Regression From Prediabetes to Normal Glucose Regulation and Prevalence of Microvascular Disease in the Diabetes Prevention Program Outcomes Study (DPPOS)

Leigh Perreault, Qing Pan, Emily B Schroeder, Rita R Kalyani, George A Bray, Samuel Dagogo-Jack, Neil H White, Ronald B Goldberg, Steven E Kahn, William C Knowler, Nestoras Mathioudakis, Dana Dabelea, Diabetes Prevention Program Research Group, George A Bray, Kishore Gadde, Annie Chatellier, Jennifer Arceneaux, Amber Dragg, Crystal Duncan, Frank L Greenway, Daniel Hsia, Erma Levy, Monica Lockett, Donna H Ryan, David Ehrmann, Margaret J Matulik, Kirsten Czech, Catherine DeSandre, Barry J Goldstein, Kevin Furlong, Kellie A Smith, Wendi Wildman, Constance Pepe, Ronald B Goldberg, Jeanette Calles, Juliet Ojito, Sumaya Castillo-Florez, Hermes J Florez, Anna Giannella, Olga Lara, Beth Veciana, Steven M Haffner, Helen P Hazuda, Maria G Montez, Kathy Hattaway, Carlos Lorenzo, Arlene Martinez, Tatiana Walker, Richard F Hamman, Dana Dabelea, Lisa Testaverde, Denise Anderson, Alexis Bouffard, Tonya Jenkins, Dione Lenz, Leigh Perreault, David W Price, Sheila C Steinke, Edward S Horton, Catherine S Poirier, Kati Swift, Enrique Caballero, Barbara Fargnoli, Ashley Guidi, Mathew Guido, Sharon D Jackson, Lori Lambert, Kathleen E Lawton, Sarah Ledbury, Jessica Sansoucy, Jeanne Spellman, Steven E Kahn, Brenda K Montgomery, Wilfred Fujimoto, Robert H Knopp, Edward W Lipkin, Ivy Morgan-Taggart, Anne Murillo, Lonnese Taylor, April Thomas, Elaine C Tsai, Dace Trence, Abbas E Kitabchi, Samuel Dagogo-Jack, Mary E Murphy, Laura Taylor, Jennifer Dolgoff, Debra Clark, Uzoma Ibebuogu, Helen Lambeth, Harriet Ricks, Lily M K Rutledge, Judith E Soberman, Mark E Molitch, Boyd E Metzger, Mariana K Johnson, Mimi M Giles, Diane Larsen, Samsam C Pen, David M Nathan, Mary Larkin, Charles McKitrick, Heather Turgeon, Ellen Anderson, Laurie Bissett, Kristy Bondi, Enrico Cagliero, Kali D'Anna, Linda Delahanty, Jose C Florez, Valerie Goldman, Peter Lou, Alexandra Poulos, Elyse Raymond, Christine Stevens, Beverly Tseng, Elizabeth Barrett-Connor, Mary Lou Carrion-Petersen, Lauren N Claravall, Jonalle M Dowden, Javiva Horne, Diana Leos, Sundar Mudaliar, Jean Smith, Simona Szerdi Janisch, Karen Vejvoda, F Xavier Pi-Sunyer, Jane E Lee, Sandra T Foo, Susan Hagamen, David G Marrero, Kieren J Mather, Susie M Kelly, Paula Putenney, Marcia A Jackson, Gina McAtee, Ronald T Ackermann, Carolyn M Cantrell, Edwin S Fineberg, Angela Hadden, Mario S Kirkman, Erin O'Kelly, Paris J Phillips, Robert E Roach, Vanita Ratner, Sue Aroda, Catherine Shapiro, Peggy Bavido-Arrage, Gabriel Gibbs, Renee Uwaifo, Mohammed F Wiggins, Karol Saad, Medhat Watson, Sujata Botrous, Maria Jinagouda, Claudia Budget, Perpetua Conzues, Kathy Magpuri, Kathy Ngo, Neil H Xapthalamous, Angela L White, Samia Brown, Prajakta Das, Tamara Khare-Ranade, Ana Stich, Cormarie Santiago, Christopher D Wernimont, Sherita Saudek, Tracy Hill Golden, Frederick L Whittington, Jeanne M Brancati, Alicia Clark, Dawn Greene, Henry Jiggetts, John Mosley, Richard R Reusing, Shawne Rubin, Evonne Stephens, David S Utsey, Karwyn S Schade, Claire Adams, Penny Hemphill, Janene L Hyde, Kathleen Canady, Ysela Colleran, Doris A Gonzales, Carolyn Hernandez-McGinnis, Jill King, Janet O Crandall, Gilda Brown, Elsie