Randomized Controlled Trial

. 2019 Nov;20(7):871-879.

doi: 10.1111/pedi.12906. Epub 2019 Aug 27.

Predictors of response to insulin therapy in youth with poorly-controlled type 2 diabetes in the TODAY trial

Collaborators, Affiliations

Collaborators

TODAY Study Group:
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, D Flomo, 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

Affiliations

¹ Children's Nutrition Research Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.
² Biostatistics Center, George Washington University, Rockville, Maryland.
³ UPMC, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
⁴ University of Colorado Anschutz Medical Campus, Aurora, Colorado.
⁵ Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts.
⁶ Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
⁷ Columbia University, New York, New York.
⁸ Children's Hospital of Los Angeles, Los Angeles, Louisiana.
⁹ Washington University in St. Louis, St. Louis, Missouri.
¹⁰ Case Western Reserve University, Cleveland, Ohio.

PMID: 31418516
PMCID: PMC6953481
DOI: 10.1111/pedi.12906

Randomized Controlled Trial

Predictors of response to insulin therapy in youth with poorly-controlled type 2 diabetes in the TODAY trial

Fida Bacha et al. Pediatr Diabetes. 2019 Nov.

. 2019 Nov;20(7):871-879.

doi: 10.1111/pedi.12906. Epub 2019 Aug 27.

Authors

Collaborators

TODAY Study Group:
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, D Flomo, 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

Affiliations

¹ Children's Nutrition Research Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.
² Biostatistics Center, George Washington University, Rockville, Maryland.
³ UPMC, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
⁴ University of Colorado Anschutz Medical Campus, Aurora, Colorado.
⁵ Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts.
⁶ Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
⁷ Columbia University, New York, New York.
⁸ Children's Hospital of Los Angeles, Los Angeles, Louisiana.
⁹ Washington University in St. Louis, St. Louis, Missouri.
¹⁰ Case Western Reserve University, Cleveland, Ohio.

PMID: 31418516
PMCID: PMC6953481
DOI: 10.1111/pedi.12906

Abstract

Objective: To understand the factors associated with glycemic control after starting insulin in youth with type 2 diabetes following glycemic failure (persistent HbA1c ≥8%) with metformin alone, metformin + rosiglitazone or metformin + lifestyle in the TODAY study.

Methods: Change in HbA1c after add-on insulin therapy and the factors predictive of glycemic response were evaluated. At 1-year postinsulin initiation, 253 youth had a mean of 3.9 ± 1.0 visits since the time of insulin initiation. Participants were divided into three groups according to glycemic control: consistent decrease in HbA1c by ≥0.5%, change <0.5%, or consistent increase in HbA1c ≥0.5%, at 75% or more of the visits.

Results: Within 1-year postinsulin initiation, 33.2% of participants had a consistent HbA1c decrease of ≥0.5%, 46.2% changed HbA1c <0.5%, and 20.6% had an increase ≥0.5%. At randomization into TODAY and at time of insulin initiation, the three glycemia groups were similar in age, sex, race-ethnicity, pubertal stage, BMI z-score, diabetes duration, and insulin secretion indices. Consistent HbA1c improvement was associated with higher insulin sensitivity (1/fasting insulin) at randomization and at time of failure, higher adiponectin at randomization, and was not associated with indices of β-cell function.

Conclusions: Response to add-on insulin was highly variable among youth in TODAY. Greater insulin sensitivity and higher adiponectin concentrations at randomization were associated with improved glycemic control after initiation of insulin. Due to limited information on adherence to insulin injections, the roles of adherence to the prescribed insulin regimen or psychosocial factors are unknown.

Keywords: adolescent; glycemic control; insulin; type 2 diabetes mellitus.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest. No potential conflicts of interest relevant to this article were reported.

Figures

**Figure 1.**
Trajectory of HbA1c before and after initiation of insulin therapy in the 3 glycemic response groups showing consistent HbA1c decrease (≥0.5%), <0.5% change in HbA1c, and consistent HbA1c increase (≥0.5%) within 1 year of insulin initiation

See this image and copyright information in PMC

References

1. TODAY Study Group, Zeitler P, Epstein L, Grey M, et al. Treatment options for type 2 diabetes in adolescents and youth: a study of the comparative efficacy of metformin alone or in combination with rosiglitazone or lifestyle intervention in adolescents with type 2 diabetes. Pediatr Diabetes. 2007. April;8(2):74–87. - PMC - PubMed
1. TODAY Study Group. Effects of metformin, metformin plus rosiglitazone, and metformin plus lifestyle on insulin sensitivity and β-cell function in TODAY. Diabetes Care. 2013. June;36(6):1749–57. - PMC - PubMed
1. Riddle MC. Timely initiation of basal insulin. Am J Med. 2004. February 2;116 Suppl 3A:3S–9S. Review. - PubMed
1. Wright A, Burden AC, Paisey RB, Cull CA, Holman RR; U.K. Prospective Diabetes Study Group. Sulfonylurea inadequacy: efficacy of addition of insulin over 6 years in patients with type 2 diabetes in the U.K. Prospective Diabetes Study (UKPDS 57). Diabetes Care. 2002. February;25(2):330–6. Erratum in: Diabetes Care 2002 Jul;25(7):1268. - PubMed
1. Levitt Katz LE, Bacha F, Gidding SS, et al.; TODAY Study Group. Lipid Profiles, Inflammatory Markers, and Insulin Therapy in Youth with Type 2 Diabetes. J Pediatr. 2018. May;196:208–216.e2. - PMC - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Medical
- ClinicalTrials.gov
- MedlinePlus Health Information
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Predictors of response to insulin therapy in youth with poorly-controlled type 2 diabetes in the TODAY trial

Collaborators

Affiliations

Predictors of response to insulin therapy in youth with poorly-controlled type 2 diabetes in the TODAY trial

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous