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  1. 1
    دورية أكاديمية

    المؤلفون: C Wright, C Sanders, C Wilson, L Tucker, S Jones, S Douglass, C Patel, A Kumar, S Smith, A Ghosh, C Adams, R Hill, D Martin, J Hu, M Lee, N Patel, O Smith, J Cook, J Day, M Jackson, G Riera, P McGee, J Park, J Jiménez, S Yang, A Carlson, C Martin, H Liu, Y Li, A Krol, K Wright, S Golden, A Sood, J Martinez, D Sanchez, K Burton, Y Gao, S Martin, O Sanchez, C DeSouza, M Johnson, L Estrada, A Jackson, J Higgins, K Martin, J Craig, A Kuhn, L Ngo, Deborah J Wexler, R Chatterjee, E Walker, J Kerr, W Taylor, J Lim, M Perez, R Henry, Vanita R Aroda, R Fraser, Cyrus Desouza, E King, C Campbell, J González, E Diaz, P Zhang, J Marks, S Abraham, A Ross, M Khalid, T Young, J Myers, J Barzilay, B Chambers, G Montes, C Jensen, J McConnell, R Nelson, L Prosser, S Morton, M Curtis, P Wilson, L Young, M Fürst, S Warren, C Newman, S Kuo, N Rasouli, A Werner, L Morton, A Ghazi, M Salam, F Ismail-Beigi, P Kringas, C Baker, E Ellis, A Cherian, L Holloway, M Madden, B Hollis, G Fuller, B Steiner, K Stokes, R Ayala, T Lowe, K Chu, S Durán, D Dyer, A Alfred, J Leger, Nicole M Butera, T Hamilton, J Costello, E Burgess, R Garg, A Maxwell, C Stevens, W Ye, T Tran, L Fischer, M Hurtado, H Schneier, C Lund, R Lorch, M Mullen, J Bantle, K Arnold, D Wexler, A TURCHIN, MS Lee, D Howard, J Tejada, S Hernandez, Tasma Harindhanavudhi, E Schroeder, K Pham, S Kunkel, A Fagan, G Lord, H CHONG, A Smiley, E Debnam, H Petrovitch, M Bäckman, B Kauffman, V Jenkins, B Cramer, JP Crandall, MD McKee, S Behringer-Massera, J Brown-Friday, E Xhori, K Ballentine-Cargill, H Estrella, S Gonzalez de la torre, J Lukin, LS Phillips, D Olson, M Rhee, TS Raines, J Boers, C Gullett, M Maher-Albertelli, R Mungara, L Savoye, CA White, F Morehead, S Person, M Sibymon, S Tanukonda, A Balasubramanyam, R Gaba, P Hollander, E Roe, P Burt, K Chionh, C Falck-Ytter, L Sayyed Kassem, M Tiktin, T Kulow, KA Stancil, J Iacoboni, MV Kononets, L Colosimo, R Goland, J Pring, L Alfano, C Hausheer, K Gumpel, A Kirpitch, JB Green, H AbouAssi, MN Feinglos, J English Jones, RP Zimmer, BM Satterwhite, K Evans Kreider, CR Thacker, CN Mariash, KJ Mather, A Lteif, V Pirics, D Aguillar, S Hurt, R Bergenstal, T Martens, J Hyatt, H Willis, W Konerza, K Kleeberger, R Passi, S Fortmann, M Herson, K Mularski, H Glauber, J Prihoda, B Ash, C Carlson, PA Ramey, E Schield, B Torgrimson-Ojerio, E Panos, S Sahnow, K Bays, K Berame, D Ghioni, J Gluth, K Schell, J Criscola, C Friason, S Nazarov, N Rassouli, R Puttnam, B Ojoawo, C Sanders-Jones, Z El-Haqq, A Kolli, J Meigs, A Dushkin, G Rocchio, M Yepes, H Dulin, M Cayford, A DeManbey, M Hillard, N Thangthaeng, L Gurry, R Kochis, E Raymond, V Ripley, V Aroda, A Loveland, M Hamm, HJ Florez, WM Valencia, S Casula, L Oropesa-Gonzalez, L Hue, AK Riccio Veliz, R Nieto-Martinez, M Gutt, A Ahmann, D Aby-Daniel, F Joarder, V Morimoto, C Sprague, D Yamashita, N Cady, N Rivera-Eschright, P Kirchhoff, B Morales Gomez, J Adducci, A Goncharova, SH Hox, M Matwichyna, NO Bermudez, L