101 results on '"Dana K. Andersen"'
Search Results
2. Development of a Clinical Prediction Model for Diabetes in Chronic Pancreatitis: The PREDICT3c Study
- Author
-
Christie Jeon, Phil A. Hart, Liang Li, Yunlong Yang, Eleanor Chang, Melena D. Bellin, William E. Fisher, Evan L. Fogel, Christopher E. Forsmark, Walter G. Park, Stephen K. Van Den Eeden, Santhi Swaroop Vege, Jose Serrano, David C. Whitcomb, Dana K. Andersen, Darwin L. Conwell, Dhiraj Yadav, and Mark O. Goodarzi
- Subjects
Male ,Advanced and Specialized Nursing ,Cross-Sectional Studies ,Models, Statistical ,Diabetes Mellitus, Type 2 ,Risk Factors ,Pancreatitis, Chronic ,Endocrinology, Diabetes and Metabolism ,Acute Disease ,Internal Medicine ,Humans ,Obesity ,Prognosis - Abstract
OBJECTIVE Diabetes that arises from chronic pancreatitis (CP) is associated with increased morbidity and mortality. Methods to predict which patients with CP are at greatest risk for diabetes are urgently needed. We aimed to examine independent risk factors for diabetes in a large cohort of patients with CP. RESEARCH DESIGN AND METHODS This cross-sectional study comprised 645 individuals with CP enrolled in the PROCEED study, of whom 276 had diabetes. We conducted univariable and multivariable regression analyses of potential risk factors for diabetes. Model performance was assessed by area under the receiver operating characteristic curve (AUROC) analysis, and accuracy was evaluated by cross validation. Exploratory analyses were stratified according to the timing of development of diabetes relative to the diagnosis of pancreatitis. RESULTS Independent correlates of diabetes in CP included risk factors for type 2 diabetes (older age, overweight/obese status, male sex, non-White race, tobacco use) as well as pancreatic disease–related factors (history of acute pancreatitis complications, nonalcoholic etiology of CP, exocrine pancreatic dysfunction, pancreatic calcification, pancreatic atrophy) (AUROC 0.745). Type 2 diabetes risk factors were predominant for diabetes occurring before pancreatitis, and pancreatic disease–related factors were predominant for diabetes occurring after pancreatitis. CONCLUSIONS Multiple factors are associated with diabetes in CP, including canonical risk factors for type 2 diabetes and features associated with pancreatitis severity. This study lays the groundwork for the future development of models integrating clinical and nonclinical data to identify patients with CP at risk for diabetes and identifies modifiable risk factors (obesity, smoking) on which to focus for diabetes prevention.
- Published
- 2022
3. Assessing the Pathophysiology of Hyperglycemia in the Diabetes RElated to Acute Pancreatitis and Its Mechanisms Study
- Author
-
Kathleen M, Dungan, Phil A, Hart, Dana K, Andersen, Marina, Basina, Vernon M, Chinchilli, Kirstie K, Danielson, Carmella, Evans-Molina, Mark O, Goodarzi, Carla J, Greenbaum, Rita R, Kalyani, Maren R, Laughlin, Ariana, Pichardo-Lowden, Richard E, Pratley, Jose, Serrano, Emily K, Sims, Cate, Speake, Dhiraj, Yadav, Melena D, Bellin, and Frederico G S, Toledo
- Subjects
Blood Glucose ,Hepatology ,Endocrinology, Diabetes and Metabolism ,Pancreatic Polypeptide ,Incretins ,Article ,Diabetes Mellitus, Type 1 ,Glucose ,Endocrinology ,Pancreatitis ,Hyperglycemia ,Acute Disease ,Internal Medicine ,Humans ,Insulin ,Insulin Resistance - Abstract
OBJECTIVES: The metabolic abnormalities that lead to diabetes mellitus (DM) following an episode of acute pancreatitis (AP) have not been extensively studied. This manuscript describes the objectives, hypotheses, and methods of mechanistic studies of glucose metabolism that comprise secondary outcomes of the Diabetes RElated to Acute pancreatitis and its Mechanisms (DREAM) Study. METHODS: Three months after an index episode of AP, participants without pre-existing DM will undergo baseline testing with an oral glucose tolerance test. Participants will be followed longitudinally in three sub-cohorts with distinct metabolic tests. In the first and largest subcohort, oral glucose tolerance tests will be repeated 12 months after AP and annually to assess changes in β-cell function, insulin secretion, and insulin sensitivity. In the second, mixed meal tolerance tests will be performed at 3 and 12 months, then annually, and following incident DM to assess incretin and pancreatic polypeptide responses. In the third, frequently-sampled intravenous glucose tolerance tests will be performed at 3 months and 12 months to assess the first-phase insulin response and more precisely measure β-cell function and insulin sensitivity. CONCLUSIONS: The DREAM study will comprehensively assess the metabolic and endocrine changes that precede and lead to the development of DM after AP.
- Published
- 2022
4. Rationale and Design for the Diabetes RElated to Acute Pancreatitis and Its Mechanisms Study
- Author
-
Phil A, Hart, Georgios I, Papachristou, Walter G, Park, Anne-Marie, Dyer, Vernon M, Chinchilli, Elham, Afghani, Venkata S, Akshintala, Dana K, Andersen, James L, Buxbaum, Darwin L, Conwell, Kathleen M, Dungan, Jeffrey J, Easler, Evan L, Fogel, Carla J, Greenbaum, Rita R, Kalyani, Murray, Korc, Richard, Kozarek, Maren R, Laughlin, Peter J, Lee, Jennifer L, Maranki, Stephen J, Pandol, Anna Evans, Phillips, Jose, Serrano, Vikesh K, Singh, Cate, Speake, Temel, Tirkes, Frederico G S, Toledo, Guru, Trikudanathan, Santhi Swaroop, Vege, Ming, Wang, Cemal, Yazici, Atif, Zaheer, Christopher E, Forsmark, Melena D, Bellin, and Dhiraj, Yadav
- Subjects
Diabetes Mellitus, Type 1 ,Endocrinology ,Pancreatitis ,Hepatology ,Incidence ,Endocrinology, Diabetes and Metabolism ,Acute Disease ,Internal Medicine ,Humans ,Prospective Studies ,Article - Abstract
Acute pancreatitis (AP) is a disease characterized by an acute inflammatory phase followed by a convalescent phase. Diabetes mellitus (DM) was historically felt to be a transient phenomenon related to acute inflammation; however, it is increasingly recognized as an important late and chronic complication. There are several challenges that have prevented precisely determining the incidence rate of DM following AP and understanding the underlying mechanisms. The Diabetes RElated to Acute Pancreatitis and its Mechanisms (DREAM) Study is a prospective cohort study designed to address these and other knowledge gaps to provide the evidence needed to screen for, prevent, and treat DM following AP. In the following article, we summarize literature regarding the epidemiology of DM following AP, and provide the rationale and an overview of the DREAM study.
- Published
- 2022
5. Pancreatic Pain—Knowledge Gaps and Research Opportunities in Children and Adults
- Author
-
Gwendolyn Sowa, Asbjørn Mohr Drewes, A. Vania Apkarian, Tonya M. Palermo, Aliye Uc, Pankaj J. Pasricha, Chris E. Forsmark, Sarah Jane Schwarzenberg, Leonardo Kapural, Thomas B. Strouse, Ellyn K Dunbar, John A. Windsor, Luana Colloca, Dana K. Andersen, Stephen J. Pandol, George F. Koob, Marc T. Goodman, Jami L. Saloman, Anna E. Phillips, Glenn J. Treisman, Melena D. Bellin, Vikesh K. Singh, Dhiraj Yadav, and Daniele Piomelli
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,Endocrinology, Diabetes and Metabolism ,media_common.quotation_subject ,medicine.medical_treatment ,MEDLINE ,Research opportunities ,medicine.disease ,Article ,Cognitive behavioral therapy ,Endocrinology ,Pancreatic pain ,Pain assessment ,Perception ,Diabetes mellitus ,Internal Medicine ,Medicine ,Genetic risk ,business ,Intensive care medicine ,media_common - Abstract
A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to focus on research gaps and opportunities in pancreatic pain. The event was held on July 21, 2021, and structured into 4 sessions: (1) pathophysiology; (2) biomarkers, mediators, and pharmacology of pain; (3) pain assessment; and (4) pain treatment challenges and opportunities. The current state of knowledge was reviewed; many knowledge gaps and research needs were identified that require further investigation. Common themes included the need to better understand the underlying mechanisms of pain in pancreatic diseases, the relationship of visceral neural pathways and central pain centers, the role of behavioral factors and disorders on the perception of pain, and differences in pain perception and processes in children when compared with adults. In addition, the role of genetic risk factors for pain and the mechanisms and role of placebos in pain treatment were discussed. Methods of pain assessment including quantitative sensory testing were examined, as well as the process of central sensitization of pain. Finally, newer approaches to pain management including cognitive behavioral therapy, nerve stimulation, experimental (nonopioid) drugs, and cannabinoid compounds were covered.
- Published
- 2021
6. Diabetes in chronic pancreatitis: risk factors and natural history
- Author
-
Mark O. Goodarzi, Maxim S. Petrov, Phil A. Hart, and Dana K. Andersen
- Subjects
medicine.medical_specialty ,business.industry ,Gastroenterology ,Type 2 diabetes ,medicine.disease ,Obesity ,Article ,Pancreatic Neoplasms ,Natural history ,Diabetes Mellitus, Type 2 ,Risk Factors ,Pancreatitis, Chronic ,Internal medicine ,Diabetes mellitus ,Pancreatic cancer ,medicine ,Humans ,Pancreatitis ,High incidence ,business ,Pancreas ,Pancreatic calcification - Abstract
PURPOSE OF REVIEW: The purpose of this review is to delineate risk factors for the development of diabetes in patients with chronic pancreatitis. The natural history including progression to diabetes and complications that develop once diabetes occurs in chronic pancreatitis is also reviewed. RECENT FINDINGS: Studies have found that predictors of diabetes in chronic pancreatitis include both risk factors for type 2 diabetes (e.g., obesity, genetic variants) as well as pancreas-specific factors (e.g., pancreatic calcification, exocrine insufficiency). Rates of diabetes in chronic pancreatitis are strongly related to the duration of chronic pancreatitis, reflecting progressive dysfunction and damage to the insulin-secreting beta-cells. Patients with diabetes and chronic pancreatitis experience an excess burden of complications, including higher all-cause and cancer-related mortality. SUMMARY: The high incidence and significant impact of diabetes on the morbidity and mortality of patients with chronic pancreatitis highlights the urgent need for clinically applicable models to predict diabetes in those with chronic pancreatitis, allowing efforts for targeted interventions to prevent diabetes. Research being carried out in the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) holds promise to fulfill these goals.
- Published
- 2021
7. New‐onset Diabetes as a Harbinger of Pancreatic Cancer: is Early Diagnosis Possible?
- Author
-
Suresh T. Chari, Stephen J. Pandol, Eithne Costello, Tatjana Crnogorac-Jurcevic, Dana K. Andersen, Anirban Maitra, and Phil A. Hart
- Subjects
Oncology ,medicine.medical_specialty ,New onset diabetes ,business.industry ,Internal medicine ,Pancreatic cancer ,medicine ,medicine.disease ,business - Published
- 2021
8. Unique circulating immune signatures for recurrent acute pancreatitis, chronic pancreatitis and pancreatic cancer: A pilot study of these conditions with and without diabetes
- Author
-
Savitri Appana, Walter G. Park, Dhiraj Yadav, Liang Li, Kimberly Stello, Steven J. Hughes, Aida Habtezion, Dana K. Andersen, Randall E. Brand, Wei Wei, and David C. Whitcomb
- Subjects
Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Recurrent acute pancreatitis ,Pilot Projects ,Gastroenterology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Recurrence ,Internal medicine ,Diabetes mellitus ,Pancreatic cancer ,Humans ,Medicine ,Aged ,Hepatology ,business.industry ,Area under the curve ,Middle Aged ,medicine.disease ,Pancreatic Neoplasms ,Gene Expression Regulation ,Pancreatitis ,030220 oncology & carcinogenesis ,Cohort ,Cytokines ,Adenocarcinoma ,Female ,030211 gastroenterology & hepatology ,business ,Biomarkers - Abstract
Objective This exploratory study seeks to identify distinct circulating immune signatures among patients having recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic adenocarcinoma (PDAC). Methods A retrospective analysis of human serum samples from collaborating institutions of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) was performed. Samples came from the North American Pancreatitis Studies 2 (NAPS2) cohort and the Pancreatic Adenocarcinoma Gene Environment Risk Study (PAGER) and were analyzed using a 62-plex Luminex assay in a blinded fashion. Group and pairwise comparisons were performed to identify unique immune signature panels and to calculate diagnostic utility using area under the curve analysis. Results A total of 179 patients’ samples were included: 41 controls, 40 CP, 78 PDAC and 20 RAP patients, of which 20 controls, 20 CP, and 58 PDAC patients had diabetes mellitus (DM). A unique immune signature panel could discriminate RAP, CP, and PDAC from controls with an AUC range from 0.77 to 0.86 (95% CI range: 0.64–0.94), RAP from CP, and CP from PDAC with an AUC of 0.77 (95% CI 0.64–0.90) and 0.76 (95% CI 0.67–0.86), respectively. Furthermore, an immune signature panel could also discriminate PDAC-DM from DM controls with an AUC of 0.96 (95% CI: 0.93–1.00) Conclusion This study identifies unique immune analytes that may serve as novel diagnostic and predictive non-invasive biomarkers of RAP, CP, and PDAC. Further validation is warranted in prospective cohorts as developed by the CPDPC.
