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5. Cystic Fibrosis–Related Diabetes: Pathophysiology and Therapeutic Challenges

Author

Ryan Kelsey, Fiona N Manderson Koivula, Neville H McClenaghan, and Catriona Kelly

Subjects
Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Cystic fibrosis–related diabetes (CFRD) is among the most common extrapulmonary co-morbidity associated with cystic fibrosis (CF), affecting an estimated 50% of adults with the condition. Cystic fibrosis is prevalent in 1 in every 2500 Caucasian live births and is caused by a mutation in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene. Mutated CFTR leads to dehydrated epithelial surfaces and a build-up of mucus in a variety of tissues including the lungs and pancreas. The leading cause of mortality in CF is repeated respiratory bacterial infections, which prompts a decline in lung function. Co-morbid diabetes promotes bacterial colonisation of the airways and exacerbates the deterioration in respiratory health. Cystic fibrosis–related diabetes is associated with a 6-fold higher mortality rate compared with those with CF alone. The management of CFRD adds a further burden for the patient and creates new therapeutic challenges for the clinical team. Several proposed hypotheses on how CFRD develops have emerged, including exocrine-driven fibrosis and destruction of the entire pancreas and contrasting theories on the direct or indirect impact of CFTR mutation on islet function. The current review outlines recent data on the impact of CFTR on endocrine pancreatic function and discusses the use of conventional diabetic therapies and new CFTR-correcting drugs on the treatment of CFRD.

Published
2019
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13. Contributors

