Longitudinal Metabolic Trajectories in Diabetes Prevention Program Participants Reveal Subgroups With Varying Micro- and Macrovascular Complication Risks

作者：Emily Kobayashi, Nathaniel Linden-Santangeli, Nicholas Chan, Christopher B. Toomey, Sunder Mudaliar, Marinella Temprosa, Sharon L. Edelstein, Ravi Goyal, Padmini Rangamani, Amit R. Majithia, George A. Bray, Kishore M. Gadde, Iris W. Culbert, Jennifer Arceneaux, Annie Chatellier, Amber Dragg, Catherine M. Champagne, Crystal Duncan, Barbara Eberhardt, Frank L. Greenway, Fonda G. Guillory, April A. Herbert, Michael L. Jeffirs, Betty M. Kennedy, Erma Levy, Monica Lockett, Jennifer C. Lovejoy, Laura H. Morris, Lee E. Melancon, Donna H. Ryan, Deborah A. Sanford, Kenneth G. C. Smith, Lisa L. Smith, Julia A. St. Amant, Richard T. Tulley, Paula C. Vicknair, Donald Williamson, Jeffery J. Zachwieja, Kenneth S. Polonsky, Janet Tobian, David A. Ehrmann, Margaret J. Matulik, Karla A. Temple, Bart Clark, Kirsten Czech, Catherine DeSandre, Brittnie Dotson, Ruthanne Hilbrich, Wylie McNabb, Ann R. Semenske, Celeste C. Thomas, Jose F. Caro, Kevin Furlong, Barry J. Goldstein, Pamela G. Watson, Kellie A. Smith, Jewel Mendoza, Marsha Simmons, Wendi Wildman, Renee Liberoni, John Spandorfer, Constance Pepe, Richard P. Donahue, Ronald Goldberg, Ronald J. Prineas, Jeanette Calles, Anna Giannella, Patricia M. Rowe, Juliet Sanguily, Paul Cassanova-Romero, Sumaya Castillo-Florez, Hermes Flórez, Rajesh Garg, Lascelles Kirby, Olga Lara, Carmen Larreal, Valerie McLymont, Jadell Mendez, Arlette Perry, Patrice G. Saab, Bertha Veciana, Steven M. Haffner, Helen P. Hazuda, Maria G. Montez, Kathy Hattaway, Juan Isaac, Carlos Lorenzo, Arlene Martinez, Monica Salazar, Tatiana Walker, Dana Dabelea, Richard F. Hamman, Patricia V. Nash, Sheila C. Steinke, Lisa Testaverde, Jennifer Truong, Denise Anderson, Larry B. Ballonoff, Alexis Bouffard, Brian C. Bucca, B. Ned Calonge, Lynne Delve, Martha Farago, James O. Hill, Shelley R. Hoyer, Tonya Jenkins, Bonnie T. Jortberg, Dione Lenz, Marsha Miller, Thomas Nilan, Leigh Perreault, David W. Price, Judith G. Regensteiner, Emily B. Schroeder, Helen Seagle, Carissa M. Smith, Brent VanDorsten, Edward S. Horton, Medha Munshi, Kathleen E. Lawton, Sharon D. Jackson, Catherine S. Poirier, Kati Swift, Ronald A. Arky, Marybeth Bryant, Jacqueline P. Burke, Enrique Caballero, Karen M. Callaphan, Barbara Fargnoli, Therese Franklin, Om P. Ganda, Ashley Guidi, Mathew Guido, Alan M. Jacobsen, Lyn M. Kula, Margaret Kocal, Lori Lambert, Kathleen E. Lawton, Sarah Ledbury, Maureen A. Malloy, Roeland J.W. Middelbeek, Maryanne Nicosia, Cathryn F. Oldmixon, Jocelyn Pan, Marizel Quitingon, Riley Rainville, Stacy Rubtchinsky, Ellen W. Seely, Jessica Sansoucy, Dana Schweizer, Donald C. Simonson, Fannie Smith, Caren G. Solomon, Jeanne Spellman, James H. Warram, Steven E. Kahn, Brenda K. Montgomery, Basma Fattaleh, Celeste Colegrove, Wilfred Y. Fujimoto, Robert H. Knopp, Edward W. Lipkin, Michelle Marr, Ivy Morgan-Taggart, Anne Murillo, Kayla O’Neal, Dace Trence, Lonnese Taylor, April Thomas, Elaine C. Tsai, Samuel Dagogo‐Jack, Abbas E. Kitabchi, Mary E. Murphy, Laura Taylor, Jennifer Dolgoff, William B. Applegate, Michael Bryer‐Ash, Debra Clark, Sandra L. Frieson, Uzoma N. Ibebuogu, Raed Imseis, Helen Lambeth, Lynne C. Lichtermann, Hooman Oktaei, Harriet Ricks, Lily M.K. Rutledge, Amy