- Published
- 2020
9. Heterogeneity of Diabetes: β-Cells, Phenotypes, and Precision Medicine: Proceedings of an International Symposium of the Canadian Institutes of Health Research’s Institute of Nutrition, Metabolism and Diabetes and the U.S. National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases
- Author
-
William T. Cefalu, Dana K. Andersen, Guillermo Arreaza-Rubín, Christopher L. Pin, Sheryl Sato, C. Bruce Verchere, Minna Woo, Norman D. Rosenblum, Norman Rosenblum, William Cefalu, Christine Dhara, Stephen P. James, Mary-Jo Makarchuk, Bruce Verchere, Alvin Powers, Jennifer Estall, Corrine Hoesli, Jeffrey Millman, Amelia Linnemann, James Johnson, Meredith Hawkins, Anna Gloyn, Mark O. Huising, Richard K.P. Benninger, Joana Almaça, Rebecca L. Hull-Meichle, Patrick MacDonald, Francis Lynn, Juan Melero-Martin, Eiji Yoshihara, Cherie Stabler, Maike Sander, Carmella Evans-Molina, Feyza Engin, Peter Thompson, Anath Shalev, Maria J. Redondo, Kristen Nadeau, Melena Bellin, Miriam S. Udler, John Dennis, Satya Dash, Wenyu Zhou, Michael Snyder, Gillian Booth, Atul Butte, and Jose Florez
- Subjects
Gerontology ,Canada ,Chronic condition ,Endocrinology, Diabetes and Metabolism ,MEDLINE ,Diabetes treatment ,Pediatrics ,Perspectives in Care ,Endocrinology ,Diabetes mellitus ,Diabetes Mellitus ,Internal Medicine ,medicine ,Humans ,Precision Medicine ,Clinical care ,Advanced and Specialized Nursing ,business.industry ,General Medicine ,medicine.disease ,Precision medicine ,United States ,Phenotype ,National Institutes of Health (U.S.) ,National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) ,Cohort ,Perspectives in Diabetes ,business - Abstract
One hundred years have passed since the discovery of insulin—an achievement that transformed diabetes from a fatal illness into a manageable chronic condition. The decades since that momentous achievement have brought ever more rapid innovation and advancement in diabetes research and clinical care. To celebrate the important work of the past century and help to chart a course for its continuation into the next, the Canadian Institutes of Health Research’s Institute of Nutrition, Metabolism and Diabetes and the U.S. National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases recently held a joint international symposium, bringing together a cohort of researchers with diverse interests and backgrounds from both countries and beyond to discuss their collective quest to better understand the heterogeneity of diabetes and thus gain insights to inform new directions in diabetes treatment and prevention. This article summarizes the proceedings of that symposium, which spanned cutting-edge research into various aspects of islet biology, the heterogeneity of diabetic phenotypes, and the current state of and future prospects for precision medicine in diabetes.
- Published
- 2021
10. Metabolic Surveillance for Those at High Risk for Developing Pancreatic Cancer
- Author
-
Dana K. Andersen and Suresh T. Chari
- Subjects
Pancreatic Neoplasms ,Oncology ,medicine.medical_specialty ,Hepatology ,business.industry ,Internal medicine ,Pancreatic cancer ,Gastroenterology ,medicine ,MEDLINE ,Humans ,business ,medicine.disease - Published
- 2021
11. Accelerating the Drug Delivery Pipeline for Acute and Chronic Pancreatitis
- Author
-
Mark E. Lowe, Marc T. Goodman, Gregory A. Coté, Marshall J. Glesby, Mark Haupt, Nicholas J. Schork, Vikesh K. Singh, Dana K. Andersen, Stephen J. Pandol, Aliye Uc, and David C. Whitcomb
- Subjects
Biomedical Research ,Endocrinology, Diabetes and Metabolism ,Clinical Sciences ,pancreatitis ,Article ,Oral and gastrointestinal ,03 medical and health sciences ,Rare Diseases ,0302 clinical medicine ,Endocrinology ,Drug Development ,Recurrence ,Clinical Research ,Internal Medicine ,Humans ,Chronic ,Cancer ,Clinical Trials as Topic ,Gastroenterology & Hepatology ,Hepatology ,drug trials ,Diabetes ,United States ,Good Health and Well Being ,Pharmaceutical Preparations ,National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) ,patient-reported outcomes ,030220 oncology & carcinogenesis ,Acute Disease ,030211 gastroenterology & hepatology ,Digestive Diseases - Abstract
Recurrent acute pancreatitis (RAP) is a complex clinical syndrome with significant morbidity, unpredictable outcomes, and limited treatment options. The National Institute of Diabetes and Digestive and Kidney Disease sponsored a workshop on July 25, 2018, in Pittsburgh, Pennsylvania, to address research gaps impeding development of effective therapies for pancreatitis. The RAP working group identified challenges to clinical progress using existing definitions, risk assessment, diagnostic and severity criteria, disease trajectories, outcomes, and research methods. Recurrent acute pancreatitis includes all the risk of acute pancreatitis and often progresses to chronic pancreatitis with variable complications of chronic pain, exocrine insufficiency, diabetes, and pancreatic cancer. However, the great variability among individuals with RAP requires better precision in defining the risks, individual episodes, as well as their frequency, pathogenic pathways, and specific outcome measures for each of the systems affected by pancreatic inflammation. Because of disease complexity, few patients are similar enough for traditional studies and methods to conduct clinical trials with small sample sizes are required. The need for genetic testing, biomarker development, and better imaging methods was highlighted. Adaptive and N-of-one study designs, better endpoints, and outcome measures including patient-reported outcomes should considered early in developing future therapeutic trial design and include all stakeholders.
- Published
- 2018
12. Accelerating the Drug Delivery Pipeline for Acute and Chronic Pancreatitis
- Author
-
Dhiraj Yadav, Julia Mayerle, Megan Golden, Zixi Zhu, Stephen J. Pandol, Dana K. Andersen, John T. Farrar, Sohail Z. Husain, Aliye Uc, Chris E. Forsmark, Aida Habtezion, and Liang Li
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Biomedical Research ,Kidney Disease ,acute pancreatitis ,molecular targets ,Endocrinology, Diabetes and Metabolism ,Clinical Sciences ,MEDLINE ,Disease ,Oral and gastrointestinal ,Article ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Pharmacotherapy ,Drug Development ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Chronic ,Intensive care medicine ,Clinical Trials as Topic ,Gastroenterology & Hepatology ,Hepatology ,business.industry ,Clinical study design ,trials ,medicine.disease ,United States ,drug therapy ,Good Health and Well Being ,030104 developmental biology ,Pancreatitis ,Pharmaceutical Preparations ,Drug development ,National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) ,5.1 Pharmaceuticals ,Acute Disease ,Acute pancreatitis ,030211 gastroenterology & hepatology ,Development of treatments and therapeutic interventions ,Digestive Diseases ,business - Abstract
A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to focus on research gaps and opportunities on drug development for pancreatitis. This conference was held on July 25, 2018, and structured into 3 working groups (WG): acute pancreatitis (AP) WG, recurrent AP WG, and chronic pancreatitis WG. This article reports the outcome of the work accomplished by the AP WG to provide the natural history, epidemiology, and current management of AP; inform about the role of preclinical models in therapy selection; and discuss clinical trial designs with clinical and patient-reported outcomes to test new therapies.
- Published
- 2018
13. Accelerating the Drug Delivery Pipeline for Acute and Chronic Pancreatitis
- Author
-
Christopher E. Forsmark, Dana K. Andersen, John T. Farrar, Megan Golden, Aida Habtezion, Sohail Z. Husain, Liang Li, Julia Mayerle, Stephen J. Pandol, Aliye Uc, Zixi Zhu, and Dhiraj Yadav
- Subjects
pain in chronic pancreatitis ,Biomedical Research ,Endocrinology, Diabetes and Metabolism ,Clinical Trials and Supportive Activities ,Clinical Sciences ,Article ,Oral and gastrointestinal ,chronic pancreatitis ,natural history of chronic pancreatitis ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Drug Development ,Clinical Research ,Internal Medicine ,Humans ,Chronic ,Clinical Trials as Topic ,Gastroenterology & Hepatology ,Hepatology ,Pain Research ,United States ,clinical trial design ,Good Health and Well Being ,Pancreatitis ,Pharmaceutical Preparations ,National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) ,5.1 Pharmaceuticals ,Musculoskeletal ,Acute Disease ,030211 gastroenterology & hepatology ,Generic health relevance ,Chronic Pain ,Development of treatments and therapeutic interventions ,Digestive Diseases ,030217 neurology & neurosurgery - Abstract
The lack of effective therapeutic agents specifically tailored for chronic pancreatitis has hampered clinical care and negatively impacted patients’ lives. New mechanistic insights now point to novel therapies, which involve both recently developed and/or repurposed agents. This working group focused on two main outcomes for chronic pancreatitis: pain and progression of disease. The goal is to frame the essential aspects of trial design including patient-centered outcomes, proposed methods to measure the outcomes of pain and progression, and study design considerations for future trials to facilitate rapid drug development for patients with chronic pancreatitis.
- Published
- 2018
14. Artificial Intelligence and Early Detection of Pancreatic Cancer:2020 Summative Review
- Author
-
Julie Fleshman, Sung Poblete, Bruce F. Field, Laura J. Rothschild, Michael H. Rosenthal, Adam Yala, Chris Sander, Graham P. Lidgard, Marcia Irene Canto, Lawrence H. Schwartz, Barbara J. Kenner, Brian M. Wolpin, Debiao Li, Elliot K. Fishman, James A. Taylor, Dana K. Andersen, Ann E. Goldberg, Stephen J. Pandol, David P. Kelsen, David I. Bernstein, Noura S. Abul-Husn, Jane M. Holt, Suresh T. Chari, Anirban Maitra, Yonina C. Eldar, Uri Shalit, Vay Liang W. Go, Anil K. Rustgi, Sudhir Srivastava, Lynn M. Matrisian, Christine A. Iacobuzio-Donahue, William Arthur Hoos, David S. Klimstra, and Søren Brunak
- Subjects
Endocrinology, Diabetes and Metabolism ,pancreatic cancer ,Clinical Sciences ,MEDLINE ,Disease ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,White paper ,Rare Diseases ,Pancreatic cancer ,Internal Medicine ,medicine ,Biomarkers, Tumor ,Humans ,early detection ,Survival rate ,Early Detection of Cancer ,Cancer ,geography ,Government ,Summit ,geography.geographical_feature_category ,Tumor ,Hepatology ,Gastroenterology & Hepatology ,business.industry ,Prevention ,Carcinoma ,Conference Report ,Genomics ,medicine.disease ,Prognosis ,artificial intelligence ,Survival Analysis ,Pancreatic Neoplasms ,Good Health and Well Being ,machine learning ,Summative assessment ,Pancreatic Ductal ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Interdisciplinary Communication ,Artificial intelligence ,Psychology ,business ,Digestive Diseases ,Biomarkers ,Carcinoma, Pancreatic Ductal - Abstract
Despite considerable research efforts, pancreatic cancer is associated with a dire prognosis and a 5-year survival rate of only 10%. Early symptoms of the disease are mostly nonspecific. The premise of improved survival through early detection is that more individuals will benefit from potentially curative treatment. Artificial intelligence (AI) methodology has emerged as a successful tool for risk stratification and identification in general health care. In response to the maturity of AI, Kenner Family Research Fund conducted the 2020 AI and Early Detection of Pancreatic Cancer Virtual Summit (www.pdac-virtualsummit.org) in conjunction with the American Pancreatic Association, with a focus on the potential of AI to advance early detection efforts in this disease. This comprehensive presummit article was prepared based on information provided by each of the interdisciplinary participants on one of the 5 following topics: Progress, Problems, and Prospects for Early Detection; AI and Machine Learning; AI and Pancreatic Cancer-Current Efforts; Collaborative Opportunities; and Moving Forward-Reflections from Government, Industry, and Advocacy. The outcome from the robust Summit conversations, to be presented in a future white paper, indicate that significant progress must be the result of strategic collaboration among investigators and institutions from multidisciplinary backgrounds, supported by committed funders.
- Published
- 2021
15. Endoscopic Ultrasound and Related Technologies for the Diagnosis and Treatment of Pancreatic Disease - Research Gaps and Opportunities
- Author
-
Christopher C. Thompson, John M. DeWitt, Kenneth J. Chang, William R. Brugge, Mark Topazian, Walter G. Park, Suresh T. Chari, Irving Waxman, Joo Ha Hwang, Mouen A. Khashab, Michael B. Wallace, Aatur D. Singhi, Reiko Ashida, Vikesh K. Singh, Dhiraj Yadav, Linda S. Lee, Michael J. Levy, Mimi I. Canto, Sachin Wani, Kang Kim, Tyler Stevens, Dana K. Andersen, and Kevin McGrath
- Subjects
Endoscopic ultrasound ,medicine.medical_specialty ,Pancreatic disease ,Endocrinology, Diabetes and Metabolism ,Disease ,Cellular level ,Gastroenterology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,medicine ,Intensive care medicine ,Hepatology ,medicine.diagnostic_test ,business.industry ,Research needs ,medicine.disease ,digestive system diseases ,030220 oncology & carcinogenesis ,Disease early ,030211 gastroenterology & hepatology ,business - Abstract
A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to address the research gaps and opportunities in pancreatic endoscopic ultrasound (EUS). The event occurred on July 26, 2017 in 4 sessions: (1) benign pancreatic diseases, (2) high-risk pancreatic diseases, (3) diagnostic and therapeutics, and (4) new technologies. The current state of knowledge was reviewed, with identification of numerous gaps in knowledge and research needs. Common themes included the need for large multicenter consortia of various pancreatic diseases to facilitate meaningful research of these entities; to standardize EUS features of different pancreatic disorders, the technique of sampling pancreatic lesions, and the performance of various therapeutic EUS procedures; and to identify high-risk disease early at the cellular level before macroscopic disease develops. The need for specialized tools and accessories to enable the safe and effective performance of therapeutic EUS procedures also was discussed.
- Published
- 2017
16. The Agenda for Accelerating Pancreatic Research
- Author
-
Chris E. Forsmark, Stephen J. Pandol, and Dana K. Andersen
- Subjects
Hepatology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Article ,United States ,Pancreatic Neoplasms ,Translational Research, Biomedical ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Pancreatitis ,National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) ,Research Support as Topic ,030220 oncology & carcinogenesis ,Diabetes Mellitus ,Internal Medicine ,Humans ,Medicine ,030211 gastroenterology & hepatology ,business - Published
- 2018
17. Diabetes, Pancreatogenic Diabetes, and Pancreatic Cancer
- Author
-
Dana K. Andersen, Donghui Li, Gloria M. Petersen, James L. Abbruzzese, Murray Korc, Guido Eibl, Michael R. Rickels, and Suresh T. Chari
- Subjects
0301 basic medicine ,Oncology ,Blood Glucose ,medicine.medical_specialty ,Pathology ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Type 2 diabetes ,Medical and Health Sciences ,03 medical and health sciences ,Endocrinology & Metabolism ,0302 clinical medicine ,Diabetes management ,Risk Factors ,Internal medicine ,Pancreatic cancer ,Diabetes mellitus ,Pancreatitis, Chronic ,Epidemiology ,Internal Medicine ,Diabetes Mellitus ,Medicine ,Humans ,Hypoglycemic Agents ,Genetic Predisposition to Disease ,Obesity ,Risk factor ,Chronic ,Inflammation ,business.industry ,Carcinoma ,medicine.disease ,digestive system diseases ,3. Good health ,Causality ,Pancreatic Neoplasms ,030104 developmental biology ,Pancreatitis ,Diabetes Mellitus, Type 2 ,Pancreatic Ductal ,030220 oncology & carcinogenesis ,Perspectives in Diabetes ,business ,Pancreatogenic diabetes ,Type 2 ,Carcinoma, Pancreatic Ductal - Abstract
The relationships between diabetes and pancreatic ductal adenocarcinoma (PDAC) are complex. Longstanding type 2 diabetes (T2DM) is a risk factor for pancreatic cancer, but increasing epidemiological data point to PDAC as also a cause of diabetes due to unknown mechanisms. New-onset diabetes is of particular interest to the oncology community as the differentiation of new-onset diabetes caused by PDAC as distinct from T2DM may allow for earlier diagnosis of PDAC. To address these relationships and raise awareness of the relationships between PDAC and diabetes, a symposium entitled Diabetes, Pancreatogenic Diabetes, and Pancreatic Cancer was held at the American Diabetes Association’s 76th Scientific Sessions in June 2016. This article summarizes the data presented at that symposium, describing the current understanding of the interrelationships between diabetes, diabetes management, and pancreatic cancer, and identifies areas where additional research is needed.
- Published
- 2017
18. Genetic Risk Score in Diabetes Associated With Chronic Pancreatitis Versus Type 2 Diabetes Mellitus
- Author
-
Vikesh K. Singh, Phil J. Greer, Georgios I. Papachristou, Thiruvengadam Muniraj, Jinrui Cui, Tanvi Nagpal, Jerome I. Rotter, Yii-Der Ida Chen, Walter G. Park, David C. Whitcomb, Gregory A. Cote, Melena D. Bellin, Phil A. Hart, Xiuqing Guo, Stuart Sherman, Chris E. Forsmark, Jessica LaRusch, Darwin L. Conwell, Mary E. Money, John Baillie, Mark O. Goodarzi, James S. Pankow, Samer Alkaade, Stephen T. Amann, Stephen J. Pandol, Dhiraj Yadav, C. Mel Wilcox, Michele D. Lewis, Nalini M. Guda, Dana K. Andersen, Andres Gelrud, Randall E. Brand, Timothy B. Gardner, Bimaljit S. Sandhu, Peter A. Banks, and Joseph Romagnuolo
- Subjects
medicine.medical_specialty ,endocrine system diseases ,Extramural ,business.industry ,Gastroenterology ,nutritional and metabolic diseases ,Type 2 Diabetes Mellitus ,medicine.disease ,Article ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Diabetes mellitus ,Internal medicine ,medicine ,Pancreatitis ,030211 gastroenterology & hepatology ,Genetic risk ,Complication ,business ,Pancreatogenic diabetes ,Pancreas - Abstract
Introduction: Diabetes mellitus (DM) is a complication of chronic pancreatitis (CP). Whether pancreatogenic diabetes associated with CP-DM represents a discrete pathophysiologic entity from type 2 DM (T2DM) remains uncertain. Addressing this question is needed for development of specific measures to manage CP-DM. We approached this question from a unique standpoint, hypothesizing that if CP-DM and T2DM are separate disorders, they should be genetically distinct. To test this hypothesis, we sought to determine whether a genetic risk score (GRS) based on validated single nucleotide polymorphisms for T2DM could distinguish between groups with CP-DM and T2DM. Methods: We used 60 T2DM single nucleotide polymorphisms to construct a weighted GRS in 1,613 subjects from the North American Pancreatitis Study 2 and 2,685 subjects from the Multi-Ethnic Study of Atherosclerosis, all of European origin. Results: The mean GRS was identical between 321 subjects with CP-DM and 423 subjects with T2DM (66.53 vs 66.42, P = 0.95), and the GRS of both diabetic groups was significantly higher than that of nondiabetic controls (n = 3,554, P < 0.0001). Exploratory analyses attempting to enrich the CP-DM group for pancreatogenic diabetes, such as eliminating diabetes diagnosed before CP, requiring pancreas-specific comorbidities, or removing those with a family history of diabetes, did not improve the ability of the GRS to distinguish between CP-DM and T2DM. Discussion: Recognizing that we lacked a gold standard to define CP-DM, our study suggests that CP-DM may be a subtype of T2DM, a notion that should be tested in future, large prospective studies.
- Published
- 2019
19. Precision Medicine in Pancreatic Disease—Knowledge Gaps and Research Opportunities: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop
- Author
-
Sylvia K. Plevritis, Richard M. Caprioli, Chris E. Forsmark, Zobeida Cruz-Monserrate, Fred S. Gorelick, Mark E. Lowe, Noa Rappaport, Hanno Steen, Dana K. Andersen, Temel Tirkes, David C. Whitcomb, Joe W. Gray, Mark Haupt, Jyoti S. Choudhary, Kimberly A. Kelly, Aliye Uc, Kirill Veselkov, Aida Habtezion, Holger R. Roth, Kenneth P. Olive, S. Joshua Swamidass, Anil K. Dasyam, and The Vodafone Foundation
- Subjects
medicine.medical_specialty ,Biomedical Research ,Endocrinology, Diabetes and Metabolism ,MEDLINE ,Datasets as Topic ,Context (language use) ,Article ,03 medical and health sciences ,Deep Learning ,0302 clinical medicine ,Endocrinology ,Pancreatic cancer ,Health care ,Internal Medicine ,medicine ,Information system ,Metabolomics ,Humans ,Medical physics ,Precision Medicine ,Gastroenterology & Hepatology ,Hepatology ,business.industry ,Research ,Computational Biology ,Pancreatic Diseases ,1103 Clinical Sciences ,medicine.disease ,Precision medicine ,Prognosis ,Clinical trial ,Pancreatitis ,030220 oncology & carcinogenesis ,Acute Disease ,030211 gastroenterology & hepatology ,Personalized medicine ,Neural Networks, Computer ,business ,Biomarkers - Abstract
A workshop on research gaps and opportunities for Precision Medicine in Pancreatic Disease was sponsored by the National Institute of Diabetes and Digestive Kidney Diseases on July 24, 2019, in Pittsburgh. The workshop included an overview lecture on precision medicine in cancer and 4 sessions: (1) general considerations for the application of bioinformatics and artificial intelligence; (2) omics, the combination of risk factors and biomarkers; (3) precision imaging; and (4) gaps, barriers, and needs to move from precision to personalized medicine for pancreatic disease. Current precision medicine approaches and tools were reviewed, and participants identified knowledge gaps and research needs that hinder bringing precision medicine to pancreatic diseases. Most critical were (a) multicenter efforts to collect large-scale patient data sets from multiple data streams in the context of environmental and social factors; (b) new information systems that can collect, annotate, and quantify data to inform disease mechanisms; (c) novel prospective clinical trial designs to test and improve therapies; and (d) a framework for measuring and assessing the value of proposed approaches to the health care system. With these advances, precision medicine can identify patients early in the course of their pancreatic disease and prevent progression to chronic or fatal illness.
- Published
- 2019
20. Advances in Biomedical Imaging, Bioengineering, and Related Technologies for the Development of Biomarkers of Pancreatic Disease
- Author
-
Vikesh K. Singh, Kimberly A. Kelly, Christina H. Liu, Dhiraj Yadav, Michael A. Hollingsworth, Randall E. Brand, Dana K. Andersen, Ajay D. Wasan, and Sudhir Srivastava
- Subjects
medicine.medical_specialty ,Pathology ,Pancreatic disease ,Hepatology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Cellular imaging ,medicine.disease ,Article ,Endocrinology ,Diabetes mellitus ,Pancreatic cancer ,Internal Medicine ,Medical imaging ,Medicine ,Pancreatitis ,Pancreatitis, chronic ,Molecular imaging ,business ,Intensive care medicine - Abstract
A workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Biomedical Imaging and Bioengineering focused on research gaps and opportunities in the development of new biomarkers of pancreatic disease. The session was held on July 22, 2015, and structured into six sessions: 1) introduction and overview, 2) keynote address, 3) new approaches to the diagnosis of chronic pancreatitis, 4) biomarkers of pain and inflammation, 5) new approaches to the detection of pancreatic cancer, and 6) shed exosomes, shed cells, and shed proteins. Recent advances in the fields of pancreatic imaging, functional markers of pancreatic disease, proteomics, molecular and cellular imaging, and detection of circulating cancer cells and exosomes were reviewed. Knowledge gaps and research needs were highlighted. The development of new methods for the non-invasive determination of pancreatic pathology, the use of cellular markers of pancreatic function, inflammation, pain, and malignancy, and the refinement of methods to identify cells and cellular constituents of pancreatic cancer were discussed. The further refinement of sophisticated technical methods, and the need for clinical studies to validate these new approaches in large-scale studies of patients at risk for the development of pancreatic disease was repeatedly emphasized.
