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2. Optimization of Metformin in the GRADE Cohort: Effect on Glycemia and Body Weight

Author

Sivitz, William I, Phillips, Lawrence S, Wexler, Deborah J, Fortmann, Stephen P, Camp, Anne W, Tiktin, Margaret, Perez, Magalys, Craig, Jacqueline, Hollander, Priscilla A, Cherrington, Andrea, Aroda, Vanita R, Tan, Meng Hee, Krakoff, Jonathan, Rasouli, Neda, Butera, Nicole M, Younes, Naji, Crandall, Jill P, Diane McKee, Melissa, Brown-Friday, Janet, Xhori, Entila, Ballentine-Cargill, Keisha, Duran, Sally, Lukin, Jennifer, Beringher, Stephanie, Gonzalez de la torre, Susana, Phillips, Lawrence, Burgess, Elizabeth, Olson, Darin, Rhee, Mary, Wilson, Peter, Stephanie Raines, Tasha, Costello, Julie, Gullett, Chona, Maher-Albertelli, Maxine, Morehead, Folayan, Mungara, Radhika, Person, Saranjit, Savoye, Louise, Sibymon, Mabil, Tanukonda, Sridhar, Ann White, Carol, Holloway, Leah, Adams, Cynthia, Ross, April, Balasubramanyam, Ashok, Gonzalez, Erica, Wright, Charlyne, Hollander, Priscilla, Roe, Erin, Uy, Analyn, Burt, Polly, Estrada, Lorie, Chionh, Kris, Ismail-Beigi, Faramarz, Falck-Ytter, Corinna, Sayyed Kassem, Laure, Sood, Ajay, Cramer, Bethany, Iacoboni, Jacalyn, Kononets, Maria V, Kulow, Tanya, Newman, Cynthia, Stancil, Katherine A, Sanders, Cristina, Tucker, Lisa, Werner, Amanda, Krol, Adrienne, McPhee, Gloria, Patel, Christine, Colosimo, Linda, Goland, Robin, Pring, James, Kringas, Patricia, Tejada, Jessica, Hausheer, Camille, Schneier, Harvey, Gumpel, Kelly, Kirpitch, Amanda, Green, Jennifer B, AbouAssi, Hiba, Chatterjee, Ranee, Feinglos, Mark N, English Jones, Jennifer, Khan, Shubi A, Kimpel, Jeanne B, Zimmer, Ronna P, Furst, Mary, Satterwhite, Barbara M, Thacker, Connie R, Evans Kreider, Kathryn, Mather, Kieren J, Lteif, Amale, Hamilton, Tonya, Patel, Nick, Riera, Gabriela, Jackson, Marcia, Pirics, Vivian, Howard, Devin, and Aguillar, Danielle

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Prevention, Clinical Research, Diabetes, Nutrition, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Metabolic and endocrine, Adult, Aged, Blood Glucose, Body Weight, Calibration, Comparative Effectiveness Research, Diabetes Mellitus, Type 2, Dose-Response Relationship, Drug, Drug Therapy, Combination, Female, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Insulin, Liraglutide, Male, Maximum Tolerated Dose, Metformin, Middle Aged, Sitagliptin Phosphate, Sulfonylurea Compounds, Weight Loss, GRADE Research Group, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences, Health sciences
Abstract

ObjectiveWe evaluated the effect of optimizing metformin dosing on glycemia and body weight in type 2 diabetes.Research design and methodsThis was a prespecified analysis of 6,823 participants in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) taking metformin as the sole glucose-lowering drug who completed a 4- to 14-week (mean ± SD 7.9 ± 2.4) run-in in which metformin was adjusted to 2,000 mg/day or a maximally tolerated lower dose. Participants had type 2 diabetes for

Published
2020

8. Validation of total water intake from the Automated Self-Administered 24-h recall, 4-d food records, and a food-frequency questionnaire using doubly labeled water

