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1. Oxidative Stress and Cardiovascular Risk in Type 1 Diabetes Mellitus: Insights From the DCCT/EDIC Study

Author

W.H. Wilson Tang, Paula McGee, John M. Lachin, Daniel Y. Li, Byron Hoogwerf, Stanley L. Hazen, D.M. Nathan, B. Zinman, O. Crofford, S. Genuth, J. Brown‐Friday, J. Crandall, H. Engel, S. Engel, H. Martinez, M. Phillips, M. Reid, H. Shamoon, J. Sheindlin, R. Gubitosi‐Klug, L. Mayer, S. Pendegast, H. Zegarra, D. Miller, L. Singerman, S. Smith‐Brewer, M. Novak, J. Quin, Saul Genuth, M. Palmert, E. Brown, J. McConnell, P. Pugsley, P. Crawford, W. Dahms, N.S. Gregory, M.E. Lackaye, S. Kiss, R. Chan, A. Orlin, M. Rubin, D. Brillon, V. Reppucci, T. Lee, M. Heinemann, S. Chang, B. Levy, L. Jovanovic, M. Richardson, B. Bosco, A. Dwoskin, R. Hanna, S. Barron, R. Campbell, A. Bhan, D. Kruger, J.K. Jones, P.A. Edwards, J.D. Carey, E. Angus, A. Thomas, A. Galprin, M. McLellan, F. Whitehouse, R. Bergenstal, M. Johnson, K. Gunyou, L. Thomas, J. Laechelt, P. Hollander, M. Spencer, D. Kendall, R. Cuddihy, P. Callahan, S. List, J. Gott, N. Rude, B. Olson, M. Franz, G. Castle, R. Birk, J. Nelson, D. Freking, L. Gill, W. Mestrezat, D. Etzwiler, K. Morgan, L.P. Aiello, E. Golden, P. Arrigg, V. Asuquo, R. Beaser, L. Bestourous, J. Cavallerano, R. Cavicchi, O. Ganda, O. Hamdy, R. Kirby, T. Murtha, D Schlossman, S. Shah, G. Sharuk, P. Silva, P. Silver, M. Stockman, J. Sun, E. Weimann, H. Wolpert, L.M. Aiello, A. Jacobson, L. Rand, J. Rosenzwieg, M.E. Larkin, M. Christofi, K. Folino, J. Godine, P. Lou, C. Stevens, E. Anderson, H. Bode, S. Brink, C. Cornish, D. Cros, L. Delahanty, eManbey, C. Haggan, J. Lynch, C. McKitrick, D. Norman, D. Moore, M. Ong, C. Taylor, D. Zimbler, S. Crowell, S. Fritz, K. Hansen, C. Gauthier‐Kelly, F.J. Service, G. Ziegler, A. Barkmeier, L. Schmidt, B. French, R. Woodwick, R. Rizza, W.F. Schwenk, M. Haymond, J. Pach, J. Mortenson, B. Zimmerman, A. Lucas, R. Colligan, L. Luttrell, M. Lopes‐Virella, S. Caulder, C. Pittman, N. Patel, K. Lee, M. Nutaitis, J. Fernandes, K. Hermayer, S. Kwon, A