Intensive Weight Loss Intervention and Cancer Risk in Adults with Type 2 Diabetes: Analysis of the Look AHEAD Randomized Clinical Trial

Hsin Chieh Yeh; John P. Bantle; Maria Cassidy-Begay; George Blackburn; George A. Bray; Tim Byers; Jeanne M. Clark; Mace Coday; Caitlin Egan; Mark A. Espeland; John P. Foreyt; Katelyn Garcia; Valerie Goldman; Edward W. Gregg; Helen P. Hazuda; Louise Hesson; James O. Hill; Edward S. Horton; John M. Jakicic; Robert W. Jeffery; Karen C. Johnson; Steven E. Kahn; William C. Knowler; Mary Korytkowski; Anne Kure; Cora E. Lewis; Christos Mantzoros; Maria Meacham; Maria G. Montez; David M. Nathan; Nicholas Pajewski; Jennifer Patricio; Anne Peters; F. Xavier Pi-Sunyer; Henry Pownall; Donna H. Ryan; Monika Safford; Rebecca L. Sedjo; Helmut Steinburg; Mara Vitolins; Thomas A. Wadden; Lynne E. Wagenknecht; Rena R. Wing; Antonio C. Wolff; Holly Wyatt; Susan Z. Yanovski

doi:10.1002/oby.22936

Intensive Weight Loss Intervention and Cancer Risk in Adults with Type 2 Diabetes: Analysis of the Look AHEAD Randomized Clinical Trial

Hsin Chieh Yeh, John P. Bantle, Maria Cassidy-Begay, George Blackburn, George A. Bray, Tim Byers, Jeanne M. Clark, Mace Coday, Caitlin Egan, Mark A. Espeland, John P. Foreyt, Katelyn Garcia, Valerie Goldman, Edward W. Gregg, Helen P. Hazuda, Louise Hesson, James O. Hill, Edward S. Horton, John M. Jakicic, Robert W. JefferyKaren C. Johnson, Steven E. Kahn, William C. Knowler, Mary Korytkowski, Anne Kure, Cora E. Lewis, Christos Mantzoros, Maria Meacham, Maria G. Montez, David M. Nathan, Nicholas Pajewski, Jennifer Patricio, Anne Peters, F. Xavier Pi-Sunyer, Henry Pownall, Donna H. Ryan, Monika Safford, Rebecca L. Sedjo, Helmut Steinburg, Mara Vitolins, Thomas A. Wadden, Lynne E. Wagenknecht, Rena R. Wing, Antonio C. Wolff, Holly Wyatt, Susan Z. Yanovski

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Abstract

Objective: This study was designed to determine whether intensive lifestyle intervention (ILI) aimed at weight loss lowers cancer incidence and mortality. Methods: Data from the Look AHEAD trial were examined to investigate whether participants randomized to ILI designed for weight loss would have reduced overall cancer incidence, obesity-related cancer incidence, and cancer mortality, as compared with the diabetes support and education (DSE) comparison group. This analysis included 4,859 participants without a cancer diagnosis at baseline except for nonmelanoma skin cancer. Results: After a median follow-up of 11 years, 684 participants (332 in ILI and 352 in DSE) were diagnosed with cancer. The incidence rates of obesity-related cancers were 6.1 and 7.3 per 1,000 person-years in ILI and DSE, respectively, with a hazard ratio (HR) of 0.84 (95% CI: 0.68-1.04). There was no significant difference between the two groups in total cancer incidence (HR, 0.93; 95% CI: 0.80-1.08), incidence of nonobesity-related cancers (HR, 1.02; 95% CI: 0.83-1.27), or total cancer mortality (HR, 0.92; 95% CI: 0.68-1.25). Conclusions: An ILI aimed at weight loss lowered incidence of obesity-related cancers by 16% in adults with overweight or obesity and type 2 diabetes. The study sample size likely lacked power to determine effect sizes of this magnitude and smaller.

