1. Islet Autoimmunity is Highly Prevalent and Associated With Diminished β-Cell Function in Patients With Type 2 Diabetes in the Grade Study
- Author
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Brooks-Worrell, Barbara, Hampe, Christiane S., Hattery, Erica G., Palomino, Brenda, Zangeneh, Sahar Z., Utzschneider, Kristina, Kahn, Steven E., Larkin, Mary E., Johnson, Mary L., Mather, Kieren J., Younes, Naji, Rasouli, Neda, Desouza, Cyrus, Cohen, Robert M., Park, Jean Y., Florez, Hermes J., Valencia, Willy Marcos, Shojaie, Ali, Palmer, Jerry P., Balasubramanyam, Ashok, Crandall, Jill P., McKee, Melissa Diane, Brown-Friday, Janet, Xhori, Entila, Ballentine-Cargill, Keisha, Duran, Sally, Lukin, Jennifer, Beringher, Stephanie, Gonzalez de la Torre, Susana, Phillips, Lawrence, Burgess, Elizabeth, Olson, Darin, Rhee, Mary, Wilson, Peter, Raines, Tasha Stephanie, Costello, Julie, Gullett, Chona, Maher-Albertelli, Maxine, Morehead, Folayan, Mungara, Radhika, Person, Saranjit, Savoye, Louise, Sibymon, Mabil, Tanukonda, Sridhar, White, Carol Ann, Holloway, Leah, Adams, Cynthia, Ross, April, Gonzalez Hattery, Erica, Gaba, Ruchi, Montes, Graciela, Wright, Charlyne, Hollander, Priscilla, Roe, Erin, Uy, Analyn, Burt, Polly, Estrada, Lorie, Chionh, Kris, Ismail-Beigi, Faramarz, Falck-Ytter, Corinna, Sayyed Kassem, Laure, Sood, Ajay, Tiktin, Margaret, Cramer, Bethany, Iacoboni, Jacalyn, Kononets, Maria V., Kulow, Tanya, Newman, Cynthia, Stancil, Katherine A., Sanders, Cristina, Tucker, Lisa, Werner, Amanda, Krol, Adrienne, McPhee, Gloria, Patel, Christine, Colosimo, Linda, Goland, Robin, Pring, James, Kringas, Patricia, Tejada, Jessica, Hausheer, Camille, Schneier, Harvey, Gumpel, Kelly, Kirpitch, Amanda, Green, Jennifer B., AbouAssi, Hiba, Chatterjee, Ranee, Feinglos, Mark N., English Jones, Jennifer, Khan, Shubi A., Kimpel, Jeanne B., Zimmer, Ronna P., Furst, Mary, Satterwhite, Barbara M., Thacker, Connie, Evans Kreider, Kathryn, Lteif, Amale, Hamilton, Tonya, Patel, Nick, Riera, Gabriela, Jackson, Marcia, Pirics, Vivian, Howard, Devin, Aguillar, Danielle, Hurt, Sloan, Bergenstal, Richard, Carlson, Anders, Martens, Thomas, Johnson, Mary, Hill, Renae, Hyatt, Jamie, Jensen, Connie, Madden, Marcia, Martin, Dianna, Willis, Holly, Konerza, Wanda, Passi, Rebecca, Kleeberger, Kathleen, Fortmann, Stephen, Herson, Michael, Mularski, Karen, Glauber, Harry, Prihoda, James, Ash, Britt, Carlson, Christina, Ramey, Phyllis Anne, Schield, Emily, Torgrimson-Ojerio, Britta, Arnold, Kathy, Kauffman, Bryan, Panos, Elease, Sahnow, Samantha, Bays, Kristi, Cook, Jennifer, Gluth, Jennifer, Sasaki, Debra, Schell, Katrina, Criscola, Jennifer, Friason, Camille, Jones, Suzi, Nazarov, Sergey, Barzilay, Joshua, Rassouli, Negah, Puttnam, Rachel, Curtis, Michelle, Stokes, Kia, Hollis, Bonita, Sanders-Jones, Cynthia, Nelson, Roslin, El-Haqq, Zakiah, Kolli, Abby, Tran, Tu, Wexler, Deborah, Larkin, Mary, Meigs, James, Dushkin, Amy, Rocchio, Gianna, Chambers, Brittany, Yepes, Mike, Steiner, Barbara, Dulin, Hilary, Cayford, Melody, DeManbey, Andrea, Gurry, Lindsey, Hillard, Mallory, Martin, Kimberly, Stevens, Christine, Thangthaeng, Nopporn, Kochis, Raquel, Raymond, Elyse, Ripley, Valerie, Park, Jean, Aroda, Vanita, Ghazi, Adline, Loveland, Amy, Hurtado, Maria, Kuhn, Alexander, Mofor, Florence, Marks, Jennifer, Oropesa-Gonzalez, Lisset, Riccio