Broadwater, RR Ishii, DS Hsia, WT Cefalu, FL Greenway, C Waguespack, N Haynes, A Thomassie, B Bourgeois, C Hazlett, S Mudaliar, S Boeder, J Pettus, D Garcia-Acosta, S Maggs, C DeLue, E Castro, J Krakoff, JM Curtis, T Killean, E Joshevama, K Tsingine, T Karshner, J Albu, FX Pi-Sunyer, S Frances, C Maggio, J Bastawrose, X Gong, MA Banerji, D Lorber, NM Brown, DH Josephson, LL Thomas, M Tsovian, MH Jacobson, MM Mishko, MS Kirkman, JB Buse, J Dostou, K Bergamo, A Goley, JF Largay, S Guarda, J Cuffee, D Culmer, H Almeida, S Coffer, L Kiker, K Josey, WT Garvey, A Agne, S McCullars, RM Cohen, MC Rogge, K Kersey, S Lipp, MB Vonder Meulen, C Underkofler, S Steiner, E Cline, WH Herman, R Pop-Busui, MH Tan, A Waltje, A Katona, L Goodhall, R Eggleston, K Whitley, S Bule, N Kessler, E LaSalle, ER Seaquist, A Bantle, T Harindhanavudhi, B Redmon, M Coe, M Mech, A Taddese, L Lesne, L Kuechenmeister, V Shivaswamy, AL Morales, K Seipel, J Eggert, R Tillson, DS Schade, A Adolphe, M Burge, E Duran-Valdez, P August, MG Rodriguez, O Griffith, A Naik, Barbara I Gulanski, Heidi Krause-Steinrauf, Judith H Lichtman, Jennifer B Green, Colleen E Suratt, Hiba AbouAssi, Andrew J Ahmann, E Gonzalez Hattery, A Ideozu, G McPhee, SA Khan, JB Kimpel, HM Ismail, ME Larkin, M Magee, A Ressing, L Manandhar, F Mwicigi, V Lagari-Libhaber, A Cuadot, YJ Kendal, B Veciana, G Fry, A Dragg, B Gildersleeve, J Arceneaux, M Pavlionis, A Stallings, S Machineni, AL Cherrington, MCR Lawson, C Adkins, T Onadeko, M Razzaghi, C Lyon, R Penaloza, WI Sivitz, LK Knosp, S Bojescu, S Burbach, A Bancroft, FA Jamaleddin Ahmad, D Hernandez McGinnis, B Pucchetti, E Scripsick, A Zamorano, RA DeFronzo, E Cersosimo, M Abdul-Ghani, C Triplitt, D Juarez, RI Garza, H Verastiqui, C Puckett, P Raskin, C Rhee, LF Jordan, S Sao, L Osornio Walker, L Schnurr-Breen, RB Kreymer, D Sturgess, KM Utzschneider, SE Kahn, L Alarcon-Casas Wright, EJ Boyko, EC Tsai, DL Trence, S Trikudanathan, BN Fattaleh, BK Montgomery, KM Atkinson, A Kozedub, T Concepcion, C Moak, N Prikhodko, S Rhothisen, TA Elasy, L Shackelford, R Goidel, N Hinkle, C Lovell, J Lipps Hogan, JB McGill, T Schweiger, S Kissel, C Recklein, MJ Clifton, W Tamborlane, A Camp, B Gulanski, SE Inzucchi, M Alguard, P Gatcomb, K Lessard, L Iannone, A Montosa, E Magenheimer, J Fradkin, HB Burch, AA Bremer, DM Nathan, JM Lachin, H Krause-Steinrauf, N Younes, I Bebu, N Butera, CJ Buys, MR Gramzinski, SD Hall, E Kazemi, E Legowski, C Suratt, M Tripputi, A Arey, J Bethepu, P Mangat Dhaliwal, E Mesimer, M Steffes, J Seegmiller, A Saenger, V Arends, D Gabrielson, T Conner, J Huminik, A Scrymgeour, EZ Soliman, Y Pokharel, ZM Zhang, L Keasler, S Hensley, R Mihalcea, DJ Min, V Perez-Rosas, K Resnicow, H Shao, J Luchsinger, S Assuras, E Groessl, F Sakha, N Hillery, BM Everett, I Abdouch, G Bahtiyar, P Brantley, FE Broyles, G Canaris, P Copeland, JJ Craine, WL Fein, A Gliwa, L Hope, R Meiners, V Meiners, H O’Neal, JE Park, A Sacerdote, E Sledge, L Soni, J Steppel-Reznik, B Brooks-Worrell, CS Hampe, JP Palmer, A Shojaie, L Doner Lotenberg, JM Gallivan, DM Tuncer

