 75 g OGTT prior to and at 3, 12 and 24 months (M) after GBP. Glucose, insulin secretion rates (ISR), BCGS, and glucagon were measured with and without EX9. The cohort was retrospectively divided into 3 groups based on T2D remission status determined at the latest study time point (24 or 12M): remitters (REM, n=5), persistent T2D (P-T2D, n=8), impaired (IGT, n=16). Results: Prior to GBP, patients were 42.9±8.3y old, had a BMI of 42.4±4.6 kg/m2, 7.7±7.3 y known T2D duration, an HbA1c of 7.8±1.1% (35% on insulin) and an HOMA-IR of 11.5±5.8. Both magnitude and temporal increases in BCGS varied according to remission status: greater (up to 6.5 fold, p&amp;lt;0.03) and sustained in REM, variable in IGT (∼3 fold, p&amp;lt;0.01), minimal and only transient (3M, p=0.014) in P-T2D. These differences were not explained by weight-loss since it did not differ between the 3 groups at any time. EX9 reversed the effect of GBP on ISR at 3, 12 and 24M (p&amp;lt;0.003); it further enhanced the rise in post-prandial glucagon, but this effect was only significant at 3M (p=0.005). Both effects varied in magnitude overtime and by remission status. Glucose improved after GBP, as expected; EX9 decreased glucose levels at 3M in the whole cohort (p&amp;lt;0.001), but had no effect on glucose at 12 and 24M. EX9 increased significantly, albeit minimally, glucose at 120 and/or 180 minutes during the OGTT in REM and IGT, but not in P-T2D. Conclusions: Our data suggest that the effect of endogenous GLP-1 on pancreatic endocrine function and glucose varies with time and according to remission status after GBP. Disclosure M.A. Prasad: None. A. Shah: None. V.M. Mark: None. N. Nair: None. J.J. Holst: Advisory Panel; Self; AstraZeneca, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Spouse/Partner; Antag Therapeutics. Funding National Institutes of Health (R01DK67561, DK007559, P30DK26687, UL1RR024156, UL1TR000040, F32DK113747)

Designing a bioelectronic treatment for Type 1 diabetes: targeted parasympathetic modulation of insulin secretion.

The pancreas is a visceral organ with exocrine functions for digestion and endocrine functions for maintenance of blood glucose homeostasis. In pancreatic diseases such as Type 1 diabetes, islets of the endocrine pancreas become dysfunctional and normal regulation of blood glucose concentration ceases. In healthy individuals, parasympathetic signaling to islets via the vagus nerve, triggers release of insulin from pancreatic β-cells and glucagon from α-cells. Using electrical stimulation to augment parasympathetic signaling may provide a way to control pancreatic endocrine functions and ultimately control blood glucose. Historical data suggest that cervical vagus nerve stimulation recruits many visceral organ systems. Simultaneous modulation of liver and digestive function along with pancreatic function provides differential signals that work to both raise and lower blood glucose. Targeted pancreatic vagus nerve stimulation may provide a solution to minimizing off-target effects through careful electrode placement just prior to pancreatic insertion.

Investigation of morphological and functional changes in the liver and pancreas during bevacizumab treatment

Objectives: Recently, there have been reports regarding the atrophy of various organs caused by molecular targeted drugs. We investigated morphological and clinical changes in the liver and pancreas caused by treatment with bevacizumab.Methods: We investigated 30 patients with colorectal cancer who received bevacizumab-containing chemotherapy (study group) and 11 patients with colorectal cancer who received chemotherapy without bevacizumab (control group) from 2010 to 2014. We obtained computed tomography data of the liver and pancreas and performed three-dimensional image analysis and volumetry. Laboratory data before and after chemotherapy were analyzed.Results: There was no significant difference in liver volume before and after bevacizumab-containing chemotherapy, but the pancreatic volume was found to be significantly reduced after bevacizumab-containing chemotherapy (57.9 ± 16 mL versus 47.4 ± 15.3 mL; p = .005). The liver and pancreatic volume did not change statistically in the control group. With regard to complete blood cell counts and laboratory data, no significant differences were observed in the leukocyte count and hemoglobin, hemoglobin A1c, triglyceride, albumin, and C-reactive protein levels. In contrast, there was a significant decrease in the platelet count, total cholesterol level and a significant increase in the amylase level. A chemotherapy regimen that included bevacizumab reduced pancreatic volume and significantly altered the morphology of the pancreas.Conclusions: Although bevacizumab caused atrophy of the pancreas and reduced pancreatic volume, pancreatic endocrine function showed no change. Future studies should investigate the survival rate and functional changes caused by bevacizumab treatment.

