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1. Interaction Between Type 2 Diabetes Prevention Strategies and Genetic Determinants of Coronary Artery Disease on Cardiometabolic Risk Factors

Author

Merino, Jordi, Jablonski, Kathleen A, Mercader, Josep M, Kahn, Steven E, Chen, Ling, Harden, Maegan, Delahanty, Linda M, Araneta, Maria Rosario G, Walford, Geoffrey A, Jacobs, Suzanne BR, Ibebuogu, Uzoma N, Franks, Paul W, Knowler, William C, Florez, Jose C, Bray, George A, Gadde, Kishore, Chatellier, Annie, Arceneaux, Jennifer, Dragg, Amber, Duncan, Crystal, Greenway, Frank L, Hsia, Daniel, Levy, Erma, Lockett, Monica, Ryan, Donna H, Ehrmann, David, Matulik, Margaret J, Czech, Kirsten, DeSandre, Catherine, Goldstein, Barry J, Furlong, Kevin, Smith, Kellie A, Wildman, Wendi, Pepe, Constance, Goldberg, Ronald B, Calles, Jeanette, Ojito, Juliet, Castillo-Florez, Sumaya, Florez, Hermes J, Giannella, Anna, Lara, Olga, Veciana, Beth, Haffner, Steven M, Hazuda, Helen P, Montez, Maria G, Hattaway, Kathy, Lorenzo, Carlos, Martinez, Arlene, Walker, Tatiana, Hamman, Richard F, Dabelea, Dana, Testaverde, Lisa, Anderson, Denise, Bouffard, Alexis, Jenkins, Tonya, Lenz, Dione, Perreault, Leigh, Price, David W, Steinke, Sheila C, Horton, Edward S, Poirier, Catherine S, Swift, Kati, Caballero, Enrique, Fargnoli, Barbara, Guidi, Ashley, Guido, Mathew, Jackson, Sharon D, Lambert, Lori, Lawton, Kathleen E, Ledbury, Sarah, Sansoucy, Jessica, Spellman, Jeanne, Montgomery, Brenda K, Fujimoto, Wilfred, Knopp, Robert H, Lipkin, Edward W, Morgan-Taggart, Ivy, Murillo, Anne, Taylor, Lonnese, Thomas, April, Tsai, Elaine C, Trence, Dace, Kitabchi, Abbas E, Dagogo-Jack, Samuel, Murphy, Mary E, Taylor, Laura, Dolgoff, Jennifer, Clark, Debra, Ibebuogu, Uzoma, Lambeth, Helen, Ricks, Harriet, Rutledge, Lily MK, Soberman, Judith E, Molitch, Mark E, Metzger, Boyd E, Johnson, Mariana K, Giles, Mimi M, Larsen, Diane, and Pen, Samsam C

Subjects
Biomedical and Clinical Sciences, Diabetes, Clinical Research, Atherosclerosis, Clinical Trials and Supportive Activities, Cardiovascular, Heart Disease, Prevention, Heart Disease - Coronary Heart Disease, Nutrition, Obesity, Metabolic and endocrine, Good Health and Well Being, Adult, Cardiovascular Diseases, Coronary Artery Disease, Diabetes Mellitus, Type 2, Exercise, Exercise Therapy, Female, Gene-Environment Interaction, Genetic Predisposition to Disease, Humans, Life Style, Male, Metabolic Syndrome, Metformin, Middle Aged, Prediabetic State, Preventive Health Services, Risk Factors, United States, Diabetes Prevention Program Research Group, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences
Abstract

Coronary artery disease (CAD) is more frequent among individuals with dysglycemia. Preventive interventions for diabetes can improve cardiometabolic risk factors (CRFs), but it is unclear whether the benefits on CRFs are similar for individuals at different genetic risk for CAD. We built a 201-variant polygenic risk score (PRS) for CAD and tested for interaction with diabetes prevention strategies on 1-year changes in CRFs in 2,658 Diabetes Prevention Program (DPP) participants. We also examined whether separate lifestyle behaviors interact with PRS and affect changes in CRFs in each intervention group. Participants in both the lifestyle and metformin interventions had greater improvement in the majority of recognized CRFs compared with placebo (P < 0.001) irrespective of CAD genetic risk (P interaction > 0.05). We detected nominal significant interactions between PRS and dietary quality and physical activity on 1-year change in BMI, fasting glucose, triglycerides, and HDL cholesterol in individuals randomized to metformin or placebo, but none of them achieved the multiple-testing correction for significance. This study confirms that diabetes preventive interventions improve CRFs regardless of CAD genetic risk and delivers hypothesis-generating data on the varying benefit of increasing physical activity and improving diet on intermediate cardiovascular risk factors depending on individual CAD genetic risk profile.

Published
2020

2. Pioglitazone is equally effective for diabetes prevention in older versus younger adults with impaired glucose tolerance

Author

Espinoza, Sara E, Wang, Chen-pin, Tripathy, Devjit, Clement, Stephen C, Schwenke, Dawn C, Banerji, Mary Ann, Bray, George A, Buchanan, Thomas A, Henry, Robert R, Kitabchi, Abbas E, Mudaliar, Sunder, Stentz, Frankie B, Reaven, Peter D, DeFronzo, Ralph A, and Musi, Nicolas

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Prevention, Aging, Clinical Trials and Supportive Activities, Diabetes, Nutrition, Clinical Research, Obesity, 6.1 Pharmaceuticals, Metabolic and endocrine, Adipokines, Adult, Aged, Aged, 80 and over, Biomarkers, Blood Glucose, Diabetes Mellitus, Type 2, Double-Blind Method, Female, Glucose Intolerance, Humans, Hypoglycemic Agents, Incidence, Insulin, Insulin Resistance, Kaplan-Meier Estimate, Male, Metabolome, Middle Aged, Pioglitazone, Prediabetic State, Random Allocation, Thiazolidinediones, Treatment Outcome, Young Adult, Geriatrics, Endocrinology, Genetics, Clinical sciences
Abstract

To determine the efficacy of pioglitazone to prevent type 2 diabetes in older compared to younger adults with pre-diabetes. Six hundred two participants with impaired glucose tolerance (IGT) were randomized in double blind fashion to placebo or pioglitazone for diabetes prevention in the ACT NOW study (NEJM 364:1104-1115, 2011). Cox proportional hazard regression was used to compare time to development of diabetes over a mean of 2 years between older (≥61 years) and younger participants. We compared effects of pioglitazone versus placebo on metabolic profiles, inflammatory markers, adipokines, β cell function (disposition index), insulin sensitivity (Matsuda index), and body composition by ANOVA. Diabetes incidence was reduced by 85 % in older and 69 % in younger subjects (p = 0.41). β cell function (disposition index) increased by 35.0 % in the older and 26.7 % in younger subjects (p = 0.83). Insulin sensitivity (Matsuda index) increased by 3.07 (5.2-fold) in older and by 2.54 (3.8-fold) in younger participants (p = 0.58). Pioglitazone more effectively increased adiponectin in older versus younger subjects (22.9 ± 3.2 μg/mL [2.7-fold] vs. 12.7 ± 1.4 μg/mL [2.2-fold], respectively; p = 0.04). Younger subjects tended to have a greater increase in whole body fat mass compared to older subjects (3.6 vs. 3.1 kg; p = 0.061). Younger and older subjects had similar decreases in bone mineral density (0.018 ± 0.0071 vs. 0.0138 ± 0.021 g/cm2). Younger and older pre-diabetic adults taking pioglitazone had similar reductions in conversion to diabetes and older adults had similar or greater improvements in metabolic risk factors, demonstrating that pioglitazone is useful in preventing diabetes in older adults.

Published
2016

3. Intensive Lifestyle Intervention Reduces Urinary Incontinence in Overweight/Obese Men with Type 2 Diabetes: Results from the Look AHEAD Trial

Author

Breyer, Benjamin N, Phelan, Suzanne, Hogan, Patricia E, Rosen, Raymond C, Kitabchi, Abbas E, Wing, Rena R, Brown, Jeanette S, and Group, Look AHEAD Research

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Prevention, Physical Activity, Clinical Trials and Supportive Activities, Aging, Diabetes, Obesity, Nutrition, Clinical Research, Urologic Diseases, Renal and urogenital, Metabolic and endocrine, Diabetes Mellitus, Type 2, Humans, Life Style, Male, Middle Aged, Overweight, Single-Blind Method, Urinary Incontinence, diabetes mellitus, weight loss, urinary incontinence, nocturia, Look AHEAD Research Group
Abstract

PurposeWe determined the effect of an intensive lifestyle intervention on the prevalence, incidence and resolution of bothersome nocturia, increased daytime urinary voiding and urinary incontinence in overweight/obese men with type 2 diabetes after 1 year in the Look AHEAD trial.Materials and methodsA subset of male Look AHEAD participants was selected for this secondary data analysis. Overall 1,910 men with an average (mean ± SD) age of 59.9 ± 6.7 years and body mass index of 35.2 ± 5.5 kg/m(2) were randomized to an intensive lifestyle intervention or diabetes support and education group. All participants self-reported information regarding incontinence, nocturia and daytime urinary voiding at entry and 1 year.ResultsAfter 1 year the intensive lifestyle intervention group lost significantly more weight than the diabetes support and education group (9.4% ± 7.0% vs 0.7% ± 4.5%, respectively; p

Published
2014

5. Circulating sex hormone binding globulin levels are modified with intensive lifestyle intervention, but their changes did not independently predict diabetes risk in the Diabetes Prevention Program

