Prevalence of Distal Symmetrical Polyneuropathy by Diabetes Prevention Program Treatment Group, Diabetes Status, Duration of Diabetes, and Cumulative Glycemic Exposure
Authors: Lee Christine G. , Ciarleglio Adam , Edelstein Sharon L. , Crandall Jill P. , Dabelea Dana , Goldberg Ronald B. , Kahn Steven E. , Knowler William C. , Ma Maxwell T. , White Neil H. , Herman William H. ,   Diabetes Prevention Program Research Group, Bray George A. , Gadde Kishore M. , Culbert Iris W. , Arceneaux Jennifer , Chatellier Annie , Dragg Amber , Champagne Catherine M. , Duncan Crystal , Eberhardt Barbara , Greenway Frank , Guillory Fonda G. , Herbert April A. , Jeffirs Michael L. , Kennedy Betty M. , Levy Erma , Lockett Monica , Lovejoy Jennifer C. , Morris Laura H. , Melancon Lee E. , Ryan Donna H. , Sanford Deborah A. , Smith Kenneth G. , Smith Lisa L. , St.Amant Julia A. , Tulley Richard T. , Vicknair Paula C. , Williamson Donald , Zachwieja Jeffery J. , Polonsky Kenneth S. , Tobian Janet , Ehrmann David A. , Matulik Margaret J. , Temple Karla A. , Clark Bart , Czech Kirsten , DeSandre Catherine , Dotson Brittnie , Hilbrich Ruthanne , McNabb Wylie , Semenske Ann R. , Thomas Celeste C. , Caro Jose F. , Furlong Kevin , Goldstein Barry J. , Watson Pamela G. , Smith Kellie A. , Mendoza Jewel , Simmons Marsha , Wildman Wendi , Liberoni Renee , Spandorfer John , Pepe Constance , Donahue Richard P. , Goldberg Ronald B. , Prineas Ronald , Calles Jeanette , Giannella Anna , Rowe Patricia , Sanguily Juliet , Cassanova-Romero Paul , Castillo-Florez Sumaya , Florez Hermes J. , Garg Rajesh , Kirby Lascelles , Lara Olga , Larreal Carmen , McLymont Valerie , Mendez Jadell , Perry Arlette , Saab Patrice , Veciana Bertha , Haffner Steven M. , Hazuda Helen P. , Montez Maria G. , Hattaway Kathy , Isaac Juan , Lorenzo Carlos , Martinez Arlene , Salazar Monica , Walker Tatiana , Dabelea Dana , Hamman Richard F. , Nash Patricia V. , Steinke Sheila C. , Testaverde Lisa , Truong Jennifer , Anderson Denise R. , Ballonoff Larry B. , Bouffard Alexis , Bucca Brian , Calonge B. Ned , Delve Lynne , Farago Martha , Hill James O. , Hoyer Shelley R. , Jenkins Tonya , Jortberg Bonnie T. , Lenz Dione , Miller Marsha , Nilan Thomas , Perreault Leigh , Price David W. , Regensteiner Judith G. , Schroeder Emily B. , Seagle Helen , Smith Carissa M. , VanDorsten Brent , Horton Edward S. , Munshi Medha , Lawton Kathleen E. , Jackson Sharon D. , Poirier Catherine S. , Swift Kati , Arky Ronald A. , Bryant Marybeth , Burke Jacqueline P. , Caballero Enrique , Callaphan Karen M. , Fargnoli Barbara , Franklin Therese , Ganda Om P. , Guidi Ashley , Guido Mathew , Jacobsen Alan M. , Kula Lyn M. , Kocal Margaret , Lambert Lori , Ledbury Sarah , Malloy Maureen A. , Middelbeek Roeland J.W. , Nicosia Maryanne , Oldmixon Cathryn F. , Pan Jocelyn , Quitingon Marizel , Rainville Riley , Rubtchinsky Stacy , Seely Ellen W. , Sansoucy Jessica , Schweizer Dana , Simonson Donald , Smith Fannie , Solomon Caren G. , Spellman Jeanne , Warram James , Kahn Steven E. , Montgomery Brenda K. , Fattaleh Basma , Colegrove Celeste , Fujimoto Wilfred , Knopp Robert H. , Lipkin Edward W. , Marr Michelle , Morgan-Taggart Ivy , Murillo Anne , O’Neal Kayla , Trence Dace , Taylor Lonnese , Thomas April , Tsai Elaine C. , Dagogo-Jack Samuel , Kitabchi Abbas E. , Murphy Mary E. , Taylor Laura , Dolgoff Jennifer , Applegate William B. , Bryer-Ash Michael , Clark Debra , Frieson Sandra L. , Ibebuogu Uzoma , Imseis Raed , Lambeth Helen , Lichtermann