Blevins, J. Parker, J. Colwell, D. Lee, J. Soule, P. Lindsey, M. Bracey, A. Farr, S. Elsing, T. Thompson, J. Selby, T. Lyons, S. Yacoub‐Wasef, M. Szpiech, D. Wood, R. Mayfield, M. Molitch, D. Adelman, S. Colson, L. Jampol, A. Lyon, M. Gill, Z. Strugula, L. Kaminski, R. Mirza, E. Simjanoski, D. Ryan, C. Johnson, A. Wallia, S. Ajroud‐Driss, P. Astelford, N. Leloudes, A. Degillio, B. Schaefer, S. Mudaliar, G Lorenzi, M. Goldbaum, K. Jones, M. Prince, M. Swenson, I. Grant, R. Reed, R. Lyon, O. Kolterman, M. Giotta, T. Clark, G. Friedenberg, W.I. Sivitz, B. Vittetoe, J. Kramer, M. Bayless, R. Zeitler, H. Schrott, N. Olson, L. Snetselaar, R. Hoffman, J. MacIndoe, T. Weingeist, C. Fountain, R. Miller, S. Johnsonbaugh, M. Patronas, M. Carney, S. Mendley, P. Salemi, R. Liss, M. Hebdon, D. Counts, T. Donner, J. Gordon, R. Hemady, A. Kowarski, D. Ostrowski, S. Steidl, B. Jones, W.H. Herman, C.L. Martin, R. Pop‐Busui, D.A. Greene, M.J. Stevens, N. Burkhart, T. Sandford, J. Floyd, J. Bantle, N. Flaherty, J. Terry, D. Koozekanani, S. Montezuma, N. Wimmergren, B. Rogness, M. Mech, T. Strand, J. Olson, L. McKenzie, C. Kwong, F. Goetz, R. Warhol, D. Hainsworth, D. Goldstein, S. Hitt, J. Giangiacomo, D.S Schade, J.L. Canady, M.R. Burge, A. Das, R.B. Avery, L.H. Ketai, J.E. Chapin, M.L. Schluter, J. Rich, C. Johannes, D. Hornbeck, M. Schutta, P.A. Bourne, A. Brucker, S. Braunstein, S. Schwartz, B.J. Maschak‐Carey, L. Baker, T. Orchard, L. Cimino, T. Songer, B. Doft, S. Olson, D. Becker, D. Rubinstein, R.L. Bergren, J. Fruit, R. Hyre, C. Palmer, N. Silvers, L. Lobes, P. Paczan Rath, P.W. Conrad, S. Yalamanchi, J. Wesche, M. Bratkowksi, S. Arslanian, J. Rinkoff, J. Warnicki, D. Curtin, D. Steinberg, G. Vagstad, R. Harris, L. Steranchak, J. Arch, K. Kelly, P. Ostrosaka, M. Guiliani, M. Good, T. Williams, K. Olsen, A. Campbell, C. Shipe, R. Conwit, D. Finegold, M. Zaucha, A. Drash, A. Morrison, J.I. Malone, M.L. Bernal, P.R. Pavan, N. Grove, E.A. Tanaka, D. McMillan, J. Vaccaro‐Kish, L. Babbione, H. Solc, T.J. DeClue, S. Dagogo‐Jack, C. Wigley, H. Ricks, A. Kitabchi, E. Chaum, M.B. Murphy, S. Moser, D. Meyer, A. Iannacone, S. Yoser, M. Bryer‐Ash, S. Schussler, H. Lambeth, P. Raskin, S. Strowig, M. Basco, S. Cercone, A. Barnie, R. Devenyi, M. Mandelcorn, M. Brent, S. Rogers, A. Gordon, N. Bakshi, B. Perkins, L. Tuason, F. Perdikaris, R. Ehrlich, D. Daneman, K. Perlman, S