TY - JOUR
T1 - Predictors of response to insulin therapy in youth with poorly-controlled type 2 diabetes in the TODAY trial
AU - the TODAY Study Group
AU - Bacha, Fida
AU - El ghormli, Laure
AU - Arslanian, Silva
AU - Zeitler, Philip
AU - Laffel, Lori M.
AU - Levitt Katz, Lorraine E.
AU - Gandica, Rachelle
AU - Chang, Nancy T.
AU - Sprague, Jennifer E.
AU - Macleish, Sarah A.
AU - McKay, S.
AU - Haymond, M.
AU - Anderson, B.
AU - Bush, C.
AU - Gunn, S.
AU - Holden, H.
AU - Jones, S. M.
AU - Jeha, G.
AU - McGirk, S.
AU - Thamotharan, S.
AU - Cuttler, L.
AU - Abrams, E.
AU - Casey, T.
AU - Dahms, W.
AU - Ievers-Landis, C.
AU - Kaminski, B.
AU - Koontz, M.
AU - MacLeish, S.
AU - McGuigan, P.
AU - Narasimhan, S.
AU - Geffner, M.
AU - Barraza, V.
AU - Chang, N.
AU - Conrad, B.
AU - Dreimane, D.
AU - Estrada, S.
AU - Fisher, L.
AU - Fleury-Milfort, E.
AU - Hernandez, S.
AU - Hollen, B.
AU - Kaufman, F.
AU - Law, E.
AU - Mansilla, V.
AU - Miller, D.
AU - Muñoz, C.
AU - Ortiz, R.
AU - Ward, A.
AU - Wexler, K.
AU - Xu, Y. K.
AU - Hale, D.
N1 - Funding Information:
information National Center for Research Resources Clinical and Translational Science Awards, Grant/Award Numbers: UL1-RR025780, UL1-RR025758, UL1-RR024992, UL1-RR024989, UL1-RR024153, UL1-RR024139, UL1-RR024134; National Center for Research Resources, Grant/Award Numbers: M01-RR14467, M01-RR00125, M01-RR01066, M01-RR00084, M01-RR00069, M01-RR00043-45, M01-RR00036; National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health, Grant/Award Numbers: T32-DK063687, U01-DK61254, U01-DK61242, U01-DK61239, U01-DK61230, U01-DK61212A complete list of participants in the TODAY Study Group is presented in Supporting Information. The TODAY Study Group thanks the following companies for their donations: Becton, Dickinson and Company; Bristol-Myers Squibb; Eli Lilly and Company; GlaxoSmithKline; LifeScan, Inc.; Pfizer; Sanofi Aventis. We also gratefully acknowledge the participation and guidance of the American Indian partners associated with the clinical center located at the University of Oklahoma Health Sciences Center, including members of the Absentee Shawnee Tribe, Cherokee Nation, Chickasaw Nation, Choctaw Nation of Oklahoma, and Oklahoma City Area Indian Health Service; the opinions expressed in this article are those of the authors and do not necessarily reflect the views of the respective Tribes and the Indian Health Service. Materials developed and used for the TODAY standard diabetes education program and the intensive lifestyle intervention program are available to the public at https://today.bsc.gwu.edu/. The study was funded by National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health which did not have any input on the study design or data analyses. This work was completed with funding grant numbers U01-DK61212, U01-DK61230, U01-DK61239, U01-DK61242, U01-DK61254, and T32-DK063687; from the National Center for Research Resources General Clinical Research Centers Program grant numbers M01-RR00036 (Washington University School of Medicine), M01-RR00043-45 (Children's Hospital Los Angeles), M01-RR00069 (University of Colorado Denver), M01-RR00084 (Children's Hospital of Pittsburgh), M01-RR01066 (Massachusetts General Hospital), M01-RR00125 (Yale University), and M01-RR14467 (University of Oklahoma Health Sciences Center); and from the National Center for Research Resources Clinical and Translational Science Awards grant numbers UL1-RR024134 (Children's Hospital of Philadelphia), UL1-RR024139 (Yale University), UL1-RR024153 (Children's Hospital of Pittsburgh), UL1-RR024989 (Case Western Reserve University), UL1-RR024992 (Washington University in St Louis), UL1-RR025758 (Massachusetts General Hospital), and UL1-RR025780 (University of Colorado Denver).
Funding Information:
A complete list of participants in the TODAY Study Group is presented in Supporting Information. The TODAY Study Group thanks the following companies for their donations: Becton, Dickinson and Company; Bristol‐Myers Squibb; Eli Lilly and Company; GlaxoSmithKline; LifeScan, Inc.; Pfizer; Sanofi Aventis. We also gratefully acknowledge the participation and guidance of the American Indian partners associated with the clinical center located at the University of Oklahoma Health Sciences Center, including members of the Absentee Shawnee Tribe, Cherokee Nation, Chickasaw Nation, Choctaw Nation of Oklahoma, and Oklahoma City Area Indian Health Service; the opinions expressed in this article are those of the authors and do not necessarily reflect the views of the respective Tribes and the Indian Health Service. Materials developed and used for the TODAY standard diabetes education program and the intensive lifestyle intervention program are available to the public at https://today.bsc.gwu.edu/ . The study was funded by National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health which did not have any input on the study design or data analyses. This work was completed with funding grant numbers U01‐DK61212, U01‐DK61230, U01‐DK61239, U01‐DK61242, U01‐DK61254, and T32‐DK063687; from the National Center for Research Resources General Clinical Research Centers Program grant numbers M01‐RR00036 (Washington University School of Medicine), M01‐RR00043‐45 (Children's Hospital Los Angeles), M01‐RR00069 (University of Colorado Denver), M01‐RR00084 (Children's Hospital of Pittsburgh), M01‐RR01066 (Massachusetts General Hospital), M01‐RR00125 (Yale University), and M01‐RR14467 (University of Oklahoma Health Sciences Center); and from the National Center for Research Resources Clinical and Translational Science Awards grant numbers UL1‐RR024134 (Children's Hospital of Philadelphia), UL1‐RR024139 (Yale University), UL1‐RR024153 (Children's Hospital of Pittsburgh), UL1‐RR024989 (Case Western Reserve University), UL1‐RR024992 (Washington University in St Louis), UL1‐RR025758 (Massachusetts General Hospital), and UL1‐RR025780 (University of Colorado Denver).
Publisher Copyright:
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85071699665&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071699665&partnerID=8YFLogxK
U2 - 10.1111/pedi.12906
DO - 10.1111/pedi.12906
M3 - Article
C2 - 31418516
AN - SCOPUS:85071699665
SN - 1399-543X
VL - 20
SP - 871
EP - 879
JO - Pediatric Diabetes
JF - Pediatric Diabetes
IS - 7
ER -