Author

Mike Reidy, Christine Lee, Michael Brändle, Sherita Hill Golden, Samuel Dagogo-Jack, David Kessler, Elizabeth Barrett-Connor, Steve Jones, Ling Chen, Judith Wylie-Rosett, Ping Zhang, Paula Williamson, Carlos Lorenzo, Leigh Perreault, Dana Dabelea, Santica Marcovina, Rachel Williams, Marie Smith, Carmen Pal, Patricia Katz, William H. Herman, Sharon L Edelstein, Yong Ma, Vanita R Aroda, Costas A Christophi, Catherine Kim, Sherita H Golden, Edward Horton, Kieren J Mather, George A. Bray, Kishore Gadde, Iris W. Culbert, Jennifer Arceneaux, Annie Chatellier, Amber Dragg, Catherine M. Champagne, Crystal Duncan, Barbara Eberhardt, Frank 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. Smith, Lisa L. Smith, Julia A. St, Richard T. Tulley Amant, Paula C. Vicknair, Donald Williamson, Jeffery J. Zachwieja, Kenneth S. Polonsky, Janet Tobian, David A. Ehrmann, Margaret J. Matulik, Bart Clark, Kirsten Czech, Catherine DeSandre, Ruthanne Hilbrich, Wylie McNabb, Ann R. Semenske, Jose F. Caro, Kevin Furlong, Barry J. Goldstein, Pamela G. Watson, Kellie A. Smith, Jewel Mendoza, Wendi Wildman, Renee Liberoni, John Spandorfer, Constance Pepe, Richard P. Donahue, Ronald B. Goldberg, Ronald Prineas, Jeanette Calles, Juliet Ojito, Patricia Rowe, Paul Cassanova-Romero, Sumaya Castillo-Florez, Hermes J. Florez, Anna Giannella, Lascelles Kirby, Carmen Larreal, Olga Lara, Valerie McLymont, Jadell Mendez, Arlette Perry, Patrice Saab, Beth Veciana, Steven M. Haffner, Helen P. Hazuda, Maria G. Montez, Kathy Hattaway, Arlene Martinez, Tatiana Walker, Richard F. Hamman, Patricia V. Nash, Sheila C. Steinke, Lisa Testaverde, Denise R. Anderson, Larry B. Ballonoff, Alexis Bouffard, Brian Bucca, B. Ned Calonge, Lynne Delve, Martha Farago, James O. Hill, Shelley R. Hoyer, Tonya Jenkins, Bonnie T. Jortberg, Dione Lenz, Marsha Miller, David W. Price, Judith G. Regensteiner, Helen Seagle, Carissa M. Smith, Brent VanDorsten, Edward S. Horton, Kathleen E. Lawton, 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, Sharon D. Jackson, Alan M. Jacobsen, Lori Lambert, Sarah Ledbury, Margaret Kocal, Lyn M. Kula, Maureen A. Malloy, Maryanne Nicosia, Cathryn F. Oldmixon, Jocelyn Pan, Marizel Quitingon, Stacy Rubtchinsky, Jessica Sansoucy, Dana Schweizer, Ellen W. Seely, Donald Simonson, Fannie Smith, Caren G. Solomon, Jeanne Spellman, James Warram, Steven E. Kahn, Brenda K. Montgomery, Wilfred Fujimoto, Robert H. Knopp, Edward W. Lipkin, Michelle Marr, Ivy Morgan-Taggart, Anne Murillo, Dace Trence, Lonnese Taylor, April Thomas, Elaine C. Tsai, Abbas E. Kitabchi, Mary E. Murphy, Laura Taylor, Jennifer Dolgoff, William B. Applegate, Michael Bryer-Ash, Debra Clark, Sandra L. Frieson, Uzoma 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, Boyd E. Metzger, Mark E. Molitch, Mariana K. Johnson, Daphne T. Adelman, Catherine Behrends, Michelle Cook, Marian Fitzgibbon, Mimi M. Giles, Deloris Heard, Cheryl K.H. Johnson, Diane Larsen, Anne Lowe, Megan Lyman, David McPherson, Samsam C. Penn, Thomas Pitts, Renee Reinhart, Susan Roston, Pamela A. Schinleber, David M. Nathan, Charles McKitrick, Heather Turgeon, Mary Larkin, Kathy Abbott, Ellen Anderson, Laurie Bissett, Kristy Bondi, Enrico Cagliero, Jose C. Florez, Kali D’Anna, Linda Delahanty, Valerie Goldman, Peter Lou, Alexandra Poulos, Elyse Raymond, Christine Stevens, Beverly Tseng, Jerrold M. Olefsky, Mary Lou Carrion-Petersen, Madeline Beltran, Lauren N. Claravall, Jonalle M. Dowden, Steven V. Edelman, Robert R. Henry, Javiva Horne, Marycie Lamkin, Simona Szerdi Janesch, Diana Leos, Sunder Mudaliar, William Polonsky, Jean Smith, Jennifer Torio-Hurley, Karen Vejvoda, F. Xavier Pi-Sunyer, Jane E. Lee, David B. Allison, Nnenna Agharanya, Nancy J. Aronoff, Maria Baldo, Jill P. Crandall, Sandra T. Foo, Susan Hagamen, Jose A. Luchsinger, Kathy Parkes, Mary Beth Pena, Ellen S. Rooney, Gretchen E.H. Van Wye, Kristine A. Viscovich, David G. Marrero, Kieren J. Mather, Melvin J. 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, Beverly D. Porter, Paris J. Roach, Nancy D. Rowland, Madelyn L. Wheeler, Vanita Aroda, Robert E. Ratner, Gretchen Youssef, Sue Shapiro, Catherine Bavido-Arrage, Geraldine Boggs, Marjorie Bronsord, Ernestine Brown, Wayman W. Cheatham, Susan Cola, Cindy Evans, Peggy Gibbs, Tracy Kellum, Renee Wiggins, Milvia Lagarda, Lilia Leon, Claresa Levatan, Milajurine Lindsay, Asha K. Nair, Maureen Passaro, Angela Silverman, Gabriel Uwaifo, Debra Wells-Thayer, Mohammed F. Saad, Karol Watson, Maria Budget, Sujata Jinagouda, Medhat Botrous, Khan Akbar, Claudia Conzues, Perpetua Magpuri, Kathy Ngo, Amer Rassam, Debra Waters, Kathy Xapthalamous, Julio V. Santiago, Neil H. White, Angela L. Brown, Samia Das, Prajakta Khare-Ranade, Tamara Stich, Ana Santiago, Edwin Fisher, Emma Hurt, Tracy Jones, Michelle Kerr, Lucy Ryder, Cormarie Wernimont, Christopher D. Saudek, Vanessa Bradley, Emily Sullivan, Tracy Whittington, Caroline Abbas, Adrienne Allen, Frederick L. Brancati, Sharon Cappelli, Jeanne M. Clark, Jeanne B. Charleston, Janice Freel, Katherine Horak, Alicia Greene, Dawn Jiggetts, Deloris Johnson, Hope Joseph, Kimberly Loman, Henry Mosley, John Reusing, Richard R. Rubin, Alafia Samuels, Thomas Shields, Shawne Stephens, Kerry J. Stewart, LeeLana Thomas, Evonne Utsey, 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, Ysela Gonzales, Doris A. Hernandez-McGinnis, Carolyn King, Sofya Rubinchik, Willette Senter, Jill Crandall, Harry Shamoon, Janet O. Brown, Gilda Trandafirescu, Elsie Adorno, Liane Cox, Helena Duffy, Samuel 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, Elise Zimmerman, Joel Zonszein, Trevor Orchard, Rena R. Wing, Susan Jeffries, Gaye Koenning, M. Kaye Kramer, Susan Barr, Catherine Benchoff, Miriam Boraz, Lisa Clifford, Rebecca Culyba, Marlene Frazier, Ryan Gilligan, Stephanie Guimond, Susan Harrier, Louann Harris, Andrea Kriska, Bonny Rockette-Wagner, Qurashia Manjoo, Monica Mullen, Alicia Noel, Amy Otto, Jessica Pettigrew, Debra Rubinstein, Linda Semler, Cheryl F. Smith, Elizabeth Venditti, Valarie Weinzierl, Katherine V. Williams, Tara Wilson, Richard F. Arakaki, Renee W. Latimer, Narleen K. Baker-Ladao, Mae K. Isonaga, Ralph Beddow, Nina E. Bermudez, Lorna Dias, Jillian Inouye, Marjorie K. Mau, John S. Melish, Kathy Mikami, Pharis Mohideen, Sharon K. Odom, Raynette U. Perry, Robin E. Yamamoto, William C. Knowler, Norman Cooeyate, Mary A. Hoskin, Carol A. 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, Charlotte Dodge, Cyndy Edgerton, Jacqueline M. Ghahate, Justin Glass, Martia Glass, Dorothy Gohdes, Wendy Grant, Robert L. Hanson, Ellie Horse, Louise E. Ingraham, Merry Jackson, Priscilla Jay, Roylen S. Kaskalla, 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, Jeanine Roumain, Debra Rowse, Robert J. Roy, Sandra Sangster, Janet Sewenemewa, Miranda Smart, Darryl Tonemah, Charlton Wilson, Michelle Yazzie, Raymond Bain, Sarah Fowler, Marinella Temprosa, Michael D. Larsen, Tina Brenneman, Sharon L. Edelstein, Solome Abebe, Julie Bamdad, Melanie Barkalow, Joel Bethepu, Tsedenia Bezabeh, Nicole Butler, Jackie Callaghan, Caitlin E. Carter, Costas Christophi, Gregory M. Dwyer, Mary Foulkes, Yuping Gao, Robert Gooding, Adrienne Gottlieb, Kristina L. Grimes, Nisha Grover-Fairchild, Lori Haffner, Heather Hoffman, Kathleen Jablonski, Tara L. Jones, Richard Katz, Preethy Kolinjivadi, John M. Lachin, Pamela Mucik, Robert Orlosky, Qing Pan, Susan Reamer, James Rochon, Alla Sapozhnikova, Hanna Sherif, Charlotte Stimpson, Ashley Hogan Tjaden, Fredricka Walker-Murray, Elizabeth M. Venditti, Andrea M. Kriska, Valerie Weinzierl, Jessica Harting, F. Alan Aldrich, John Albers, Greg Strylewicz, R. Eastman, Judith Fradkin, Sanford Garfield, Edward Gregg, Morton B. Brown, David Altshuler, Liana K. Billings, Maegan Harden, Toni I. Pollin, Alan R. Shuldiner, Paul W. Franks, and Marie-France Hivert