Veliz, Ana K., Nieto-Martinez, Ramfis, Gutt, Miriam, Ahmann, Andrew, Aby-Daniel, Diana, Joarder, Farahnaz, Morimoto, Victoria, Sprague, Carol, Yamashita, Daisuke, Cady, Nancy, Kirchhoff, Patricia, Rivera-Eschright, Nadia, Adducci, Joseph, Morales Gomez, Brianna, Goncharova, Alina, Hox, Sophia H., Petrovitch, Helen, Matwichyna, Michael, Jenkins, Victoria, Bermudez, Nina O., Ishii, Renée R., Hsia, Daniel S., Cefalu, William T., Greenway, Frank L., Waguespack, Celeste, King, Erin, Haynes, Natalie, Thomassie, Amy, Bourgeois, Brandi, Hazlett, Claire, Henry, Robert, Mudaliar, Sunder, Boeder, Schafer, Pettus, Jeremy, Diaz, Elsa, DeLue, Catherine, Castro, Erick, Hernandez, Sylvia, Krakoff, Jonathan, Curtis, Jeffrey M., Killean, Tina, Joshevama, Erica, Diaz, Enrique, Martin, Denelle, Karshner, Tracey, Albu, Jeanine, Pi-Sunyer, F. Xavier, Frances, Sylvaine, Maggio, Carol, Ellis, Emily, Bastawrose, Joseph, Gong, Xiuqun, Banerji, Mary Ann, August, Phyllis, Lorber, Daniel, Brown, Necole M., Josephson, Debra H., Thomas, Lorraine L., Tsovian, Mari, Cherian, Ajini, Jacobson, Marlo H., Mishko, Motria M., Kirkman, M. Sue, Bergamo, Katherine, Buse, John B., Dostou, Jean, Young, Laura, Goley, April, Kerr, Jeffrey, Largay, Joseph F., Guarda, Sonia, Cuffee, Juanita, Culmer, Dawn, Fraser, Rachael, Almeida, Hope, Coffer, Samantha, Debnam, Elizabeth, Kiker, Lauren, Morton, Sarah, Josey, Kim, Fuller, Gail, Garvey, W. Timothy, Cherrington, Andrea, Golson, Dana, Griffith, Olivia, Robertson, Mary Catherine, Agne, April, McCullars, Steve, Craig, Jacqueline, Kersey, Kimberly, Rogge, M. Colleen, Wilson, Carla, Burton, Kathryn, Lipp, Sonia, Vonder Meulen, Mary Beth, Schroeder, Emily, Steiner, Stephanie, Baker, Chelsea, Underkofler, Chantal, Douglass, Sara, Sivitz, William, Cline, Erin, Knosp, Laura, McConnell, Jennifer, Lowe, Tamara, Herman, William H., Pop-Busui, Rodica, Tan, Meng H., Martin, Catherine, Waltje, Andrea, Goodhall, Lynn, Eggleston, Rebecca, Kuo, Shihchen, Bule, Stephanie, Kessler, Nancy, LaSalle, Elizabeth, Seaquist, Elizabeth R., Bantle, Anne, Kumar, Anjali, Redmon, Bruce, Bantle, John, Harindhanavudhi, Tasma, Coe, Mary, Mech, Michael, Taddese, Abdisa, Lesne, Lesia, Smith, Shannon, Kuechenmeister, Lisa, Shivaswamy, Vijay, Morales, Ana Laura, Rodriguez, Maria Grace, Seipel, Kris, Alfred, Alissa, Eggert, Jenna, Lord, Grace, Taylor, William, Tillson, Renee, Schade, David S., Adolphe, Allen, Burge, Mark, Duran-Valdez, Elizabeth, Martinez, Janae, Hernandez McGinnis, Doris, Pucchetti, Benjamin, Scripsick, Elizabeth, DeFronzo, Ralph A., Cersosimo, Eugenio, Abdul-Ghani, Muhammad, Triplitt, Curtis, Verastiqui, Hector, Garza, Rosa Irene, Wright, Kathryn, Puckett, Curtiss, Raskin, Philip, Rhee, Chanhaeng, Abraham, Soma, Jordan, Lin Fan, Sao, Serey, Morton, Luisa, Smith, Oralenda, Osornio Walker, Laura, Schnurr-Breen, Laura, Ayala, Rosa, Kraymer, Robert, Sturgess, Daytheon, Utzschneider, Kristina M., Alarcon-Casas Wright, Lorena, Boyko, Edward, Tsai, Elaine C., Trence, Dace L., Fattaleh, Basma N., Montgomery, Brenda K., Atkinson, Karen M., Concepcion, Tessa, Kozedub, Alexandra, Moak, Cameron, Rhothisen, Samantha, Elasy, Tom A., Martin, Stephanie, Shackelford, Laura, Goidel, Rita, Hinkle, Nina, Lipps Hogan, Janie, Lovell, Cynthia, Myers, Janet, McGill, Janet