Author

Abzug, Mark J., Acharya, Krishna K., Adams, Denise M., Adelson, Stewart, Adrian, Molly C., Ahlfeld, Shawn K., Aiken, John J., Akdis, Cezmi A., Albokhari, Daniah, Alderman, Elizabeth M., Ali, Omar, Allen-Rhoades, Wendy A., Almutlaq, Nourah N., Amos, Louella B., Anari, Jason B., Anderson, Karl E., Anupindi, Sudha A., Appleby, Brian S., Ardoin, Stacy P., Arkader, Alexandre, Armangué, Thaís, Arndt, Carola A.S., Arnold, Danielle E., Artis, Adrianne R., Asher, David M., Asselin, Barbara L., Astley, Christina M., Atkinson, Norrell K., Augustine, Erika F., Augustyn, Marilyn C., Bacharier, Leonard B., Bacino, Carlos A., Bailey, Zinzi D., Balamuth, Frances B., Baldassano, Robert N., Baldwin, Keith D., Bales, Christina B., Balistreri, William F., Balwani, Manisha, Bamba, Vaneeta, Banerji, Aleena, Bang, Janet Y., Barai, Nikita, Baranowski, Katherine, Barclay, Sarah F., Barkoudah, Elizabeth, Barrero-Castillero, Alejandra, Barrett, Katherine J., Barron, Karyl S., Basel, Donald, Bass, Dorsey M., Bassett, Mary T., Bassiri, Hamid, Baum, Rebecca A., Behrens, Edward M., Bell, Michael J., Benjamin, Daniel K., Jr., Bennett, Amanda E., Bergerson, Jenna R.E., Bernstein, Daniel, Bernstein, Henry H., Bice-Urbach, Brittany J., Bielory, Brett P., Bielory, Leonard, Blanchard, Samra S., Blanchette, Eliza, Blatter, Joshua A., Bleyer, Archie, Boas, Steven R., Bock, Margret E., Boggs, Sarah R., Boivin, Michael J., Bonn, Julie, Bonthius, Daniel J., Boppana, Suresh B., Bordini, Brett J., Borst, Alexandra J., Bosse, Kristopher R., Boyer, Kenneth M., Brady, Patrick W., Brady, Rebecca C., Brady, Samuel L., Branchford, Brian R., Brandow, Amanda M., Brandsma, Erik, Breault, David T., Breuner, Cora Collette, Bridgemohan, Carolyn F., Britt, William J., Brower, Laura, Brown, Maria D., Brownell, Jefferson N., Browning, Meghen B., Brunetti-Pierri, Nicola, Bunyavanich, Supinda, Burstein, Danielle S., Bustinduy, Amaya L., Buyon, Jill P., Cabada, Miguel M., Cada, Michaela, Cairo, Mitchell S., Calello, Diane P., Cameron, Lindsay H., Campbell, Angela J.P., Candelaria, Margo, Cannon, Laura, Carlin, Rebecca F., Carlucci, James G., Carr, Michael R., Carrigan, Robert B., Carter, Rebecca G., Carter-Hamilton, Gail V., Case, Abigail, Chang, Pearl W., Chelimsky, Gisela G., Chelimsky, Thomas, Chemaitilly, Wassim, Chiotos, Kathleen, Chiu, Yvonne E., Chong, Hey Jin, Chou, Stella T., Christ, Lori A., Christenson, John C., Chugh, Ankur A., Cieslak, Theodore J., Claes, Donna J., Coates, Thomas D., Sánchez Códez, María I., Coffin, Susan E., Cohen, Mitchell B., Cohen, Susan S., Cole, F. Sessions, III, Collaco, J. Michael, Collins, James W., Jr., Congeni, Joseph A., Conrad, Máire A., Corcoran, Justin N., Corley, Alexandra M.S., Cox, Amanda L., Coyle, Anne M., Coyne-Beasley, Tamera, Craig, Sansanee S., Creighton, Sarah M., Crigger, Chad B., Crowe, James E., Jr., Culbert, Gabriel, Czinn, Steven J., Dalal, Aarti S., Dalmau, Josep, D’Andrea, Lynn A., Danziger-Isakov, Lara A., Darville, Toni, David, Richard J., Davidoff, Katharine, Davidson, Loren T., Davidson, Richard S., Davies, H. Dele, Davis, Stephanie D., Davis-Kankanamge, Christina, Daw, Najat C., Dean, Shannon L., DeBiasi, Roberta L., Delair, Shirley, DeLaroche, Amy M., De León-Crutchlow, Diva D., Oquendo Del Toro, Helen M., Del Valle Mojica, Coralee, DeMaso, David R., Dendrinos, Melina L., Dent, Arlene E., Desnick, Robert J., Deterding, Robin R., Devarajan, Prasad, deVeber, Gabrielle A., Dhar, Vineet K., Dhossche, Julie M., Diab, Liliane K., Di Carlo, Heather N., Dietz, Harry C., III, Dietze-Fiedler, Megan L., DiMeglio, Linda A., Dixon, Bradley P., DiVasta, Amy D., Dlamini, Nomazulu, Dobbs, Katherine R., Dodhia, Sonam N., Doerholt, Katja, Dolin, Cara D., Dominguez, Samuel R., Donohoue, Patricia A., Dow, Jennifer, Downes, Kevin J., Doyle, Daniel A., Doyle, Jefferson J., Dror, Yigal, Dubowitz, Howard, Dumler, J. Stephen, Duncan, Andrea F., Durant, Nefertiti H., Dvergsten, Jeffrey A., Earing, Michael G., Eberly, Col. Matthew D., Egan, Marie E., Eichenwald, Eric C., Elkadri, Abdul-Aziz K., Englander, Elizabeth, Ericson, Jessica E., Erkan, Elif, Etzel, Ruth A., Evans, Sarah Helen, Faherty, Erin, Falk, Marni J., Familiar-Lopez, Itziar, Fargo, John H., Feemster, Kristen A., Fehnel, Katie P., Feigelman, Susan, Feldman, Amy G., Feldman, Heidi M., Fels, Edward C., Felner, Eric I., Feng, Sing-Yi, Ferkol, Thomas W., Jr., Finberg, Karin E., Finder, Jonathan D., Fiorino, Kristin N., Fischer, Philip R., Fitzpatrick, Anne M., Flannery, Dustin D., Fleming, Nicholas L., Flood, Veronica H., Flores, Francisco X., Flynn, Joseph T., Flynn, Patricia M., Foglia, Elizabeth E., Forkey, Heather C., Forman, Joel A., Freeman, Alexandra F., Friedman, Deborah M., Friedman, Susan A., Friehling, Erika D., Fritz, Stephanie A., Frush, Donald P., Fuleihan, Ramsay L., Gahagan, Sheila, Gallagher, Patrick G., Galloway, David P., Gans, Hayley A., Garber, Andrea K., Gardiner, Paula M., Garibaldi, Luigi R., Gauthier, Gregory M., Gerber, Jeffrey S., Gershon, Anne A., Ghadersohi, Saied, Gibbs, Kathleen A., Gibson, Mark, Gigante, Joseph, Gigliotti, Francis, Gilley, Stephanie P., Gilliam, Walter S., Ginde, Salil, Girotto, John A., Goldfarb, Samuel B., Goldman, David L., Goldman, Stanton C., Gómez-Duarte, Oscar G., Good, Misty, Goodbody, Christine M., Goodman, Denise M., Goodman, Tracey, Goodyer, William