    المصدر: BMJ Open Diabetes Research & Care, Vol 11, Iss 2 (2023)

    الوصف: Introduction Type 2 diabetes mellitus (T2DM) is a powerful risk factor for cardiovascular disease (CVD), conferring a greater relative risk in women than men. We sought to examine sex differences in cardiometabolic risk factors and management in the contemporary cohort represented by the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).Research design and methods GRADE enrolled 5047 participants (1837 women, 3210 men) with T2DM on metformin monotherapy at baseline. The current report is a cross-sectional analysis of baseline data collected July 2013 to August 2017.Results Compared with men, women had a higher mean body mass index (BMI), greater prevalence of severe obesity (BMI≥40 kg/m2), higher mean LDL cholesterol, greater prevalence of low HDL cholesterol, and were less likely to receive statin treatment and achieve target LDL, with a generally greater prevalence of these risk factors in younger women. Women with hypertension were equally likely to achieve blood pressure targets as men; however, women were less likely to receive ACE inhibitors or angiotensin receptor blockers. Women were more likely to be divorced, separated or widowed, and had fewer years of education and lower incomes.Conclusions This contemporary cohort demonstrates that women with T2DM continue to have a greater burden of cardiometabolic and socioeconomic risk factors than men, particularly younger women. Attention to these persisting disparities is needed to reduce the burden of CVD in women.Trial registration number ClinicalTrials.gov (NCT01794143)

    وصف الملف: electronic resource

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    دورية أكاديمية

    المؤلفون: C Wright, C Sanders, C Wilson, L Tucker, S Jones, S Douglass, C Patel, A Kumar, S Smith, C Adams, R Hill, D Martin, M Lee, J Cook, M Jackson, G Riera, E González, J Park, S Yang, A Carlson, C Martin, A Krol, A Sood, J Martinez, C DeSouza, M Johnson, L Estrada, A Jackson, K Martin, SA Khan, J Craig, A Kuhn, Deborah J Wexler, R Chatterjee, J Kerr, W Taylor, R Henry, R Fraser, Kieren J Mather, M Larkin, E King, E Diaz, J Marks, A Ross, M Khalid, J Barzilay, B Chambers, G Montes, C Jensen, J McConnell, R Nelson, S Morton, M Curtis, P Wilson, L Young, M Fürst, C Newman, S Kuo, N Rasouli, A Werner, A Ghazi, F Ismail-Beigi, P Kringas, C Baker, E Ellis, Philip Raskin, A Cherian, L Holloway, M Madden, B Hollis, G Fuller, B Steiner, K Stokes, T Lowe, K Chu, S Durán, A Alfred, John M Lachin, T Hamilton, J Costello, E Burgess, R Garg, C Stevens, T Tran, M Hurtado, H Schneier, R Lorch, M Mullen, J Bantle, K Arnold, D Wexler, Neda Rasouli, D Howard, J Tejada, S Hernandez, E Schroeder, S Kunkel, G Lord, A Smiley, E Debnam, H Petrovitch, B Kauffman, V Jenkins, B