Author

Chang, Douglas C., primary, Stinson, Emma J., additional, Dodd, Kevin W., additional, Bowles, Heather R., additional, Herrick, Kirsten A., additional, Schoeller, Dale A., additional, Barrett, Brian, additional, Votruba, Susanne B., additional, Krakoff, Jonathan, additional, and Kavouras, Stavros A., additional

Published
2023
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10. Associations of Fatty Acids in Cerebrospinal Fluid with Peripheral Glucose Concentrations and Energy Metabolism

Author

Jumpertz, Reiner, Guijarro, Ana, Pratley, Richard E., Mason, Clinton C., Piomelli, Daniele, and Krakoff, Jonathan

Subjects
estimated desaturase activities, diet-induced obesity, skeletal-muscle, insulin sensitivity, alzheimers-disease, palmitoleic acid, risk-factors, food-intake, brain, mice
Abstract

Rodent experiments have emphasized a role of central fatty acid (FA) species, such as oleic acid, in regulating peripheral glucose and energy metabolism. Thus, we hypothesized that central FAs are related to peripheral glucose regulation and energy expenditure in humans. To test this we measured FA species profiles in cerebrospinal fluid (CSF) and plasma of 32 individuals who stayed in our clinical inpatient unit for 6 days. Body composition was measured by dual energy X-ray absorptiometry and glucose regulation by an oral glucose test (OGTT) followed by measurements of 24 hour (24EE) and sleep energy expenditure (SLEEP) as well as respiratory quotient (RQ) in a respiratory chamber. CSF was obtained via lumbar punctures; FA concentrations were measured by liquid chromatography/mass spectrometry. As expected, FA concentrations were higher in plasma compared to CSF. Individuals with high concentrations of CSF very-long-chain saturated FAs had lower rates of SLEEP. In the plasma moderate associations of these FAs with higher 24EE were observed. Moreover, CSF monounsaturated long-chain FA (palmitoleic and oleic acid) concentrations were associated with lower RQs and lower glucose area under the curve during the OGTT. Thus, FAs in the CSF strongly correlated with peripheral metabolic traits. These physiological parameters were most specific to long-chain monounsaturated (C16∶1, C18∶1) and very-long-chain saturated (C24∶0, C26∶0) FAs. Conclusions: Together with previous animal experiments these initial cross-sectional human data indicate that central FA species are linked to peripheral glucose and energy homeostasis.

Published
2012

12. Central and peripheral endocannabinoids and cognate acylethanolamides in humans: association with race, adiposity, and energy expenditure.

Author

Jumpertz, Reiner, Guijarro, Ana, Pratley, Richard E, Piomelli, Daniele, and Krakoff, Jonathan

Subjects
Obesity, Clinical Research, Nutrition, Neurosciences, Absorptiometry, Photon, Adiposity, Amides, Anti-Obesity Agents, Arachidonic Acids, Blood Glucose, Cannabinoid Receptor Modulators, Endocannabinoids, Energy Metabolism, Ethanolamines, Ethnicity, Glycerides, Humans, Insulin, Leptin, Palmitic Acids, Piperidines, Polyunsaturated Alkamides, Pyrazoles, Receptor, Cannabinoid, CB1, Rimonabant, Ethnic Groups, Clinical Sciences, Paediatrics and Reproductive Medicine, Endocrinology & Metabolism
Abstract