Original language	English (US)
Pages (from-to)	1678-1686
Number of pages	9
Journal	Obesity
Volume	28
Issue number	9
DOIs	https://doi.org/10.1002/oby.22936
State	Published - Sep 1 2020

Bibliographical note

Funding Information:
Writing group members: Hsin-Chieh Yeh, PhD (Chair), Christos Mantzoros, MD, DSc, Mara Vitolins, DrPH, Rebecca Sedjo, PhD, Lynne Wagenknecht, DrPH, Jeanne M. Clark, MD, MPH, Katelyn Garcia, MS, Antonio Wolff, MD, Edward Horton, MD, George Blackburn, MD, PhD (deceased), Tim Byers, MD, MPH. A deidentified database will be prepared and submitted to the NIDDK Central Repository. Included will be documentation including protocols, forms, and data dictionaries. Access is guided by NIDDK Central Repository policy.

Funding Information:
This work was supported by the National Institutes of Health (NIH) through cooperative agreements with the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992). Additional funding was provided by the National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; NIH Office of Research on Women’s Health; and the Centers for Disease Control and Prevention. This research was supported in part by the Intramural Research Program of the NIDDK. The Indian Health Service (IHS) provided personnel, medical oversight, and use of facilities. The opinions expressed in this paper are those of the authors and do not necessarily reflect the views of the IHS or other funding sources. Additional support was received from The Johns Hopkins Medical Institutions Bayview General Clinical Research Center (M01RR02719); the Massachusetts General Hospital Mallinckrodt General Clinical Research Center and the Massachusetts Institute of Technology General Clinical Research Center (M01RR01066); the Harvard Clinical and Translational Science Center (RR025758‐04); the University of Colorado Health Sciences Center General Clinical Research Center (M01RR00051) and Clinical Nutrition Research Unit (P30 DK48520); the University of Tennessee at Memphis General Clinical Research Center (M01RR0021140); the University of Pittsburgh General Clinical Research Center (M01RR000056), the Clinical Translational Research Center funded by the Clinical & Translational Science Award (UL1 RR 024153) and NIH grant (DK 046204); the VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs; and the Frederic C. Bartter General Clinical Research Center (M01RR01346). The following organizations have committed to make major contributions to Look AHEAD: FedEx Corporation; Health Management Resources; LifeScan, Inc., a Johnson & Johnson Company; OPTIFAST of Nestle HealthCare Nutrition, Inc.; Hoffmann‐La Roche Inc.; Abbott Nutrition; and Slim‐Fast Brand of Unilever North America. Some of the information contained herein was derived from data provided by the Bureau of Vital Statistics, New York City Department of Health and Mental Hygiene.

Publisher Copyright:
© 2020 The Obesity Society.

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Yeh, H. C., Bantle, J. P., Cassidy-Begay, M., Blackburn, G., Bray, G. A., Byers, T., Clark, J. M., Coday, M., Egan, C., Espeland, M. A., Foreyt, J. P., Garcia, K., Goldman, V., Gregg, E. W., Hazuda, H. P., Hesson, L., Hill, J. O., Horton, E. S., Jakicic, J. M., ... Yanovski, S. Z. (2020). Intensive Weight Loss Intervention and Cancer Risk in Adults with Type 2 Diabetes: Analysis of the Look AHEAD Randomized Clinical Trial. Obesity, 28(9), 1678-1686. https://doi.org/10.1002/oby.22936

Yeh, HC, Bantle, JP, Cassidy-Begay, M, Blackburn, G, Bray, GA, Byers, T, Clark, JM, Coday, M, Egan, C, Espeland, MA, Foreyt, JP, Garcia, K, Goldman, V, Gregg, EW, Hazuda, HP, Hesson, L, Hill, JO, Horton, ES, Jakicic, JM, Jeffery, RW, Johnson, KC, Kahn, SE, Knowler, WC, Korytkowski, M, Kure, A, Lewis, CE, Mantzoros, C, Meacham, M, Montez, MG, Nathan, DM, Pajewski, N, Patricio, J, Peters, A, Xavier Pi-Sunyer, F, Pownall, H, Ryan, DH, Safford, M, Sedjo, RL, Steinburg, H, Vitolins, M, Wadden, TA, Wagenknecht, LE, Wing, RR, Wolff, AC, Wyatt, H & Yanovski, SZ 2020, 'Intensive Weight Loss Intervention and Cancer Risk in Adults with Type 2 Diabetes: Analysis of the Look AHEAD Randomized Clinical Trial', Obesity, vol. 28, no. 9, pp. 1678-1686. https://doi.org/10.1002/oby.22936