Cramer, Kristina M Utzschneider, Naji Younes, Joshua I Barzilay, Mary Ann Banerji, Robert M Cohen, Erica V Gonzalez, Faramarz Ismail-Beigi, Steven E Kahn, JP Crandall, MD McKee, S Behringer-Massera, J Brown-Friday, E Xhori, K Ballentine-Cargill, H Estrella, S Gonzalez de la torre, J Lukin, LS Phillips, D Olson, M Rhee, TS Raines, J Boers, C Gullett, M Maher-Albertelli, R Mungara, L Savoye, CA White, F Morehead, S Person, M Sibymon, S Tanukonda, A Balasubramanyam, R Gaba, P Hollander, E Roe, P Burt, K Chionh, C Falck-Ytter, L Sayyed Kassem, M Tiktin, T Kulow, KA Stancil, J Iacoboni, MV Kononets, G McPhee AMaxwell, L Colosimo, R Goland, J Pring, L Alfano, C Hausheer, K Gumpel, A Kirpitch, JB Green, H AbouAssi, MN Feinglos, J English Jones, RP Zimmer, BM Satterwhite, K Evans Kreider, CR Thacker, CN Mariash, KJ Mather, A Lteif, V Pirics, D Aguillar, S Hurt, R Bergenstal, T Martens, J Hyatt, H Willis, W Konerza, K Kleeberger, R Passi, S Fortmann, M Herson, K Mularski, H Glauber, J Prihoda, B Ash, C Carlson, PA Ramey, E Schield, B Torgrimson-Ojerio, E Panos, S Sahnow, K Bays, K Berame, D Ghioni, J Gluth, K Schell, J Criscola, C Friason, S Nazarov, N Rassouli, R Puttnam, B Ojoawo, C Sanders-Jones, Z El-Haqq, A Kolli, J Meigs, A Dushkin, G Rocchio, M Yepes, H Dulin, M Cayford, A DeManbey, M Hillard, N Thangthaeng, L Gurry, R Kochis, E Raymond, V Ripley, V Aroda, Ann Ressing, A Loveland, M Hamm, F Mofor, HJ Florez, WM Valencia, S Casula, L Oropesa-Gonzalez, L Hue, AK Riccio Veliz, R Nieto-Martinez, M Gutt, A Ahmann, D Aby-Daniel, F Joarder, V Morimoto, C Sprague, D Yamashita, N Cady, N Rivera-Eschright, P Kirchhoff, B Morales Gomez, J Adducci, A Goncharova, SH Hox, M Matwichyna, NO Bermudez, L Broadwater, RR Ishii, DS Hsia, WT Cefalu, FL Greenway, C Waguespack, N Haynes, A Thomassie, B Bourgeois, C Hazlett, S Mudaliar, S Boeder, J Pettus, D Garcia-Acosta, S Maggs, C DeLue, E Castro, J Krakoff, JM Curtis, T Killean, E Joshevama, K Tsingine, T Karshner, J Albu, FX Pi-Sunyer, S Frances, C Maggio, J Bastawrose, X Gong, MA Banerji, D Lorber, NM Brown, DH Josephson, LL Thomas, M Tsovian, MH Jacobson, MM Mishko, MS Kirkman, JB Buse, J Dostou, K Bergamo, A Goley, JF Largay, S Guarda, J Cuffee, D Culmer, H Almeida, S Coffer, L Kiker, K Josey, WT Garvey, A Cherrington, D Golson, MC Robertson, A Agne, S McCullars, RM Cohen, MC Rogge, K Kersey, S Lipp, MB Vonder Meulen, C Underkofler, S Steiner, W Sivitz, E Cline, L Knosp, WH Herman, R Pop-Busui, MH Tan, A Waltje, A Katona, L Goodhall, R Eggleston, K Whitley, S Bule, N Kessler, E LaSalle, ER Seaquist, A Bantle, T Harindhanavudhi, B Redmon, M Coe, M Mech, A Taddese, L Lesne, L Kuechenmeister, V Shivaswamy, AL Morales, K Seipel, J Eggert, R Tillson, DS Schade, A Adolphe, M Burge, E Duran-Valdez, P August, MG Rodriguez, JB Kimpel, O Griffith

    المصدر: BMJ Open Diabetes Research & Care, Vol 9, Iss 1 (2021)

    وصف الملف: electronic resource

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    الوصف: BACKGROUND Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. METHODS In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 μg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days. RESULTS A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P=0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P=0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups. CONCLUSIONS In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. Copyright © 2019 Massachusetts Medical Society.

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    المؤلفون: Petter Bjornstad, Edward Nehus, Laure El ghormli, Fida Bacha, Ingrid M. Libman, Siripoom McKay, Steven M. Willi, Lori Laffel, Silva Arslanian, Kristen J. Nadeau, S. McKay, M. Haymond, B. Anderson, C. Bush, S. Gunn, H. Holden, S.M. Jones, G. Jeha, S. McGirk, S. Thamotharan, L. Cuttler, E. Abrams, T. Casey, W. Dahms, C. Ievers-Landis, B. Kaminski, M. Koontz, S. MacLeish, P. McGuigan, S. Narasimhan, M. Geffner, V. Barraza, N. Chang, B. Conrad, D. Dreimane, S. Estrada, L. Fisher, E. Fleury-Milfort, S. Hernandez, B. Hollen, F. Kaufman, E. Law, V. Mansilla, D. Miller, C. Muñoz, R. Ortiz, A. Ward, K. Wexler, Y.K. Xu, P. Yasuda, L. Levitt Katz, R. Berkowitz, S. Boyd, B. Johnson, J. Kaplan, C. Keating, C. Lassiter, T. Lipman, G. McGinley, H. McKnight, B. Schwartzman, S. Willi, S. Arslanian, F. Bacha, S. Foster, B. Galvin, T. Hannon, A. Kriska, I. Libman, M. Marcus, K. Porter, T. Songer, E. Venditti, R. Goland, D. Gallagher, P. Kringas, N. Leibel, D. Ng, M. Ovalles, D. Seidman, L. Laffel, A. Goebel-Fabbri, M. Hall, L. Higgins, J. Keady, M. Malloy, K. Milaszewski, L. Rasbach, D.M. Nathan, A. Angelescu, L. Bissett, C. Ciccarelli, L. Delahanty, V. Goldman, O. Hardy, M. Larkin, L. Levitsky, R. McEachern, D. Norman, D. Nwosu, S. Park-Bennett, D. Richards, N. Sherry, B. Steiner, S. Tollefsen, S. Carnes, D. Dempsher, D. Flomo, T. Whelan, B. Wolff, R. Weinstock, D. Bowerman, S. Bristol, J. Bulger, J. Hartsig, R. Izquierdo, J. Kearns, R. Saletsky, P. Trief, P. Zeitler, N. Abramson, A. Bradhurst, N. Celona-Jacobs, J. Higgins, M. Kelsey, G. Klingensmith, K. Nadeau, T. Witten, K. Copeland, E. Boss, R. Brown, J. Chadwick, L. Chalmers, S. Chernausek, A. Hebensperger, C. Macha, R. Newgent, A. Nordyke, D. Olson, T. Poulsen, L. Pratt, J. Preske, J. Schanuel, S. Sternlof, J. Lynch, N. Amodei, R. Barajas, C. Cody, D. Hale, J. Hernandez, C. Ibarra, E. Morales, S. Rivera, G. Rupert, A. Wauters, N. White, A. Arbeláez, J. Jones, T. Jones, M. Sadler, M. Tanner, A. Timpson, R. Welch, S. Caprio, M. Grey, C. Guandalini, S. Lavietes, P. Rose, A. Syme, W. Tamborlane, K. Hirst, S. Edelstein, P. Feit, N. Grover, C. Long, L. Pyle, B. Linder, S.M. Marcovina, J. Harting, J. Shepherd, B. Fan, L. Marquez, M. Sherman, J. Wang, M. Nichols, E. Mayer-Davis, Y. Liu, J. Lima, S. Gidding, J. Puccella, E. Ricketts, R. Danis, A. Domalpally, A. Goulding, S. Neill, P. Vargo, D. Wilfley, D. Aldrich-Rasche, K. Franklin, C. Massmann, D. O’Brien, J. Patterson, T. Tibbs, D. Van Buren, M. Palmert, R. Ratner, D. Dremaine, J. Silverstein

    الوصف: Background Diabetic kidney disease is a major cause of premature mortality in type 2 diabetes mellitus (T2DM). Worsening insulin sensitivity independent of glycemic control may contribute to the development of diabetic kidney disease. We investigated the longitudinal association of insulin sensitivity with hyperfiltration and increased albumin excretion in adolescents with T2DM. Study Design Observational prospective cohort study. Setting & Participants 532 TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) participants aged 12 to 17 years with T2DM duration less than 2 years at baseline. The TODAY Study was a multicenter randomized clinical trial that examined the efficacy of 3 treatment regimens (metformin monotherapy, metformin plus rosiglitazone, or metformin plus an intensive lifestyle intervention program) to achieve durable glycemic control. Predictors Natural log–transformed estimated insulin sensitivity (reciprocal of fasting insulin), hemoglobin A1c concentration, age, race-ethnicity, treatment group, body mass index, loss of glycemic control, and hypertension. Outcomes Hyperfiltration was defined as 99th percentile or higher of estimated glomerular filtration rate (≥140mL/min/1.73m2) when referenced to healthy adolescents (NHANES 1999-2002) and albumin-creatinine ratio ≥ 30μg/mg at 3 consecutive annual visits. Results Hyperfiltration was observed in 7.0% of participants at baseline and in 13.3% by 5 years, with a cumulative incidence of 5.0% over 5 years. The prevalence of increased albumin excretion was 6% at baseline and 18% by 5 years, with a cumulative incidence of 13.4%. There was an 8% increase in risk for hyperfiltration per 10% lower estimated insulin sensitivity in unadjusted and adjusted models (P=0.01). Increased albumin excretion was associated with hemoglobin A1c concentration, but not estimated insulin sensitivity. Limitations Longer follow-up is needed to capture the transition from hyperfiltration to rapid glomerular filtration rate decline in youth-onset T2DM. Conclusions Lower estimated insulin sensitivity was associated with risk for hyperfiltration over time, whereas increased albumin excretion was associated with hyperglycemia in youth-onset T2DM.