R., Gordon, Catherine M., Gordon, Leslie B., Gordon, Rebecca J., Gordon-Lipkin, Eliza, Gorelik, Michael, Gower, W. Adam, Graber, Evan G., Graff, Zachary T., Graham, Robert J., Green, Cori M., Green, Michael, Greenbaum, Larry A., Greenbaum, V. Jordan, Greiner, Mary V., Griffiths, Anne G., Grizzle, Kenneth L., Groner, Judith A., Grumach, Anete Sevciovic, Gueye-Ndiaye, Seyni, Guz-Mark, Anat, Haamid, Fareeda, Haddad, Gabriel G., Haddad, Joseph, Jr., Haemer, Matthew A., Hagan, Joseph F., Jr., Haider, Suraiya K., Hakim, Hana, Haldeman-Englert, Chad R., Halstead, Scott B., Hamie, Lamiaa, Hammerschlag, Margaret R., Hammershaimb, E. Adrianne, Hampton, Elisa, Hamvas, Aaron, Hanchard, Neil A., Hanley, Patrick C., Hanna, Melisha G., Harijan, Pooja D., Harrison, Douglas J., Harstad, Elizabeth B., Haslam, David B., Hauck, Fern R., Havers, Fiona P., Hayes, Ericka V., Heard-Garris, Nia J., Hedrick, Holly L., Hemingway, Cheryl, Heneghan, Chelsea, Hernandez, Michelle L., Hernandez-Trujillo, Vivian P., Hernandez Tejada, Fiorela N., Herrick, Heidi M., Hershey, Andrew D., Herzog, Cynthia E., Heston, Sarah M., Hijazi, Ghada, Hill, Samantha V., Hochberg, Jessica, Hodes, Deborah, Hoefgen, Holly R., Holinger, Lauren D., Holland-Hall, Cynthia M., Hollenbach, Laura L., Holler-Managan, Yolanda F., Hooper, David K., Hooven, Thomas A., Hoover-Fong, Julie E., Hopper, Rachel K., Hord, Jeffrey D., Horn, B. David, Horstmann, Helen M., Hotez, Peter J., House, Samantha A., Howard, Ashley C., Howard, Mary Beth, Hsu, Evelyn K., Hsu, Katherine, Huddleston, Heather G., Huh, Winston W., Humphrey, Stephen R., Hunstad, David A., Hunger, Stephen P., Hunt, Carl E., Huppert, Stacey S., Huppler, Anna R., Hurt, Hallam, Izumi, Kosuke, Jackson, Allison M., Jackson, Mary Anne, Jaffe, Ashlee M., James, Kiera M., Janowski, Andrew B., Jenssen, Brian P., Jinnah, H.A., John, Chandy C., Johansen, Kari, Johnson, Susan L., Johnston, Brian D., Jongco, Artemio M., III, Josephson, Cassandra D., Joyce, Joel C., Jyonouchi, Soma, Kabbany, Mohammad Nasser, Kabbouche, Marielle, Kacperski, Joanne, Kadry, Nadia A., Kaj-Carbaidwala, Batul, Kalish, Jennifer M., Kamat, Deepak, Kansra, Alvina R., Kanter, David M., Kao, Carol M., Kapavarapu, Prasanna K., Kattan, Jacob, Kelly, Andrea, Kelly, Desmond P., Kelly, Matthew S., Kelly, Michael E., Kendi, Sadiqa, Kerem, Eitan, Kerr, Julie M., Khan, David A., Khan, Seema, Khatami, Ameneh, Khaytin, Ilya, Kier, Catherine, Kilinsky, Alexandra, Kim, Chong-Tae, Kim, Jung Won, Kim, Rosa K., King, J. Michael, Kirschen, Matthew P., Kishnani, Priya S., Klawonn, Meghan A., Klein, Bruce L., Klein, Bruce S., Kliegman, Alison S., Kliegman, Robert M., Kneyber, Martin C.J., Koch, William C., Kochanek, Patrick M., Kodish, Eric, Kohlhoff, Stephan A., Kortepeter, Mark G., Kotloff, Karen L., Koumbourlis, Anastassios C., Krause, Peter J., Krebs, Nancy F., Kreipe, Richard E., Krug, Steven E., Kwiatkowski, Janet L., Kwon, Jennifer M., Ladisch, Stephan, Lakser, Oren J., Lalor, Leah, Lam, Simon, Lambert, Michele P., Lampe, Christina, Landry, Gregory L., Lane, Wendy G., Larson, A. Noelle, LaRussa, Phillip S., Lawrence, J. Todd R., Lee, Brendan, Lee, Erica H., Leiding, Jennifer W., Lemmon, Monica E., Lesser, Daniel J., Lestrud, Steven O., Leung, Donald Y.M., Levas, Michael N., Liacouras, Chris A., Lipkin, Paul H., Liptzin, Deborah R., Liu, Andrew H., Lo, Mindy S., Lo, Stanley F., Long, Sarah S., Lord, Katherine, Macias, Charles G., Macias, Michelle M., Macumber, Ian R., Magnusson, Mark R., Magoulas, Pilar L., Maguire, Kathleen J., Mahajan, Prashant V., Majzoub, Joseph A., Mamula, Petar, Manak, Colleen K., Mangus, Courtney W., Manoli, Irini, Manzur, Adnan Y., Maqbool, Asim, Maranich, Col. Ashley M., Margetts, Miranda, Margolis, David, Marin, Mona, Marini, Joan C., Markowitz, Morri, Maroushek, Stacene R., Marsh, Justin D., Marshall, Trisha L., Martin, Kari L., Masson, Vicki K., Matalon, Dena R., Matalon, Reuben K., Mathijssen, Irene M.J., Reddy Matta, Sravan Kumar, Maxwell, Elizabeth C., Maybank, Aletha, McCabe, Megan E., McCain, Darla H., McColley, Susanna A., McConnico, Neena, McCormick, Elizabeth M., McDonald, Christine M., McGovern, Margaret M., McGrath-Morrow, Sharon A., McInerney, Alissa, McKinney, Jeffrey S., McLeod, Rima, McVay-Gillam, Marcene R., Meade, Julia C., Meehan, William P., III, Mejias, Asuncion, Melby, Peter C., Melzer-Lange, Marlene D., Merves, Jamie F., Messacar, Kevin B., Michaels, Marian G., Michniacki, Thomas F., Mikati, Mohamad A., Miller-Handley, Hilary E., Mink, Jonathan W., Mirasola, Karolyn, Mistovich, R. Justin, Mohr, Emma L., Montoya-Williams, Diana, Moon, Rachel Y., Morava, Eva, Moreno, Megan A., Morgan, Ryan W., Morrison, Peter E., Morrison, Wynne, Mukhopadhyay, Sagori, Munoz, Flor M., Munson, David A., Murphy, Timothy F., Murray, Karen F., Murray, Thomas S., Mutlu, Levent, Nagata, Jason M., Narula, Sona, Nataro, James P., Navsaria, Dipesh, Nduati, Ruth W., Nehus, Edward J., Nelson, Maureen R., Neri, Caitlin M., Nevin, Mary A., Newburger, Jane W., Newmark, Jonathan, Nield, Linda S., Niermeyer, Susan, Nocton, James J., Nogee, Lawrence M., Noje, Corina, Nowak-Wegrzyn, Anna H., Obaro, Stephen K., Obeid, Makram M., O’Callaghan, Kevin P., Oleszek, Joyce L., Olitsky, Scott E., Olsson, John M., O’Neill, Meghan E., Onigbanjo, Mutiat T., Opoka, Robert O., Orenstein, Walter A., Orkin, Sarah