ContextPeripheral and central endocannabinoids and cognate acylethanolamides (AEs) may play important but distinct roles in regulating energy balance.ObjectiveWe hypothesized that in humans central/peripheral endocannabinoids are differently associated with adiposity and energy expenditure and differ by race.DesignWe examined associations of arachindonoylethanolamide, 2-arachidonoylglycerol, palmitoylethanolamide, and oleoylethanolamide (OEA) assayed in plasma and cerebrospinal fluid (CSF) with race, adiposity, and energy expenditure.Setting/participantsIn this monitored clinical inpatient study, CSF was obtained by lumbar puncture in 27 individuals (12 Caucasian, 11 American Indian, and four African-American). Twenty-four hour and sleep energy expenditure were measured by indirect calorimetry in a respiratory chamber.Main outcome measureSamples were analyzed from a previous study originally designed to test a blood-brain barrier leptin transport deficit in human obesity.ResultsCSF (but not peripheral) 2-arachidonoylglycerol was significantly increased in American Indians compared with Caucasians (18.48 ± 6.17 vs. 10.62 ± 4.58 pmol/ml, P < 0.01). In the whole group, peripheral AEs were positively but in CSF negatively associated with adiposity. However, in multivariate models adjusted for the other peripheral and CSF AEs, peripheral arachindonoylethanolamide was the only AE significantly associated with adiposity. Interestingly, CSF OEA concentrations were positively associated with adjusted 24 hour and sleep energy expenditure (r = 0.47, P < 0.05; r = 0.42, P < 0.05), but peripheral OEA was not.ConclusionsThese data indicate a central alteration of the endocannabinoid system in American Indians and furthermore show that AEs in both compartments play an important but distinct role in human energy balance regulation.

Published
2011

15. 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

30. The association between gut hormones and diet‐induced metabolic flexibility in metabolically healthy adults.

Author

Unlu, Yigit, Vinales, Karyne L., Hollstein, Tim, Chang, Douglas, Cabeza de Baca, Tomás, Walter, Mary, Krakoff, Jonathan, and Piaggi, Paolo

Subjects
GASTROINTESTINAL hormones, RESPIRATORY quotient, PEPTIDES, FASTING, GLUCAGON-like peptides, CARBOHYDRATES
Abstract

Objective: This study investigated whether interindividual variance in diet‐induced metabolic flexibility is explained by differences in gut hormone concentrations. Methods: A total of 69 healthy volunteers with normal glucose regulation underwent 24‐hour assessments of respiratory quotient (RQ) in a whole‐room indirect calorimeter during eucaloric feeding (EBL; 50% carbohydrate, 30% fat) and then, in a crossover design, during 24‐hour fasting and three normal‐protein (20%) overfeeding diets (200% energy requirements). Metabolic flexibility was defined as the change in 24‐hour RQ from EBL during standard (50% carbohydrate), high‐fat (60%), and high‐carbohydrate (75%) overfeeding diets. Plasma concentrations of glucagon‐like peptide‐1 (GLP‐1) and peptide YY (PYY) after an overnight fast were measured prior to and after each diet. Results: Compared with EBL, on average, 24‐hour RQ decreased by ~4% during high‐fat overfeeding, whereas it increased by ~4% during standard overfeeding and by ~9% during high‐carbohydrate overfeeding. During high‐carbohydrate overfeeding, but not during any other overfeeding diet or fasting, increased GLP‐1 concentration was associated with increased RQ (r = 0.44, p < 0.001), higher/lower carbohydrate/lipid oxidation rates (r = 0.34 and r = −0.51, both p < 0.01), respectively, and increased plasma insulin concentration (r = 0.38, p = 0.02). Conclusions: Increased GLP‐1 concentration following high‐carbohydrate overfeeding associated with a greater shift to carbohydrate oxidation, suggesting that GLP‐1 may be implicated in diet‐induced metabolic flexibility to carbohydrate overload. [ABSTRACT FROM AUTHOR]

Published
2023
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35. Islet Autoimmunity is Highly Prevalent and Associated With Diminished β-Cell Function in Patients With Type 2 Diabetes in the Grade Study

Author

Brooks-Worrell, Barbara, Hampe, Christiane S., Hattery, Erica G., Palomino, Brenda, Zangeneh, Sahar Z., Utzschneider, Kristina, Kahn, Steven E., Larkin, Mary E., Johnson, Mary L., Mather, Kieren J., Younes, Naji, Rasouli, Neda, Desouza, Cyrus, Cohen, Robert M., Park, Jean Y., Florez, Hermes J., Valencia, Willy Marcos, Shojaie, Ali, Palmer, Jerry P., Balasubramanyam, Ashok, Crandall, Jill P., McKee, Melissa Diane, Brown-Friday, Janet, Xhori, Entila, Ballentine-Cargill, Keisha, Duran, Sally, Lukin, Jennifer, Beringher, Stephanie, Gonzalez de la Torre, Susana, Phillips, Lawrence, Burgess, Elizabeth, Olson, Darin, Rhee, Mary, Wilson, Peter, Raines, Tasha Stephanie, Costello, Julie, Gullett, Chona, Maher-Albertelli, Maxine, Morehead, Folayan, Mungara, Radhika, Person, Saranjit, Savoye, Louise, Sibymon, Mabil, Tanukonda, Sridhar, White, Carol Ann, Holloway, Leah, Adams, Cynthia, Ross, April, Gonzalez Hattery, Erica, Gaba, Ruchi, Montes, Graciela, Wright, Charlyne, Hollander, Priscilla, Roe, Erin, Uy, Analyn, Burt, Polly, Estrada, Lorie, Chionh, Kris, Ismail-Beigi, Faramarz, Falck-Ytter, Corinna, Sayyed Kassem, Laure, Sood, Ajay, Tiktin, Margaret, Cramer, Bethany, Iacoboni, Jacalyn, Kononets, Maria V., Kulow, Tanya, Newman, Cynthia, Stancil, Katherine A., Sanders, Cristina, Tucker, Lisa, Werner, Amanda, Krol, Adrienne, McPhee, Gloria, Patel, Christine, Colosimo, Linda, Goland, Robin, Pring, James, Kringas, Patricia, Tejada, Jessica, Hausheer, Camille, Schneier, Harvey, Gumpel, Kelly, Kirpitch, Amanda, Green, Jennifer B., AbouAssi, Hiba, Chatterjee, Ranee, Feinglos, Mark N., English Jones, Jennifer, Khan, Shubi A., Kimpel, Jeanne B., Zimmer, Ronna P., Furst, Mary, Satterwhite, Barbara M., Thacker, Connie, Evans Kreider, Kathryn, Lteif, Amale, Hamilton, Tonya, Patel, Nick, Riera, Gabriela, Jackson, Marcia, Pirics, Vivian, Howard, Devin, Aguillar, Danielle, Hurt, Sloan, Bergenstal, Richard, Carlson, Anders, Martens, Thomas, Johnson, Mary, Hill, Renae, Hyatt, Jamie, Jensen, Connie, Madden, Marcia, Martin, Dianna, Willis, Holly, Konerza, Wanda, Passi, Rebecca, Kleeberger, Kathleen, Fortmann, Stephen, Herson, Michael, Mularski, Karen, Glauber, Harry, Prihoda, James, Ash, Britt, Carlson, Christina, Ramey, Phyllis Anne, Schield, Emily, Torgrimson-Ojerio, Britta, Arnold, Kathy, Kauffman, Bryan, Panos, Elease, Sahnow, Samantha, Bays, Kristi, Cook, Jennifer, Gluth, Jennifer, Sasaki, Debra, Schell, Katrina, Criscola, Jennifer, Friason, Camille, Jones, Suzi, Nazarov, Sergey, Barzilay, Joshua, Rassouli, Negah, Puttnam, Rachel, Curtis, Michelle, Stokes, Kia, Hollis, Bonita, Sanders-Jones, Cynthia, Nelson, Roslin, El-Haqq, Zakiah, Kolli, Abby, Tran