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    المؤلفون: Samuel S. Gidding, Fida Bacha, Petter Bjornstad, Lorraine E. Levitt Katz, Lynne L. Levitsky, Jane Lynch, Jeanie B. Tryggestad, Ruth S. Weinstock, Laure El ghormli, Joao A.C. Lima, S. McKay, M. Haymond, B. Anderson, C. Bush, S. Gunn, H. Holden, S.M. Jones, G. Jeha, S. McGirk, S. Thamotharan, L. Cuttler, E. Abrams, T. Casey, W. Dahms, C. Ievers-Landis, B. Kaminski, M. Koontz, S. MacLeish, P. McGuigan, S. Narasimhan, M. Geffner, V. Barraza, N. Chang, B. Conrad, D. Dreimane, S. Estrada, L. Fisher, E. Fleury-Milfort, S. Hernandez, B. Hollen, F. Kaufman, E. Law, V. Mansilla, D. Miller, C. Muñoz, R. Ortiz, A. Ward, K. Wexler, Y.K. Xu, P. Yasuda, L. Levitt Katz, R. Berkowitz, S. Boyd, B. Johnson, J. Kaplan, C. Keating, C. Lassiter, T. Lipman, G. McGinley, H. McKnight, B. Schwartzman, S. Willi, S. Arslanian, F. Bacha, S. Foster, B. Galvin, T. Hannon, A. Kriska, I. Libman, M. Marcus, K. Porter, T. Songer, E. Venditti, R. Goland, D. Gallagher, P. Kringas, N. Leibel, D. Ng, M. Ovalles, D. Seidman, L. Laffel, A. Goebel-Fabbri, M. Hall, L. Higgins, J. Keady, M. Malloy, K. Milaszewski, L. Rasbach, D.M. Nathan, A. Angelescu, L. Bissett, C. Ciccarelli, L. Delahanty, V. Goldman, O. Hardy, M. Larkin, L. Levitsky, R. McEachern, D. Norman, D. Nwosu, S. Park-Bennett, D. Richards, N. Sherry, B. Steiner, S. Tollefsen, S. Carnes, D. Dempsher, D. Flomo, T. Whelan, B. Wolff, R. Weinstock, D. Bowerman, S. Bristol, J. Bulger, J. Hartsig, R. Izquierdo, J. Kearns, R. Saletsky, P. Trief, P. Zeitler, N. Abramson, A. Bradhurst, N. Celona-Jacobs, J. Higgins, M. Kelsey, G. Klingensmith, K. Nadeau, T. Witten, K. Copeland, E. Boss, R. Brown, J. Chadwick, L. Chalmers, S. Chernausek, A. Hebensperger, C. Macha, R. Newgent, A. Nordyke, D. Olson, T. Poulsen, L. Pratt, J. Preske, J. Schanuel, S. Sternlof, J. Lynch, N. Amodei, R. Barajas, C. Cody, D. Hale, J. Hernandez, C. Ibarra, E. Morales, S. Rivera, G. Rupert, A. Wauters, N. White, A. Arbeláez, J. Jones, T. Jones, M. Sadler, M. Tanner, A. Timpson, R. Welch, S. Caprio, M. Grey, C. Guandalini, S. Lavietes, P. Rose, A. Syme, W. Tamborlane, K. Hirst, S. Edelstein, P. Feit, N. Grover, C. Long, L. Pyle, B. Linder, S.M. Marcovina, J. Harting, J. Shepherd, B. Fan, L. Marquez, M. Sherman, J. Wang, M. Nichols, E. Mayer-Davis, Y. Liu, J. Lima, S. Gidding, J. Puccella, E. Ricketts, R. Danis, A. Domalpally, A. Goulding, S. Neill, P. Vargo, D. Wilfley, D. Aldrich-Rasche, K. Franklin, C. Massmann, D. O'Brien, J. Patterson, T. Tibbs, D. Van Buren, M. Palmert, R. Ratner, D. Dremaine, J. Silverstein

    المصدر: The Journal of pediatrics. 192

    الوصف: Objectives To examine cardiac biomarkers over time in youth-onset type 2 diabetes, and relate serum concentrations to cardiovascular disease risk factors, and left ventricular structure and function. Study design TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) was a multicenter randomized trial of 3 treatments including 521 participants with type 2 diabetes, aged 10-17 years, and with 2-6 years of follow-up. Participants were 36% male, obese, and ethnically diverse. Annual serum concentrations of brain natriuretic peptide, troponin, tumor necrosis factor (TNF)-α, receptors 1 and 2 were related to blood pressure, body mass index, hemoglobin A1c, and left ventricular ejection fraction, diastolic function, relative wall thickness, and mass. Results Elevated concentrations of brain natriuretic peptide (≥100 pg/mL), TNF-α (≥5.6 pg/mL) and troponin (≥0.01 ng/mL), were present in 17.8%, 18.3%, and 34.2% of the cohort, respectively, at baseline, and in 15.4%, 17.1%, and 31.1% at the end of the study, with wide variability over time, without persistence in individuals or clear relationship to glycemia or cardiovascular structure/function. TNF receptors concentrations were increased at baseline and not significantly different from end-of-study concentrations. Adverse echocardiographic measures were more likely in the highest TNF receptor tertile (all P Conclusions Elevated serum concentrations of cardiac biomarkers were common in youth with type 2 diabetes, but their clinical significance is unclear and will require further long-term study. Trial registration ClinicalTrials.gov NCT00081328 .