B., Salam, Maamoun, Kissel, Sarah, Schweiger, Toni, Recklein, Carol, Tamborlane, William, Gatcomb, Patricia, Camp, Anne, Gulanski, Barbara, Inzucchi, Silvio, Pham, Kim, Alguard, Michele, Lessard, Katarzyna, Perez, Magalys, Magenheimer, Elizabeth, Montoza, Abmaridel, Nathan, David M., Lachin, John, Krause-Steinrauf, Heidi, Burch, Henry, Linder, Barbara, Bremer, Andrew, Backman, Michael, Bebu, Ionut, Buys, C.J., Fagan Murphy, Anna, Gao, Yuping, Gramzinski, Michaela, Hall, Stephanie, Legowski, Elizabeth, Arey, Alyssa, Bethepu, Joel, Lund, Claire, Mangat Dhaliwal, Pam, McGee, Paula, Mesimer, Emily, Ngo, Lisa, Steffes, Michael, Seegmiller, Jesse, Saenger, Amy, Arends, Valerie, Gabrielson, Deanna, Conner, Todd, Stuart, Warren, Day, Jolene, Scrymgeour, Alexandra, Soliman, Elsayed Z., Zhang, Zhu-Ming, Campbell, Charles, Hu, Julie, Keasler, Lisa, Hensley, Susan, Li, Yabing, Herman, William, Mihalcea, Rada, Perez-Rosas, Veronica, Prosser, Lisa, Resnicow, Kenneth, Ye, Wen, Shao, Hui, Zhang, Ping, Luchsinger, Jose, Sanchez, Danurys, Burch, Henry B., Fradkin, Judith, Groessl, Erik, Chong, Helen, Hillery, Naomi, Abdouch, Ivan, Brantley, Paula, Broyles, Frances E., Canaris, Gay, Copeland, Paul, Craine, Jeri J., Fein, Warren L., Lee, Melissa S., Meiners, Rebecca, Meiners, Vaughn, O’Neal, Hollis, Park, James E., Sledge, Edward, Steppel-Resnick, Jeanne, Turchin, Alexander, Higgins, John, Fischer, Lawrence, Golden, Sherita, Gonzalez, Jeffrey, Naik, Aanand, Walker, Elizabeth, Doner Lotenberg, Lynne, Gallivan, Joanne M., Lim, Joanne, Tuncer, Diane M., and Behringer-Massera, Stephanie
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endocrine system diseases ,Diabetes Mellitus, Type 2 ,Endocrinology, Diabetes and Metabolism ,Smoke ,T-Lymphocytes ,Internal Medicine ,Humans ,Pathophysiology ,Fires - Abstract
Islet autoimmunity may contribute to β-cell dysfunction in type 2 diabetes (T2D). Its prevalence and clinical significance have not been rigorously determined. In this ancillary study to the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE), we investigated the prevalence of cellular and humoral islet autoimmunity in patients with T2D duration of 4.0 ± 3.0 years (HbA1c 7.5 ± 0.5% on metformin alone). We measured T-cell autoreactivity against islet proteins, islet autoantibodies against 65-kDa GAD antigen, IA-2, and zinc transporter-8, and β-cell function. Cellular islet autoimmunity was present in 41.3%, humoral islet autoimmunity in 13.5%, and both in 5.3%. β-Cell function calculated as incremental area under the curve of glucose from 0–120 min (iAUC-CG) and ΔC-peptide(0–30)/Δglucose(0–30) from an oral glucose tolerance test was lower among T-cell–positive (T+) than T-cell–negative (T−) individuals using two different adjustments for insulin sensitivity (iAUC-CG: 13.2% [95% CI 0.3, 24.4] or 11.4% [95% CI 0.4, 21.2] lower; ΔC-peptide[0–30]/Δglucose[0–30]: 19% [95% CI 3.1, 32.3] or 17.7% [95% CI 2.6, 30.5%] lower). T+ patients had 17% higher HbA1c (95% CI 0.07, 0.28) and 7.7 mg/dL higher fasting plasma glucose levels (95% CI 0.2, 15.3) than T− patients. We conclude that islet autoimmunity is much more prevalent in patients with T2D than previously reported. T-cell–mediated autoimmunity is associated with diminished β-cell function and worse glycemic control.
- Published
- 2021