@article{48c6f51be366433ea5781d1304701223,

title = "Intensive Weight Loss Intervention and Cancer Risk in Adults with Type 2 Diabetes: Analysis of the Look AHEAD Randomized Clinical Trial",

abstract = "Objective: This study was designed to determine whether intensive lifestyle intervention (ILI) aimed at weight loss lowers cancer incidence and mortality. Methods: Data from the Look AHEAD trial were examined to investigate whether participants randomized to ILI designed for weight loss would have reduced overall cancer incidence, obesity-related cancer incidence, and cancer mortality, as compared with the diabetes support and education (DSE) comparison group. This analysis included 4,859 participants without a cancer diagnosis at baseline except for nonmelanoma skin cancer. Results: After a median follow-up of 11 years, 684 participants (332 in ILI and 352 in DSE) were diagnosed with cancer. The incidence rates of obesity-related cancers were 6.1 and 7.3 per 1,000 person-years in ILI and DSE, respectively, with a hazard ratio (HR) of 0.84 (95% CI: 0.68-1.04). There was no significant difference between the two groups in total cancer incidence (HR, 0.93; 95% CI: 0.80-1.08), incidence of nonobesity-related cancers (HR, 1.02; 95% CI: 0.83-1.27), or total cancer mortality (HR, 0.92; 95% CI: 0.68-1.25). Conclusions: An ILI aimed at weight loss lowered incidence of obesity-related cancers by 16% in adults with overweight or obesity and type 2 diabetes. The study sample size likely lacked power to determine effect sizes of this magnitude and smaller.",

author = "Yeh, {Hsin Chieh} and Bantle, {John P.} and Maria Cassidy-Begay and George Blackburn and Bray, {George A.} and Tim Byers and Clark, {Jeanne M.} and Mace Coday and Caitlin Egan and Espeland, {Mark A.} and Foreyt, {John P.} and Katelyn Garcia and Valerie Goldman and Gregg, {Edward W.} and Hazuda, {Helen P.} and Louise Hesson and Hill, {James O.} and Horton, {Edward S.} and Jakicic, {John M.} and Jeffery, {Robert W.} and Johnson, {Karen C.} and Kahn, {Steven E.} and Knowler, {William C.} and Mary Korytkowski and Anne Kure and Lewis, {Cora E.} and Christos Mantzoros and Maria Meacham and Montez, {Maria G.} and Nathan, {David M.} and Nicholas Pajewski and Jennifer Patricio and Anne Peters and {Xavier Pi-Sunyer}, F. and Henry Pownall and Ryan, {Donna H.} and Monika Safford and Sedjo, {Rebecca L.} and Helmut Steinburg and Mara Vitolins and Wadden, {Thomas A.} and Wagenknecht, {Lynne E.} and Wing, {Rena R.} and Wolff, {Antonio C.} and Holly Wyatt and Yanovski, {Susan Z.}",

note = "Funding Information: Writing group members: Hsin-Chieh Yeh, PhD (Chair), Christos Mantzoros, MD, DSc, Mara Vitolins, DrPH, Rebecca Sedjo, PhD, Lynne Wagenknecht, DrPH, Jeanne M. Clark, MD, MPH, Katelyn Garcia, MS, Antonio Wolff, MD, Edward Horton, MD, George Blackburn, MD, PhD (deceased), Tim Byers, MD, MPH. A deidentified database will be prepared and submitted to the NIDDK Central Repository. Included will be documentation including protocols, forms, and data dictionaries. Access is guided by NIDDK Central Repository policy. Funding Information: This work was supported by the National Institutes of Health (NIH) through cooperative agreements with the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992). Additional funding was provided by the National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; NIH Office of Research on Women{\textquoteright}s Health; and the Centers for Disease Control and Prevention. This research was supported in part by the Intramural Research Program of the NIDDK. The Indian Health Service (IHS) provided personnel, medical oversight, and use of facilities. The opinions expressed in this paper are those of the authors and do not necessarily reflect the views of the IHS or other funding sources. Additional support was received from The Johns Hopkins Medical Institutions Bayview General Clinical Research Center (M01RR02719); the Massachusetts General Hospital Mallinckrodt General Clinical Research Center and the Massachusetts Institute of Technology General Clinical Research Center (M01RR01066); the Harvard Clinical and Translational Science Center (RR025758‐04); the University of Colorado Health Sciences Center General Clinical Research Center (M01RR00051) and Clinical Nutrition Research Unit (P30 DK48520); the University of Tennessee at Memphis General Clinical Research Center (M01RR0021140); the University of Pittsburgh General Clinical Research Center (M01RR000056), the Clinical Translational Research Center funded by the Clinical & Translational Science Award (UL1 RR 024153) and NIH grant (DK 046204); the VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs; and the Frederic C. Bartter General Clinical Research Center (M01RR01346). The following organizations have committed to make major contributions to Look AHEAD: FedEx Corporation; Health Management Resources; LifeScan, Inc., a Johnson & Johnson Company; OPTIFAST of Nestle HealthCare Nutrition, Inc.; Hoffmann‐La Roche Inc.; Abbott Nutrition; and Slim‐Fast Brand of Unilever North America. Some of the information contained herein was derived from data provided by the Bureau of Vital Statistics, New York City Department of Health and Mental Hygiene. Publisher Copyright: {\textcopyright} 2020 The Obesity Society.",

