The Effect of Interventions to Prevent Type 2 Diabetes on the Development of Diabetic Retinopathy: The DPP/DPPOS Experience
Authors: White Neil H. , Pan Qing , Knowler William C. , Schroeder Emily B. , Dabelea Dana , Chew Emily Y. , Blodi Barbara , Goldberg Ronald B. , Pi-Sunyer Xavier , Darwin Christine , Schlögl Mathias , Nathan David M. ,   Diabetes Prevention Program Research Group, Goldstein Barry J. , Furlong Kevin , Smith Kellie A. , Mendoza Jewel , Wildman Wendi , Simmons Marsha , Jensen Genine , Liberoni Renee , Spandorfer John , Pepe Constance , Donahue Richard P. , Goldberg Ronald B. , Prineas Ronald , Rowe Patricia , Giannella Anna , Calles Jeanette , 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. , Isaac Juan , Hattaway Kathy , Lorenzo Carlos , Martinez Arlene , Salazar Monica , Walker Tatiana , Hamman Richard F. , Dabelea Dana , Nash Patricia V. , Steinke Sheila C. , Testaverde Lisa , Truong Jennifer , Anderson Denise R. , Ballonoff Larry B. , Bouffard Alexis , Boxer Rebecca S. , 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. , Poirier Catherine S. , Swift Kati , Jackson Sharon D. , 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 , Lawton Kathleen E. , 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. , Kitabchi Abbas E. , Dagogo-Jack Samuel , Murphy Mary E. , Taylor Laura , Dolgoff Jennifer , Hampton Ethel Faye , 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. , Williamsleaves Beverly , Patel Avnisha , Nyenwe Ebenezer A. , Metzger Boyd E. , Molitch Mark E. , Wallia Amisha , Johnson Mariana K. , VanderMolen Sarah , Adelman Daphne T. , Behrends Catherine , Cook Michelle , Fitzgibbon Marian , Giles Mimi M. , Hartmuller Monica , Johnson Cheryl K.H. , Larsen Diane , Lowe Anne , Lyman Megan , McPherson David , Penn Samsam C. , Pitts Thomas , Reinhart Renee , Roston Susan , Schinleber Pamela A. , Nathan David M. , McKitrick Charles , Turgeon Heather , Larkin Mary , Mugford Marielle , Thangthaeng Nopporn , Leander Fernelle , Abbott Kathy , Anderson Ellen , Bissett Laurie , Bondi Kristy , Cagliero Enrico , Florez Jose C. , Delahanty Linda , Goldman Valerie , Grassa Elaine , Gurry Lindsey , D’Anna Kali , Leandre Fernelle , Lou Peter , Poulos Alexandra , Raymond Elyse , Ripley Valerie , Stevens Christine , Tseng Beverly , Olefsky Jerrold M. , Barrettonnor 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 , Kelly-Dinham Kim , Allison David B. , Agharanya Nnenna , Aronoff Nancy J. , Baldo Maria , Crandall Jill P. , Foo Sandra T. , Luchsinger Jose A. , Pal Carmen , Parkes Kathy , Pena Mary Beth , Roman Julie , Rooney Ellen S. , VanWye Gretchen E.H. , Viscovich Kristine A. , Prince Melvin J. , Marrero David G. , Mather Kieren J. , De Groot Mary , 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. , Ratner Robert E. , Aroda Vanita , Magee Michelle , 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 , Budget Maria , Jinagouda Sujata , Botrous Medhat , Sosa Anthony , Tadros Sameh , Akbar Khan , Conzues Claudia , Magpuri Perpetua , Ngo Kathy , Rassam Amer , Waters Debra , Xapthalamous Kathy , Santiago Julio V. , Dagogo-Jack Samuel , White Neil H. , Brown Angela L. , Santiago Ana , Das Samia , Khare-Ranade Prajakta , Stich Tamara , Fisher Edwin , Hurt Emma , Jones Jackie , Jones Tracy , Kerr Michelle , McCowan Sherri , Ryder Lucy , Wernimont Cormarie , Saudek Christopher D. , Hill Golden Sherita , 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 Delois , Joseph Hope , Kalyani Rita , Loman Kimberly , Mathioudakis Nestoras , Maruthur Nisa , 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. , Johannes Carolyn , Hemphill Claire , Hyde Penny , Canady Janene L. , 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 , Rassam Amer , Rubinchik Sofya , Senter Willette , Waters Debra , Shamoon Harry , Crandall Jill , Brown Janet O. , Trandafirescu Gilda , Powell Danielle , Adorno Elsie , Cox Liane , Duffy Helena , Engel Samuel , Friedler Allison , Goldstein Angela , Howardentury Crystal J. , Lukin Jennifer , Kloiber Stacey , Longchamp Nadege , Martinez Helen , Pompi Dorothy , Scheindlin Jonathan , Tomuta Norica , Violino Elissa , Walker Elizabeth A. , Wylie-Rosett Judith , Zimmerman Elise , Zonszein Joel , Wing Rena R. , Orchard Trevor , Venditti Elizabeth , Koenning Gaye , Kramer M. Kaye , Smith Marie , Jeffries Susan , Weinzierl Valarie , 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. , Williams Katherine V. , Wilson Tara , Arakaki Richard F. , Mau Marjorie K. , Latimer Renee W. , Isonaga Mae K. , Baker-Ladao Narleen K. , Bow Ralph , Bermudez Nina E. , Dias Lorna , Inouye Jillian , Melish John S. , Mikami Kathy , Mohideen Pharis , Odom Sharon K. , Perry Raynette U. , Yamamoto Robin E. , Knowler William C. , Hanson Robert L. , Shah Vallabh , Hoskin Mary A. , Percy Carol A. , Cooeyate Norman , Natewa Camille , Dodge Charlotte , Enote Alvera , Anderson Harelda , 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 , Larsen Michael D. , Jablonski Kathleen , Temprosa Marinella , 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 , Venditti Elizabeth M. , Kriska Andrea M. , Semler Linda , Weinzierl Valerie , Marcovina Santica , Aldrich F. Alan , Harting Jessica , Albers John , Strylewicz Greg , 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. , Soliman Elsayed Z. , Alexander Teresa , Campbell Charles , Hall Sharon , Li Yabing , Mills Margaret , Pemberton Nancy , Rautaharju Farida , Zhang Zhuming , Hu Julie , Hensley Susan , Keasler Lisa , Taylor Tonya , Danis Ronald , Davis Matthew , Hubbard Larry , Blodi Barbara , 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 , Luchsinger Jose A. , 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. , Florez Jose C. , Altshuler David , Billings Liana K. , Chen Ling , Harden Maegan , Hanson Robert L. , Knowler William C. , Pollin Toni I. , Shuldiner Alan R. , Jablonski Kathleen , Franks Paul W. , Hivert Marie-France 
Published: May 2022

OBJECTIVE
To determine whether interventions that slow or prevent the development of type 2 diabetes in those at risk reduce the subsequent prevalence of diabetic retinopathy.

RESEARCH DESIGN AND METHODS
The Diabetes Prevention Program (DPP) randomized subjects at risk for developing type 2 diabetes because of overweight/obesity and dysglycemia to metformin (MET), intensive lifestyle intervention (ILS), or placebo (PLB) to assess the prevention of diabetes. During the DPP and DPP Outcome Study (DPPOS), we performed fundus photography over time on study participants, regardless of their diabetes status. Fundus photographs were graded using the Early Treatment Diabetic Retinopathy Study grading system, with diabetic retinopathy defined as typical lesions of diabetic retinopathy (microaneurysms, exudates, or hemorrhage, or worse) in either eye.

RESULTS
Despite reduced progression to diabetes in the ILS and MET groups compared with PLB, there was no difference in the prevalence of diabetic retinopathy between treatment groups after 1, 5, 11, or 16 years of follow-up. No treatment group differences in retinopathy were found within prespecified subgroups (baseline age, sex, race/ethnicity, baseline BMI). In addition, there was no difference in the prevalence of diabetic retinopathy between those exposed to metformin and those not exposed to metformin, regardless of treatment group assignment.

CONCLUSIONS
Interventions that delay or prevent the onset of type 2 diabetes in overweight/obese subjects with dysglycemia who are at risk for diabetes do not reduce the development of diabetic retinopathy for up to 20 years.