R. Sherman, Clara M. Smith, Judith E. Soberman, Beverly Williams-Cleaves, Avnisha Patel, Ebenezer A. Nyenwe, Ethel Faye Hampton, Boyd E. Metzger, Mark E. Molitch, Amisha Wallia, Mariana K. Johnson, Daphne T. Adelman, Catherine Behrends, Michelle Cook, Marian Fitzgibbon, Mimi M. Giles, Deloris Heard, Cheryl K.H. Johnson, Diane Larsen, A. V. Lowe, Megan Lyman, David D. McPherson, Samsam C. Penn, Thomas Pitts, Renee Reinhart, Susan Roston, Pamela A. Schinleber, Matthew J. O’Brien, Monica Hartmuller, David M. Nathan, Charles McKitrick, Heather Turgeon, Mary Larkin, Marielle Mugford, Kathy Abbott, Ellen J. Anderson, Laurie Bissett, Kristy Bondi, Enrico Cagliero, José C. Florez, Linda M. Delahanty, Valerie Goldman, Elaine Grassa, Lindsery Gurry, Kali D’Anna, Fernelle Leandre, Peter Lou, Alexandra Poulos, Elyse Raymond, Valerie Ripley, Christine Stevens, Beverly Tseng, Kathy Chu, Nopporn Thangthaeng, Jerrold M. Olefsky, Elizabeth Barrett‐Connor, Sunder Mudaliar, Maria Rosario G. Araneta, Mary Lou Carrion-Petersen, Karen Vejvoda, Sarah Bassiouni, Madeline Beltran, Lauren N. Claravall, Jonalle M. Dowden, Steven V. Edelman, Pranav S. Garimella, Robert R. Henry, Javiva Horne, Marycie Lamkin, Simona Szerdi Janesch, Diana Leos, William H. Polonsky, Rosa Ruiz, Jean Louise M. Smith, Jennifer Torio-Hurley, F. Xavier Pi‐Sunyer, Blandine Laferrère, Jane E. Lee, Susan Hagamen, David B. Allison, Nnenna Agharanya, Nancy J. Aronoff, Maria Baldo, Jill P. Crandall, Sandra T. Foo, Kim Kelly-Dinham, José A. Luchsinger, Carmen Pal, Kathy Parkes, Mary Beth Pena, Ellen S. Rooney, Gretchen E.H. Van Wye, Kristine A. Viscovich, Mary de Groot, David G. Marrero, Kieren J. Mather, Melvin Prince, Susie M. Kelly, Marcia A. Jackson, Gina McAtee, Paula Putenney, Ronald T. Ackermann, Carolyn M. Cantrell, Yolanda F. Dotson, Edwin S. Fineberg, Megan Fultz, John C. Guare, Angela Hadden, James M. Ignaut, Marion S. Kirkman, Erin O’Kelly Phillips, Kisha L. Pinner, Beverly D. Porter, Paris Roach, Nancy Rowland, Madelyn L. Wheeler, Vanita R. Aroda, Michelle Magee, Robert E. Ratner, Michelle Magee, Gretchen Youssef, Sue Shapiro, Natalie Andon, Catherine Bavido-Arrage, Geraldine Boggs, Marjorie Bronsord, Ernestine Brown, Holly Love Burkott, Wayman W. Cheatham, Susan Cola, Cindy Evans, Peggy Gibbs, Tracy Kellum, Lilia Leon, Milvia Lagarda, Claresa Levatan, Milajurine Lindsay, Asha K. Nair, Jean Park, Maureen Passaro, Angela Silverman, Gabriel I. Uwaifo, Debra Wells-Thayer, Renee Wiggins, Mohammed F. Saad, Karol E. Watson, Christine Darwin, Preethi Srikanthan, Tamara B. Horwich, Adrian Casillas, Arleen F. Brown, Maria Budget, Sujata Jinagouda, Medhat Botrous, Anthony Sosa, Sameh Tadros, Khan Akbar, Claudia Conzues, Perpetua Magpuri, C Di Muro, Noemi Neira, Kathy Ngo, Michelle Chan, Verónica Villarreal, Amer Rassam, Debra Waters, Kathy Xapthalamous, Julio V. Santiago, Samuel Dagogo‐Jack, Neil H. White, Angela L. Brown, Samia Das, Prajakta Khare-Ranade, Tamara Stich, Ana Santiago, Edwin B. Fisher, Emma Hurt, Tracy Jones, Michelle Kerr, Lucy Ryder, Cormarie Wernimont, Sherita Hill Golden, Christopher D. Saudek, Vanessa Bradley, Emily Sullivan, Tracy Whittington, Caroline Abbas, Adrienne Allen, Frederick L. Brancati, Sharon Cappelli, Jeanne M. Clark, Jeanne Charleston, Janice Freel, Katherine Horak, Alicia Greene, Dawn Jiggetts, Deloris Johnson, Hope