The Effect of Intentional Weight Loss on Fracture Risk in Persons With Diabetes: Results From the Look AHEAD Randomized Clinical Trial

Karen C. Johnson, George A. Bray, Lawrence J. Cheskin, Jeanne M. Clark, Caitlin M. Egan, John P. Foreyt, Katelyn R. Garcia, Stephen Glasser, Frank L. Greenway, Edward W. Gregg, Helen P. Hazuda, Andrea Hergenroeder, James O. Hill, Edward S. Horton, John M. Jakicic, Robert W. Jeffery, Steven E. Kahn, William C. Knowler, Cora E. Lewis, Marsha MillerMaria G. Montez, David M. Nathan, Jennifer L. Patricio, Anne L. Peters, Xavier Pi-Sunyer, Henry J. Pownall, David Reboussin, J. Bruce Redmon, Helmut Steinberg, Thomas A. Wadden, Lynne E. Wagenknecht, Rena R. Wing, Catherine R. Womack, Susan Z. Yanovski, Ping Zhang, Ann V. Schwartz, for the Look AHEAD Study Group

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Intentional weight loss is an important treatment option for overweight persons with type 2 diabetes mellitus (DM), but the effects on long-term fracture risk are not known. The purpose of this Look AHEAD analysis was to evaluate whether long-term intentional weight loss would increase fracture risk in overweight or obese persons with DM. Look AHEAD is a multicenter, randomized clinical trial. Recruitment began in August 2001 and follow-up continued for a median of 11.3 years at 16 academic centers. A total of 5145 persons aged 45 to 76 years with DM were randomized to either an intensive lifestyle intervention (ILI) with reduced calorie consumption and increased physical activity designed to achieve and maintain ≥7% weight loss or to diabetes support and education intervention (DSE). Incident fractures were ascertained every 6 months by self-report and confirmed with central adjudication of medical records. The baseline mean age of participants was 59 years, 60% were women, 63% were white, and the mean BMI was 36 kg/m2. Weight loss over the intervention period (median 9.6 years) was 6.0% in ILI and 3.5% in DSE. A total of 731 participants had a confirmed incident fracture (358 in DSE versus 373 in ILI). There were no statistically significant differences in incident total or hip fracture rates between the ILI and DSE groups. However, compared to the DSE group, the ILI group had a statistically significant 39% increased risk of a frailty fracture (HR 1.39; 95% CI, 1.02 to 1.89). An intensive lifestyle intervention resulting in long-term weight loss in overweight/obese adults with DM was not associated with an overall increased risk of incident fracture but may be associated with an increased risk of frailty fracture. When intentional weight loss is planned, consideration of bone preservation and fracture prevention is warranted.

Original languageEnglish (US)
Pages (from-to)2278-2287
Number of pages10
JournalJournal of Bone and Mineral Research
Volume32
Issue number11
DOIs
StatePublished - Nov 2017

Bibliographical note

Funding Information:
This work was funded by the 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, and 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 National Institute of Diabetes and Digestive and Kidney Diseases. The Indian Health Service (I.H.S.) 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 I.H.S. 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 (GCRC) (M01RR000056), the Clinical Translational Research Center (CTRC) 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).

Funding Information:
LJC: reports membership on Medifast, Inc. Scientific Advisory Board. FLG: reports Consultant to Beachbody, Baronova, Basic Research, Eisai Inc. and General Nutrition Corporation. Advisory Board to Zafgen, Endo Pharmaceuticals, Plensat, Novo Nordisk, Nerium, Microbiome Therapeutics and Jenny Craig/Curves. Stock/Stock Options in Plensat, Neothetics and Microbiome Therapeutics. HPH: reports grants from National Institute of Diabetes, Digestive, and Kidney Disease (NIDDK) and GE stock owned as part of an IRA. JMJ: received an honorarium for serving on the Scientific Advisory Board for Weight Watchers International, was the Principal Investigator on a grant to examine the validity of activity monitors awarded to the University of Pittsburgh by Jawbone, Inc., was a co-investigator on a grant award to the University of Pittsburgh by HumanScale, and was a co-investigator on a grant awarded to the University of Pittsburgh by Weight Watchers International. ALP: reports consulting/speaking for: Eli Lilly and Company, Boehringer Ingleheim, NovoNordisk, Sanofi, Janssen, Merck, Lexicon. The remaining authors have nothing to disclose.

Funding Information:
This work was funded by the 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, and 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 National Institute of Diabetes and Digestive and Kidney Diseases. The Indian Health Service (I.H.S.) 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 I.H.S. 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 (GCRC) (M01RR000056), the Clinical Translational Research Center (CTRC) 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.

Publisher Copyright:
© 2017 American Society for Bone and Mineral Research

Keywords

  • CLINICAL TRIAL
  • FRACTURE
  • INTENTIONAL WEIGHT LOSS
  • TYPE 2 DIABETES

Fingerprint Dive into the research topics of 'The Effect of Intentional Weight Loss on Fracture Risk in Persons With Diabetes: Results From the Look AHEAD Randomized Clinical Trial'. Together they form a unique fingerprint.

Cite this