year = "2020",

month = sep,

day = "1",

doi = "10.1002/oby.22936",

language = "English (US)",

volume = "28",

pages = "1678--1686",

journal = "Obesity",

issn = "1930-7381",

publisher = "Wiley-Blackwell",

number = "9",

}

TY - JOUR

T1 - Intensive Weight Loss Intervention and Cancer Risk in Adults with Type 2 Diabetes

T2 - Analysis of the Look AHEAD Randomized Clinical Trial

AU - Yeh, Hsin Chieh

AU - Bantle, John P.

AU - Cassidy-Begay, Maria

AU - Blackburn, George

AU - Bray, George A.

AU - Byers, Tim

AU - Clark, Jeanne M.

AU - Coday, Mace

AU - Egan, Caitlin

AU - Espeland, Mark A.

AU - Foreyt, John P.

AU - Garcia, Katelyn

AU - Goldman, Valerie

AU - Gregg, Edward W.

AU - Hazuda, Helen P.

AU - Hesson, Louise

AU - Hill, James O.

AU - Horton, Edward S.

AU - Jakicic, John M.

AU - Jeffery, Robert W.

AU - Johnson, Karen C.

AU - Kahn, Steven E.

AU - Knowler, William C.

AU - Korytkowski, Mary

AU - Kure, Anne

AU - Lewis, Cora E.

AU - Mantzoros, Christos

AU - Meacham, Maria

AU - Montez, Maria G.

AU - Nathan, David M.

AU - Pajewski, Nicholas

AU - Patricio, Jennifer

AU - Peters, Anne

AU - Xavier Pi-Sunyer, F.

AU - Pownall, Henry

AU - Ryan, Donna H.

AU - Safford, Monika

AU - Sedjo, Rebecca L.

AU - Steinburg, Helmut

AU - Vitolins, Mara

AU - Wadden, Thomas A.

AU - Wagenknecht, Lynne E.

AU - Wing, Rena R.

AU - Wolff, Antonio C.

AU - Wyatt, Holly

AU - Yanovski, Susan Z.