- Published
- 2015
21. The Interface of Pancreatic Cancer With Diabetes, Obesity, and Inflammation: Research Gaps and Opportunities: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop
- Author
-
Carl A.K. Borrebaeck, Seung K. Kim, Dana K. Andersen, Costas A. Lyssiotis, Bruce M. Wolfe, Stephen J. Pandol, Suresh T. Chari, Eithne Costello, Zobeida Cruz-Monserrate, Murray Korc, Lei Zheng, James L. Abbruzzese, Guido Eibl, Aida Habtezion, Edgar G. Engleman, Craig D. Logsdon, Alvin C. Powers, Anil K. Rustgi, and William E. Fisher
- Subjects
0301 basic medicine ,Oncology ,obesity ,Biomedical Research ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,pancreatic cancer ,Comorbidity ,0302 clinical medicine ,Endocrinology ,Risk Factors ,Hyperinsulinemia ,2.1 Biological and endogenous factors ,Aetiology ,Cancer ,Kidney ,diabetes ,medicine.anatomical_structure ,Pancreatic Ductal ,030220 oncology & carcinogenesis ,medicine.symptom ,Diabetes obesity ,medicine.medical_specialty ,Clinical Sciences ,Adipokine ,Inflammation ,Article ,03 medical and health sciences ,Rare Diseases ,research gaps ,Pancreatic cancer ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Diabetes Mellitus ,Humans ,Metabolic and endocrine ,Nutrition ,Hepatology ,Gastroenterology & Hepatology ,business.industry ,Prevention ,Carcinoma ,medicine.disease ,Obesity ,United States ,digestive system diseases ,Pancreatic Neoplasms ,030104 developmental biology ,National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) ,business ,Energy Metabolism ,Digestive Diseases - Abstract
A workshop on "The Interface of Pancreatic Cancer with Diabetes, Obesity, and Inflammation: Research Gaps and Opportunities" was held by the National Institute of Diabetes and Digestive and Kidney Diseases on October 12, 2017. The purpose of the workshop was to explore the relationship and possible mechanisms of the increased risk of pancreatic ductal adenocarcinoma (PDAC) related to diabetes, the role of altered intracellular energy metabolism in PDAC, the mechanisms and biomarkers of diabetes caused by PDAC, the mechanisms of the increased risk of PDAC associated with obesity, and the role of inflammatory events and mediators as contributing causes of the development of PDAC. Workshop faculty reviewed the state of the current knowledge in these areas and made recommendations for future research efforts. Further knowledge is needed to elucidate the basic mechanisms contributing to the role of hyperinsulinemia, hyperglycemia, adipokines, and acute and chronic inflammatory events on the development of PDAC.
- Published
- 2018
22. Evaluation of a Mixed Meal Test for Diagnosis and Characterization of PancrEaTogEniC DiabeTes Secondary to Pancreatic Cancer and Chronic Pancreatitis: Rationale and Methodology for the DETECT Study From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer
- Author
-
Kieren J. Mather, Maxim S. Petrov, Mandeep Bajaj, Noemy Contreras, David C. Whitcomb, Mark O. Goodarzi, Jose Serrano, Murray Korc, David Bradley, Sudhir Srivastava, Aida Habtezion, Jo Ann Rinaudo, Melena D. Bellin, Phil A. Hart, Yogish C. Kudva, Dana K. Andersen, Alicia C. Castonguay, Ying Yuan, and Dhiraj Yadav
- Subjects
Research design ,Adult ,medicine.medical_specialty ,Biomedical Research ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Type 2 diabetes ,Gastroenterology ,Sensitivity and Specificity ,Article ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Internal medicine ,Diabetes mellitus ,Pancreatic cancer ,Pancreatitis, Chronic ,Internal Medicine ,Diabetes Mellitus ,Medicine ,Pancreatic polypeptide ,Humans ,Multicenter Studies as Topic ,Aged ,Hepatology ,business.industry ,Diagnostic Tests, Routine ,Insulin ,Clinical Studies as Topic ,Reproducibility of Results ,Middle Aged ,medicine.disease ,Pancreatic Neoplasms ,Biorepository ,Pancreatitis ,Research Design ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,business - Abstract
Pancreatogenic diabetes mellitus is most commonly the result of chronic pancreatitis, but can also occur secondary to pancreatic cancer. The early identification of pancreatogenic diabetes and distinction from the more prevalent type 2 diabetes is clinically significant; however, currently there is no validated method to differentiate these diabetes subtypes. We describe a study, “Evaluation of a Mixed Meal Test for Diagnosis and Characterization of PancrEaTogEniC DiabeTes Secondary to Pancreatic Cancer and Chronic Pancreatitis: the DETECT study,” which seeks to address this knowledge gap. The DETECT study is a multicenter study that will examine differences in hormone and glucose excursions following a mixed meal test. The study will also create a biorepository that will be used to evaluate novel diagnostic biomarkers for differentiating these diabetes subtypes.
- Published
- 2018
23. Total Pancreatectomy With Islet Autotransplantation
- Author
-
Sarah Jane Schwarzenberg, Melena D. Bellin, Bashoo Naziruddin, Cristiana Rastellini, Michael R. Rickels, Abhinav Humar, Katherine A. Morgan, Andres Gelrud, Dana K. Andersen, Ty B. Dunn, and Guillermo Arreaza-Rubin
- Subjects
medicine.medical_specialty ,education.field_of_study ,Hepatology ,business.industry ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,General surgery ,Population ,MEDLINE ,medicine.disease ,Autotransplantation ,Endocrinology ,Quality of life ,Diabetes mellitus ,Pancreatectomy ,Internal Medicine ,medicine ,Pancreatitis ,Pancreatitis, chronic ,education ,business - Abstract
A workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases focused on research gaps and opportunities in total pancreatectomy with islet autotransplantation (TPIAT) for the management of chronic pancreatitis (CP). The session was held on July 23, 2014, and structured into 5 sessions: (1) patient selection, indications, and timing; (2) technical aspects of TPIAT; (3) improving success of islet autotransplantation; (4) improving outcomes after total pancreatectomy; and (5) registry considerations for TPIAT. The current state of knowledge was reviewed; knowledge gaps and research needs were specifically highlighted. Common themes included the need to identify which patients best benefit from and when to intervene with TPIAT, current limitations of the surgical procedure, diabetes remission and the potential for improvement, opportunities to better address pain remission, gastrointestinal complications in this population, and unique features of children with CP considered for TPIAT. The need for a multicenter patient registry that specifically addresses the complexities of CP and total pancreatectomy outcomes as well as postsurgical diabetes outcomes was repeatedly emphasized.
- Published
- 2014
24. Mechanisms of type 2 diabetes resolution after Roux-en-Y gastric bypass
- Author
-
Dariush Elahi, Richard P. Shannon, Franca S. Angeli, Panagis Galiatsatos, Amin Vakilipour, Atoosa Rabiee, Josephine M. Egan, Olga D. Carlson, Rocio Salas-Carrillo, and Dana K. Andersen
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Gastric Bypass ,Enzyme-Linked Immunosorbent Assay ,Type 2 diabetes ,Article ,Body Mass Index ,Absorptiometry, Photon ,Glucagon-Like Peptide 1 ,Internal medicine ,Weight Loss ,medicine ,Hyperinsulinemia ,Insulin ,Humans ,Meal ,C-Peptide ,business.industry ,Type 2 Diabetes Mellitus ,Middle Aged ,Glucagon ,medicine.disease ,Roux-en-Y anastomosis ,Obesity, Morbid ,Surgery ,Endocrinology ,Diabetes Mellitus, Type 2 ,Body Composition ,Glucose Clamp Technique ,Female ,business ,Body mass index ,Biomarkers ,Hormone - Abstract
BACKGROUND: Bariatric surgery is the most effective treatment for the reduction of weight and resolution of type 2 diabetes mellitus (T2 DM). The objective of this study was to longitudinally assess hormonal and tissue responses after RYGB. METHODS: Eight patients (5 with T2 DM) were studied before and after RYGB. A standardized test meal (STM) was administered before and at 1, 3, 6, 9, 12, and 15 months. Separately, a 2-hour hyperinsulinemic-euglycemic clamp (E-clamp) and a 2-hour hyperglycemic clamp (H-clamp) were performed before and at 1, 3, 6, and 12 months. Glucagon-like peptide-1 (GLP-1) was infused during the last hour of the H-clamp. Body composition was assessed with DXA methodology. RESULTS: Enrollment body mass index was 49 ± 3 kg/m(2) (X ± SE). STM glucose and insulin responses were normalized by 3 and 6 months. GLP-1 level increased dramatically at 1, 3, and 6 months, normalizing by 12 and 15 months. Insulin sensitivity (M of E-clamp) increased progressively at 3–12 months as fat mass decreased. The insulin response to glucose alone fell progressively over 12 months but the glucose clearance/metabolism (M of H-clamp) did not change significantly until 12 months. In response to GLP-1 infusion, insulin levels fell progressively throughout the 12 months. CONCLUSION: The early hypersecretion of GLP-1 leads to hyperinsulinemia and early normalization of glucose levels. The GLP-1 response normalizes within 1 year after surgery. Enhanced peripheral tissue sensitivity to insulin starts at 3 months and is associated with fat mass loss. β-cell sensitivity improves at 12 months and after the loss of ≈ 33% of excess weight. There is a tightly controlled feedback loop between peripheral tissue sensitivity and β-cell and L-cell (GLP-1) responses. (Surg Obes Relat Dis 2014;10: 1028–1040.)
- Published
- 2014
25. Pancreatogenic diabetes: etiology, implications, and management
- Author
-
Dana K. Andersen
- Subjects
medicine.medical_specialty ,business.industry ,Internal medicine ,Pancreatic cancer ,medicine ,Etiology ,Pancreatic resection ,medicine.disease ,business ,Pancreatogenic diabetes ,Gastroenterology ,Cystic fibrosis - Published
- 2017
26. A Population-Based Evaluation of Severity and Mortality Among Transferred Patients With Acute Pancreatitis
- Author
-
Vikesh K. Singh, Venkata S. Akshintala, Kenzo Hirose, Susan Hutfless, Martin A. Makary, Anthony N. Kalloo, Dana K. Andersen, Mouen A. Khashab, Anne Marie Lennon, and Gobind S. Anand
- Subjects
Adult ,Male ,Patient Transfer ,medicine.medical_specialty ,Critical Care ,Multiple Organ Failure ,Endocrinology, Diabetes and Metabolism ,Decision Making ,Population based ,Severity of Illness Index ,Tertiary Care Centers ,Endocrinology ,Renal Dialysis ,Administrative database ,Ethnicity ,Internal Medicine ,medicine ,Retrospective analysis ,Humans ,Hospital Mortality ,Healthcare Disparities ,Hospitals, Teaching ,Referral and Consultation ,Secondary Care Centers ,Aged ,Retrospective Studies ,Medically Uninsured ,Maryland ,Hepatology ,business.industry ,Mortality rate ,Middle Aged ,medicine.disease ,Respiration, Artificial ,Patient Discharge ,Pancreatitis ,Hospital Bed Capacity ,Acute Disease ,Emergency medicine ,Acute pancreatitis ,Female ,Medical emergency ,business ,Hospitals, High-Volume - Abstract
This study aimed to compare severity of acute pancreatitis (AP) and mortality rates between transferred and nontransferred patients and to determine the factors that influence the decision to transfer.A retrospective analysis coding a statewide administrative database in Maryland was conducted. Severity was defined by presence of organ failure (OF), need for intensive care unit (ICU), mechanical ventilation (MV), or hemodialysis.There were 71,035 discharges for AP, with 1657 (2.3%) patient transfers. Transferred patients had more multisystem OF (5.6% vs 1.2%), need for ICU (22.8% vs 4.3%), MV (13.1% vs 1.4%), hemodialysis (4.2% vs 2.7%), and higher mortality (6.1% vs 1.1%) compared with nontransferred patients (P0.0001). After adjusting for disease severity, mortality was similar between the transferred patients and the nontransferred patients (OR, 1.37; 95% confidence interval, 0.96-1.97). Younger (OR, 0.99), African American (OR, 0.55), and uninsured (OR, 0.46) patients were less likely to be transferred, whereas patients with multisystem OF (OR, 3.5), need for ICU (OR, 2.3), or MV (OR, 2.1) were more likely to be transferred (P0.0001).Transferred patients with AP have more severe disease and higher overall mortality. Mortality is similar after adjusting for disease severity. Disease severity, insurance status, race, and age all influence the decision to transfer patients with AP.