Ferguson, J. Palmer, R. Fahlstrom, I.H. de Boer, J. Kinyoun, L. Van Ottingham, S. Catton, J. Ginsberg, C. McDonald, J. Harth, M. Driscoll, T. Sheidow, J. Mahon, C. Canny, D. Nicolle, P. Colby, J. Dupre, I. Hramiak, N.W. Rodger, M. Jenner, T. Smith, W. Brown, M. May, J. Lipps Hagan, A. Agarwal, T. Adkins, R. Lorenz, S. Feman, L. Survant, N.H. White, L. Levandoski, G. Grand, M. Thomas, D. Joseph, K. Blinder, G. Shah, D. Burgess, I. Boniuk, J. Santiago, W. Tamborlane, P. Gatcomb, K. Stoessel, P. Ramos, K. Fong, P. Ossorio, J. Ahern, L. Meadema‐Mayer, C. Beck, K. Farrell, J Quin, P. Gaston, R. Trail, J. Lachin, J. Backlund, I. Bebu, B. Braffett, L. Diminick, X. Gao, W. Hsu, K. Klumpp, H. Pan, V. Trapani, P. Cleary, P. McGee, W. Sun, S. Villavicencio, K. Anderson, L. Dews, Naji Younes, B. Rutledge, K. Chan, D. Rosenberg, B. Petty, A. Determan, D. Kenny, C. Williams, C. Cowie, C. Siebert, M. Steffes, V. Arends, J. Bucksa, M. Nowicki, B. Chavers, D. O'Leary, J. Polak, A. Harrington, L. Funk, R Crow, B. Gloeb, S. Thomas, C. O'Donnell, E.Z. Soliman, Z.M. Zhang, Y. Li, C. Campbell, L. Keasler, S. Hensley, J. Hu, M. Barr, T. Taylor, R. Prineas, E.L. Feldman, J.W. Albers, P. Low, C. Sommer, K. Nickander, T. Speigelberg, M. Pfiefer, M. Schumer, M. Moran, J. Farquhar, C. Ryan, D. Sandstrom, M. Geckle, E. Cupelli, F. Thoma, B. Burzuk, T. Woodfill, R. Danis, B. Blodi, D. Lawrence, H. Wabers, S. Gangaputra, S. Neill, M. Burger, J. Dingledine, V. Gama, R. Sussman, M. Davis, L. Hubbard, M. Budoff, S. Darabian, P. Rezaeian, N. Wong, M. Fox, R. Oudiz, L Kim, R. Detrano, K. Cruickshanks, D. Dalton, K. Bainbridge, J. Lima, D. Bluemke, E. Turkbey, der Geest, C. Liu, A. Malayeri, A. Jain, C. Miao, H. Chahal, R. Jarboe, V. Monnier, D. Sell, C. Strauch, S. Hazen, A. Pratt, W. Tang, J. Brunzell, J. Purnell, R. Natarajan, F. Miao, L. Zhang, Z. Chen, A. Paterson, A. Boright, S. Bull, L. Sun, S. Scherer, T.J. Lyons, A. Jenkins, R. Klein, G. Virella, A. Jaffa, R. Carter, J. Stoner, W.T. Garvey, D. Lackland, M. Brabham, D. McGee, D. Zheng, R.K. Mayfield, J. Maynard, H. Wessells, A Sarma, R. Dunn, S. Holt, J. Hotaling, C. Kim, Q. Clemens, J. Brown, and K. McVary