N1 - Funding Information: Writing group members: Hsin-Chieh Yeh, PhD (Chair), Christos Mantzoros, MD, DSc, Mara Vitolins, DrPH, Rebecca Sedjo, PhD, Lynne Wagenknecht, DrPH, Jeanne M. Clark, MD, MPH, Katelyn Garcia, MS, Antonio Wolff, MD, Edward Horton, MD, George Blackburn, MD, PhD (deceased), Tim Byers, MD, MPH. A deidentified database will be prepared and submitted to the NIDDK Central Repository. Included will be documentation including protocols, forms, and data dictionaries. Access is guided by NIDDK Central Repository policy. Funding Information: This work was supported by the National Institutes of Health (NIH) through cooperative agreements with the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992). Additional funding was provided by the National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; NIH Office of Research on Women’s Health; and the Centers for Disease Control and Prevention. This research was supported in part by the Intramural Research Program of the NIDDK. The Indian Health Service (IHS) provided personnel, medical oversight, and use of facilities. The opinions expressed in this paper are those of the authors and do not necessarily reflect the views of the IHS or other funding sources. Additional support was received from The Johns Hopkins Medical Institutions Bayview General Clinical Research Center (M01RR02719); the Massachusetts General Hospital Mallinckrodt General Clinical Research Center and the Massachusetts Institute of Technology General Clinical Research Center (M01RR01066); the Harvard Clinical and Translational Science Center (RR025758‐04); the University of Colorado Health Sciences Center General Clinical Research Center (M01RR00051) and Clinical Nutrition Research Unit (P30 DK48520); the University of Tennessee at Memphis General Clinical Research Center (M01RR0021140); the University of Pittsburgh General Clinical Research Center (M01RR000056), the Clinical Translational Research Center funded by the Clinical & Translational Science Award (UL1 RR 024153) and NIH grant (DK 046204); the VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs; and the Frederic C. Bartter General Clinical Research Center (M01RR01346). The following organizations have committed to make major contributions to Look AHEAD: FedEx Corporation; Health Management Resources; LifeScan, Inc., a Johnson & Johnson Company; OPTIFAST of Nestle HealthCare Nutrition, Inc.; Hoffmann‐La Roche Inc.; Abbott Nutrition; and Slim‐Fast Brand of Unilever North America. Some of the information contained herein was derived from data provided by the Bureau of Vital Statistics, New York City Department of Health and Mental Hygiene. Publisher Copyright: © 2020 The Obesity Society.

PY - 2020/9/1

Y1 - 2020/9/1

N2 - Objective: This study was designed to determine whether intensive lifestyle intervention (ILI) aimed at weight loss lowers cancer incidence and mortality. Methods: Data from the Look AHEAD trial were examined to investigate whether participants randomized to ILI designed for weight loss would have reduced overall cancer incidence, obesity-related cancer incidence, and cancer mortality, as compared with the diabetes support and education (DSE) comparison group. This analysis included 4,859 participants without a cancer diagnosis at baseline except for nonmelanoma skin cancer. Results: After a median follow-up of 11 years, 684 participants (332 in ILI and 352 in DSE) were diagnosed with cancer. The incidence rates of obesity-related cancers were 6.1 and 7.3 per 1,000 person-years in ILI and DSE, respectively, with a hazard ratio (HR) of 0.84 (95% CI: 0.68-1.04). There was no significant difference between the two groups in total cancer incidence (HR, 0.93; 95% CI: 0.80-1.08), incidence of nonobesity-related cancers (HR, 1.02; 95% CI: 0.83-1.27), or total cancer mortality (HR, 0.92; 95% CI: 0.68-1.25). Conclusions: An ILI aimed at weight loss lowered incidence of obesity-related cancers by 16% in adults with overweight or obesity and type 2 diabetes. The study sample size likely lacked power to determine effect sizes of this magnitude and smaller.

AB - Objective: This study was designed to determine whether intensive lifestyle intervention (ILI) aimed at weight loss lowers cancer incidence and mortality. Methods: Data from the Look AHEAD trial were examined to investigate whether participants randomized to ILI designed for weight loss would have reduced overall cancer incidence, obesity-related cancer incidence, and cancer mortality, as compared with the diabetes support and education (DSE) comparison group. This analysis included 4,859 participants without a cancer diagnosis at baseline except for nonmelanoma skin cancer. Results: After a median follow-up of 11 years, 684 participants (332 in ILI and 352 in DSE) were diagnosed with cancer. The incidence rates of obesity-related cancers were 6.1 and 7.3 per 1,000 person-years in ILI and DSE, respectively, with a hazard ratio (HR) of 0.84 (95% CI: 0.68-1.04). There was no significant difference between the two groups in total cancer incidence (HR, 0.93; 95% CI: 0.80-1.08), incidence of nonobesity-related cancers (HR, 1.02; 95% CI: 0.83-1.27), or total cancer mortality (HR, 0.92; 95% CI: 0.68-1.25). Conclusions: An ILI aimed at weight loss lowered incidence of obesity-related cancers by 16% in adults with overweight or obesity and type 2 diabetes. The study sample size likely lacked power to determine effect sizes of this magnitude and smaller.

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Intensive Weight Loss Intervention and Cancer Risk in Adults with Type 2 Diabetes: Analysis of the Look AHEAD Randomized Clinical Trial

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