Recent Advances in Understanding the Complexity of Alcohol-Induced Pancreatic Dysfunction and Pancreatitis Development.

Chronic excessive alcohol use is a well-recognized risk factor for pancreatic dysfunction and pancreatitis development. Evidence from in vivo and in vitro studies indicates that the detrimental effects of alcohol on the pancreas are from the direct toxic effects of metabolites and byproducts of ethanol metabolism such as reactive oxygen species. Pancreatic dysfunction and pancreatitis development are now increasingly thought to be multifactorial conditions, where alcohol, genetics, lifestyle, and infectious agents may determine the initiation and course of the disease. In this review, we first highlight the role of nonoxidative ethanol metabolism in the generation and accumulation of fatty acid ethyl esters (FAEEs) that cause multi-organellar dysfunction in the pancreas which ultimately leads to pancreatitis development. Further, we discuss how alcohol-mediated altered autophagy leads to the development of pancreatitis. We also provide insights into how alcohol interactions with other co-morbidities such as smoking or viral infections may negatively affect exocrine and endocrine pancreatic function. Finally, we present potential strategies to ameliorate organellar dysfunction which could attenuate pancreatic dysfunction and pancreatitis severity.

Pheochromocytoma With Adrenergic Biochemical Phenotype Shows Decreased GLP-1 Secretion and Impaired Glucose Tolerance.

Impaired glucose homeostasis is a common finding in pheochromocytoma (PHEO), especially with adrenergic phenotype. The possible contribution of incretin dysfunction to dysglycemia in PHEO patients has not been studied. To compare changes in pancreatic endocrine function and gut hormones' production during a liquid meal test before and 1 year after adrenalectomy. In a prospective study, we included 18 patients with PHEO (13 females) with adrenergic biochemical phenotype. A liquid meal test with predefined isocaloric enteral nutrition was performed to evaluate dynamic changes in pancreatic hormones and incretins. During the meal test, insulin levels were significantly lower before adrenalectomy only in the early phase of insulin secretion, but changes in area under the curve (AUC) did not reach statistical significance (AUC = 0.07). Plasma glucagon (AUC < 0.01) and pancreatic polypeptide levels (AUC < 0.01) were suppressed in comparison with the postoperative state. Impaired response to the meal was found preoperatively for glucagon-like peptide-1 (GLP-1; AUC P < 0.05), but not glucose-dependent insulinotropic polypepide (GIP; AUC P = 0.21). No significant changes in insulin resistance indices were found, except for the homeostatic model assessment-beta index, an indicator of the function of islet β cells, which negatively correlated with plasma metanephrine (R = -0.66, P < 0.01). Our study shows suppression of pancreatic α and β cell function and impaired GLP-1 secretion during a dynamic meal test in patients with PHEO, which is improved after its surgical treatment. These data demonstrate a novel and potentially significant interconnection between excessive catecholamine production and the secretion of glucoregulatory hormones.

The possible protective effect of Nano-Selenium on the endocrine and exocrine pancreatic functions in a rat model of acute pancreatitis