H., Orscheln, Rachel C., Ortega, Camile, O’Toole, Timothy R., Owens, Judith A., Ozen, Seza, Pach, Sophie, Pachter, Lee M., Padhye, Amruta, Pandurangi, Sindhu, Pak-Gorstein, Suzinne, Palla, John, Palmieri, Tina L., Palmieri, Jessica M., Pappas, Diane E., Parent, John J., Parga-Belinkie, Joanna J., Parikh, Bijal A., Parker, Alasdair P.J., Partridge, Emily A., Patel, Ami B., Patel, Trusha, Patrick, Stephen W., Patterson, Briana C., Pelosi, Emanuele, Permar, Sallie R., Perry, Michael, Perry, Tamara T., Peters, Mark J., Peters, Timothy R., Peterson, Stacy J.B., Phelan, Rachel A., Pinto, Anna L., Pipan, Mary, Player, Brittany, Prince, William Benjamin, Proctor, Mark R., Prozora, Stephanie, Pryor, Howard I., II, Pyles, Lee A., Quinn, Molly M., Quint, Elisabeth H., Rabinovich, C. Egla, Raffini, Leslie J., Ragoonanan, Dristhi S., Rahman, Shamima, Ralston, Shawn L., Ram, Sanjay, Ramilo, Octavio, Ramirez, Kacy A., Rand, Casey M., Rasmussen, Sonja A., Rathke, Kevin M., Ratner, Adam J., Ratner, Lee, Reed, Ann M., Reich, Patrick J., Reif, Shimon, Reller, Megan E., Remick, Katherine E., Remiker, Allison S., Reyes, Jorge D., Richardson, Katherine M., Rintoul, Natalie E., Ritchey, A. Kim, Robinson, Angela Byun, Rodrigues, Kristine Knuti, Rogers, Michael E., Romano, Mary E., Roosevelt, Genie E., Roper, Stephen M., Rosenthal, Stephen M., Ross, A. Catharine, Rossano, Joseph W., Rothman, Jennifer A., Rotta, Alexandre T., Rozenfeld, Ranna A., Russo, Michael E., Ryan, Kelsey S., Ryan, Monique M., Ryu, Julie, Sabbagh, Sara E., Sachdev, H.P.S., Sadarangani, Manish, Sadun, Rebecca E., Sahin, Mustafa, Saint-Cyr, Martine, Salata, Robert A., Salazar, José H., Salvana, Edsel Maurice T., Samelson-Jones, Benjamin J., Sammons, Julia S., Sampson, Hugh A., Samsel, Chase B., Sandora, Thomas J., Sankar, Wudbhav N., Sarnaik, Ashok P., Sato, Alice I., Satter, Lisa Forbes, Scaggs Huang, Felicia A., Schaffzin, Joshua K., Schechter, Michael S., Schilling, Samantha, Schleiss, Mark R., Schluter, W. William, Schondelmeyer, Amanda C., Schroeder, James W., Jr., Schulte, Elaine E., Schuster, Jennifer E., Schuster, Marcy, Schuster, Mark A., Scott, Daryl A., Scott, John P., Seaborg, Kristin A., Seed, Patrick C., Serwint, Janet R., Shah, Dheeraj, Shah, Samir S., Shah, Shivang S., Shamir, Raanan, Shanti, Christina M., Shapiro, Bruce K., Shaywitz, Bennett A., Shaywitz, Sally E., Shchelochkov, Oleg A., Shulman, Stanford T., Sicherer, Scott H., Simmons, Jeffrey M., Simões, Eric A.F., Simonsen, Kari A., Simpson, Tess S., Sinclair-McBride, Keneisha R., Singh, Arunjot, Sink, Jacquelyn R., Sisk, Bryan A., Sivaraman, Vidya, Slattery, Susan M., Slavotinek, Anne M., Smith, Jessica R., Smith-Whitley, Kim, Solensky, Roland, Son, Mary Beth F., Soranno, Danielle E., Sosa, Tina K., Soto-Rivera, Carmen L., Sosinsky, Laura Stout, Souder, Emily E., Souverbielle, Cristina Tomatis, Spearman, Paul, Spiegel, David A., Spinks-Franklin, Adiaha I.A., Sprecher, Alicia J., Squires, James E., Srivastava, Siddharth, St. Geme, Joseph W., III, St. John, Rachel D., Stambough, Kathryn C., Stanberry, Lawrence R., Starke, Jeffrey R., Starr, Taylor B., Steenhoff, Andrew P., Stein, Ronen E., Steinbach, William J., Stillwell, Terri L., Stone, Deborah L., Su, Stefani, Sucato, Gina S., Suchy, Frederick J., Sullivan, Kathleen E., Swami, Sanjeev K., Szafron, Vibha A., Szilagyi, Moira, Taha, Dalal, Tan, Libo, Tantisira, Kelan G., Taylor, Alex M., Tchapyjnikov, Dmitry, Tesini, Brenda L., Theobald, Jillian L., Thielen, Beth K., Thom, Christopher S., Thornburg, Courtney D., Tieder, Joel S., Tissières, Pierre, Tolentino, Victorio R., Jr., Topjian, Alexis A., Tower, Richard L., Trachtman, Rebecca, Triebwasser, Jourdan E., Trowbridge, Sara K., Truglio, Joseph M., Tubergen, David G., Turk, Margaret A., Tymon-Rosario, Joan R., Ufberg, Paul J., Ullrich, Christina, Ullrich, Nicole, Valika, Taher S., Van Hare, George F., Van Mater, Heather A., Varnell, Charles D., Jr., Vash-Margita, Alla, Vece, Timothy J., Vemana, Aarthi P., Venditti, Charles P., Vepraskas, Sarah, Verbsky, James W., Vermilion, Jennifer A., Vickery, Brian P., Vockley, Jerry, Voynow, Judith A., Walch, Abby, Waldrop, Stephanie W., Walker, David M., Walkovich, Kelly J., Walter, Heather J., Wambach, Jennifer A., Wamithi, Susan, Wang, Julie, Wang, Marie E., Wangler, Michael F., Ware, Stephanie M., Washam, Matthew C., Wasserman, Jonathan D., Wassner, Ari J., Watson, Andrew M., Wattier, Rachel L., Weber, David R., Webster, Jennifer, Weese-Mayer, Debra E., Weinberg, Jason B., Weinman, Jason P., Weisman, Steven J., Weiss, Anna K., Weiss, Scott L., Weiss, Pamela F., Weitzman, Carol C., Wells, Lawrence, Wen, Jessica W., Wendel, Danielle R., Werlin, Steven L., Wexler, Isaiah D., Whitaker, Alexander S., White, A. Clinton, Jr., White, Perrin C., Willoughby, Rodney E., Jr., Wilschanski, Michael, Wiley, Susan E., Williams, Brendan A., Wilson, Karen M., Wilson, Pamela E., Winell, Jennifer J., Witters, Peter, Wolf, Joshua, Wolfe, Joanne, Wolfgram, Peter M., Woods, Brandon T., Wright, Benjamin L., Wright, Terry W., Wu, Eveline Y., Yagupsky, Pablo, Yang, Edward, Yang, Kesi C., Yang, Ming, Yaron, Michael, Younger, Sarah B., Yuskaitis, Christopher J., Zachariah, Philip, Zafar, Muhammad S., Zahler, Stacey G., Zajac, Lauren M., Zaky, Wafik, Zaspel, Jennifer A., Zerra, Patricia E., Zhou, Amy, Zuckerman, Barry S., and Zur, Karen B.