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    المؤلفون: Lorraine E. Levitt Katz, Fida Bacha, Samuel S. Gidding, Ruth S. Weinstock, Laure El ghormli, Ingrid Libman, Kristen J. Nadeau, Kristin Porter, Santica Marcovina, S. McKay, M. Haymond, B. Anderson, C. Bush, S. Gunn, H. Holden, S.M. Jones, G. Jeha, S. McGirk, S. Thamotharan, L. Cuttler, E. Abrams, T. Casey, W. Dahms, C. Ievers-Landis, B. Kaminski, M. Koontz, S. MacLeish, P. McGuigan, S. Narasimhan, M. Geffner, V. Barraza, N. Chang, B. Conrad, D. Dreimane, S. Estrada, L. Fisher, E. Fleury-Milfort, S. Hernandez, B. Hollen, F. Kaufman, E. Law, V. Mansilla, D. Miller, C. Muñoz, R. Ortiz, A. Ward, K. Wexler, Y.K. Xu, P. Yasuda, R. Berkowitz, S. Boyd, B. Johnson, J. Kaplan, C. Keating, C. Lassiter, T. Lipman, G. McGinley, H. McKnight, B. Schwartzman, S. Willi, S. Arslanian, S. Foster, B. Galvin, T. Hannon, A. Kriska, M. Marcus, T. Songer, E. Venditti, R. Goland, D. Gallagher, P. Kringas, N. Leibel, D. Ng, M. Ovalles, D. Seidman, L. Laffel, A. Goebel-Fabbri, M. Hall, L. Higgins, J. Keady, M. Malloy, K. Milaszewski, L. Rasbach, D.M. Nathan, A. Angelescu, L. Bissett, C. Ciccarelli, L. Delahanty, V. Goldman, O. Hardy, M. Larkin, L. Levitsky, R. McEachern, D. Norman, D. Nwosu, S. Park-Bennett, D. Richards, N. Sherry, B. Steiner, S. Tollefsen, S. Carnes, D. Dempsher, D. Flomo, T. Whelan, B. Wolff, D. Bowerman, S. Bristol, J. Bulger, J. Hartsig, R. Izquierdo, J. Kearns, R. Saletsky, P. Trief, P. Zeitler, N. Abramson, A. Bradhurst, N. Celona-Jacobs, J. Higgins, M. Kelsey, G. Klingensmith, T. Witten, K. Copeland, E. Boss, R. Brown, J. Chadwick, L. Chalmers, S. Chernausek, A. Hebensperger, C. Macha, R. Newgent, A. Nordyke, D. Olson, T. Poulsen, L. Pratt, J. Preske, J. Schanuel, S. Sternlof, J. Lynch, N. Amodei, R. Barajas, C. Cody, D. Hale, J. Hernandez, C. Ibarra, E. Morales, S. Rivera, G. Rupert, A. Wauters, N. White, A. Arbeláez, J. Jones, T. Jones, M. Sadler, M. Tanner, A. Timpson, R. Welch, S. Caprio, M. Grey, C. Guandalini, S. Lavietes, P. Rose, A. Syme, W. Tamborlane, K. Hirst, S. Edelstein, P. Feit, N. Grover, C. Long, L. Pyle, B. Linder, J. Harting, J. Shepherd, B. Fan, L. Marquez, M. Sherman, J. Wang, M. Nichols, E. Mayer-Davis, Y. Liu, J. Lima, J. Puccella, E. Ricketts, R. Danis, A. Domalpally, A. Goulding, S. Neill, P. Vargo, D. Wilfley, D. Aldrich-Rasche, K. Franklin, C. Massmann, D. O'Brien, J. Patterson, T. Tibbs, D. Van Buren, M. Palmert, R. Ratner, D. Dremaine, J. Silverstein