BackgroundAcute pancreatitis is a serious condition with multi-factorial etiology. The negative impact of acute pancreatitis on the exocrine pancreatic function is well documented; however, its impact on the endocrine function needs more elucidation. Our study aimed to investigate the effect of Nano-Selenium (Nano-Se) on both pancreatic functions in acute pancreatitis. Methodsl-arginine induced acute pancreatitis in rats was used as a model. Fifty adult male albino rats were separated into groups: 1- control group (C), 2- C+ Nano-Se, 3-acute pancreatitis group (AP) and 4- AP+ Nano-Se. Nano-Se was administered before induction of acute pancreatitis. Serum levels of amylase, lipase, selenium, glucose, insulin and interleukin-1β (IL-1β) were measured. Homeostatic model assessment of beta cell function (HOMA-β) was also calculated. Oxidative stress markers, selenium content and the anti-apoptotic factor, B-cell leukemia/lymphoma-2 (Bcl-2) were assayed in pancreatic tissue along with immuno-expression of nuclear transcription factor-kappa B (NF-κB). ResultsAcute pancreatitis negatively affected both pancreatic functions. Nano-Se administration lessened the developed pancreatic injury and improved both pancreatic functions. ConclusionNano-Se could improve the deteriorated pancreatic functions in acute pancreatitis via its anti-inflammatory, antioxidant and pro-apoptotic actions. Thus, it may be used in prevention of acute pancreatitis and the associated hyperglycemia in vulnerable individuals such as patients undergoing endoscopic retrograde cholangio-pancreatography.

Psoas muscle size as a magnetic resonance imaging biomarker of progression of pancreatitis

Pancreatitis often represents a continuous inflammatory process, from the first episode of acute pancreatitis (FAP) to recurrent acute pancreatitis (RAP) to chronic pancreatitis (CP). Psoas muscle size is a validated surrogate for global skeletal mass, changes in which are associated with inflammation. The objective was to investigate psoas muscle size in individuals following FAP, RAP, and CP, as well as its associations with pro-inflammatory cytokines. Individuals following pancreatitis and healthy individuals were recruited. All participants underwent magnetic resonance imaging, from which psoas muscle volume was derived independently by two raters in a blinded fashion. Circulating levels of four major cytokines (interleukin-6, tumour necrosis factor-α, C-C motif chemokine ligand 2, and leptin) were measured. Five linear regression additive models were built to adjust for possible confounders (age, sex, body composition, physical activity, tobacco smoking, alcohol consumption, comorbidities, and endocrine and exocrine pancreatic functions). A total of 145 participants were enrolled. A significant downward trend in psoas muscle volume was observed between healthy controls and individuals following FAP, RAP, and CP in all adjusted models (p = 0.047, 0.005, 0.004, and < 0.001). Leptin was significantly associated with psoas muscle volume in all models (β = - 0.16, p = 0.030 in the most adjusted model). The other studied cytokines were not significantly associated with psoas muscle volume. Psoas muscle size is significantly reduced along the continuum from FAP to RAP to CP. Leptin appears to be one of the factors implicated in this. Further studies are warranted to investigate the relationship between skeletal muscle and inflammation of the pancreas. • First acute pancreatitis, recurrent acute pancreatitis, and chronic pancreatitis were associated with progressively reduced psoas muscle size. • The findings were independent of age, sex, body fat composition, physical activity, tobacco smoking, alcohol consumption, comorbidities, and exocrine and endocrine functions of the pancreas. • The mechanism underlying the observed findings may involve hyperleptinaemia.

Glucose-responsive insulin patch for the regulation of blood glucose in mice and minipigs.

Glucose-responsive insulin delivery systems that mimic pancreatic endocrine function could enhance health and improve quality of life for people with type 1 and type 2 diabetes with reduced β-cell function. However, insulin delivery systems with rapid in vivo glucose-responsive behaviour typically have limited insulin-loading capacities and cannot be manufactured easily. Here, we show that a single removable transdermal patch, bearing microneedles loaded with insulin and a non-degradable glucose-responsive polymeric matrix, and fabricated via in situ photopolymerization, regulated blood glucose in insulin-deficient diabetic mice and minipigs (for minipigs >25 kg, glucose regulation lasted >20 h with patches of ~5 cm2). Under hyperglycaemic conditions, phenylboronic acid units within the polymeric matrix reversibly form glucose-boronate complexes that-owing to their increased negative charge-induce the swelling of the polymeric matrix and weaken the electrostatic interactions between the negatively charged insulin and polymers, promoting the rapid release of insulin. This proof-of-concept demonstration may aid the development of other translational stimuli-responsive microneedle patches for drug delivery.

Pancreatic senescence and its clinical manifestations.