- Published
- 2014
27. Chronic Pancreatitis in the 21st Century - Research Challenges and Opportunities:Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop
- Author
-
John F. Engelhardt, Markus M. Lerch, Mark E. Lowe, Melena D. Bellin, Brent A. Neuschwander-Tetri, Dana K. Andersen, Tonya M. Palermo, Vikesh K. Singh, Asbjørn Mohr Drewes, Chris E. Forsmark, Stephen J. O'Keefe, Aliye Uc, Darwin L. Conwell, David C. Whitcomb, Pankaj J. Pasricha, Ashok K. Saluja, Dhiraj Yadav, Jason I.E. Bruce, and Eva Szigethy
- Subjects
medicine.medical_specialty ,Hereditary pancreatitis ,Pathology ,Hepatology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Genetic enhancement ,MEDLINE ,Gene mutation ,medicine.disease ,Cystic fibrosis ,Article ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,030220 oncology & carcinogenesis ,Diabetes mellitus ,Internal Medicine ,Medicine ,Pancreatitis ,030211 gastroenterology & hepatology ,Pancreatitis, chronic ,business ,Intensive care medicine - Abstract
A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to focus on research gaps and opportunities in chronic pancreatitis (CP) and its sequelae. This conference marked the 20th year anniversary of the discovery of the cationic trypsinogen (PRSS1) gene mutation for hereditary pancreatitis. The event was held on July 27, 2016, and structured into 4 sessions: (1) pathophysiology; (2) exocrine complications; (3) endocrine complications; and (4) pain. The current state of knowledge was reviewed; many knowledge gaps and research needs were identified that require further investigation. Common themes included the need to design better tools to diagnose CP and its sequelae early and reliably, identify predisposing risk factors for disease progression, develop standardized protocols to distinguish type 3c diabetes mellitus from other types of diabetes and design effective therapeutic strategies through novel cell culture technologies, animal models mimicking human disease, and pain management tools. Gene therapy and cystic fibrosis conductance regulator (CFTR) potentiators as possible treatments for CP were discussed. Importantly, the need for chronic pancreatitis endpoints and intermediate targets for future drug trials was emphasized.
- Published
- 2016
28. Response
- Author
-
Linda S, Lee, Dana K, Andersen, and Vikesh K, Singh
- Subjects
Endocrinology ,Hepatology ,Endocrinology, Diabetes and Metabolism ,Internal Medicine - Published
- 2018
29. Pancreatitis-Diabetes-Pancreatic Cancer
- Author
-
David C. Whitcomb, Åke Andrén-Sandberg, Murray Korc, Dana K. Andersen, Gloria M. Petersen, Jill P. Smith, Michael Goggins, and Eric J. Duell
- Subjects
Oncology ,medicine.medical_specialty ,Pathology ,Pancreatic ductal adenocarcinoma ,endocrine system diseases ,Hepatology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Early detection ,Cancer ,medicine.disease ,digestive system diseases ,Food and drug administration ,Endocrinology ,Pancreatic cancer ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Pancreatitis ,Risk factor ,business - Abstract
A workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Cancer Institute (NCI) on "Pancreatitis-Diabetes-Pancreatic Cancer" focused on the risk factors of chronic pancreatitis (CP) and diabetes mellitus (DM) on the development of pancreatic ductal adenocarcinoma (PDAC). Sessions were held on (a) an overview of the problem of PDAC; (b) CP as a risk factor of PDAC; (c) DM as a risk factor of PDAC; (d) pancreatogenic, or type 3c, DM; (e) genomic associations of CP, DM, and PDAC; (f) surveillance of high-risk populations and early detection of PDAC; and (g) effects of DM treatment on PDAC. Recent data and current understandings of the mechanisms of CP- and DM-associated factors on PDAC development were discussed, and a detailed review of the possible risks of DM treatment on the development of PDAC was provided by representatives from academia, industry, and the Food and Drug Administration. The current status of possible biomarkers of PDAC and surveillance strategies for high-risk populations were discussed, and the gaps in knowledge and opportunities for further research were elucidated. A broad spectrum of expertise of the speakers and the discussants provided an unusually productive workshop, the highlights of which are summarized in the accompanying article.
- Published
- 2013
30. A Population-Based Study of Severity in Patients With Acute on Chronic Pancreatitis
- Author
-
Kenzo Hirose, Anthony N. Kalloo, Mouen A. Khashab, Vikesh K. Singh, Anne Marie Lennon, Dhiraj Yadav, Dana K. Andersen, Susan Hutfless, Venkata S. Akshintala, and Martin A. Makary
- Subjects
Adult ,Male ,medicine.medical_specialty ,Databases, Factual ,Endocrinology, Diabetes and Metabolism ,Comorbidity ,Risk Assessment ,Severity of Illness Index ,Health services ,Sex Factors ,Endocrinology ,Risk Factors ,Sex factors ,Pancreatitis, Chronic ,Internal medicine ,Severity of illness ,Internal Medicine ,Humans ,Medicine ,In patient ,Mortality ,Maryland ,Hepatology ,business.industry ,Age Factors ,Middle Aged ,medicine.disease ,Patient Discharge ,Population based study ,Pancreatitis ,Population Surveillance ,Acute Disease ,Multivariate Analysis ,Acute pancreatitis ,Female ,business - Abstract
The objectives of this study were to evaluate the severity of patients with acute pancreatitis (AP) on chronic pancreatitis (CP) and compare this to patients with AP without CP.The Maryland Health Services database was queried for all adult inpatient discharges with a primary diagnosis of AP from 1994 to 2010. Acute pancreatitis on CP and AP without CP were defined by the presence of the associated diagnosis code for CP. Severity was defined as organ failure, intensive care unit stay, or mortality.Acute pancreatitis on CP accounted for 13.7% of all AP discharges (9747/70,944). The proportion of AP-on-CP discharges doubled during the study period (8.8% to 17.6%; P0.0001). When compared with patients with AP without CP, AP-on-CP patients were younger, were more likely to be male and black, had higher rates of alcohol and drug abuse, and had less severe disease with lower rates of mortality, organ failure, need for mechanical ventilation, and intensive care unit stay. Among AP-on-CP patients, significant predictors of severity included advanced age, weight loss, and 2 or more comorbidities.Patients with AP on CP have less severe disease than do those with AP without CP. Weight loss, advanced age, and comorbidity increase the risk of severity in patients with AP on CP.
- Published
- 2013
31. Diabetes and cancer
- Author
-
Dana K. Andersen
- Subjects
Blood Glucose ,Male ,Oncology ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,MEDLINE ,Diabetes Complications ,Endocrinology ,Risk Factors ,Hyperinsulinism ,Intervention (counseling) ,Diabetes mellitus ,Pancreatic cancer ,Internal medicine ,Internal Medicine ,Carcinoma ,Humans ,Hypoglycemic Agents ,Medicine ,Obesity ,Early Detection of Cancer ,Nutrition and Dietetics ,business.industry ,Cancer ,medicine.disease ,Metformin ,Pancreatic Neoplasms ,Cell Transformation, Neoplastic ,Diabetes Mellitus, Type 1 ,Diabetes Mellitus, Type 2 ,Female ,Peptides ,business ,Carcinoma, Pancreatic Ductal ,medicine.drug - Abstract
The association of diabetes and cancer has received increased attention as data have emerged to indicate that the type of diabetes treatment may influence the risk of cancer, and that the risk of cancer among diabetic individuals can be reduced by intervention. The association of diabetes and pancreatic cancer is particularly strong, but often misunderstood. Long-standing type 1 diabetes and type 2 diabetes increase the risk for this malignancy, but the cancer can also induce pancreatogenic, or type 3c, diabetes as well.This review covers the recent findings which help to clarify these relationships, and offers guidance for prevention, early detection, and treatment. Obesity and, separately, diabetes increase the risk of several common malignancies by about two-fold. This risk is reduced by successful treatments. Type 3c diabetes is more common than previously realized, and strategies to differentiate type 3c diabetes from type 2 diabetes, to identify those candidates who will benefit from screening studies, are discussed.The death rate because of pancreatic and other cancers can be reduced by an aggressive approach to reversing obesity and hyperinsulinemia, achieving good glycemic control in diabetic patients, and identifying at an early timepoint those patients with pancreatogenic diabetes.
- Published
- 2013
32. Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer
- Author
-
David Bradley, Dana K. Andersen, Aida Habtezion, Suresh T. Chari, Mark O. Goodarzi, Zobeida Cruz-Monserrate, Stephen J. Pandol, Melena D. Bellin, Dhiraj Yadav, Phil A. Hart, Yogish C. Kudva, Murray Korc, and Chris E. Forsmark
- Subjects
medicine.medical_specialty ,Type 2 diabetes ,Gastroenterology ,Cystic fibrosis ,Article ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Pancreatic cancer ,Diabetes mellitus ,Internal medicine ,Pancreatitis, Chronic ,Epidemiology ,medicine ,Diabetes Mellitus ,Humans ,Clinical significance ,Hepatology ,business.industry ,medicine.disease ,Pancreatic Neoplasms ,030220 oncology & carcinogenesis ,Pancreatitis ,030211 gastroenterology & hepatology ,business ,Carcinoma, Pancreatic Ductal - Abstract
Summary Diabetes mellitus is a group of diseases defined by persistent hyperglycaemia. Type 2 diabetes, the most prevalent form, is characterised initially by impaired insulin sensitivity and subsequently by an inadequate compensatory insulin response. Diabetes can also develop as a direct consequence of other diseases, including diseases of the exocrine pancreas. Historically, diabetes due to diseases of the exocrine pancreas was described as pancreatogenic or pancreatogenous diabetes mellitus, but recent literature refers to it as type 3c diabetes. It is important to note that type 3c diabetes is not a single entity; it occurs because of a variety of exocrine pancreatic diseases with varying mechanisms of hyperglycaemia. The most commonly identified causes of type 3c diabetes are chronic pancreatitis, pancreatic ductal adenocarcinoma, haemochromatosis, cystic fibrosis, and previous pancreatic surgery. In this Review, we discuss the epidemiology, pathogenesis, and clinical relevance of type 3c diabetes secondary to chronic pancreatitis and pancreatic ductal adenocarcinoma, and highlight several important knowledge gaps.
- Published
- 2016
33. Pancreatogenic Diabetes: Special Considerations for Management
- Author
-
Dana K. Andersen and Yun Feng Cui
- Subjects
Male ,medicine.medical_specialty ,Pancreatic disease ,Dipeptidyl Peptidase 4 ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Administration, Oral ,Type 2 diabetes ,Pancreatic Polypeptide ,Gastroenterology ,Receptor, IGF Type 1 ,Insulin resistance ,Pancreatitis, Chronic ,Internal medicine ,Diabetes mellitus ,Pancreatic cancer ,Diabetes Mellitus ,Animals ,Humans ,Hypoglycemic Agents ,Insulin ,Medicine ,Glycated Hemoglobin ,Dipeptidyl-Peptidase IV Inhibitors ,Hepatology ,business.industry ,Pancreatic Ducts ,Disease Management ,Pancreatic Diseases ,medicine.disease ,Metformin ,Pancreatic Neoplasms ,Pancreatitis ,Female ,Insulin Resistance ,business ,medicine.drug - Abstract
Background/Aims: Pancreatogenic, or type 3c, diabetes (T3cDM) occurs due to inherited or acquired pancreatic disease or resection. Although similar to the more prevalent type 1 and type 2 diabetes, pancreatogenic diabetes has a unique pattern of hormonal and metabolic characteristics and a high incidence of pancreatic carcinoma in the majority of patients with T3cDM. Despite these differences, no guidelines for therapy have been described. Methods: Published studies on the prevalence, pathophysiology, and cancer associations of T3cDM were reviewed. The recent studies on the protective role and mechanism of metformin therapy as both an anti-diabetic and anti-neoplastic agent were reviewed, and studies on the cancer risk of other anti-diabetic drugs were surveyed. Results: T3cDM accounts for 5–10% of Western diabetic populations and is associated with mild to severe disease. Hepatic insulin resistance is characteristic of T3cDM and is caused by deficiencies of both insulin and pancreatic polypeptide. 75% of T3cDM is due to chronic pancreatitis, which carries a high risk for pancreatic carcinoma. Insulin and insulin secretagogue treatment increases the risk of malignancy, whereas metformin therapy reduces it. Pancreatic exocrine insufficiency associated with T3cDM contributes to nutritional deficiencies and the development of metabolic bone disease. Conclusions: Until consensus recommendations are reached, the glycemic treatment of T3cDM should avoid insulin and insulin secretagogues if possible. Metformin should be the first line of therapy, and continued if insulin treatment must be added for adequate glucose control. Pancreatic enzyme therapy should be added to prevent secondary nutritional and metabolic complications.