Published
2025
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20. Gastric electrical stimulation improves symptoms and need for supplemental nutrition in children with severe nausea and vomiting: A ten‐year experience

Author

Orsagh‐Yentis, Danielle K., primary, Ryan, Kelsey, additional, Hurwitz, Nicole, additional, Diefenbach, Karen A., additional, Teich, Steven, additional, Mousa, Hayat, additional, Bali, Neetu, additional, Vaz, Karla, additional, Yacob, Desale, additional, Di Lorenzo, Carlo, additional, and Lu, Peter L., additional

Published
2021
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25. Cystic Fibrosis–Related Diabetes: Pathophysiology and Therapeutic Challenges

Author

Neville H. McClenaghan, Ryan Kelsey, Fiona N. Manderson Koivula, and Catriona Kelly

Subjects
0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, Endocrinology, Diabetes and Metabolism, Cystic fibrosis-related diabetes, 030209 endocrinology & metabolism, Review Article, Cystic fibrosis, lcsh:Diseases of the endocrine glands. Clinical endocrinology, cystic fibrosis, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, Diabetes mellitus, Internal Medicine, medicine, CFTR, Respiratory system, cystic fibrosis–related diabetes, lcsh:RC648-665, islet, biology, business.industry, Mortality rate, medicine.disease, Cystic fibrosis transmembrane conductance regulator, 030104 developmental biology, medicine.anatomical_structure, exocrine pancreas, Immunology, biology.protein, Pancreas, business
Abstract

Cystic fibrosis–related diabetes (CFRD) is among the most common extrapulmonary co-morbidity associated with cystic fibrosis (CF), affecting an estimated 50% of adults with the condition. Cystic fibrosis is prevalent in 1 in every 2500 Caucasian live births and is caused by a mutation in the cystic fibrosis transmembrane conductance regulator ( CFTR) gene. Mutated CFTR leads to dehydrated epithelial surfaces and a build-up of mucus in a variety of tissues including the lungs and pancreas. The leading cause of mortality in CF is repeated respiratory bacterial infections, which prompts a decline in lung function. Co-morbid diabetes promotes bacterial colonisation of the airways and exacerbates the deterioration in respiratory health. Cystic fibrosis–related diabetes is associated with a 6-fold higher mortality rate compared with those with CF alone. The management of CFRD adds a further burden for the patient and creates new therapeutic challenges for the clinical team. Several proposed hypotheses on how CFRD develops have emerged, including exocrine-driven fibrosis and destruction of the entire pancreas and contrasting theories on the direct or indirect impact of CFTR mutation on islet function. The current review outlines recent data on the impact of CFTR on endocrine pancreatic function and discusses the use of conventional diabetic therapies and new CFTR-correcting drugs on the treatment of CFRD.