Joseph, Kimberly Loman, Nestoras Mathioudakis, Henry Mosley, John Reusing, Richard R. Rubin, Alafia Samuels, Thomas W. Shields, Shawne Stephens, Kerry J. Stewart, LeeLana Thomas, Evonne Utsey, Paula Williamson, David S. Schade, Karwyn S. Adams, Janene L. Canady, Carolyn Johannes, Claire Hemphill, Penny Hyde, Leslie F. Atler, Patrick J. Boyle, Mark R. Burge, Lisa Chai, Kathleen Colleran, Ateka Fondino, Ysela Gonzales, Doris A. Hernandez-McGinnis, Patricia Katz, Carolyn King, Julia Middendorf, Amer Rassam, Sofya Rubinchik, Willette Senter, Debra Waters, Jill P. Crandall, Harry Shamoon, Janet O. Brown, Gilda Trandafirescu, Danielle Powell, Norica Tomuta, Elsie Adorno, Liane Cox, Helena Duffy, Samuel S. Engel, Allison Friedler, Angela Goldstein, Crystal J. Howard-Century, Jennifer Lukin, Stacey Kloiber, Nadege Longchamp, Helen Martinez, Dorothy Pompi, Jonathan Scheindlin, Elissa Violino, Elizabeth A. Walker, Judith Wylie‐Rosett, Elise Zimmerman, Joel Zonszein, Trevor J. Orchard, Elizabeth M. Venditti, Rena R. Wing, Susan Jeffries, Gaye Koenning, M. Kaye Kramer, Marie Smith, Susan I. Barr, Catherine Benchoff, Miriam Boraz, Lisa Clifford, Rebecca Culyba, Marlene Frazier, Ryan Gilligan, Stephanie Guimond, Susan Harrier, Louann Harris, Andrea M. Kriska, Qurashia Manjoo, Monica Mullen, Alicia Noel, Amy D. Otto, Jessica Pettigrew, Bonny Rockette‐Wagner, Debra Rubinstein, Linda Semler, Cheryl F. Smith, Valarie Weinzierl, Katherine V. Williams, Tara Wilson, Bonnie Gillis, Marjorie K. Mau, Narleen K. Baker-Ladao, John S. Melish, Richard F. Arakaki, Renée W. Latimer, Mae K. Isonaga, Ralph Beddow, Nina E. Bermudez, Lorna Dias, Jillian Inouye, Kathy Mikami, Pharis Mohideen, Sharon K. Odom, Raynette U. Perry, Robin E. Yamamoto, William C. Knowler, Robert L. Hanson, Harelda Anderson, Norman Cooeyate, Charlotte Dodge, Mary A. Hoskin, Carol Percy, Alvera Enote, Camille Natewa, Kelly J. Acton, Vickie L. Andre, Rosalyn Barber, Shandiin Begay, Peter H. Bennett, Mary Beth Benson, Evelyn C. Bird, Brenda A. Broussard, Brian C. Bucca, Marcella Chavez, Sherron Cook, Jeff Curtis, Tara Dacawyma, Matthew S. Doughty, Roberta Duncan, Cyndy Edgerton, Jacqueline M. Ghahate, Justin Glass, Martia Glass, Dorothy Gohdes, Wendy Grant, Ellie Horse, Louise E. Ingraham, Merry Jackson, Priscilla Jay, Roylen S. Kaskalla, Karen Kavena, David Keßler, Kathleen M. Kobus, Jonathan Krakoff, Jason Kurland, Catherine Manus, Cherie McCabe, Sara Michaels, Tina Morgan, Yolanda Nashboo, Julie A. Nelson, Steven Poirier, Evette Polczynski, Christopher Piromalli, Mike Reidy, Jeanine Roumain, Debra Rowse, Robert J. Roy, Sandra Sangster, Janet Sewenemewa, Miranda Smart, Chelsea Spencer, Darryl Tonemah, Rachel Williams, Charlton Wilson, Michelle Yazzie, Raymond P. Bain, Sarah Fowler, Marinella Temprosa, Michael Larsen, Kathleen Jablonski, Tina Brenneman, Sharon L. Edelstein, Solome Abebe, Julie Bamdad, Melanie Barkalow, Joel Bethepu, Tsedenia Bezabeh, Anna Bowers, Nicole Butler, Jackie Callaghan, Caitlin E. Carter, Costas A. Christophi, Gregory M. Dwyer, Mary A. Foulkes, Yuping Gao, Robert Gooding, Adrienne Gottlieb, Kristina L. Grimes, Nisha Grover-Fairchild, Lori Haffner, Heather J. Hoffman, Steve Jones, Tara L. Jones, Richard S. Katz, Preethy Kolinjivadi, John M. Lachin, Yong Ma, Pamela Mucik, Robert Orlosky, Qing Pan, Susan Reamer, James Rochon, Alla Sapozhnikova, Hanna