The pancreas is a vital organ which has both endocrine and exocrine functions and plays an essential role in food digestion and glucose metabolism. Pancreatic structure and function undergo a series of changes with aging and senescence. Pancreatic exocrine and endocrine function gradually change, which may lead to conditions such as dyspepsia and diabetes mellitus. Hence, clinicians need to be familiar with the characteristics of pancreatic senescence. This article reviews the manifestations of pancreatic senescence and its significance for clinical practice.

Duodenal-preserving pancreatic head resection with limited distal pancreatectomy: A novel, tailored approach for chronic pancreatitis

Presenter: Thomas Maatman MD | Indiana University Background: Operative management of chronic pancreatitis (CP) must be tailored to individual patient’s anatomy to achieve durable symptom relief. Incomplete drainage of an atrophic pancreatic tail is a common cause of symptom recurrence in patients undergoing drainage procedures. We have selectively applied limited distal pancreatectomy (DP) with duodenal-preserving pancreatic head resection (DPPHR) to patients with appropriate anatomy and hypothesized that this novel procedure provides durable therapy. Methods: Ten patients underwent DPPHR combined with limited DP between 2013-2018. Patient demographics, comorbidities, perioperative outcomes, and long-term CP-specific outcomes were recorded. Measurements of the pathology specimen determined pancreas tail volume. Chronic pancreatitis specific outcomes included endocrine/exocrine insufficiency, pain relief, and nutritional status. The amount of opioid pain medication was reported as daily morphine equivalents. Body mass index (BMI) and albumin were reported as surrogates for nutritional status. Descriptive statistics were applied. Continuous data are reported as means ± standard error of the mean. Results: Ten patients (8 females; age 49 ± 3 years) had etiology of idiopathic (n = 4), alcohol (n = 2), sequelae of severe acute pancreatitis (n = 1), hereditary (n = 1), autoimmune (n = 1), and pancreas divisum (n = 1). Operation was 57 ± 14 months after CP diagnosis. Patients had 6 ± 1 endoscopic procedures prior to operation. Mean operative time was 215 ± 11 minutes; estimated blood loss was 110 ± 28 mL. On average, 6 ± 1 cm of pancreatic tail was resected. Splenic preservation was possible in 7 patients. Postoperative LOS was 13 ± 2 days. Postoperative morbidity occurred in two patients; one grade B postoperative pancreatic fistula and one perforated duodenal ulcer. Readmission occurred in 5/10 patients at median time of 36 days (range, 16-78 days) postoperatively. Causes included abdominal pain (n = 2), small bowel obstruction (n = 1), intraabdominal abscess requiring antibiotic therapy (n = 1), and failure to thrive (n = 1). No perioperative mortality occurred. Overall, analgesic requirements and nutrition (measured by albumin) improved substantially (Figure 1). In addition, improvement in BMI (preoperative, 23.5 ± 1 kg/m2) was sustained at one- (23.7 ± 1 kg/m2), three- (25.6 ± 1 kg/m2), and five-years postoperatively (24.2 ± 1 kg/m2). At operation, 20% of patients required insulin; at five-year follow up this number was 25%. Eighty percent of patients were prescribed exocrine replacement preoperatively; all patients were on exocrine replacement at five-year follow up. During follow up (mean, 38 ± 7 months), one patient with hereditary CP underwent salvage total pancreatectomy with islet cell auto-transplantation 13 months postoperatively. Conclusion: In select chronic pancreatitis patients, including limited distal pancreatectomy with duodenal-preserving pancreatic head resection provides durable, long-term pain relief and improves nutritional parameters with minimal effect on pancreatic endocrine and exocrine function. This operation should be considered in select patients with appropriate anatomy.

First-Phase Insulin and Amylin after Bariatric Surgery: A Prospective Randomized Trial on Patients with Insulin Resistance or Diabetes after Gastric Bypass or Sleeve Gastrectomy