    المصدر: The Journal of Pediatrics. 196:208-216.e2

    الوصف: Objectives Data regarding atherogenic dyslipidemia and the inflammation profile in youth with type 2 diabetes is limited and the effect of insulin therapy on these variables has not previously been studied in youth. We determined the impact of insulin therapy on lipid and inflammatory markers in youth with poorly controlled type 2 diabetes. Study design In the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) multicenter trial, 285 participants failed to sustain glycemic control on randomized treatment (primary outcome, glycated hemoglobin A1c [HbA1c] at ≥8% for 6 months); 363 maintained glycemic control (never reached primary outcome). Statins were used for a low-density lipoprotein cholesterol of ≥130 mg/dL. Upon reaching the primary outcome, insulin was started. Changes in lipids and inflammatory markers (slopes over time) were examined. Results Progression of dyslipidemia was related to glycemic control. In those with the primary outcome, insulin therapy impacted HbA1c modestly, and dampened the increase in total cholesterol, low-density lipoprotein cholesterol, and total apolipoprotein B, although statin use increased from 8.6% to 22% year after the primary outcome. The increase in triglycerides and plasma nonesterified fatty acids stabilized after insulin was started, independent of HbA1c. There was an increase in high-sensitivity C-reactive protein that continued after insulin initiation, related to HbA1c and percent overweight. Conclusions Worsening dyslipidemia and inflammation over time raise concern regarding premature development of atherosclerosis in youth with type 2 diabetes. Insulin therapy has a limited benefit in the absence of glycemic control. Strategies to achieve better glycemic control are needed. Trial registration ClinicalTrials.gov : NCT00081328 .

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    الوصف: Aims We aimed to determine the relation between baseline systolic blood pressure (SBP), change in SBP, and worsening renal function (WRF) in acute heart failure (AHF) patients enrolled in the Pre-RELAX-AHF trial. Methods and resultsThe Pre-RELAX-AHF study enrolled 234 patients within 16 h of admission (median 7 h) for AHF and randomized them to relaxin given intravenous (i.v.) for 48 h or placebo. Blood pressure was measured at baseline, at 3, 6, 9, 12, 24, 36, and 48 h and at 3, 4, and 5 days after enrolment. Worsening renal function was defined as a serum creatinine increase of

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    المصدر: The Journal of clinical endocrinology and metabolism. 81(7)

    الوصف: The actions of human corticotropin-releasing factor (hCRF) in brain, pituitary, and plasma are modulated by a 37-kDa protein [CRF-binding protein (CRF-BP)] that binds to hCRF and neutralizes the peptide's biological activity, suggesting that only the free unbound peptide is biologically active. To accurately predict the biological consequences resulting from changes in total hCRF levels, we have developed two-site enzyme-linked immunosorbent assays (ELISAs) for hCRF-BP, free hCRF, and the hCRF-BP/hCRF complex. The assays were validated by measuring each factor in 1) maternal plasma at times when CRF and hCRF-BP levels are altered, and 2) plasma from normal elderly human subjects who have undergone a hCRF stimulation test. The hCRF-BP ELISA has a sensitivity of 2.7 fmol and a range of detection from 2.7-8000 fmol. Both the hCRF and hCRF-BP/ hCRF assays have a sensitivity of 0.4 fmol, with a useful range of detection from 0.4-40 fmol. Maternal plasma hCRF-BP levels remained unaltered between the 16-21 and 34-39 month gestational age groups. However, levels rose from 0.88 +/- 0.069 nmol/L in the 16-21 month gestational age group to 1.01 +/- 0.09 nmol/L in the 28-33 month gestational age group. Bound hCRF levels dramatically rose from undetectable at 16-21 months of gestation to 200 +/- 69 and 442 +/- 106 pmol/L in the 28-33 and 34-39 month gestational age groups, respectively. In comparison, free hCRF levels remained low throughout gestation, but dramatically rose to 318 +/- 120 pmol/L from 34-39 months of gestation. Binding site occupancy on the hCRF-BP decreased when bound and free hCRF levels were elevated. After treating the third trimester plasma sample with the high affinity hCRF-BP ligand, alpha-helical CRF-(9-41), all of the bound hCRF was displaced from the binding protein, and free hCRF levels rose from 87 to 284 pmol/L. The plasma hCRF-BP level was 0.9 +/- 0.08 nmol/L in normal human volunteers (10 men and 9 women; mean +/- SD age, 74.2 +/- 7.7 yr), decreased to 60% of basal levels 15 min after a bolus injection of 1 microgram/kg synthetic hCRF, and gradually returned to preinjection levels after 120 min. Conversely, bound and free hCRF levels increased from undetectable levels before hCRF injection to 0.58 +/- 0.03 nmol/L at 15 min and then rapidly decreased to undetectable levels at 120 min. These data validate the ELISAs in combination with high affinity hCRF-BP ligands for measuring bound and free hCRF in human plasma and suggest the utility of these assays for further determining alterations in peripheral CRF in conditions such as pregnancy.

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