Sherif, Charlotte Stimpson, Ashley H. Tjaden, Fredricka Walker-Murray, Lindsay Doherty, Audrey McMaster, Rhea Mundra, Hannah Rapoport, Nolan Kuenster, Elizabeth M. Venditti, Andrea M. Kriska, Linda Semler, Valerie Weinzierl, Santica Marcovina, François Aldrich, Jessica Harting, John J. Albers, Greg Strylewicz, Robert Janicek, Anthony A. Killeen, Deanna Gabrielson, R. Eastman, Judith Fradkin, Sanford Garfield, Christine Lee, Edward W. Gregg, Ping Zhang, Dan O’Leary, Gregory W. Evans, Matthew J. Budoff, Chris Dailing, Elizabeth Stamm, Ann V. Schwartz, Caroline Navy, Lisa Palermo, Pentti M. Rautaharju, Ronald J. Prineas, Teresa Alexander, Charles J. Campbell, Sharon M. Hall, Yabing Li, Margaret Mills, Nancy Pemberton, Farida Rautaharju, Zhuming Zhang, Elsayed Z. Soliman, Julie Hu, Susan Hensley, Lisa Keasler, Tonya Taylor, Barbara Blodi, Ronald P. Danis, Matthew Davis, Larry D. Hubbard, Ryan Endres, Deborah Elsas, Samantha Johnson, Dawn Myers, Nancy Barrett, Heather Baumhauer, Wendy Benz, Holly Cohn, Ellie Corkery, Kristi Dohm, Amitha Domalpally, Vonnie Gama, Anne Goulding, Andy Ewen, Cynthia Hurtenbach, Daniel Lawrence, Kyle McDaniel, Jeong W. Pak, James Reimers, Ruth Shaw, Maria Swift, Pamela Vargo, Sheila Watson, José A. Luchsinger, Jennifer J. Manly, Elizabeth J. Mayer‐Davis, Robert R. Moran, Ted Ganiats, Kristin David, Andrew J. Sarkin, Erik J. Groessl, Naomi Katzir, Helen Chong, William H. Herman, Michael Brändle, Morton B. Brown, José C. Florez, David Altshuler, Liana K. Billings, Ling Chen, Maegan Harden, Robert L. Hanson, William C. Knowler, Toni I. Pollin, Alan R. Shuldiner, Kathleen Jablonski, Paul W. Franks, Marie‐France Hivert · 发表于：Diabetes Care · 年份：2025 · DOI：10.2337/dc25-0866 · 被引用次数：9 · 研究领域：Diabetes, Cardiovascular Risks, and Lipoproteins、Diabetes Management and Research、Chronic Kidney Disease and Diabetes

OBJECTIVE: Type 2 diabetes (T2D) and its associated complications develop heterogeneously over decades, but few studies span the progression from prediabetes to clinical events. We investigated whether long-term metabolic trajectories beginning in prediabetes delineate subgroups with differential complication risk. RESEARCH DESIGN AND METHODS: Clinical data from 1,732 Diabetes Prevention Program/Outcomes Study participants (follow-up 19 years) were analyzed across 12 phenotypes. Tensor decomposition was used to capture longitudinal patterns, and Gaussian mixture modeling was used to define longitudinal clusters. Cluster-specific complications were quantified with Cox and logistic regression. RESULTS: Four clusters emerged. Clusters 1 and 2 (73% of participants) maintained stable glycemia, blood pressure, and lipids. Although 49% and 71%, respectively, developed T2D, cumulative micro- and macrovascular events remained low. Cluster 3 (12%) showed the steepest rise in insulin resistance and hyperglycemia, with 92% of the subgroup progressing to T2D and a markedly higher rate of retinopathy (odds ratio [OR] 8.8, 95% CI 3.9-20.1) and neuropathy (OR 3.4, 95% CI 2.1-5.5). Cluster 4 (15%) presented with baseline microalbuminuria often prior to the development of T2D (73%). It was distinguished by progressive estimated glomerular filtration rate decline and a doubling of cardiovascular events (hazard ratio 2.0, 95% CI 1.4-3.0), despite serum lipids comparable with other groups. CONCLU...