Background: Most patients with severe obesity show glucose intolerance. Early after sleeve gastrectomy (LSG) or gastric bypass (LRYGB), a marked amelioration in glycemic control occurs. The underlying mechanism is not yet clear. Objective: To determine whether the improvement in glycemic control on the level of endocrine pancreatic function is due to an increased first-phase insulin secretion comparing LRYGB to LSG. Setting: University of Basel Hospital and St. Clara Research Ltd., Basel, Switzerland. Methods: Sixteen morbidly obese patients with severe obesity and different degrees of insulin resistance were randomized to LSG or LRYGB, and islet cell functions were tested by intravenous glucose and intravenous arginine administration before and 4 weeks after surgery. Results: Fasting insulin and glucose levels and homeostasis model assessment insulin resistance were significantly lower in both groups after surgery compared to baseline, while no change was seen in fasting C-peptide, amylin, and glucagon. After intravenous glucose stimulation, no statistically significant pre- to postoperative change in area under the curve (AUC 0–60 min) was seen for insulin, glucagon, amylin, and C-peptide. No statistically significant pre- to postoperative change in incremental AUC for first-phase insulin release (AUC 0–10 min), second-phase insulin secretion (AUC 10–60 min), and insulin/glucose ratio could be shown in either group. Arginine-stimulated insulin and glucagon release showed no pre- to postoperative change. Conclusion: Intravenous glucose and arginine administrations show no pre- to postoperative changes of insulin release, amylin, glucagon, or C-peptide concentrations, and no differences between LRYGB and LSG were found. The postoperative improvement in glycemic control is not caused by changes in endocrine pancreatic hormone secretion.

A Case of Type 2 Diabetes Mellitus With Elevated Pancreatic Exocrine Enzyme Levels and Decreased Pancreatic Endocrine Function During Immunosuppressive Therapy for Systemic Lupus Erythematosus

A Case of Type 2 Diabetes Mellitus With Elevated Pancreatic Exocrine Enzyme Levels and Decreased Pancreatic Endocrine Function During Immunosuppressive Therapy for Systemic Lupus Erythematosus

Efficiency of Shidnitsa mineral waters in complex rehabilitation of patients with chronic pancreatitis with concomitant diabetes mellitus

Relevance. Rehabilitation of patients with chronic pancreatitis (CP) combined with diabetes mellitus (DM) requires a complex systemic and personified approach, since such comorbidity is characterized by complicated interactions of these nosology items, with more lesions of pancreas as the main organ involved in the formation and depth pathological manifestations of each patient, as well as the involvement of adjacent organs of the gastrointestinal tract, other organs and systems. Process of integrated rehabilitation, which purpose is to maximally restore the lost functions of the above organs, especially the pancreas, should include, in addition to standard protocol approaches, the adjuvant effective techniques that showed their practical effectiveness but require research and scientific substantiation. Such techniques include the use of therapeutic mineral water (MW) both in resorts and in outpatient practice according to the place of residence of patients.&#x0D; The aim of the study is to investigate the effectiveness of rehabilitation of patients with CP and concomitant DM with the use of the drug ademetionin in the sublingual form (Agepta) and the course of treatment with drinking MW of the Shidnitsa deposit.&#x0D; Material and methods of research. 77 patients with CP and concomitant DM were examined. According to treatment programs, patients were divided into 3 groups: Group 1 (protocol treatment (PT) — 26 patients) — received enzyme preparation of pure pancreatin, proton pump inhibitor (pantoprazole 40 mg), anesthetics (mebeverin) and/or prokinetic (motilium), metformin 1000 mg twice a day); Group 2 (PT + ademetionin — 26 patients) — in addition to PT received a drug ademetionin (sublingual tablets Agepta 400 mg) 1 tablet 2 times per day 30–60 min before eating, holding under tongue at least 15–20 min — until complete dissolution, 1 month course; Group 3 — in addition to PT and Agepta in the above-mentioned scheme, they took the course of treatment by drinking MW of the Shidnitsa deposit according to the proposed scheme.&#x0D; Results. Positive dynamics in all groups of comparison was revealed, but its intensity differed in those groups. Improvement of exocrine and endocrine pancreatic function was found: level of fecal α-elastase increased by 58.5% in Group 1, by 82.6% in Group 2, by 93.4% in Group 3; level of blood glucose decreased by 9.2% in Group 1, by 13.3% in Group 2, by 19.5% in Group 3; level of HbA1c — by 4.9% in Group 1, by 9.2% in Group 2, by 12.2% in Group 3; changes in the coprogram — by 24.5% in Group 1, by 38.6% in Group 2, by 55.2% in Group 3.&#x0D; Discussion. There was a statistically significant improvement in the results of Group 2 as compared to Group 1 (p&lt;0.05), which indicates the effectiveness of use of ademetionin (Agepta sublingual tablets) in a comprehensive correction program for patients with CP and DM. However, the most evident dynamics of indicators of exocrine and endocrine pancreatic function was found in Group 3 as compared to Groups 2 and 1, respectively, indicating the expediency of the additional appointment of the therapeutic course of drinking MW of the Shidnitsa deposit according to the proposed scheme.&#x0D; Conclusion. The effectiveness of inclusion of ademetionin in complex standard protocol program of treatment of patients with CP with concomitant DM in sublingual tablets (Agepta) with 400 mg twice a day during 1 month and 14-day course of treatment with drinking MW of the Shidnitsa deposit according to the proposed scheme was proved by statistically significant improvement of the indices of exocrine and endocrine pancreatic function (p&lt;0.05).