- Published
- 2011
34. Advances in the Etiology and Management of Hyperinsulinemic Hypoglycemia After Roux-en-Y Gastric Bypass
- Author
-
Yunfeng Cui, Dana K. Andersen, and Dariush Elahi
- Subjects
endocrine system ,medicine.medical_specialty ,Gastric Bypass ,Octreotide ,Incretin ,Nesidioblastosis ,Hypoglycemia ,medicine.disease_cause ,Hyperinsulinism ,Internal medicine ,Diabetes mellitus ,Weight Loss ,medicine ,Humans ,Obesity ,Hyperinsulinemic hypoglycemia ,business.industry ,Neuroglycopenia ,Gastroenterology ,nutritional and metabolic diseases ,Type 2 Diabetes Mellitus ,medicine.disease ,Endocrinology ,Diabetes Mellitus, Type 2 ,Surgery ,business ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
Hyperinsulinemic hypoglycemia with severe neuroglycopenia has been identified as a late complication of Roux-en-Y gastric bypass (RYGB) in a small number of patients. The rapid resolution of type 2 diabetes mellitus after RYGB is probably related to increased secretion of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), and patients with post-RYGB hypoglycemia demonstrate prolonged elevations of GIP and GLP-1 compared to non-hypoglycemic post-RYGB patients. Nesidioblastosis has been identified in some patients with post-RYGB hypoglycemia and is likely due to the trophic effects of GIP and GLP-1 on pancreatic islets. Treatment of hypoglycemia after RYGB should begin with strict dietary (low carbohydrate) alteration and may require a trial of diazoxide, octreotide, or calcium-channel antagonists, among other drugs. Surgical therapy should include consideration of a restrictive form of bariatric procedure, with or without reconstitution of gastrointestinal continuity. Partial or total pancreatic resection should be avoided.
- Published
- 2011
35. Accuracy and Reliability of the Nova StatStrip® Glucose Meter for Real-Time Blood Glucose Determinations during Glucose Clamp Studies
- Author
-
Jeffrey DuBois, Dariush Elahi, Audrey Gillette, Rocio Salas-Carrillo, Dana K. Andersen, Crystal Grant, Atoosa Rabiee, J. Trent Magruder, and Richard P. Shannon
- Subjects
Plasma samples ,business.industry ,Endocrinology, Diabetes and Metabolism ,Grid analysis ,Glucose meter ,Biomedical Engineering ,Bioengineering ,Nova (laser) ,Glucose clamp technique ,Clamp ,Blood Glucose Self-Monitoring ,Internal Medicine ,Nuclear medicine ,business ,Reliability (statistics) ,Mathematics - Abstract
Aims/Hypothesis: The Andres clamp technique, which requires accurate and timely determination of glucose, utilizes the Beckman or Yellow Springs Instruments (YSI) glucose analyzers. Both instruments require maintenance, a dedicated operator, preparation of a plasma sample, and a duplicate measurement that takes ≥2 minutes. The Nova StatStrip glucose meter was evaluated for accuracy, reliability, and near-real-time availability of glucose. Methods: Blood samples from 24 patients who underwent 6-hour clamp studies and 12 patients who had a standardized meal tolerance test (SMT) were measured. Specimens were analyzed simultaneously and immediately upon collection by Beckman, YSI, and Nova. Results: Of 1004 data pairs for the Nova device versus Beckman, the Nova data points ranged from 32 to 444, while Beckman ranged from 42 to 412. The coefficient for the slope of Beckman versus Nova was 1.009 ( r = 0.978). Using error grid analysis, the number and percentage of values for Nova were 976 (97.2%) in the A zone and 28 (2.8%) in the B zone. Of 399 data pairs for the Nova device versus YSI, the Nova data points ranged from 46 to 255, whereas YSI ranged from 47 to 231. The coefficient for the slope of YSI versus Nova was 1.023 ( r = 0.989). All Nova readings fell in the A zone. Time required for final reading, in duplicate, was 15 seconds for Nova and 120–180 seconds for Beckman and YSI. Conclusions: The simplicity of Nova and its reliability, accuracy, and speed make it an acceptable replacement device for Beckman and YSI in the conduct of clamps, especially when perturbations require rapid glucose determination.
- Published
- 2010
36. Delayed release pancrelipase for treatment of pancreatic exocrine insufficiency associated with chronic pancreatitis
- Author
-
Sanjay B. Jagannath, Atoosa Rabiee, Devi Mukkai Krishnamurty, and Dana K. Andersen
- Subjects
Drug ,medicine.medical_specialty ,media_common.quotation_subject ,Review ,Disease ,RM1-950 ,Bioequivalence ,Gastroenterology ,chronic pancreatitis ,In vivo ,Internal medicine ,Pancrelipase ,medicine ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,media_common ,pancreatic exocrine insufficiency ,Chemical Health and Safety ,business.industry ,General Medicine ,pancreatic enzyme supplement ,medicine.disease ,Enteric coating ,Steatorrhea ,Endocrinology ,Pancreatitis ,Therapeutics. Pharmacology ,medicine.symptom ,business ,Safety Research ,medicine.drug - Abstract
Devi Mukkai Krishnamurty,1 Atoosa Rabiee,2 Sanjay B Jagannath,1 Dana K Andersen2Johns Hopkins University School of Medicine; 1Department of Medicine; 2Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA; 2Johns Hopkins University School of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, MD, USAAbstract: Pancreatic enzyme supplements (PES) are used in chronic pancreatitis (CP) for correction of pancreatic exocrine insufficiency (PEI) as well as pain and malnutrition. The use of porcine pancreatic enzymes for the correction of exocrine insufficiency is governed by the pathophysiology of the disease as well as pharmacologic properties of PES. Variability in bioequivalence of PES has been noted on in vitro and in vivo testing and has been attributed to the differences in enteric coating and the degree of micro-encapsulation. As a step towards standardizing pancreatic enzyme preparations, the Food and Drug Administration now requires the manufacturers of PES to obtain approval of marketed formulations by April 2010. In patients with treatment failure, apart from evaluating drug and dietary interactions and compliance, physicians should keep in mind that patients may benefit from switching to a different formulation. The choice of PES (enteric coated versus non-enteric coated) and the need for acid suppression should be individualized. There is no current standard test for evaluating adequacy of therapy in CP patients and studies have shown that optimization of therapy based on symptoms may be inadequate. Goals of therapy based on overall patient presentation and specific laboratory tests rather than mere correction of steatorrhea are needed.Keywords: pancreatic exocrine insufficiency, chronic pancreatitis, pancreatic enzyme supplement
- Published
- 2009
37. Numerical and Clinical Accuracy of a Continuous Glucose Monitoring System during Intravenous Insulin Therapy in the Surgical and Burn Intensive Care Units
- Author
-
B. Robert Gibson, Zeina A. Khouri, Rania Abu-Hamdah, Atoosa Rabiee, Dana K. Andersen, Panagis Galiatsatos, Virginia Andreasik, and Dariush Elahi
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Critical Illness ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Biomedical Engineering ,Bioengineering ,law.invention ,Insulin Infusion Systems ,DEVELOPMENTS in Continuous Glucose Monitoring ,law ,Intensive care ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Insulin ,Intensive care medicine ,Aged ,Monitoring, Physiologic ,Glycemic ,business.industry ,Type 2 Diabetes Mellitus ,Middle Aged ,Glucose clamp technique ,medicine.disease ,Intensive care unit ,Intensive Care Units ,Glucose ,Glycemic index ,Diabetes Mellitus, Type 2 ,Glucose Clamp Technique ,Female ,business - Abstract
Intensive insulin therapy (IIT) for glycemic control in critically ill patients has been shown to be beneficial. Continuous glucose monitoring systems (CGMSs) have been approved as an adjunct to complement standard glucose monitoring in type 2 diabetes mellitus. This study was designed to evaluate the accuracy of a real-time CGMS (DexCom STS) in the intensive care unit (ICU). We also evaluated its reliability and accuracy using a hyperinsulinemic-euglycemic and a hyperglycemic clamp study.Nineteen patients were enrolled in this 7-day study [13 = surgical intensive care unit (SICU), 6 = burn intensive care unit (BICU)]. The patients were on IIT for at least 2 h prior the subcutaneous sensor insertion. Mean age and body mass index for SICU and BICU patients were 60.3 +/- 3.7 and 64.5 +/- 6.2 years and 36.6 +/- 5.0 and 33.85 +/- 3.4 kg/m2, respectively. DexCom accuracy was analyzed separately for the JohnsonJohnson (JJ) calibration finger sticks, Roche Accucheck finger sticks, and the Hitachi 917 analyzer measurements on serum using Clarke error grid analysis and Bland-Altman analysis. In the clamp studies, 20 patients were enrolled, and the data were analyzed similarly.There were 1065 pairs of DexCom-Accucheck, 232 pairs of DexCom-JJ, and 84 pairs of DexCom-Hitachi in ICU patients. For DexCom-Accucheck, 68.26% of the pairs fell into zone A, 31.83% into zone B, and 0.75% into zone C. There were no values in zones D or E. From the 1102 matching DexCom-Beckman pairs in clamp studies, 42.29% were in zone A, 55.90% were in zone B, and 4.08% were in zone C.Despite the high percentage of measurements in zones A and B, underestimation of hypoglycemia by DexCom measurements makes it an unreliable device in the ICU setting.
- Published
- 2009
38. The Extrapancreatic Effects of Glucagon-Like Peptide-1 and Related Peptides
- Author
-
Rania Abu-Hamdah, Dana K. Andersen, Richard P. Shannon, Graydon S. Meneilly, Atoosa Rabiee, and Dariush Elahi
- Subjects
Central Nervous System ,Clinical Review ,endocrine system ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Context (language use) ,Biology ,Cardiovascular System ,Models, Biological ,Biochemistry ,Endocrinology ,Glucagon-Like Peptide 1 ,Internal medicine ,medicine ,Animals ,Humans ,Hypoglycemic Agents ,Glucose homeostasis ,Receptor ,Pancreas ,Gastric emptying ,Pancreatic Exocrine Secretion ,digestive, oral, and skin physiology ,Biochemistry (medical) ,Glucagon-like peptide-1 ,Peptide Fragments ,Gastrointestinal Tract ,Liver ,Gastrointestinal hormone ,Gastric acid ,hormones, hormone substitutes, and hormone antagonists - Abstract
Context: Glucagon-like peptide-1 (GLP-1) 7-36 amide, an insulinotropic hormone released from the intestinal L cells in response to nutrient ingestion, has been extensively reviewed with respect to β-cell function. However GLP-1 receptors are abundant in many other tissues. Thus, the function of GLP-1 is not limited to the islet cells, and it has regulatory actions on many other organs. Evidence Acquisition: A review of published, peer-reviewed medical literature (1987 to September 2008) on the extrapancreatic actions of GLP-1 was performed. Evidence Synthesis: The extrapancreatic actions of GLP-1 include inhibition of gastric emptying and gastric acid secretion, thereby fulfilling the definition of GLP-1 as an enterogastrone. Other important extrapancreatic actions of GLP-1 include a regulatory role in hepatic glucose production, the inhibition of pancreatic exocrine secretion, cardioprotective and cardiotropic effects, the regulation of appetite and satiety, and stimulation of afferent sensory nerves. The primary metabolite of GLP-1, GLP-1 (9-36) amide, or GLP-1m, is the truncated product of degradation by dipeptidyl peptidase-4. GLP-1m has insulinomimetic effects on hepatic glucose production and cardiac function. Exendin-4 present in the salivary gland of the reptile, Gila monster (Heloderma suspectum), is a high-affinity agonist for the mammalian GLP-1 receptor. It is resistant to degradation by dipeptidyl peptidase-4, and therefore has a prolonged half-life. Conclusion: GLP-1 and its metabolite have important extrapancreatic effects particularly with regard to the cardiovascular system and insulinomimetic effects with respect to glucose homeostasis. These effects may be particularly important in the obese state. GLP-1, GLP-1m, and exendin-4 therefore have potential therapeutic roles because of their diffuse extrapancreatic actions.