Subjects
Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Introduction Sex hormone binding globulin (SHBG) levels are reported to be inversely associated with diabetes risk. It is unknown whether diabetes prevention interventions increase SHBG and whether resultant changes in SHBG affect diabetes risk. The purpose of this analysis was to determine whether intensive lifestyle intervention (ILS) or metformin changed circulating SHBG and if resultant changes influenced diabetes risk in the Diabetes Prevention Program (DPP).Research design and methods This is a secondary analysis from the DPP (1996–2001), a randomized trial of ILS or metformin versus placebo on diabetes risk over a mean follow-up of 3.2 years. The DPP was conducted across 27 academic study centers in the USA. Men, premenopausal and postmenopausal women without hormone use in the DPP were evaluated. The DPP included overweight/obese persons with elevated fasting glucose and impaired glucose tolerance. Main outcomes measures were changes in SHBG levels at 1 year and risk of diabetes over 3 years.Results ILS resulted in significantly higher increases (postmenopausal women: p

Published
2020
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6. Actos Now for the Prevention of Diabetes (ACT NOW) Study

Author

DeFronzo, Ralph A, Banerji, MaryAnn, Bray, George A, Buchanan, Thomas A, Clement, Stephen, Henry, Robert R, Kitabchi, Abbas E, Mudaliar, Sunder, Musi, Nicolas, Ratner, Robert, Reaven, Peter D, Schwenke, Dawn, Stentz, Frankie B, and Tripathy, Devjit

Abstract

Abstract Background Impaired glucose tolerance (IGT) is a prediabetic state. If IGT can be prevented from progressing to overt diabetes, hyperglycemia-related complications can be avoided. The purpose of the present study was to examine whether pioglitazone (ACTOS®) can prevent progression of IGT to type 2 diabetes mellitus (T2DM) in a prospective randomized, double blind, placebo controlled trial. Methods/Design 602 IGT subjects were identified with OGTT (2-hour plasma glucose = 140–199 mg/dl). In addition, IGT subjects were required to have FPG = 95–125 mg/dl and at least one other high risk characteristic. Prior to randomization all subjects had measurement of ankle-arm blood pressure, systolic/diastolic blood pressure, HbA1C, lipid profile and a subset had frequently sampled intravenous glucose tolerance test (FSIVGTT), DEXA, and ultrasound determination of carotid intima-media thickness (IMT). Following this, subjects were randomized to receive pioglitazone (45 mg/day) or placebo, and returned every 2–3 months for FPG determination and annually for OGTT. Repeat carotid IMT measurement was performed at 18 months and study end. Recruitment took place over 24 months, and subjects were followed for an additional 24 months. At study end (48 months) or at time of diagnosis of diabetes the OGTT, FSIVGTT, DEXA, carotid IMT, and all other measurements were repeated. Primary endpoint is conversion of IGT to T2DM based upon FPG ≥ 126 or 2-hour PG ≥ 200 mg/dl. Secondary endpoints include whether pioglitazone can: (i) improve glycemic control (ii) enhance insulin sensitivity, (iii) augment beta cell function, (iv) improve risk factors for cardiovascular disease, (v) cause regression/slow progression of carotid IMT, (vi) revert newly diagnosed diabetes to normal glucose tolerance. Conclusion ACT NOW is designed to determine if pioglitazone can prevent/delay progression to diabetes in high risk IGT subjects, and to define the mechanisms (improved insulin sensitivity and/or enhanced beta cell function) via which pioglitazone exerts its beneficial effect on glucose metabolism to prevent/delay onset of T2DM. Trial Registration clinical trials.gov identifier: NCT00220961

Published
2009

7. The Effect of Interventions to Prevent Type 2 Diabetes on the Development of Diabetic Retinopathy: The DPP/DPPOS Experience

Author

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., 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., 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., 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., 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, 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., 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., 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, Rubinchik, Sofya, Senter, Willette, 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., 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, Reamer, Susan, Rochon, James, Sapozhnikova, Alla, Sherif, Hanna, Stimpson, Charlotte, Hogan Tjaden, Ashley, Walker-Murray, Fredricka, Venditti, Elizabeth M., Kriska, Andrea M., 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, 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., and Hivert, Marie-France

Subjects
Advanced and Specialized Nursing, Endocrinology, Diabetes and Metabolism, Internal Medicine, Pathophysiology/Complications
Abstract

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.

Published
2022
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9. Evaluation of a Nuclear Power Skill Related Training Program for Job Corps Students.

Author

Kitabchi, Gloria and Petry, John R.