Effect of the Incretin Hormones on the Endocrine Pancreas in End-Stage Renal Disease.

The insulin-stimulating and glucagon-regulating effects of the 2 incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), contribute to maintain normal glucose homeostasis. Impaired glucose tolerance occurs with high prevalence among patients with end-stage renal disease (ESRD). To evaluate the effect of the incretin hormones on endocrine pancreatic function in patients with ESRD. Twelve ESRD patients on chronic hemodialysis and 12 matched healthy controls, all with normal oral glucose tolerance test, were included. On 3 separate days, a 2-hour euglycemic clamp followed by a 2-hour hyperglycemic clamp (3 mM above fasting level) was performed with concomitant infusion of GLP-1 (1 pmol/kg/min), GIP (2 pmol/kg/min), or saline administered in a randomized, double-blinded fashion. A 30% lower infusion rate was used in the ESRD group to obtain comparable incretin hormone plasma levels. During clamps, comparable plasma glucose and intact incretin hormone concentrations were achieved. The effect of GLP-1 to increase insulin concentrations relative to placebo levels tended to be lower during euglycemia in ESRD and was significantly reduced during hyperglycemia (50 [8-72]%, P = 0.03). Similarly, the effect of GIP relative to placebo levels tended to be lower during euglycemia in ESRD and was significantly reduced during hyperglycemia (34 [13-50]%, P = 0.005). Glucagon was suppressed in both groups, with controls reaching lower concentrations than ESRD patients. The effect of incretin hormones to increase insulin release is reduced in ESRD, which, together with elevated glucagon levels, could contribute to the high prevalence of impaired glucose tolerance among ESRD patients.

Cholecystokinin Receptor Antagonist Therapy Decreases Inflammation and Fibrosis in Chronic Pancreatitis.

Chronic pancreatitis is associated with recurrent inflammation, pain, fibrosis, and loss of exocrine and endocrine pancreatic function and risk of cancer. We hypothesized that activation of the CCK receptor contributes to pancreatitis and blockade of this pathway would improve chronic pancreatitis. Two murine models were used to determine whether CCK receptor blockade with proglumide could prevent and reverse histologic and biochemical features of chronic pancreatitis: the 6-week repetitive chronic cerulein injection model and the modified 75% choline-deficient ethionine (CDE) diet. In the CDE-fed model, half the mice received water supplemented with proglumide, for 18weeks. After chronic pancreatitis was established in the cerulein model, half the mice were treated with proglumide and half with water. Histology was scored in a blinded fashion for inflammation, fibrosis and acinar ductal metaplasia (ADM) and serum lipase levels were measured. RNA was extracted and examined for differentially expressed fibrosis genes. Proglumide therapy decreased pancreatic weight in the CDE diet study and the cerulein-induced chronic pancreatitis model. Fibrosis, inflammation, and ADM scores were significantly reduced in both models. Lipase values improved with proglumide but not in controls in both models. Proglumide decreased pancreas mRNA expression of amylase, collagen-4, and TGFβR2 gene expression by 44, 38, and 25%, respectively, compared to control mice. New strategies are needed to decreased inflammation and reduce fibrosis in chronic pancreatitis. CCK receptor antagonist therapy may improve chronic pancreatitis by reversing fibrosis and inflammation. The decrease in ADM may reduce the risk of the development of pancreatic cancer.