, Tu, Wexler, Deborah, Larkin, Mary, Meigs, James, Dushkin, Amy, Rocchio, Gianna, Chambers, Brittany, Yepes, Mike, Steiner, Barbara, Dulin, Hilary, Cayford, Melody, DeManbey, Andrea, Gurry, Lindsey, Hillard, Mallory, Martin, Kimberly, Stevens, Christine, Thangthaeng, Nopporn, Kochis, Raquel, Raymond, Elyse, Ripley, Valerie, Park, Jean, Aroda, Vanita, Ghazi, Adline, Loveland, Amy, Hurtado, Maria, Kuhn, Alexander, Mofor, Florence, Marks, Jennifer, Oropesa-Gonzalez, Lisset, Riccio Veliz, Ana K., Nieto-Martinez, Ramfis, Gutt, Miriam, Ahmann, Andrew, Aby-Daniel, Diana, Joarder, Farahnaz, Morimoto, Victoria, Sprague, Carol, Yamashita, Daisuke, Cady, Nancy, Kirchhoff, Patricia, Rivera-Eschright, Nadia, Adducci, Joseph, Morales Gomez, Brianna, Goncharova, Alina, Hox, Sophia H., Petrovitch, Helen, Matwichyna, Michael, Jenkins, Victoria, Bermudez, Nina O., Ishii, Renée R., Hsia, Daniel S., Cefalu, William T., Greenway, Frank L., Waguespack, Celeste, King, Erin, Haynes, Natalie, Thomassie, Amy, Bourgeois, Brandi, Hazlett, Claire, Henry, Robert, Mudaliar, Sunder, Boeder, Schafer, Pettus, Jeremy, Diaz, Elsa, DeLue, Catherine, Castro, Erick, Hernandez, Sylvia, Krakoff, Jonathan, Curtis, Jeffrey M., Killean, Tina, Joshevama, Erica, Diaz, Enrique, Martin, Denelle, Karshner, Tracey, Albu, Jeanine, Pi-Sunyer, F. Xavier, Frances, Sylvaine, Maggio, Carol, Ellis, Emily, Bastawrose, Joseph, Gong, Xiuqun, Banerji, Mary Ann, August, Phyllis, Lorber, Daniel, Brown, Necole M., Josephson, Debra H., Thomas, Lorraine L., Tsovian, Mari, Cherian, Ajini, Jacobson, Marlo H., Mishko, Motria M., Kirkman, M. Sue, Bergamo, Katherine, Buse, John B., Dostou, Jean, Young, Laura, Goley, April, Kerr, Jeffrey, Largay, Joseph F., Guarda, Sonia, Cuffee, Juanita, Culmer, Dawn, Fraser, Rachael, Almeida, Hope, Coffer, Samantha, Debnam, Elizabeth, Kiker, Lauren, Morton, Sarah, Josey, Kim, Fuller, Gail, Garvey, W. Timothy, Cherrington, Andrea, Golson, Dana, Griffith, Olivia, Robertson, Mary Catherine, Agne, April, McCullars, Steve, Craig, Jacqueline, Kersey, Kimberly, Rogge, M. Colleen, Wilson, Carla, Burton, Kathryn, Lipp, Sonia, Vonder Meulen, Mary Beth, Schroeder, Emily, Steiner, Stephanie, Baker, Chelsea, Underkofler, Chantal, Douglass, Sara, Sivitz, William, Cline, Erin, Knosp, Laura, McConnell, Jennifer, Lowe, Tamara, Herman, William H., Pop-Busui, Rodica, Tan, Meng H., Martin, Catherine, Waltje, Andrea, Goodhall, Lynn, Eggleston, Rebecca, Kuo, Shihchen, Bule, Stephanie, Kessler, Nancy, LaSalle, Elizabeth, Seaquist, Elizabeth R., Bantle, Anne, Kumar, Anjali, Redmon, Bruce, Bantle, John, Harindhanavudhi, Tasma, Coe, Mary, Mech, Michael, Taddese, Abdisa, Lesne, Lesia, Smith, Shannon, Kuechenmeister, Lisa, Shivaswamy, Vijay, Morales, Ana