Trandafirescu, Helena Adorno, Angela Duffy, Jennifer Goldstein, Helen Lukin, Dorothy Martinez, Harry Pompi, Jonathan Shamoon, Elizabeth A Scheindlin, Judith Walker, Trevor Wylie-Rosett, Andrea Orchard, Susan Kriska, M Kaye Jeffries, Marie Kramer, Catherine Smith, Stephanie Benchoff, Jessica Guimond, Debra Pettigrew, Linda Rubinstein, Elizabeth Semler, Valarie Venditti, Richard F Weinzierl, Narleen K Arakaki, Mae K Baker-Ladao, Nina E Isonaga, Marjorie K Bermudez, John S Mau, Robin E Melish, William C Yamamoto, Norman Knowler, Alvera Cooeyate, Mary A Enote, Camille Hoskin, Carol A Natewa, Kelly J Percy, Vickie L Acton, Roz Andre, Shandiin Barber, Brian C Begay, Sherron Bucca, Jeff Cook, Charlotte Curtis, Matthew S Dodge, Jason Doughty, Justin Kurland, Martia Glass, Robert L Glass, Louise E Hanson, Kathleen M Ingraham, Jonathan Kobus, Catherine Krakoff, Cherie Manus, Sara McCabe, Tina Michaels, Julie A Morgan, Christopher Nelson, Robert J Piromalli, Sandra Roy, Miranda Sangster, Darryl P Smart, Rachel Tonemah, Charlton Williams, Sarah Wilson, Marinella Fowler, Michael Temprosa, Tina Larsen, Hanna Brenneman, Sharon L Sherif, Solome Edelstein, Julie Abebe, Melanie Bamdad, Joel Barkalow, Tsedenia Bethepu, Nicole Bezabeh, Jackie Butler, Caitlin E Callaghan, Costas Carter, Gregory M Christophi, Mary Dwyer, Yuping Foulkes, Robert Gao, Adrienne Gooding, Nisha Gottlieb, Heather Grover, Ashley Hoffman, Kathleen Hogan Tjaden, Richard Jablonski, Preethy Katz, John M Kolinjivadi, Yong Lachin, Qing Ma, Susan Pan, Alla Reamer, Elizabeth M Sapozhnikova, Andrea M Venditti, Linda Kriska, Valerie Semler, Santica Weinzierl, Greg Marcovina, John Strylewicz, Judith Albers, Sanford Fradkin, Christine Garfield, Edward Lee, Gregg, Ping Zhang, Leigh Perreault, Qing Pan, Emily B Schroeder, Rita R Kalyani, George A Bray, Samuel Dagogo-Jack, Neil H White, Ronald B Goldberg, Steven E Kahn, William C Knowler, Nestoras Mathioudakis, Dana Dabelea, Diabetes Prevention Program Research Group, George A Bray, Kishore Gadde, Annie Chatellier, Jennifer Arceneaux, Amber Dragg, Crystal Duncan, Frank L Greenway, Daniel Hsia, Erma Levy, Monica Lockett, Donna H Ryan, David Ehrmann, Margaret J Matulik, Kirsten Czech, Catherine DeSandre, Barry J Goldstein, Kevin Furlong, Kellie A Smith, Wendi Wildman, Constance Pepe, Ronald B Goldberg, Jeanette Calles, Juliet Ojito, Sumaya Castillo-Florez, Hermes J Florez, Anna Giannella, Olga Lara, Beth Veciana, Steven M Haffner, Helen P Hazuda, Maria G Montez, Kathy Hattaway, Carlos Lorenzo, Arlene Martinez, Tatiana Walker, Richard F Hamman, Dana Dabelea, Lisa Testaverde, Denise Anderson, Alexis Bouffard, Tonya Jenkins, Dione Lenz, Leigh Perreault, David W Price, Sheila C Steinke, Edward S Horton, Catherine S Poirier, Kati Swift, Enrique Caballero, Barbara Fargnoli, Ashley Guidi, Mathew Guido, Sharon D Jackson, Lori Lambert, Kathleen E Lawton, Sarah Ledbury, Jessica Sansoucy, Jeanne Spellman, Steven E Kahn, Brenda K Montgomery, Wilfred Fujimoto, Robert H Knopp, Edward W Lipkin, Ivy Morgan-Taggart, Anne Murillo, Lonnese Taylor, April Thomas, Elaine C Tsai, Dace Trence, Abbas E Kitabchi, Samuel Dagogo-Jack, Mary E Murphy, Laura Taylor, Jennifer Dolgoff, Debra Clark, Uzoma Ibebuogu, Helen Lambeth, Harriet Ricks, Lily M K Rutledge, Judith E Soberman, Mark E Molitch, Boyd E Metzger, Mariana