Published
2019

26. Short-term CFTR inhibition reduces islet area in C57BL/6 mice

Author

Annie Hasib, Rashmi R. Maheshwari, Fiona N. Manderson Koivula, Nigel Irwin, Attila Ébert, Stephen Harkin, Neville H. McClenaghan, James Shaw, Virginia M. Stone, Catriona Kelly, Michael G. White, Viktória Venglovecz, Ryan Kelsey, Malin Flodström-Tullberg, Aoife Watson, and Dawood Khan

Subjects
0301 basic medicine, Male, medicine.medical_specialty, endocrine system, Cell biology, Cystic Fibrosis, medicine.medical_treatment, Intraperitoneal injection, Cell, lcsh:Medicine, Cystic Fibrosis Transmembrane Conductance Regulator, Benzoates, Article, 03 medical and health sciences, Mice, 0302 clinical medicine, Insulin resistance, Diabetes complications, Diabetes mellitus, Internal medicine, Insulin-Secreting Cells, medicine, Diabetes Mellitus, Animals, Humans, Insulin, lcsh:Science, geography, Multidisciplinary, geography.geographical_feature_category, business.industry, lcsh:R, medicine.disease, Islet, Disease Models, Animal, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Thiazolidines, lcsh:Q, Beta cell, business, 030217 neurology & neurosurgery, Hormone
Abstract

Cystic fibrosis-related diabetes (CFRD) worsens CF lung disease leading to early mortality. Loss of beta cell area, even without overt diabetes or pancreatitis is consistently observed. We investigated whether short-term CFTR inhibition was sufficient to impact islet morphology and function in otherwise healthy mice. CFTR was inhibited in C57BL/6 mice via 8-day intraperitoneal injection of CFTRinh172. Animals had a 7-day washout period before measures of hormone concentration or islet function were performed. Short-term CFTR inhibition increased blood glucose concentrations over the course of the study. However, glucose tolerance remained normal without insulin resistance. CFTR inhibition caused marked reductions in islet size and in beta cell and non-beta cell area within the islet, which resulted from loss of islet cell size rather than islet cell number. Significant reductions in plasma insulin concentrations and pancreatic insulin content were also observed in CFTR-inhibited animals. Temporary CFTR inhibition had little long-term impact on glucose-stimulated, or GLP-1 potentiated insulin secretion. CFTR inhibition has a rapid impact on islet area and insulin concentrations. However, islet cell number is maintained and insulin secretion is unaffected suggesting that early administration of therapies aimed at sustaining beta cell mass may be useful in slowing the onset of CFRD.

Published
2019

32. Tu1604 – Efficacy and Safety of Anal Sphincter Botulinum Toxin (BOTOX) Injection in Children with Anorectal and Colonic Disorders

Author

Hallagan, Alexandra, primary, Pearlstein, Haley, additional, Ryan, Kelsey, additional, Halleran, Devin R., additional, Levitt, Marc A., additional, Wood, Richard J., additional, Bali, Neetu, additional, Vaz, Karla, additional, Yacob, Desale, additional, Lorenzo, Carlo Di, additional, and Lu, Peter L., additional

Published
2019
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33. 1198

Author

Sochet, Anthony, primary, Barrie, Eddie, additional, Petrella, Anna, additional, Ryan, Kelsey, additional, Son, Sorany, additional, McKinley, Scott, additional, and Nakagawa, Thomas, additional

Published
2019
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35. Pediatric asthma severity scores distinguish suitable inpatient level of care for children admitted for status asthmaticus.

Author

Ryan, Kelsey S., Son, Sorany, Roddy, Meghan, Siraj, Shaila, McKinley, Scott D., Nakagawa, Thomas A., and Sochet, Anthony A.

Subjects
*INPATIENT care, *PEDIATRIC intensive care, *CHILD care, *PATIENT readmissions, *ASTHMA, *PEDIATRIC clinics, *PEDIATRIC emergencies
Abstract

Objective: To determine if the Pediatric Asthma Severity Score (PASS) can distinguish "late-rescues" (transfer to the pediatric intensive care unit [PICU] within 24-hours of general pediatric floor admission), "PICU readmissions" (readmission within 24-h after transfer to a lower inpatient level of care), and unplanned 30-day hospital readmission in children admitted with status asthmaticus. Methods: We performed a single center, retrospective cohort study in 328 children admitted for asthma exacerbation aged 5–18 years from May 2015 to October 2017. We sought to determine if PASS values preceding admission from the emergency department or transfer to the general pediatric unit will be greater in children with late rescues and PICU readmissions and if a cutoff PASS values exist to discriminate these events prior to intrafacility transfer. Results: Nine (5%) late-rescues and 5 (3%) PICU readmissions accounted for 14/328 (4%) composite outcomes. PASS values were greater in children with these events (8 [IQR:5–8] vs. 5 [IQR:3–6], p <.01). Logistic regression of PASS on composite outcome yielded an odds ratio of 1.4 (1.1–1.8, p <.01) and ROC curve of PASS on a composite outcome yielded an AUC of 0.74 (0.61–0.87) with a threshold of ≥ 9. Nine (3%) children experienced unplanned 30-day hospital readmissions but PASS preceding hospital discharge was neither discriminative nor associated with hospital readmission. Conclusions: PASS values ≥ 9 identify children at increased risk for late-rescue and PICU readmission. Applied with traditionally criteria for selection of inpatient level of care, PASS may assist providers in reducing acute inpatient disposition errors. [ABSTRACT FROM AUTHOR]

Published
2021
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36. Stress ulcer prophylaxis in children with status asthmaticus receiving systemic corticosteroids: a descriptive study assessing frequency of clinically important bleeding.