Abstract

An evaluation of the Nuclear Skill Related Training Program at Memphis State University was conducted to identify possible motivational and attitudinal variables that may contribute to the retention-attrition rates of Job Corps students (40 percent) admitted to the program compared to non-Job Corps students who are migrant workers (2 percent). The program consists of 26 weeks of intensive training on a daily 8 a.m. to 5 p.m. basis. A questionnaire was developed to determine personal and motivational attitudes of the 11 currently enrolled students related to the administration and content of the Nuclear Studies Program, and short personal interviews were also conducted with these students. Data gathered in the survey indicated that the students are somewhat pleased with the program, have a strong commitment to the program, and feel that academic problems would be their major reason for dropping out if they did so. Most changes suggested by students involved the instructional area, especially in relation to the professors/instructors, modules, and the practicality of course control. Another group of suggestions was about student personnel staff. In order to strengthen retention of students in the program, the study recommended that enlistment personnel in Job Corps centers be more specific about program content, difficulty, and the probability of jobs after graduation. It also recommended that the program offer more remedial services and that instructors be more available for consultations and be more practical in class. (KC)

Published
1982

10. History of Cardiovascular Disease, Intensive Lifestyle Intervention, and Cardiovascular Outcomes in the Look AHEAD Trial

Author

Lawrence J. Cheskin, John M. Jakicic, Cora E. Lewis, Helen P. Hazuda, Louise Hesson, Karen C. Johnson, Caitlin Egan, Jeffrey M. Curtis, Abbas E. Kitabchi, Edward W. Lipkin, David M. Reboussin, Thomas A. Wadden, Lynne E. Wagenknecht, John P. Bantle, George L. Blackburn, Dalane W. Kitzman, Siran Ghazarian, James O. Hill, Anne L. Peters, Edward S. Horton, David M. Nathan, Susan Z. Yanovski, Donna H. Ryan, George A. Bray, Rena R. Wing, Van S. Hubbard, Robert W. Jeffery, John P. Foreyt, Jennifer Patricio, Henry J. Pownall, Mary Evans, Sara Michaels, Maria G. Montez, Xavier Pi-Sunyer, Edward W. Gregg, Holly R. Wyatt, Bethany Barone Gibbs, Ebenezer Nyenwe, Steven E. Kahn, William C. Knowler, Frederick L. Brancati, Stephen P. Glasser, and Alain G. Bertoni

Subjects
Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Physical fitness, Medicine (miscellaneous), 030209 endocrinology & metabolism, Type 2 diabetes, Overweight, Article, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Weight loss, Diabetes mellitus, Internal medicine, medicine, Humans, 030212 general & internal medicine, Myocardial infarction, Life Style, Stroke, Nutrition and Dietetics, business.industry, Hazard ratio, Middle Aged, medicine.disease, Cardiovascular Diseases, Female, medicine.symptom, business
Abstract

Objective To examine the effects of an intensive lifestyle intervention (ILI) on cardiovascular disease (CVD), the Action for Health in Diabetes (Look AHEAD) trial randomized 5,145 participants with type 2 diabetes and overweight/obesity to a ILI or diabetes support and education. Although the primary outcome did not differ between the groups, there was suggestive evidence of heterogeneity for prespecified baseline CVD history subgroups (interaction P = 0.063). Event rates were higher in the ILI group among those with a CVD history (hazard ratio 1.13 [95% CI: 0.90-1.41]) and lower among those without CVD (hazard ratio 0.86 [95% CI: 0.72-1.02]). Methods This study conducted post hoc analyses of the rates of the primary composite outcome and components, adjudicated cardiovascular death, nonfatal myocardial infarction (MI), stroke, and hospitalization for angina, as well as three secondary composite cardiovascular outcomes. Results Interaction P values for the primary and two secondary composites were similar (0.060-0.064). Of components, the interaction was significant for nonfatal MI (P = 0.035). This interaction was not due to confounding by baseline variables, different intervention responses for weight loss and physical fitness, or hypoglycemic events. In those with a CVD history, statin use was high and similar by group. In those without a CVD history, low-density lipoprotein cholesterol levels were higher (P = 0.003) and statin use was lower (P ≤ 0.001) in the ILI group. Conclusions Intervention response heterogeneity was significant for nonfatal MI. Response heterogeneity may need consideration in a CVD-outcome trial design.

Published
2020
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15. Impact of an Intensive Lifestyle Intervention on Use and Cost of Medical Services Among Overweight and Obese Adults With Type 2 Diabetes: The Action for Health in Diabetes

Author

Espeland, Mark A., Glick, Henry A., Bertoni, Alain, Brancati, Frederick L., Bray, George A., Clark, Jeanne M., Curtis, Jeffrey M., Egan, Caitlin, Evans, Mary, Foreyt, John P., Ghazarian, Siran, Gregg, Edward W., Hazuda, Helen P., Hill, James O., Hire, Don, Horton, Edward S., Hubbard, Van S., Jakicic, John M., Jeffery, Robert W., Johnson, Karen C., Kahn, Steven E., Killean, Tina, Kitabchi, Abbas E., Knowler, William C., Kriska, Andrea, Lewis, Cora E., Miller, Marsha, Montez, Maria G., Murillo, Anne, Nathan, David M., Nyenwe, Ebenezer, Patricio, Jennifer, Peters, Anne L., Pi-Sunyer, Xavier, Pownall, Henry, Redmon, J. Bruce, Rushing, Julia, Ryan, Donna H., Safford, Monika, Tsai, Adam G., Wadden, Thomas A., Wing, Rena R., Yanovski, Susan Z., and Zhang, Ping

Published
2014
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32. DNA methylation age calculators reveal association with diabetic neuropathy in type 1 diabetes