Laura, Rodriguez, Maria Grace, Seipel, Kris, Alfred, Alissa, Eggert, Jenna, Lord, Grace, Taylor, William, Tillson, Renee, Schade, David S., Adolphe, Allen, Burge, Mark, Duran-Valdez, Elizabeth, Martinez, Janae, Hernandez McGinnis, Doris, Pucchetti, Benjamin, Scripsick, Elizabeth, DeFronzo, Ralph A., Cersosimo, Eugenio, Abdul-Ghani, Muhammad, Triplitt, Curtis, Verastiqui, Hector, Garza, Rosa Irene, Wright, Kathryn, Puckett, Curtiss, Raskin, Philip, Rhee, Chanhaeng, Abraham, Soma, Jordan, Lin Fan, Sao, Serey, Morton, Luisa, Smith, Oralenda, Osornio Walker, Laura, Schnurr-Breen, Laura, Ayala, Rosa, Kraymer, Robert, Sturgess, Daytheon, Utzschneider, Kristina M., Alarcon-Casas Wright, Lorena, Boyko, Edward, Tsai, Elaine C., Trence, Dace L., Fattaleh, Basma N., Montgomery, Brenda K., Atkinson, Karen M., Concepcion, Tessa, Kozedub, Alexandra, Moak, Cameron, Rhothisen, Samantha, Elasy, Tom A., Martin, Stephanie, Shackelford, Laura, Goidel, Rita, Hinkle, Nina, Lipps Hogan, Janie, Lovell, Cynthia, Myers, Janet, McGill, Janet B., Salam, Maamoun, Kissel, Sarah, Schweiger, Toni, Recklein, Carol, Tamborlane, William, Gatcomb, Patricia, Camp, Anne, Gulanski, Barbara, Inzucchi, Silvio, Pham, Kim, Alguard, Michele, Lessard, Katarzyna, Perez, Magalys, Magenheimer, Elizabeth, Montoza, Abmaridel, Nathan, David M., Lachin, John, Krause-Steinrauf, Heidi, Burch, Henry, Linder, Barbara, Bremer, Andrew, Backman, Michael, Bebu, Ionut, Buys, C.J., Fagan Murphy, Anna, Gao, Yuping, Gramzinski, Michaela, Hall, Stephanie, Legowski, Elizabeth, Arey, Alyssa, Bethepu, Joel, Lund, Claire, Mangat Dhaliwal, Pam, McGee, Paula, Mesimer, Emily, Ngo, Lisa, Steffes, Michael, Seegmiller, Jesse, Saenger, Amy, Arends, Valerie, Gabrielson, Deanna, Conner, Todd, Stuart, Warren, Day, Jolene, Scrymgeour, Alexandra, Soliman, Elsayed Z., Zhang, Zhu-Ming, Campbell, Charles, Hu, Julie, Keasler, Lisa, Hensley, Susan, Li, Yabing, Herman, William, Mihalcea, Rada, Perez-Rosas, Veronica, Prosser, Lisa, Resnicow, Kenneth, Ye, Wen, Shao, Hui, Zhang, Ping, Luchsinger, Jose, Sanchez, Danurys, Burch, Henry B., Fradkin, Judith, Groessl, Erik, Chong, Helen, Hillery, Naomi, Abdouch, Ivan, Brantley, Paula, Broyles, Frances E., Canaris, Gay, Copeland, Paul, Craine, Jeri J., Fein, Warren L., Lee, Melissa S., Meiners, Rebecca, Meiners, Vaughn, O’Neal, Hollis, Park, James E., Sledge, Edward, Steppel-Resnick, Jeanne, Turchin, Alexander, Higgins, John, Fischer, Lawrence, Golden, Sherita, Gonzalez, Jeffrey, Naik, Aanand, Walker, Elizabeth, Doner Lotenberg, Lynne, Gallivan, Joanne M., Lim, Joanne, Tuncer, Diane M., and Behringer-Massera, Stephanie