- Published
- 2009
39. Early detection of sporadic pancreatic cancer: summative review
- Author
-
O. Joe Hines, Marcia I. Canto, Sudhir Srivastava, Markus M. Lerch, Gloria M. Petersen, Surinder K. Batra, Diane M. Simeone, Michael A. Hollingsworth, David T.W. Wong, Masao Tanaka, Sarah P. Thayer, Barbara J. Kenner, Sean J. Mulvihill, Dana K. Andersen, Sanjiv S. Gambhir, David S. Klimstra, Andrew D. Rhim, Matthew A. Firpo, Teresa A. Brentnall, David A. Ahlquist, Deborah F. Cleeter, Suresh T. Chari, Michael J. Levy, Anirban Maitra, Kimberly A. Kelly, Aaron I. Vinik, and Vay Liang W. Go
- Subjects
Pathology ,Biomedical Research ,Endocrinology, Diabetes and Metabolism ,Biopsy ,International Cooperation ,Endocrinology ,Medicine ,Interdisciplinary communication ,Cooperative Behavior ,Early Detection of Cancer ,Cancer ,screening and diagnosis ,Summit ,geography.geographical_feature_category ,Tumor ,diabetes ,familial ,imaging ,Prognosis ,Detection ,Molecular Diagnostic Techniques ,Pancreatic Ductal ,biomarker ,Diagnostic Imaging ,medicine.medical_specialty ,Pancreatic ductal adenocarcinoma ,Clinical Sciences ,Early detection ,pancreatic ductal adenocarcinoma ,Pancreatic Cancer ,Rare Diseases ,Predictive Value of Tests ,Pancreatic cancer ,Internal Medicine ,Humans ,Cancer death ,Medical education ,geography ,Hepatology ,Gastroenterology & Hepatology ,business.industry ,screening ,Prevention ,Carcinoma ,Congresses as Topic ,medicine.disease ,Survival Analysis ,4.1 Discovery and preclinical testing of markers and technologies ,Pancreatic Neoplasms ,Summative assessment ,Interdisciplinary Communication ,Cooperative behavior ,Diffusion of Innovation ,business ,Digestive Diseases ,Biomarkers - Abstract
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Pancreatic cancer (PC) is estimated to become the second leading cause of cancer death in the United States by 2020. Early detection is the key to improving survival in PC. Addressing this urgent need, the Kenner Family Research Fund conducted the inaugural Early Detection of Sporadic Pancreatic Cancer Summit Conference in 2014 in conjunction with the 45th Anniversary Meeting of the American Pancreatic Association and Japan Pancreas Society. This seminal convening of international representatives from science, practice, and clinical research was designed to facilitate challenging interdisciplinary conversations to generate innovative ideas leading to the creation of a defined collaborative strategic pathway for the future of the field. An in-depth summary of current efforts in the field, analysis of gaps in specific areas of expertise, and challenges that exist in early detection is presented within distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. In addition, an overview of efforts in familial PC is presented in an addendum to this article. It is clear from the summit deliberations that only strategically designed collaboration among investigators, institutions, and funders will lead to significant progress in early detection of sporadic PC.
- Published
- 2015
40. Pancreatic Polypeptide (PP)
- Author
-
F. Charles Brunicardi and Dana K. Andersen
- Subjects
medicine.medical_specialty ,biology ,business.industry ,Carbohydrate metabolism ,medicine.disease ,Obesity ,Insulin receptor ,Endocrinology ,medicine.anatomical_structure ,Diabetes mellitus ,Internal medicine ,medicine ,biology.protein ,Pancreatic polypeptide ,Secretion ,Pancreas ,business ,Artificial endocrine pancreas - Abstract
Pancreatic polypeptide (PP) is secreted from islet cells in the head of the pancreas. Secretion is induced by nutrient ingestion, and is vagally dependent. PP may have a role in satiety and obesity, but its most important role appears to be its regulation of hepatic insulin receptor availability. In pancreatogenic or type 3c diabetes PP deficiency is common, and restoration of PP levels improves glucose metabolism. Pancreatic surgical procedures that spare the PP-rich region of the pancreas have a lower risk of postoperative diabetes. This article summarizes the physiology of PP related to glucose metabolism and highlights new therapeutic opportunities.
- Published
- 2015
41. Effect of glucagon-like peptide-1 (7–37) on beta-cell function after islet transplantation in type 1 diabetes
- Author
-
Dana K. Andersen, Dariush Elahi, Michelle Fung, Graydon S. Meneilly, Garth L. Warnock, David M. Thompson, and R. Jean Shapiro
- Subjects
Adult ,Blood Glucose ,Male ,endocrine system ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Islets of Langerhans Transplantation ,Incretin ,Type 2 diabetes ,Islets of Langerhans ,Endocrinology ,Glucagon-Like Peptide 1 ,Internal medicine ,Diabetes mellitus ,Diet, Diabetic ,Insulin Secretion ,Internal Medicine ,medicine ,Humans ,Insulin ,Type 1 diabetes ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Glucagon-like peptide-1 ,Peptide Fragments ,Insulin oscillation ,Transplantation ,Diabetes Mellitus, Type 1 ,Glucose Clamp Technique ,Female ,Peptides ,business - Abstract
Islet transplantation can improve glycemic control in patients with type 1 diabetes and reduce or eliminate the need for insulin. Glucagon-like peptide-1 (GLP-1) is an intestinal insulinotropic hormone that augments glucose induced insulin secretion, and has a trophic effect on beta-cells. We evaluated the effect of GLP-1 on insulin secretion after islet transplantation. Patients underwent hyperglycemic glucose clamp studies 1 month after their last transplant. GLP-1 was infused during the second hour of the hyperglycemic clamp. Results were compared to normal control subjects and patients with type 2 diabetes who underwent an identical hyperglycemic clamp. First phase insulin release was absent in patients, while second phase insulin was not significantly reduced (control: 118+/-29 pM; type 2 diabetes: 68+/-20 pM; transplant: 99+/-18 pM, p=ns for all). GLP-1 had a significant incretin effect on transplanted islets but the response was less than controls (control: 2108+/-344 pM; type 2 diabetes: 929+/-331 pM; transplant: 329+/-112 pM, p0.0001 control versus transplant). Islet transplant patients had no evidence of resistance to insulin mediated glucose disposal. We conclude that transplanted islets retain the ability to respond to GLP-1.
- Published
- 2006
42. The practical importance of recognizing pancreatogenic or type 3c diabetes
- Author
-
Dana K. Andersen
- Subjects
medicine.medical_specialty ,Endocrinology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Diabetes mellitus ,Internal Medicine ,medicine ,MEDLINE ,Intensive care medicine ,medicine.disease ,business - Published
- 2012
43. Pancreatic Resection: Effects on Glucose Metabolism
- Author
-
Lori A. Slezak and Dana K. Andersen
- Subjects
medicine.medical_specialty ,Pancreatic disease ,medicine.medical_treatment ,Pancreatic Polypeptide ,Gastroenterology ,Pancreaticoduodenectomy ,Whipple Procedure ,Pancreatectomy ,Insulin resistance ,Internal medicine ,Diabetes Mellitus ,medicine ,Humans ,Insulin ,Pancreatic polypeptide ,Pancreas ,business.industry ,Pancreatic Diseases ,Glucagon ,medicine.disease ,Glucagon Deficiency ,Surgery ,Glucose ,medicine.anatomical_structure ,business - Abstract
Pancreatic resection results in hormonal abnormalities that are dependent on the extent and location (proximal versus distal) of the resected portion of the gland. The form of glucose intolerance which results from pancreatic resection is termed pancreatogenic diabetes. It is associated with features distinct from both type I (insulin-dependent) and type II (insulin-independent, or adult-onset) diabetes. Hepatic insulin resistance with persistent endogenous glucose production and enhanced peripheral insulin sensitivity result in a brittle form of diabetes which can be difficult to manage. In addition to insulin deficiency, the endocrine abnormalities that accompany pancreatic resection can include glucagon deficiency or pancreatic polypeptide (PP) deficiency if the resection is distal or proximal, respectively. Glucagon deficiency can contribute to iatrogenic hypoglycemia, and PP deficiency can contribute to persistent hyperglycemia due to impaired hepatic insulin action. Pancreatic resections that spare the duodenum, such as distal pancreatectomy, duodenum-preserving pancreatic head resection (Beger procedure), or extended lateral pancreaticojejunostomy with excavation of the pancreatic head (Frey procedure), are associated with a lower incidence of new or worsened diabetes than the standard or pylorus-preserving pancreaticoduodenectomy (Whipple procedure) or total pancreatectomy. Operative considerations for the treatment of pancreatic disease should include strategies to minimize the hormonal impairment of pancreatic resection.
- Published
- 2001
44. Isolated Hepatic Cholinergic Denervation Impairs Glucose and Glycogen Metabolism
- Author
-
Jin Ping Wang, Lori A. Slezak, Dana K. Andersen, Chengrui Xue, Gudrun Aspelund, and Kumudesh C. Sritharan
- Subjects
Male ,medicine.medical_specialty ,medicine.medical_treatment ,Carbohydrate metabolism ,Biology ,Glucagon ,Connexins ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Parasympathetic Nervous System ,Internal medicine ,medicine ,Animals ,Denervation ,Glycogen ,Insulin ,Metabolism ,Immunohistochemistry ,Liver Glycogen ,Rats ,Perfusion ,Glucose ,Endocrinology ,Liver ,chemistry ,Cholinergic ,Surgery - Abstract
Background. Hepatic innervation plays an essential role in insulin extraction and glucose production, but the specific role of hepatic cholinergic innervation remains unclear. We sought to establish a model of isolated hepatic cholinergic denervation (IHCD), and to assess whether glycogen storage or the control of net hepatic glucose production (HGP) was altered by IHCD. Materials and Methods. Sprague–Dawley rats underwent either hepatic vagotomy or sham operation. Liver tissue was stained for vesicular acetylcholine transporter (VAChT) and (nonspecific neural) protein gene product 9.5 (PGP) for verification of IHCD. Liver glycogen content was quantified in fed and fasted IHCD or sham-operated animals. HGP was determined after single-pass isolated liver perfusion, during which a 30-min 12 ng/ml glucagon infusion was begun after equilibration, and after 10 min, a 200 μU/ml insulin infusion was added. Results. Uniform staining of PGP and absence of VAChT staining in hepatic vagotomized rats demonstrated the validity of our model. Glycogen content of sham-operated livers (n = 8) increased from 6.0 ± 1.7 in the fasting state to 10.6 ± 1.8 mg/g liver, after feeding (P < 0.05). IHCD livers (n = 8) showed no comparable increase (3.5 ± 0.6 to 4.0 ± 0.7 mg/g liver). Perfusion with glucagon alone resulted in less HGP in IHCD livers (n = 12) compared with sham-operated livers (n = 10) (integrated HGP 3.3 ± 0.3 mg/g liver min−1 vs 5.1 ± 0.5 mg/g liver min−1, P < 0.05). Insulin infusion revealed impaired responsiveness to insulin after IHCD; the ratio of HGP in the final 10 min of perfusion (glucagon and insulin) to HGP in the initial 10 min (glucagon alone) was 90.3 ± 2.4% for IHCD livers versus 68.1 ± 4.4% for sham-operated controls, respectively (P = 0.0002). Conclusions. Our study shows that IHCD results in significant impairment in liver glycogen storage and impaired hepatic sensitivity to glucagon and, possibly, to insulin. We conclude that hepatic cholinergic integrity is essential to normal hepatic glucose metabolism.