Author

Thomas Donner, P. Rezaeian, John I. Malone, Sharon B. Schwartz, Xiaoyu Gao, Szilard Kiss, Matthew J. Budoff, David R. Sell, A. Dwoskin, Ronald J. Prineas, C. Pittman, M. Reid, C. McDonald, S. Caulder, M. Szpiech, Oscar B. Crofford, Rachel G. Miller, Louis A. Lobes, M. Patronas, C. Canny, M. E. Lackaye, Sandra R. Montezuma, Richard M. Bergenstal, Patricia Gatcomb, Julie A. Stoner, H. Pan, James L. Kinyoun, J. Mortenson, Osama Hamdy, Connie Fountain, David D. Moore, Kusiel Perlman, R. Trail, David A. Lee, J. Sheindlin, Samuel Dagogo-Jack, Jeffrey L. Mahon, Jill P. Crandall, L. Gill, T. Thompson, Lee M. Jampol, K. Koushan, David S. Schade, J. Brown-Friday, M. Basco, S. Dunnigan, J. Bylsma, R. Birk, L. H. Ketai, J. Hotaling, Stephen W. Scherer, W. Mestrezat, Stephan Villavicencio, R. Lyon, M. Carney, John Kramer, Sunder Mudaliar, David M. Nathan, M. Moran, F. Leandre, James W. Albers, L. Survant, Joseph F. Polak, Manjot K. Gill, Anton Orlin, M. Prince, Pamela A. Silver, Amy K. Saenger, John D. Brunzell, Kathleen E. Bainbridge, L. Babbione, Amisha Wallia, J. Vaccaro-Kish, Bradley D. Jones, M. Hebdon, L. McKenzie, Richard M. Hoffman, S. Chang, C. Siebert, George S. Sharuk, D. Counts, A. Lucas, P. Ramos, N. Burkhart, N. Bakshi, N. Flaherty, D. Kenny, M. Driscoll, Harjit Chahal, Ronald K. Mayfield, S. Hensley, E. Weimann, M. Franz, Martin J. Stevens, N. S. Gregory, Christopher J. O'Donnell, J. Laechelt, Pamela Ossorio, Jerry P. Palmer, Rama Natarajan, G. Ziegler, K. Martin, R. Beaser, C. Beck, L. Zhang, T. J. Declue, David M. Kendall, H. Solc, A. Vella, H. Martinez, Cormac T. Taylor, S. Neill, Douglas A. Greene, P. Lee, D. Norman, Andrew J. Barkmeier, Dean P. Hainsworth, Alka Jain, Sapna Gangaputra, N. Thangthaeng, Lorraine Thomas, Michael H. Brent, M. Bracey, Philip Raskin, Q. Clemens, Barbara H. Braffett, Mark S. Mandelcorn, Lloyd Paul Aiello, John E. Godine, T. Speigelberg, R. Chan, R. Hanna, Shelley B. Bull, William I. Sivitz, R. Sussman, C. Kwong, S. Cercone, P. Hollander, N. Leloudes, Joseph M. Terry, J. Wesche, E. A. Tanaka, D. Rosenberg, Wanjie Sun, L. Sun, Tom Clark, Deborah K. Schlossman, Louis M. Luttrell, R. Dunn, A. Farr, K. McVary, Gayle M. Lorenzi, A. Joseph, Catherine C. Cowie, M. Barr, D. Zimbler, S. Mendley, S. Schussler, N. Grove, Matthew D. Davis, Jong Mu Sun, Sophie Rogers, John P. Bantle, Brandy N. Rutledge, Senda Ajroud-Driss, Vincent M. Monnier, Cladd E. Stevens, Y. G. He, M. Phillips, C. Williams, J. MacIndoe, Kaleigh Farrell, Helen Lambeth, Ayad A. Jaffa, J. Quin, Morey W. Haymond, R. Kirby, D. Steinberg, William H. Herman, M. Mech, Arup Das, Robert Detrano, J. Brown, D. McMillan, Linda Snetselaar, Mark W. Johnson, R. Zeitler, T. Taylor, Peter R. Pavan, Michael H. Goldbaum, Bruce A. Perkins, R. G. Campbell, David A. Nicolle, R. J. van der Geest, Irene Hramiak, D. Freking, Lucy A. Levandoski, S. Colson, Charles Campbell, Victoria R. Trapani, Lawrence J. Singerman, D. Meyer, W. Tang, J. Soule, Anita Harrington, Julie A. Nelson, John A. Colwell, Naji Younes, P. Salemi, K. Hansen, Trevor J. Orchard, S. Huddleston, L. Steranchak, C. Sommer, G. Castle, J. Ginsberg, Paula McGee, V. Gama, John Dupre, Z. Strugula, M. Swenson, N. Wong, David A. Bluemke, M. Nutaitis, Anita Agarwal, M. Lin, K. Nickander, Elsayed Z. Soliman, Joao A. Lima, M. L. Schluter, Fred W. Whitehouse, Lisa Diminick, C. Cornish, M. Spencer, Daniel T. Lackland, Ionut Bebu, Hunter Wessells, S. Yacoub-Wasef, A. Determan, L. Van Ottingham, Howard Wolpert, R. Ehrlich, A. Blevins, L. Jovanovic, D. Finegold, Davida F. Kruger, Jye-Yu C. Backlund, K. Chan, Timothy J. Murtha, R. K. Mayfield, Robert W. Cavicchi, Maria F. Lopes-Virella, Thomas A. Weingeist, K. Lee, Mary E. Larkin, B. Blodi, J. Gott, Timothy J. Lyons, J. Selby, Chris Ryan, J. Harth, P. Pugsley, L. Keasler, John D. Maynard, Paul G. Arrigg, Amy B. Karger, P. Colby, J. Farquhar, Mark H. Schutta, Murk-Hein Heinemann, Kathie L. Hermayer, B. Bosco, C. Lovell, A. Bhan, A. Galprin, M. Cayford, M. Schumer, John E. Chapin, D. Rubinstein, F. Miao, V. Asuquo, Catherine L. Martin, Rodney A. Lorenz, Samuel S. Engel, L. Funk, Cyndi F. Liu, Barbara J. Maschak-Carey, Stephen S. Feman, P. Lindsey, M. Giotta, Philip A. Low, S. Kwon, R. Fahlstrom, A. Iannacone, B. French, H. Remtema, L. Cimino, S. Barron, J. McConnell, Jane L. Lynch, L. Kim, T. Williams, A. Degillio, Blanche M. Chavers, M. Novak, Julio V. Santiago, Ronald P. Danis, P. Gaston, Tae Sup Lee, T. Woodfill, R. Cuddihy, Scott M. Steidl, Alanna C. Morrison, E. Ryan, D. Lawrence, D. Cros, T. Adkins, D. Adelman, L. Dews, Patricia A. Cleary, J. Parker, L. Olmos De Koo, C. Kim, Mark R. Palmert, P. Astelford, Stefan Fritz, B. Olson, Kelvin C. Fong, Alan M. Jacobson, Stanley L. Hazen, D. Hornbeck, K. Folino, M. L. Bernal, Gabriel Virella, William V. Tamborlane, Neil H. White, Daniel L. McGee, Denis Daneman, H. Shamoon, William Dahms, S. Elsing, S. Brink, J. Ahern, Delnaz Roshandel, John M. Pach, N. W. Rodger, E. Cupelli, Dara D. Koozekanani, Abbas E. Kitabchi, K. Stoessel, B. Petty, Jamie R. Wood, J. Seegmiller, T. Strand, Y. Li, Eva L. Feldman, Larry Rand, Robert C. Colligan, T. Smith, A. Carlson, David J. Brillon, Margaret L. Bayless, M. Ong, S. Darabian, W. Hsu, Janet E. Olson, B. Rogness, N. Silvers, M. Pfiefer, B. Schaefer, E. Mendelson, S. Braunstein, Maren Nowicki, R. Reed, James S. Floyd, Z. M. Zhang, T. Sandford, R. B. Avery, A. Pratt, Paolo S. Silva, H. Bode, Alexander J. Brucker, Nikhil D. Patel, Alexander R. Lyon, M. Jenner, N. Wimmergren, L. Tuason, J. Rosenzwieg, D. J. Becker, C. Gauthier-Kelly, M. Richardson, Richard S. Crow, Andrew D. Paterson, Mark E. Molitch, Suzanne M. Strowig, S. Pendegast, M. Burger, Ramzi K. Hemady, J. Dingledine, I. H. de Boer, L. Mayer, F. Perdikaris, Om P. Ganda, F. Thoma, Karen J. Cruickshanks, Abraham Thomas, K. Klumpp, Jerry D. Cavallerano, D. Zheng, Annette Barnie, J. L. Canady, C. Wigley, David G. Miller, Sheila Smith-Brewer, D. Ostrowski, P. Crawford, K. Kelly, Robert G. Devenyi, B. Zimmerman, Susan M. Hitt, C. Johnson, L. Gurry, R. Jarboe, E. Angus, David E. Goldstein, A. Killeen, H. Schrott, Orville G. Kolterman, Mark R. Burge, Michael Rubin, J. Lipps Hagan, Alicia J. Jenkins, Hugh D. Wabers, R. Warhol, Edward Chaum, Karen L. Jones, L. Spillers, C. Miao, J. K. Jones, Angelo J. Canty, Rickey E. Carter, Evrim B. Turkbey, B. Burzuk, R. Woodwick, Evica Simjanoski, Michael W. Steffes, S. Crowell, Suresh D. Shah, H. Ricks, J. D. Carey, Paul A. Edwards, S. Holt, W. F. Schwenk, Ronald J. Oudiz, E. Brown, J. Heier, R. L. Ufret-Vincenty, L. M. Aiello, Robert A. Rizza, Karen L. Anderson, Valerie L. Arends, J. Giangiacomo, R. Liss, Aruna V. Sarma, B. Levy, Ellen J. Anderson, S. Catton, P. Callahan, Rodica Pop-Busui, S. Debrabandere, S. Moser, Bernard H. Doft, A. Malayeri, C. Johannes, R. Ramker, J. Rich, M. Fox, Rukhsana G. Mirza, Katherine A. Morgan, Thomas J. Songer, C. Shah, H. Engel, Saul M. Genuth, S. Ferguson, Anushka Patel, C. Haggan, P. Lou, J. Gordon, M. B. Murphy, D. Sandstrom, Dawn M. Ryan, Daniel H. O'Leary, B. Gloeb, Lois E. Schmidt, H. Zegarra, D. Dalton, W. Brown, Tom G. Sheidow, Margaret E. Stockman, Shyam M. Thomas, Charles McKitrick, Jyotika K. Fernandes, P. A. Bourne, L. Baker, G. Friedenberg, Allan Gordon, Allan L. Drash, S. Yoser, D. Wood, S. Johnsonbaugh, A. De Manbey, L. Kaminski, M. May, L. Bestourous, A. Kowarski, M. Geckle, M. Hartmuller, Michael Bryer-Ash, S. List, F. Goetz, V. Reppucci, D. Etzwiler, Rose A. Gubitosi-Klug, M. Brabham, E. Golden, A. Nayate, J. Hu, M. McLellan, Ronald Klein, N. Rude, B. Vittetoe, John M. Lachin, M. Christofi, Zhuo Chen, Isaac Boniuk, C. Strauch, K. Gunyou, L. Delahanty, W. T. Garvey, Andrew P. Boright, Larry D. Hubbard, D. Weiss, Igor Grant, Jonathan Q. Purnell, Jean M. Bucksa, N. Olson, and B. Zinman