Subjects
medicine.medical_specialty, endocrine system diseases, 030209 endocrinology & metabolism, Disease, 030204 cardiovascular system & hematology, Lower risk, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, medicine, Diseases of the circulatory (Cardiovascular) system, Coronary Heart Disease, Glycemic, Original Research, free radical, Inflammation, Type 1 diabetes, biology, business.industry, Paraoxonase, medicine.disease, paraoxonase, 3. Good health, RC666-701, Cohort, diabetes mellitus, biology.protein, Cardiology and Cardiovascular Medicine, business, Oxidant Stress, Oxidative stress, F2Isoprostane, Biomarkers
Abstract

Background Hyperglycemia leading to increased oxidative stress is implicated in the increased risk for the development of macrovascular and microvascular complications in patients with type 1 diabetes mellitus. Methods and Results A random subcohort of 349 participants was selected from the DCCT / EDIC (Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications) cohort. This included 320 controls and 29 cardiovascular disease cases that were augmented with 98 additional known cases to yield a case cohort of 447 participants (320 controls, 127 cases). Biosamples from DCCT baseline, year 1, and closeout of DCCT , and 1 to 2 years post‐ DCCT ( EDIC years 1 and 2) were measured for markers of oxidative stress, including plasma myeloperoxidase, paraoxonase activity, urinary F 2α isoprostanes, and its metabolite, 2,3 dinor‐8 iso prostaglandin F 2α . Following adjustment for glycated hemoblobin and weighting the observations inversely proportional to the sampling selection probabilities, higher paraoxonase activity, reflective of antioxidant activity, and 2,3 dinor‐8 iso prostaglandin F 2α , an oxidative marker, were significantly associated with lower risk of cardiovascular disease (−4.5% risk for 10% higher paraoxonase, P iso prostaglandin F 2α , P =0.0092). In contrast, the oxidative markers myeloperoxidase and F 2α isoprostanes were not significantly associated with cardiovascular disease after adjustment for glycated hemoblobin. There were no significant differences between DCCT intensive and conventional treatment groups in the change in all biomarkers across time segments. Conclusions Heightened antioxidant activity (rather than diminished oxidative stress markers) is associated with lower cardiovascular disease risk in type 1 diabetes mellitus, but these biomarkers did not change over time with intensification of glycemic control. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifiers: NCT 00360815 and NCT 00360893.

Published
2018

2. Insulin Sensitivity and Diabetic Kidney Disease in Children and Adolescents With Type 2 Diabetes: An Observational Analysis of Data From the TODAY Clinical Trial

Author

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, and J. Silverstein

Subjects
medicine.medical_specialty, business.industry, Renal function, Type 2 Diabetes Mellitus, 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, medicine.disease, Article, Metformin, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Nephrology, Internal medicine, medicine, Cumulative incidence, business, Rosiglitazone, Body mass index, Glycemic, medicine.drug
Abstract

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.

Published
2017

3. Cardiac Biomarkers in Youth with Type 2 Diabetes Mellitus: Results from the TODAY Study

Author

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, and J. Silverstein

Subjects
Male, medicine.medical_specialty, Adolescent, Diet therapy, Heart Ventricles, 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, Article, Ventricular Function, Left, Rosiglitazone, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Hypoglycemic Agents, Child, Ejection fraction, biology, business.industry, Type 2 Diabetes Mellitus, Brain natriuretic peptide, medicine.disease, Troponin, Combined Modality Therapy, Metformin, Exercise Therapy, Diabetes Mellitus, Type 1, Blood pressure, Treatment Outcome, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Echocardiography, Pediatrics, Perinatology and Child Health, biology.protein, Cardiology, Drug Therapy, Combination, Female, Thiazolidinediones, business, Body mass index, Biomarkers, Diet Therapy, Follow-Up Studies
Abstract

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 .

Published
2017

4. Lipid Profiles, Inflammatory Markers, and Insulin Therapy in Youth with Type 2 Diabetes

Author

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, and J. Silverstein

Subjects
Blood Glucose, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, Overweight, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Diabetes mellitus, medicine, Humans, Insulin, Child, Dyslipidemias, Glycemic, Glycated Hemoglobin, Inflammation, business.industry, Cholesterol, Type 2 Diabetes Mellitus, Cholesterol, LDL, medicine.disease, Lipids, Diabetes Mellitus, Type 2, chemistry, Pediatrics, Perinatology and Child Health, Disease Progression, Female, Hydroxymethylglutaryl-CoA Reductase Inhibitors, medicine.symptom, business, Dyslipidemia
Abstract

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 .

Published
2018
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5. 92330936 A prospective study of postmenopausal estrogen therapy and subsequent incidence of non-insulin-dependent diabetes mellitus

Author

C H Hennekens, D.M. Nathan, JoAnn E. Manson, Walter C. Willett, Meir J. Stampfer, Graham A. Colditz, Bernard Rosner, R.A. Arky, E. B. Rimm, and Frank E. Speizer

Subjects
Oncology, medicine.medical_specialty, Endocrinology, business.industry, Incidence (epidemiology), Internal medicine, Non insulin dependent diabetes mellitus, Obstetrics and Gynecology, Medicine, Estrogen therapy, business, Prospective cohort study, General Biochemistry, Genetics and Molecular Biology
Published
1993
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