Author

Sochet, Anthony A., Son, Sorany, Ryan, Kelsey S., Roddy, Meghan, Barrie, Eddie, Wilsey, Michael, McKinley, Scott D., and Nakagawa, Thomas A.

Subjects
VENTILATOR-associated pneumonia, PEDIATRIC intensive care, SYMPTOMS, GASTROINTESTINAL hemorrhage, ULCERS, INTENSIVE care units, INTESTINAL perforation
Abstract

Objective: To determine the frequency of clinically important bleeding (CIB) among children hospitalized for status asthmaticus with and without exposure to stress ulcer prophylaxis (SUP). Methods: We performed a single-center, retrospective cohort in 217 children admitted for asthma exacerbation aged 5–18 years from May 2015 to May 2017. We assessed cohorts with and without exposure to SUP to determine if differences in frequency of CIB exist. Study outcomes included frequency of CIB, gastrointestinal complications (occult bleeding, macroscopic bleeding, gastric perforation, and acquired gastritis), and SUP-related adverse events (ventilator associated pneumonia, C. difficile colitis, necrotizing enterocolitis, and acute thrombocytopenia). Results: Ninety-two (42%) children received SUP of which 82 were admitted to the pediatric intensive care unit (PICU). There were no differences in asthma severity or known risk factors for CIB in children with and without SUP in the PICU subcohort. We observed no CIB or SUP-related adverse events. Two subjects acquired gastritis in the no-SUP cohort and one additional subject experienced occult gastrointestinal bleeding with spontaneous symptom resolution. Conclusion: Children admitted for status asthmaticus with and without SUP had no observed incidence of CIB. In this specific population, we propose a prerequisite assessment for the presence of known stress ulcer related gastrointestinal bleeding risk factors prior to the blanket administration of SUP. [ABSTRACT FROM AUTHOR]

Published
2020
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41. Additional file 1: Table S1. of The effect of dietary resistant starch type 2 on the microbiota and markers of gut inflammation in rural Malawi children

Author

M. Ordiz, Thaddaeus May, Mihindukulasuriya, Kathie, Martin, John, Crowley, Jan, Tarr, Phillip, Ryan, Kelsey, Mortimer, Elissa, Gopalsamy, Geetha, Maleta, Ken, Makedonka Mitreva, Young, Graeme, and Manary, Mark

Abstract

Number of 16S rRNA and wide genome sequences generated per sample. This table shows the number of raw (unprocessed) reads and the number of reads remaining after analytical processing of 18 samples from children fed with the habitual diet and plus the addition of RS. Table S2 Comparison of the number of reads obtained by V1–V3 and V3–V5 sequencing. Figure S1 Venn diagram showing the degree of overlap for genera captured with the V1–V3 and V3–V5 regions. While the majority of taxa are captured by both sets of primers, the fact that a significant subset were captured by only one primer set made the use of both sets more valuable. Figure S2 LEfse rank plot of differentially abundant genes in gut microbiomes initial samples vs. final samples. LDA scores were given for different abundance of genes before (habitual diet: green) and after the resistant starch was added to the habitual diet (habitual diet + RS: red). Figure S3 Principal component analysis (PCA) plot showing the differential clustering of metabolites in fecal samples collected before (blue-habitual diet) and after (red-habitual diet plus RS) the diet supplementation with RS. Brown circles represent replicate analyses of the pooled quality control (QC) fecal samples. The tight clustering of these QC replicate analyses indicates the high reproducibility and low amount of drift associated with the GC/MS-based fecal metabolomic profiling analyses conducted over several hours while the individual fecal extracts are analyzed at the same time, under identical GC/MS conditions, and on the same GC/MS instrument.

Published
2015
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42. Implementation of a couple-based HIV prevention program: a cluster randomized trial comparing manual versus Web-based approaches

Author

Robert H. Remien, Jessica C. Rowe, Katie Potocnik Medina, Timothy Hunt, Susan S. Witte, Mingway P. Chang, Elwin Wu, Louisa Gilbert, Nabila El-Bassel, and Ryan Kelsey

Subjects
Adult, Male, Adolescent, HIV prevention, New York, Psychological intervention, HIV Infections, Health Informatics, Medical sciences, Session (web analytics), Health administration, Patient Education as Topic, Nursing, Agency (sociology), Humans, Medicine, Cluster randomised controlled trial, Program Development, Health policy, Medicine(all), Family Characteristics, Internet, Medical education, Couple-based, business.industry, Research, Health Policy, Public Health, Environmental and Occupational Health, Health services research, General Medicine, Test (assessment), Multimedia, Implementation, Female, Web-based, business
Abstract

Background Despite great need, the number of HIV prevention implementation studies remains limited. The challenge for researchers, in this time of limited HIV services agency resources, is to conceptualize and test how to disseminate efficacious, practical, and sustainable prevention programs more rapidly, and to understand how to do so in the absence of additional agency resources. We tested whether training and technical assistance (TA) in a couple-based HIV prevention program using a Web-based modality would yield greater program adoption of the program compared to training and TA in the same program in a manual-based modality among facilitators who delivered the interventions at 80 agencies in New York State. Methods This study used a cluster randomized controlled design. Participants were HIV services agencies (N = 80) and up to 6 staff members at each agency (N = 253). Agencies were recruited, matched on key variables, and randomly assigned to two conditions. Staff members participated in a four-day, face-to-face training session, followed by TA calls at two and four months, and follow-up assessments at 6, 12, and 18 months post- training and TA. The primary outcomes examined number of couples with whom staff implemented the program, mean number of sessions implemented, whether staff implemented at least one session or whether staff implemented a complete intervention (all six sessions) of the program. Outcomes were measured at both the agency and participant level. Results Over 18 months following training and TA, at least one participant from 13 (33%) Web-based assigned agencies and 19 (48%) traditional agencies reported program use. Longitudinal multilevel analysis found no differences between groups on any outcomes at the agency or participant level with one exception: Web-based agencies implemented the program with 35% fewer couples compared with staff at manual-based agencies (IRR 0.35, CI, 0.13-0.94). Conclusion Greater implementation of a Web-based program may require more resources and staff exposure, especially when paired with a couple-based modality. Manual-based and traditional programs may hold some advantage or ease for implementation, particularly at a time of low economic resources. Trial registration ClinicalTrials.gov identifier: NCT01863537