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, Diabetic neuropathy, Adolescent, 030209 endocrinology & metabolism, Gastroenterology, Nephropathy, Epigenesis, Genetic, Diabetic complications, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Diabetic Neuropathies, Internal medicine, Diabetes mellitus, Albumins, Genetics, Medicine, Humans, Molecular Biology, Genetics (clinical), Whole blood, Oligonucleotide Array Sequence Analysis, Type 1 diabetes, business.industry, Research, dNaM, DNA methylation age, DNA Methylation, medicine.disease, 030104 developmental biology, Blood pressure, Peripheral neuropathy, Diabetes Mellitus, Type 1, CpG Islands, Female, business, Developmental Biology, Genome-Wide Association Study
Abstract

Background Many CpGs become hyper or hypo-methylated with age. Multiple methods have been developed by Horvath et al. to estimate DNA methylation (DNAm) age including Pan-tissue, Skin & Blood, PhenoAge, and GrimAge. Pan-tissue and Skin & Blood try to estimate chronological age in the normal population whereas PhenoAge and GrimAge use surrogate markers associated with mortality to estimate biological age and its departure from chronological age. Here, we applied Horvath’s four methods to calculate and compare DNAm age in 499 subjects with type 1 diabetes (T1D) from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study using DNAm data measured by Illumina EPIC array in the whole blood. Association of the four DNAm ages with development of diabetic complications including cardiovascular diseases (CVD), nephropathy, retinopathy, and neuropathy, and their risk factors were investigated. Results Pan-tissue and GrimAge were higher whereas Skin & Blood and PhenoAge were lower than chronological age (p < 0.0001). DNAm age was not associated with the risk of CVD or retinopathy over 18–20 years after DNAm measurement. However, higher PhenoAge (β = 0.023, p = 0.007) and GrimAge (β = 0.029, p = 0.002) were associated with higher albumin excretion rate (AER), an indicator of diabetic renal disease, measured over time. GrimAge was also associated with development of both diabetic peripheral neuropathy (OR = 1.07, p = 9.24E−3) and cardiovascular autonomic neuropathy (OR = 1.06, p = 0.011). Both HbA1c (β = 0.38, p = 0.026) and T1D duration (β = 0.01, p = 0.043) were associated with higher PhenoAge. Employment (β = − 1.99, p = 0.045) and leisure time (β = − 0.81, p = 0.022) physical activity were associated with lower Pan-tissue and Skin & Blood, respectively. BMI (β = 0.09, p = 0.048) and current smoking (β = 7.13, p = 9.03E−50) were positively associated with Skin & Blood and GrimAge, respectively. Blood pressure, lipid levels, pulse rate, and alcohol consumption were not associated with DNAm age regardless of the method used. Conclusions Various methods of measuring DNAm age are sub-optimal in detecting people at higher risk of developing diabetic complications although some work better than the others.