K Johnson, Mimi M Giles, Diane Larsen, Samsam C Pen, David M Nathan, Mary Larkin, Charles McKitrick, Heather Turgeon, Ellen Anderson, Laurie Bissett, Kristy Bondi, Enrico Cagliero, Kali D'Anna, Linda Delahanty, Jose C Florez, Valerie Goldman, Peter Lou, Alexandra Poulos, Elyse Raymond, Christine Stevens, Beverly Tseng, Elizabeth Barrett-Connor, Mary Lou Carrion-Petersen, Lauren N Claravall, Jonalle M Dowden, Javiva Horne, Diana Leos, Sundar Mudaliar, Jean Smith, Simona Szerdi Janisch, Karen Vejvoda, F Xavier Pi-Sunyer, Jane E Lee, Sandra T Foo, Susan Hagamen, David G Marrero, Kieren J Mather, Susie M Kelly, Paula Putenney, Marcia A Jackson, Gina McAtee, Ronald T Ackermann, Carolyn M Cantrell, Edwin S Fineberg, Angela Hadden, Mario S Kirkman, Erin O'Kelly, Paris J Phillips, Robert E Roach, Vanita Ratner, Sue Aroda, Catherine Shapiro, Peggy Bavido-Arrage, Gabriel Gibbs, Renee Uwaifo, Mohammed F Wiggins, Karol Saad, Medhat Watson, Sujata Botrous, Maria Jinagouda, Claudia Budget, Perpetua Conzues, Kathy Magpuri, Kathy Ngo, Neil H Xapthalamous, Angela L White, Samia Brown, Prajakta Das, Tamara Khare-Ranade, Ana Stich, Cormarie Santiago, Christopher D Wernimont, Sherita Saudek, Tracy Hill Golden, Frederick L Whittington, Jeanne M Brancati, Alicia Clark, Dawn Greene, Henry Jiggetts, John Mosley, Richard R Reusing, Shawne Rubin, Evonne Stephens, David S Utsey, Karwyn S Schade, Claire Adams, Penny Hemphill, Janene L Hyde, Kathleen Canady, Ysela Colleran, Doris A Gonzales, Carolyn Hernandez-McGinnis, Jill King, Janet O Crandall, Gilda Brown, Elsie Trandafirescu, Helena Adorno, Angela Duffy, Jennifer Goldstein, Helen Lukin, Dorothy Martinez, Harry Pompi, Jonathan Shamoon, Elizabeth A Scheindlin, Judith Walker, Trevor Wylie-Rosett, Andrea Orchard, Susan Kriska, M Kaye Jeffries, Marie Kramer, Catherine Smith, Stephanie Benchoff, Jessica Guimond, Debra Pettigrew, Linda Rubinstein, Elizabeth Semler, Valarie Venditti, Richard F Weinzierl, Narleen K Arakaki, Mae K Baker-Ladao, Nina E Isonaga, Marjorie K Bermudez, John S Mau, Robin E Melish, William C Yamamoto, Norman Knowler, Alvera Cooeyate, Mary A Enote, Camille Hoskin, Carol A Natewa, Kelly J Percy, Vickie L Acton, Roz Andre, Shandiin Barber, Brian C Begay, Sherron Bucca, Jeff Cook, Charlotte Curtis, Matthew S Dodge, Jason Doughty, Justin Kurland, Martia Glass, Robert L Glass, Louise E Hanson, Kathleen M Ingraham, Jonathan Kobus, Catherine Krakoff, Cherie Manus, Sara McCabe, Tina Michaels, Julie A Morgan, Christopher Nelson, Robert J Piromalli, Sandra Roy, Miranda Sangster, Darryl P Smart, Rachel Tonemah, Charlton Williams, Sarah Wilson, Marinella Fowler, Michael Temprosa, Tina Larsen, Hanna Brenneman, Sharon L Sherif, Solome Edelstein, Julie Abebe, Melanie Bamdad, Joel Barkalow, Tsedenia Bethepu, Nicole Bezabeh, Jackie Butler, Caitlin E Callaghan, Costas Carter, Gregory M Christophi, Mary Dwyer, Yuping Foulkes, Robert Gao, Adrienne Gooding, Nisha Gottlieb, Heather Grover, Ashley Hoffman, Kathleen Hogan Tjaden, Richard Jablonski, Preethy Katz, John M Kolinjivadi, Yong Lachin, Qing Ma, Susan Pan, Alla Reamer, Elizabeth M Sapozhnikova, Andrea M Venditti, Linda Kriska, Valerie Semler, Santica Weinzierl, Greg Marcovina, John Strylewicz, Judith Albers, Sanford Fradkin, Christine Garfield, Edward Lee, Gregg, Ping Zhang