- Published
- 2000
45. Effects of free fatty acids on glucose transport and IRS-1–associated phosphatidylinositol 3-kinase activity
- Author
-
Didier Laurent, Douglas L. Rothman, Lori A. Slezak, Gerald I. Shulman, Gary W. Cline, Dana K. Andersen, Melissa Marcucci, Ripudaman S. Hundal, Margaret E. Griffin, Alan Dresner, Kitt Falk Petersen, and Sylvie Dufour
- Subjects
Adult ,Glycerol ,Male ,medicine.medical_specialty ,Magnetic Resonance Spectroscopy ,Adolescent ,Glucose uptake ,Glucose-6-Phosphate ,Fatty Acids, Nonesterified ,Biology ,Article ,Phosphatidylinositol 3-Kinases ,chemistry.chemical_compound ,Insulin resistance ,Hyperinsulinism ,Internal medicine ,medicine ,Humans ,Insulin ,Kinase activity ,Muscle, Skeletal ,Glycogen synthase ,Glycogen ,Glucose transporter ,General Medicine ,Glucose clamp technique ,Lipid Metabolism ,Phosphoproteins ,medicine.disease ,Glucose ,Endocrinology ,chemistry ,Glucose 6-phosphate ,Glucose Clamp Technique ,Insulin Receptor Substrate Proteins ,biology.protein ,Female ,Insulin Resistance - Abstract
To examine the mechanism by which free fatty acids (FFA) induce insulin resistance in human skeletal muscle, glycogen, glucose-6-phosphate, and intracellular glucose concentrations were measured using carbon-13 and phosphorous-31 nuclear magnetic resonance spectroscopy in seven healthy subjects before and after a hyperinsulinemic-euglycemic clamp following a five-hour infusion of either lipid/heparin or glycerol/heparin. IRS-1-associated phosphatidylinositol 3-kinase (PI 3-kinase) activity was also measured in muscle biopsy samples obtained from seven additional subjects before and after an identical protocol. Rates of insulin stimulated whole-body glucose uptake. Glucose oxidation and muscle glycogen synthesis were 50%-60% lower following the lipid infusion compared with the glycerol infusion and were associated with a approximately 90% decrease in the increment in intramuscular glucose-6-phosphate concentration, implying diminished glucose transport or phosphorylation activity. To distinguish between these two possibilities, intracellular glucose concentration was measured and found to be significantly lower in the lipid infusion studies, implying that glucose transport is the rate-controlling step. Insulin stimulation, during the glycerol infusion, resulted in a fourfold increase in PI 3-kinase activity over basal that was abolished during the lipid infusion. Taken together, these data suggest that increased concentrations of plasma FFA induce insulin resistance in humans through inhibition of glucose transport activity; this may be a consequence of decreased IRS-1-associated PI 3-kinase activity.
- Published
- 1999
46. Detection, evaluation and treatment of diabetes mellitus in chronic pancreatitis: recommendations from PancreasFest 2012
- Author
-
Michael R, Rickels, Melena, Bellin, Frederico G S, Toledo, R Paul, Robertson, Dana K, Andersen, Suresh T, Chari, Randall, Brand, Luca, Frulloni, Michelle A, Anderson, David C, Whitcomb, and Hongjun, Wang
- Subjects
medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Islets of Langerhans Transplantation ,Incretin ,Disease ,Transplantation, Autologous ,Article ,chronic pancreatitis ,Diabetes mellitus ,Internal medicine ,Pancreatitis, Chronic ,Glucose Intolerance ,medicine ,Diabetes Mellitus ,Endocrine system ,Humans ,Intensive care medicine ,Pancreas ,therapy ,Glucose tolerance test ,diabetes ,Hepatology ,medicine.diagnostic_test ,business.industry ,Insulin ,Gastroenterology ,Glucose Tolerance Test ,medicine.disease ,Partial Pancreatectomy ,Pancreatitis ,business - Abstract
Description Diabetes and glucose intolerance are common complications of chronic pancreatitis, yet clinical guidance on their detection, classification, and management is lacking. Methods A working group reviewed the medical problems, diagnostic methods, and treatment options for chronic pancreatitis-associated diabetes for a consensus meeting at PancreasFest 2012 . Results Guidance Statement 1.1 : Diabetes mellitus is common in chronic pancreatitis. While any patient with chronic pancreatitis should be monitored for development of diabetes, those with long-standing duration of disease, prior partial pancreatectomy, and early onset of calcific disease may be at higher risk. Those patients developing diabetes mellitus are likely to have co-existing pancreatic exocrine insufficiency. Guidance Statement 1.2 : Diabetes occurring secondary to chronic pancreatitis should be recognized as pancreatogenic diabetes (type 3c diabetes). Guidance Statement 2.1 : The initial evaluation should include fasting glucose and HbA1c. These tests should be repeated annually. Impairment in either fasting glucose or HbA1c requires further evaluation. Guidance Statement 2.2 : Impairment in either fasting glucose or HbA1c should be further evaluated by a standard 75 g oral glucose tolerance test. Guidance Statement 2.3 : An absent pancreatic polypeptide response to mixed-nutrient ingestion is a specific indicator of type 3c diabetes. Guidance Statement 2.4 : Assessment of pancreatic endocrine reserve, and importantly that of functional beta-cell mass, should be performed as part of the evaluation and follow-up for total pancreatectomy with islet autotransplantation (TPIAT). Guidance Statement 3 : Patients with pancreatic diabetes shall be treated with specifically tailored medical nutrition and pharmacologic therapies. Conclusions Physicians should evaluate and treat glucose intolerance in patients with pancreatitis.
- Published
- 2013
47. Pancreatic polypeptide administration improves abnormal glucose metabolism in patients with chronic pancreatitis
- Author
-
R E Chance, D Elahi, Neal E. Seymour, A S Ryan, F C Brunicardi, Harold E. Lebovitz, Rochelle L Chaiken, Jules A. Hoffmann, Dana K. Andersen, and R L Gingerich
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Pancreatic disease ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Clinical Biochemistry ,Pancreatic Polypeptide ,Biochemistry ,Glucagon ,Endocrinology ,Internal medicine ,Diabetes mellitus ,medicine ,Hyperinsulinemia ,Humans ,Insulin ,Pancreatic polypeptide ,business.industry ,Biochemistry (medical) ,Middle Aged ,Glucose clamp technique ,medicine.disease ,Kinetics ,Glucose ,Liver ,Pancreatitis ,Chronic Disease ,Glucose Clamp Technique ,business ,Hyperinsulinism - Abstract
Chronic pancreatitis (CP) is associated with lowered plasma levels and a blunted nutrient-induced release of pancreatic polypeptide (PP). To investigate the possible role of PP on glucose metabolism, we studied male patients with documented CP (n = 5) and obesity-matched control subjects (NL) (n = 6). Hepatic glucose production (HGP) and overall glucose disposal rates were determined by [3-3H]glucose infusion during a hyperinsulinemic-euglycemic clamp during three separate admissions. Basal rates of HGP were higher in CP patients. In response to an infusion of insulin (60 pmol.m-2.min-1), HGP fell 91 +/- 5% in NL subjects but only 68 +/- 8% in CP subjects (P < 0.05). One month later, the clamp was repeated during the final 2 h of an 8-h infusion of bovine PP (2 pmol.kg-1.min-1). HGP before the insulin infusion and its subsequent suppression (NL: 83 +/- 5%; CP: 86 +/- 15%) were nearly identical between groups. In follow-up studies 1 month after the PP infusion, HGP both basally and in response to insulin alone were similar to the first study. During oral glucose tolerance tests (OGTT) performed 18 h after the PP infusion, subjects with normal (n = 7) baseline OGTT responses showed no effect. All patients with diabetic (n = 3) or nondiagnostic (n = 1) OGTT responses, however, demonstrated lowered mean plasma glucose levels (approximately -2.3 mmol/L; range: -0.6 to -7.2 mmol/L). OGTTs repeated 1 month after the PP treatment showed a return to pretreatment responses. We conclude that chronic pancreatitis accompanied by PP deficiency is associated with partial hepatic resistance both in the basal state and in response to hyperinsulinemia. This impairment is reversed after iv PP administration. PP deficiency may therefore play a role in the development of pancreatogenic diabetes caused by pancreatic injury.
- Published
- 1996
48. Regulation of Hepatic Insulin Receptors by Pancreatic Polypeptide in Fasting and Feeding
- Author
-
Neal E. Seymour, Amy R. Volpert, and Dana K. Andersen
- Subjects
Male ,medicine.medical_specialty ,medicine.medical_treatment ,Intraperitoneal injection ,Carbohydrate metabolism ,Pancreatic Polypeptide ,chemistry.chemical_compound ,Internal medicine ,medicine ,Animals ,Pancreatic polypeptide ,Receptor ,biology ,Glycogen ,Insulin ,Fasting ,Receptor, Insulin ,Wheat germ agglutinin ,Liver Glycogen ,Rats ,Insulin receptor ,Endocrinology ,Liver ,chemistry ,Food ,biology.protein ,Surgery - Abstract
Pancreatic polypeptide (PP) increases hepatic insulin receptor (IR) binding activity in fasted PP-deficient rats, but not fasted normal animals. PP-induced alteration of hepatic IR levels in normal animals may be detectable in the fed state when IR concentrations are lower than during fasting. In the current study, the effect of exogenous PP on IR concentrations in the fed and fasted states was determined in healthy 300- to 350-g male Sprague-Dawley rats. Ten animals were administered PP 100 microgram/kg/day for 3 days by intraperitoneal injection and 10 weight-matched control animals received saline vehicle. Five PP- and five saline-administered rats were fasted for 12 hr prior to organ procurement, while 5 PP- and 5 saline-treated rats were given free access to food for this period. Livers were removed and snap-frozen. IRs were isolated from solubilized hepatocyte membranes by affinity chromatography with agarose-bound wheat germ agglutinin. Western blots were performed using a specific antibody to the beta subunit of the IR, which was detected by a chemiluminescence technique after 45-min exposure to X-ray film. Exposed films were examined by scanning densitometry and IR concentration was expressed as absorbance units per milligram of hepatic protein (mean +/- SE). Statistical comparisons were by Student's t test with significance taken at P < 0.05. Feeding was associated with a significantly lower IR concentration in saline-administered animals compared with the fasted state (24.2 +/- 4.0 vs 53.3 +/- 11.1). PP administration in fed rats resulted in significantly increased IR concentration as compared with that seen in saline-administered fed animals (43.8 +/- 8.9 vs 24.2 +/- 4.0). This difference may be due to increased IR synthesis with long-term PP administration, and supports the role of PP as a regulatory factor in hepatic carbohydrate metabolism.
- Published
- 1996
49. Neural regulation of the endocrine pancreas
- Author
-
Dana K. Andersen, David M. Shavelle, and F. Charles Brunicardi
- Subjects
endocrine system ,geography ,medicine.medical_specialty ,geography.geographical_feature_category ,Gastroenterology ,Biology ,Neuroendocrinology ,Pancreatic Hormones ,Islet ,Glucagon ,Islets of Langerhans ,Endocrinology ,medicine.anatomical_structure ,Somatostatin ,Oncology ,Internal medicine ,medicine ,Animals ,Humans ,Pancreatic polypeptide ,Endocrine system ,Nervous System Physiological Phenomena ,Pancreas ,Hormone - Abstract
The endocrine pancreas is innervated by a rich neural supply that has a potent regulatory effect on islet hormone secretion. The innervation includes sympathetic, parasympathetic, sensory afferent, and peptidergic neurons, enteropancreatic neurons, and most recently nitric oxide synthase-containing neurons, all of which contribute to the overall regulation of the endocrine pancreas (Fig. 1). The mechanisms involving the innervation of the islet have been studied extensively in animal models with fewer studies reported on the neural regulation of the human islet. The purpose of this article is to summarize what is presently known about the innervation of the endocrine pancreas, including animal and human studies, and neural regulation of islet hormone secretion.
- Published
- 1995
50. Rapidly Progressive Sclerosing Cholangitis Following Surgical Treatment of Pancreatic Pseudotumor
- Author
-
A. Daniel Nourmand, Michael O. Blackstone, Dana K. Andersen, George Stathopoulos, and Alfred L. Baker
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Pancreatic disease ,Common Bile Duct Diseases ,medicine.medical_treatment ,Cholangitis, Sclerosing ,Anti-Inflammatory Agents ,Constriction, Pathologic ,Liver transplantation ,Gastroenterology ,Internal medicine ,medicine ,Humans ,Surgical treatment ,Cholangiopancreatography, Endoscopic Retrograde ,Common bile duct ,business.industry ,Pancreatic Diseases ,Middle Aged ,Jaundice ,medicine.disease ,Methotrexate ,Treatment Outcome ,medicine.anatomical_structure ,Disease Progression ,medicine.symptom ,Pancreas ,business ,Complication ,medicine.drug - Abstract
Two patients with sclerosing cholangitis presented with a distal stricture of the common bile duct in association with pancreatic pseudotumors. Jaundice resolved following surgery to correct biliary obstruction, but diffuse cholangiographic abnormalities and clinical evidence of sclerosing cholangitis became evident 2 and 4 months later. Rapid progression of symptomatic disease necessitated liver transplantation in one patient, but the other had a complete response to methotrexate therapy. The rapid disease progression in these two patients may have been triggered by surgery that resulted in a generalized fibroproliferative response of the biliary tree, already affected with localized sclerosing cholangitis contiguous to a pancreatic pseudotumor. We suggest that localized sclerosing cholangitis associated with pancreatic pseudotumors may be a unique variant that can progress rapidly but respond dramatically to antiinflammatory therapy.
- Published
- 1995
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.