Lynne C. , Oktaei Hooman , Ricks Harriet , Rutledge Lily M.K. , Sherman Amy R. , Smith Clara M. , Soberman Judith E. , Williams-Cleaves Beverly , Patel Avnisha , Nyenwe Ebenezer A. , Hampton Ethel Faye , Metzger Boyd E. , Molitch Mark E. , Wallia Amisha , Johnson Mariana K. , Adelman Daphne T. , Behrends Catherine , Cook Michelle , Fitzgibbon Marian , Giles Mimi M. , Heard Deloris , Johnson Cheryl K.H. , Larsen Diane , Lowe Anne , Lyman Megan , McPherson David , Penn Samsam C. , Pitts Thomas , Reinhart Renee , Roston Susan , Schinleber Pamela A. , O’Brien Matthew , Hartmuller Monica , Nathan David M. , McKitrick Charles , Turgeon Heather , Larkin Mary , Mugford Marielle , Abbott Kathy , Anderson Ellen , Bissett Laurie , Bondi Kristy , Cagliero Enrico , Florez Jose C. , Delahanty Linda , Goldman Valerie , Grassa Elaine , Gurry Lindsery , D’Anna Kali , Leandre Fernelle , Lou Peter , Poulos Alexandra , Raymond Elyse , Ripley Valerie , Stevens Christine , Tseng Beverly , Chu Kathy , Thangthaeng Nopporn , Olefsky Jerrold M. , Barrett-Connor Elizabeth , Mudaliar Sunder , Rosario Araneta Maria , Carrion-Petersen Mary Lou , Vejvoda Karen , Bassiouni Sarah , Beltran Madeline , Claravall Lauren N. , Dowden Jonalle M. , Edelman Steven V. , Garimella Pranav , Henry Robert R. , Horne Javiva , Lamkin Marycie , Szerdi Janesch Simona , Leos Diana , Polonsky William , Ruiz Rosa , Smith Jean , Torio-Hurley Jennifer , Pi-Sunyer F. Xavier , Laferrere Blandine , Lee Jane E. , Hagamen Susan , Allison David B. , Agharanya Nnenna , Aronoff Nancy J. , Baldo Maria , Crandall Jill P. , Foo Sandra T. , Kelly-Dinham Kim , Luchsinger Jose A. , Pal Carmen , Parkes Kathy , Pena Mary Beth , Rooney Ellen S. , Van Wye Gretchen E.H. , Viscovich Kristine A. , de Groot Mary , Marrero David G. , Mather Kieren J. , Prince Melvin J. , Kelly Susie M. , Jackson Marcia A. , McAtee Gina , Putenney Paula , Ackermann Ronald T. , Cantrell Carolyn M. , Dotson Yolanda F. , Fineberg Edwin S. , Fultz Megan , Guare John C. , Hadden Angela , Ignaut James M. , Kirkman Marion S. , O’Kelly Phillips Erin , Pinner Kisha L. , Porter Beverly D. , Roach Paris J. , Rowland Nancy D. , Wheeler Madelyn L. , Aroda Vanita , Magee Michelle , Ratner Robert E. , Youssef Gretchen , Shapiro Sue , Andon Natalie , Bavido-Arrage Catherine , Boggs Geraldine , Bronsord Marjorie , Brown Ernestine , Love Burkott Holly , Cheatham Wayman W. , Cola Susan , Evans Cindy , Gibbs Peggy , Kellum Tracy , Leon Lilia , Lagarda Milvia , Levatan Claresa , Lindsay Milajurine , Nair Asha K. , Park Jean , Passaro Maureen , Silverman Angela , Uwaifo Gabriel , Wells-Thayer Debra , Wiggins Renee , Saad Mohammed F. , Watson Karol , Darwin Christine , Srikanthan Preethi , Horwich Tamara , Casillas Adrian , Brown Arleen , Budget Maria , Jinagouda Sujata , Botrous Medhat , Sosa Anthony , Tadros Sameh , Akbar Khan , Conzues Claudia , Magpuri Perpetua , Muro Carmen , Neira Noemi , Ngo Kathy , Chan Michelle , Villarreal Veronica , Rassam Amer , Waters Debra , Xapthalamous Kathy , Santiago Julio V. , White Neil H. , Brown Angela L. , Das Samia , Khare-Ranade Prajakta , Stich Tamara , Santiago Ana , Fisher Edwin , Hurt Emma , Jones Tracy , Kerr Michelle , Ryder Lucy , Wernimont Cormarie , Hill Golden Sherita , Saudek Christopher D. , Bradley Vanessa , Sullivan Emily , Whittington Tracy , Abbas Caroline , Allen Adrienne , Brancati Frederick L. , Cappelli Sharon , Clark Jeanne M. , Charleston Jeanne B. , Freel Janice , Horak Katherine , Greene Alicia , Jiggetts Dawn , Johnson Deloris , Joseph Hope , Loman Kimberly , Mathioudakis Nestoras , Mosley Henry , Reusing John , Rubin Richard R. , Samuels Alafia , Shields Thomas , Stephens Shawne , Stewart Kerry J. , Thomas LeeLana , Utsey Evonne , Williamson Paula , Schade David S. , Adams Karwyn S. , Canady Janene L. , Johannes Carolyn , Hemphill Claire , Hyde Penny , Atler Leslie F. , Boyle Patrick J. , Burge Mark R. , Chai Lisa , Colleran Kathleen , Fondino Ateka , Gonzales Ysela , Hernandez-McGinnis Doris A. , Katz Patricia , King Carolyn , Middendorf Julia , Rubinchik Sofya , Senter Willette , Crandall Jill , Shamoon Harry , Brown Janet O. , Trandafirescu Gilda , Powell Danielle , Tomuta Norica , Adorno Elsie , Cox Liane , Duffy Helena , Engel Samuel , Friedler Allison , Goldstein Angela , Howard-Century Crystal J. , Lukin Jennifer , Kloiber Stacey , Longchamp Nadege , Martinez Helen , Pompi Dorothy , Scheindlin Jonathan , Violino Elissa , Walker Elizabeth A. , Wylie-Rosett Judith , Zimmerman Elise , Zonszein Joel , Orchard Trevor , Venditti Elizabeth , Wing Rena R. , Jeffries Susan , Koenning Gaye , Kramer M. Kaye , Smith Marie , Barr Susan , Benchoff Catherine , Boraz Miriam , Clifford Lisa , Culyba Rebecca , Frazier Marlene , Gilligan Ryan , Guimond Stephanie , Harrier Susan , Harris Louann , Kriska Andrea , Manjoo Qurashia , Mullen Monica , Noel Alicia , Otto Amy , Pettigrew Jessica , Rockette-Wagner Bonny , Rubinstein Debra , Semler Linda , Smith Cheryl F. , Weinzierl Valarie , Williams Katherine V. , Wilson Tara , Gillis Bonnie , Mau Marjorie K. , Baker-Ladao Narleen K. , Melish John S. , Arakaki Richard F. , Latimer Renee W. , Isonaga Mae K. , Beddow Ralph , Bermudez Nina E. , Dias Lorna , Inouye Jillian , Mikami Kathy , Mohideen Pharis , Odom Sharon K. , Perry Raynette U. , Yamamoto Robin E. , Knowler William C. , Hanson Robert L. , Anderson Harelda , Cooeyate Norman , Dodge Charlotte , Hoskin Mary A. , Percy Carol A. , Enote Alvera , Natewa Camille , Acton Kelly J. , Andre Vickie L. , Barber Rosalyn , Begay Shandiin , Bennett Peter H. , Benson Mary Beth , Bird Evelyn C. , Broussard Brenda A. , Bucca Brian C. , Chavez Marcella , Cook Sherron , Curtis Jeff , Dacawyma Tara , Doughty Matthew S. , Duncan Roberta , Edgerton Cyndy , Ghahate Jacqueline M. , Glass Justin , Glass Martia , Gohdes Dorothy , Grant Wendy , Horse Ellie , Ingraham Louise E. , Jackson Merry , Jay Priscilla , Kaskalla Roylen S. , Kavena Karen , Kessler David , Kobus Kathleen M. , Krakoff Jonathan , Kurland Jason , Manus Catherine , McCabe Cherie , Michaels Sara , Morgan Tina , Nashboo Yolanda , Nelson Julie A. , Poirier Steven , Polczynski Evette , Piromalli Christopher , Reidy Mike , Roumain Jeanine , Rowse Debra , Roy Robert J. , Sangster Sandra , Sewenemewa Janet , Smart Miranda , Spencer Chelsea , Tonemah Darryl , Williams Rachel , Wilson Charlton , Yazzie Michelle , Bain Raymond , Fowler Sarah , Temprosa Marinella , Larsen Michael D. , Jablonski Kathleen , Brenneman Tina , Edelstein Sharon L. , Abebe Solome , Bamdad Julie , Barkalow Melanie , Bethepu Joel , Bezabeh Tsedenia , Bowers Anna , Butler Nicole , Callaghan Jackie , Carter Caitlin E. , Christophi Costas , Dwyer Gregory M. , Foulkes Mary , Gao Yuping , Gooding Robert , Gottlieb Adrienne , Grimes Kristina L. , Grover-Fairchild Nisha , Haffner Lori , Hoffman Heather , Jones Steve , Jones Tara L. , Katz Richard , Kolinjivadi Preethy , Lachin John M. , Ma Yong , Mucik Pamela , Orlosky Robert , Pan Qing , Reamer Susan , Rochon James , Sapozhnikova Alla , Sherif Hanna , Stimpson Charlotte , Hogan Tjaden Ashley , Walker-Murray Fredricka , McMaster Audrey , Mundra Rhea , Rapoport Hannah , Kuenster Nolan , Venditti Elizabeth M. , Kriska Andrea M. , Weinzierl Valerie , Marcovina Santica , Aldrich F. Alan , Harting Jessica , Albers John , Strylewicz Greg , Janicek Robert , Killeen Anthony , Gabrielson Deanna , Eastman R. , Fradkin Judith , Garfield Sanford , Lee Christine , Gregg Edward , Zhang Ping , O’Leary Dan , Evans Gregory , Budoff Matthew , Dailing Chris , Stamm Elizabeth , Schwartz Ann , Navy Caroline , Palermo Lisa , Rautaharju Pentti , Prineas Ronald J. , Alexander Teresa , Campbell Charles , Hall Sharon , Li Yabing , Mills Margaret , Pemberton Nancy , Rautaharju Farida , Zhang Zhuming , Soliman Elsayed Z. , Hu Julie , Hensley Susan , Keasler Lisa , Taylor Tonya , Blodi Barbara , Danis Ronald , Davis Matthew , Hubbard Larry , Endres Ryan , Elsas Deborah , Johnson Samantha , Myers Dawn , Barrett Nancy , Baumhauer Heather , Benz Wendy , Cohn Holly , Corkery Ellie , Dohm Kristi , Domalpally Amitha , Gama Vonnie , Goulding Anne , Ewen Andy , Hurtenbach Cynthia , Lawrence Daniel , McDaniel Kyle , Pak Jeong , Reimers James , Shaw Ruth , Swift Maria , Vargo Pamela , Watson Sheila , Manly Jennifer , Mayer-Davis Elizabeth , Moran Robert R. , Ganiats Ted , David Kristin , Sarkin Andrew J. , Groessl Erik , Katzir Naomi , Chong Helen , Herman William H. , Brändle Michael , Brown Morton B. , Altshuler David , Billings Liana K. , Chen Ling , Harden Maegan , Pollin Toni I. , Shuldiner Alan R. , Franks Paul W. , Hivert Marie-France 
Published: March 2024

OBJECTIVE
To assess associations between distal symmetric polyneuropathy (DSPN) and Diabetes Prevention Program (DPP) treatment groups, diabetes status or duration, and cumulative glycemic exposure approximately 21 years after DPP randomization.

RESEARCH DESIGN AND METHODS
In the DPP, 3,234 adults ≥25 years old at high risk for diabetes were randomized to an intensive lifestyle (ILS), metformin, or placebo intervention to prevent diabetes. After the DPP ended, 2,779 joined the Diabetes Prevention Program Outcomes Study (DPPOS). Open-label metformin was continued, placebo was discontinued, ILS was provided in the form of semiannual group-based classes, and all participants were offered quarterly lifestyle classes. Symptoms and signs of DSPN were assessed in 1,792 participants at DPPOS year 17. Multivariable logistic regression models were used to evaluate DSPN associations with treatment group, diabetes status/duration, and cumulative glycemic exposure.

RESULTS
At 21 years after DPP randomization, 66% of subjects had diabetes. DSPN prevalence did not differ by initial DPP treatment assignment (ILS 21.5%, metformin 21.5%, and placebo 21.9%). There was a significant interaction between treatment assignment to ILS and age (P &lt; 0.05) on DSPN. At DPPOS year 17, the odds ratio for DSPN in comparison with ILS with placebo was 17.4% (95% CI 3.0, 29.3) lower with increasing 5-year age intervals. DSPN prevalence was slightly lower for those at risk for diabetes (19.6%) versus those with diabetes (22.7%) and was associated with longer diabetes duration and time-weighted HbA1c (P values &lt;0.001).

CONCLUSIONS
The likelihood of DSPN was similar across DPP treatment groups but higher for those with diabetes, longer diabetes duration, and higher cumulative glycemic exposure. ILS may have long-term benefits on DSPN for older adults.