Abstract

Objective: Regression from prediabetes to normal glucose regulation (NGR) was associated with reduced incidence of diabetes by 56% over 10 years in participants in the Diabetes Prevention Program Outcomes Study (DPPOS). In an observational analysis, we examined whether regression to NGR also reduced risk for microvascular disease (MVD).

Research design and methods: Generalized estimating equations were used to examine the prevalence of aggregate MVD at DPPOS year 11 in people who regressed to NGR at least once (vs. never) during the Diabetes Prevention Program (DPP). Logistic regression assessed the relationship of NGR with retinopathy, nephropathy, and neuropathy, individually. Generalized additive models fit smoothing splines to describe the relationship between average A1C during follow-up and MVD (and its subtypes) at the end of follow-up.

Results: Regression to NGR was associated with lower prevalence of aggregate MVD in models adjusted for age, sex, race/ethnicity, baseline A1C, and treatment arm (odds ratio [OR] 0.78, 95% CI 0.65-0.78, P = 0.011). However, this association was lost in models that included average A1C during follow-up (OR 0.95, 95% CI 0.78-1.16, P = 0.63) or diabetes status at the end of follow-up (OR 0.92, 95% CI 0.75-1.12, P = 0.40). Similar results were observed in examination of the association between regression to NGR and prevalence of nephropathy and retinopathy, individually. Risk for aggregate MVD, nephropathy, and retinopathy increased across the A1C range.

Conclusions: Regression to NGR is associated with a lower prevalence of aggregate MVD, nephropathy, and retinopathy, primarily due to lower glycemic exposure over time. Differential risk for the MVD subtypes begins in the prediabetes A1C range.

Trial registration: ClinicalTrials.gov NCT00004992 NCT00038727.

© 2019 by the American Diabetes Association.

Figures

Figure 1
Figure 1
Predicted, unadjusted prevalence of aggregate MVD (retinopathy, nephropathy, and/or neuropathy) (A), nephropathy (B), retinopathy (C), and neuropathy (D) as a function of A1C levels during DPPOS follow-up. Solid lines represent a smoothed, fitted relationship, whereas the dotted lines represent the pointwise 95% CI.
Figure 2
Figure 2
A1C over DPP and DPPOS for participants who ever versus never regressed from prediabetes to normoglycemia (includes those who have and have not developed diabetes). BAS, baseline.

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Source: PubMed

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