Subjects
endocrine system diseases, Diabetes Mellitus, Type 2, Endocrinology, Diabetes and Metabolism, Smoke, T-Lymphocytes, Internal Medicine, Humans, Pathophysiology, Fires
Abstract

Islet autoimmunity may contribute to β-cell dysfunction in type 2 diabetes (T2D). Its prevalence and clinical significance have not been rigorously determined. In this ancillary study to the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE), we investigated the prevalence of cellular and humoral islet autoimmunity in patients with T2D duration of 4.0 ± 3.0 years (HbA1c 7.5 ± 0.5% on metformin alone). We measured T-cell autoreactivity against islet proteins, islet autoantibodies against 65-kDa GAD antigen, IA-2, and zinc transporter-8, and β-cell function. Cellular islet autoimmunity was present in 41.3%, humoral islet autoimmunity in 13.5%, and both in 5.3%. β-Cell function calculated as incremental area under the curve of glucose from 0–120 min (iAUC-CG) and ΔC-peptide(0–30)/Δglucose(0–30) from an oral glucose tolerance test was lower among T-cell–positive (T+) than T-cell–negative (T−) individuals using two different adjustments for insulin sensitivity (iAUC-CG: 13.2% [95% CI 0.3, 24.4] or 11.4% [95% CI 0.4, 21.2] lower; ΔC-peptide[0–30]/Δglucose[0–30]: 19% [95% CI 3.1, 32.3] or 17.7% [95% CI 2.6, 30.5%] lower). T+ patients had 17% higher HbA1c (95% CI 0.07, 0.28) and 7.7 mg/dL higher fasting plasma glucose levels (95% CI 0.2, 15.3) than T− patients. We conclude that islet autoimmunity is much more prevalent in patients with T2D than previously reported. T-cell–mediated autoimmunity is associated with diminished β-cell function and worse glycemic control.

Published
2021

39. Improved food Go/No-Go scores after transcranial direct current stimulation (tDCS) to prefrontal cortex in a randomized trial.

Author

Stinson, Emma J., Travis, Katherine T., Magerowski, Greta, Alonso‐Alonso, Miguel, Krakoff, Jonathan, Gluck, Marci E., and Alonso-Alonso, Miguel

Subjects
TRANSCRANIAL direct current stimulation, PREFRONTAL cortex, RESPONSE inhibition, SNACK foods, FOOD consumption
Abstract

Objective: Reduced dorsolateral prefrontal cortex (dlPFC) activity and inhibitory control may contribute to obesity. The study objective was to assess effects of repeated transcranial direct current stimulation (tDCS) on food Go/No-Go (GNG), food Stroop performance, and snack food intake.Methods: Twenty-nine individuals with obesity (12 male; mean [SD], age 42 [11] years; BMI 39 [8]) participated in a combined inpatient/outpatient randomized parallel-design trial and received 15 sessions of anodal or sham tDCS to the left dlPFC. Food-related inhibitory control (GNG), attentional bias (Stroop), and snack food intake were assessed at baseline, completion of inpatient sessions (day 7), and follow-up (day 31).Results: GNG performance improved in the anodal group by day 31, compared with sham (p = 0.01), but Stroop scores did not differ by intervention. Greater snack food intake was associated with lower GNG scores (p = 0.01), driven by the sham group (p < 0.001) and higher food and palatable bias scores on the Stroop (all p = 0.02) across both groups. Changes on tasks were not associated with changes in intake.Conclusions: Anodal tDCS to the left dlPFC improved performance on a food-related inhibitory control task, providing evidence of potential for therapeutic benefit of neuromodulation in areas controlling executive function. Results showed that tDCS to the dlPFC reduced snack food intake and hunger; however, underlying neurocognitive mechanisms remain uncertain. [ABSTRACT FROM AUTHOR]

Published
2022
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48. The carbon isotope ratios of nonessential amino acids identify sugar-sweetened beverage (SSB) consumers in a 12-wk inpatient feeding study of 32 men with varying SSB and meat exposures

Author

Johnson, Jessica J, primary, Shaw, Pamela A, additional, Oh, Eric J, additional, Wooller, Matthew J, additional, Merriman, Sean, additional, Yun, Hee Young, additional, Larsen, Thomas, additional, Krakoff, Jonathan, additional, Votruba, Susanne B, additional, and O’Brien, Diane M, additional

Published
2021
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