Published
2014

43. Acceptability of locally produced ready-to-use therapeutic foods in Ethiopia, Ghana, Pakistan and India

Author

Weber, Jacklyn M., primary, Ryan, Kelsey N., additional, Tandon, Rajiv, additional, Mathur, Meeta, additional, Girma, Tsinuel, additional, Steiner-Asiedu, Matilda, additional, Saalia, Firibu, additional, Zaidi, Shujaat, additional, Soofi, Sajid, additional, Okos, Martin, additional, Vosti, Stephen A., additional, and Manary, Mark J., additional

Published
2016
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44. Developing food supplements for moderately malnourished children:Lessons learned from ready-to-use therapeutic foods

Author

Briend, André, Akomo, Peter, Bahwere, Paluku, De Pee, Saskia, Dibari, Filippo, Golden, Michael H, Manary, Mark, Ryan, Kelsey, Briend, André, Akomo, Peter, Bahwere, Paluku, De Pee, Saskia, Dibari, Filippo, Golden, Michael H, Manary, Mark, and Ryan, Kelsey

Abstract

Ready-to-use therapeutic foods (RUTFs) are solid foods that were developed by changing the formulation of the existing liquid diet, F-100, recommended by the World Health Organization (WHO) for the rapid catch-up phase of the treatment of children suffering from severe acute malnutrition (SAM). The resulting products proved highly effective in promoting weight gain in both severely and moderately wasted children and adults, including those infected with HIV. The formulation of the existing RUTFs, however, has never been optimized to maximize linear growth, vitamin and mineral status, and functional outcomes. The high milk content of RUTFs makes it an expensive product, and using lower quantities of milk seems desirable. However, the formulation of alternative, less expensive but more effective versions of RUTF faces difficult challenges, as there are uncertainties regarding the effect in terms of protein quality, antinutrient content, and flatulence factors that will result from the replacement of current dairy ingredients by less expensive protein-rich ingredients. The formulation of alternative RUTFs will require further research on these aspects, followed by efficacy studies comparing the future RUTFs to the existing formulations.

Published
2015

45. Masivukeni: Development of a Multimedia Based Antiretroviral Therapy Adherence Intervention for Counselors and Patients in South Africa

Author

Lara Hoppe, Nabila El-Bassel, Jenifar Chowdhury, Nuruneesa Lalkhen, Jessica C. Rowe, Susan S. Witte, Robert H. Remien, Ryan Kelsey, Claude A. Mellins, Elaine J. Abrams, Reuben N. Robbins, Dan J. Stein, and Patricia Warne

Subjects
Program evaluation, Adult, Counseling, Male, medicine.medical_specialty, Health Knowledge, Attitudes, Practice, Self Disclosure, Social Psychology, Anti-HIV Agents, Psychological intervention, Participatory action research, HIV Infections, Intervention, computer.software_genre, Article, Medication Adherence, Social support, South Africa, Highly active antiretroviral therapy, Acquired immunodeficiency syndrome (AIDS), Patient Education as Topic, Intervention (counseling), medicine, Humans, Public health, Multimedia, business.industry, Public Health, Environmental and Occupational Health, Social Support, Patient compliance, medicine.disease, Infectious Diseases, Self-disclosure, Female, business, computer, Program Evaluation
Abstract

Effective medical treatment for HIV/AIDS requires patients' optimal adherence to antiretroviral therapy (ART). In resource-constrained settings, lack of adequate standardized counseling for patients on ART remains a significant barrier to adherence. Masivukeni ("Let's Wake Up" in Xhosa) is an innovative multimedia-based intervention designed to help people living with HIV in resource-limited settings achieve and maintain high levels of ART adherence. Adapted from a couples-based intervention tested in the United States (US), Masivukeni was developed through community-based participatory research with US and South African partners and informed by Ewart's Social Action Theory. Innovative computer-based multimedia strategies were used to translate a labor- and training-intensive intervention into one that could be readily and widely used by lay counselors with relatively little training with low-literacy patients. In this paper, we describe the foundations of this new intervention, the process of its development, and the evidence of its high acceptability and feasibility.

Published
2013
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46. The effect of dietary resistant starch type 2 on the microbiota and markers of gut inflammation in rural Malawi children

Author

Ordiz, M. Isabel, primary, May, Thaddaeus D., additional, Mihindukulasuriya, Kathie, additional, Martin, John, additional, Crowley, Jan, additional, Tarr, Phillip I., additional, Ryan, Kelsey, additional, Mortimer, Elissa, additional, Gopalsamy, Geetha, additional, Maleta, Ken, additional, Mitreva, Makedonka, additional, Young, Graeme, additional, and Manary, Mark J., additional

Published
2015
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