Published
2020

46. Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome. (From Research to Practice/Acute Care of Patients with Diabetes)

Author

Umpierrez, Guillermo E., Murphy, Mary Beth, and Kitabchi, Abbas E.

Subjects
United States. Department of Health and Human Services, Health
Abstract

In Brief I Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS) are two acute complications of diabetes that can result in increased morbidity and mortality if not efficiently and effectively [...]

Published
2002

49. Change in adiponectin explains most of the change in HDL particles induced by lifestyle intervention but not metformin treatment in the Diabetes Prevention Program

Author

Leigh Perreault, Edward S. Horton, Kieren J. Mather, Marinella Temprosa, George A. Bray, Jonathan Krakoff, Ronald B. Goldberg, Neil H. White, Santica M. Marcovina, Lisa Mele, Trevor J. Orchard, and Abbas E. Kitabchi

Subjects
Male, Endocrinology, Diabetes and Metabolism, Saturated fat, 030204 cardiovascular system & hematology, Metabolic equivalent, Cohort Studies, Impaired glucose tolerance, 0302 clinical medicine, Endocrinology, Risk Factors, Weight loss, Diet, Fat-Restricted, Middle Aged, Combined Modality Therapy, Metformin, Cardiovascular Diseases, Female, lipids (amino acids, peptides, and proteins), Adiponectin, medicine.symptom, medicine.drug, medicine.medical_specialty, Diet, Reducing, 030209 endocrinology & metabolism, Motor Activity, Prediabetic State, 03 medical and health sciences, Insulin resistance, Double-Blind Method, Diabetes mellitus, Internal medicine, Weight Loss, medicine, Humans, Hypoglycemic Agents, Life Style, business.industry, Cholesterol, HDL, nutritional and metabolic diseases, Overweight, medicine.disease, United States, Diabetes Mellitus, Type 2, sense organs, business, Biomarkers, Follow-Up Studies
Abstract

Objective In addition to slowing diabetes development among participants in the Diabetes Prevention Program (DPP), intensive lifestyle change and metformin raised HDL-cholesterol (HDL-C) compared to placebo treatment. We investigated the lifestyle and metabolic determinants as well as effects of biomarkers of inflammation, endothelial dysfunction and coagulation and their changes resulting from lifestyle and metformin interventions on the increase in HDL-C in the DPP. Methods The effects of a 1 year period of intensive lifestyle change aimed at achieving 7% weight loss or metformin 850 mg twice daily versus placebo on HDL-C were assessed in 3070 participants with impaired glucose tolerance, and on HDL particle concentration (HDL-P) and size in a subgroup of 1645 individuals. Treatment-associated changes in lifestyle and metabolic factors as well as in novel biomarkers were investigated for their associations with change in HDL-C using multiple regression analysis. Results After adjusting for BMI, insulin resistance, glycemia, dietary saturated fat, alcohol intake, physical activity and nine different biomarkers, only adiponectin accounted for the effect of intensive lifestyle change on HDL-C via an increase in large HDL-P. By contrast baseline and change in BMI and tissue plasminogen activator levels attenuated the effect of metformin on HDL-C, with adiponectin having no specific effect. Conclusion While both lifestyle and metformin interventions used to prevent diabetes increase HDL-C, the mechanisms involved differ between the two treatments and may have consequences for future risk of cardiovascular disease.

Published
2016
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50. Diabetes Incidence and Glucose Tolerance after Termination of Pioglitazone Therapy: Results from ACT NOW

Author

Devjit Tripathy, Thomas A. Buchanan, Abbas E. Kitabchi, Dawn C. Schwenke, Robert E. Ratner, Mary Ann Banerji, Frankie B. Stentz, Nicolas Musi, Peter D. Reaven, Robert R. Henry, Stephen Clement, Ralph A. DeFronzo, George A. Bray, and Sunder Mudaliar

Subjects
Blood Glucose, Male, 0301 basic medicine, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, 030209 endocrinology & metabolism, Context (language use), Placebo, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Insulin resistance, Diabetes mellitus, Internal medicine, medicine, Humans, Hypoglycemic Agents, Insulin, Cumulative incidence, Pioglitazone, business.industry, Incidence, Incidence (epidemiology), Biochemistry (medical), Original Articles, Middle Aged, medicine.disease, Substance Withdrawal Syndrome, 030104 developmental biology, Diabetes Mellitus, Type 2, Female, Thiazolidinediones, Insulin Resistance, business, medicine.drug
Abstract

Thiazolidinediones have proven efficacy in preventing diabetes in high-risk individuals. However, the effect of thiazolidinediones on glucose tolerance after cessation of therapy is unclear.To examine the effect of pioglitazone (PIO) on incidence of diabetes after discontinuing therapy in ACT NOW. Design, Settings and Patients: Two-hundred ninety-three subjects (placebo [PLAC], n = 138; PIO, n = 152) completed a median followup of 11.7 mo after study medication was stopped.Diabetes developed in 138 (12.3%) of PLAC vs 17 of 152 PIO patients (11.2%; P = not significant, PIO vs PLAC). However, the cumulative incidence of diabetes from start of study medication to end of washout period remained significantly lower in PIO vs PLAC (10.7 vs 22.3%; P.005). After therapy was discontinued, 23.0% (35/152) of PIO-treated patients remained normal-glucose tolerant (NGT) vs 13.8% (19/138) of PLAC-treated patients (P = .04). Insulin secretion/insulin resistance index (I0-120/G0-120 × Matsuda index) was markedly lower in subjects with impaired glucose tolerance (IGT) who converted to diabetes during followup vs those who remained IGT or NGT. The decline in-cell function (insulin secretion/insulin resistance index) was similar in subjects with IGT who developed diabetes, irrespective of whether they were treated with PIO or PLAC.1) The protective effect of PIO on incidence of diabetes attenuates after discontinuation of therapy, 2) cumulative incidence of diabetes in individuals exposed to PIO remained significantly (56%) lower than PLAC and a greater number of PIO-treated individuals maintained NGT after median followup of 11.4 mo, and 3) low insulin secretion/insulin resistance index is a strong predictor of future diabetes following PIO discontinuation.

Published
2016
Full Text
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