Top

Published in:

Open Access 01-12-2018 | Research article

Impact of a behaviorally-based weight loss intervention on parameters of insulin resistance in breast cancer survivors

Authors: Kim L. Dittus, Jean R. Harvey, Janice Y. Bunn, Nathan D. Kokinda, Karen M. Wilson, Jeff Priest, Richard E. Pratley

Published in: BMC Cancer | Issue 1/2018

Abstract

Background

Breast cancer survivors with excess weight are more likely to have negative breast cancer outcomes. Biomarkers related to insulin resistance may help explain this negative association. Weight loss is associated with improvements in insulin sensitivity. Our goal was to identify the impact of a behaviorally based weight loss intervention on indices of insulin resistance.

Methods

Overweight, early stage breast cancer survivors who completed initial cancer therapy were enrolled in a 6 month behaviorally based weight loss intervention that included calorie reduction, exercise and behavior modification. Biomarkers related to insulin resistance were obtained at baseline and after the intervention. Results from participants who achieved ≥5% weight loss were compared to those who lost less weight.

Results

Despite not having diabetes as a preexisting diagnosis prior to the study, 69% of all participants were considered to have pre-diabetes or diabetes at baseline based on American Diabetes Association definitions. Participants who achieved ≥5% weight loss had significantly lower fasting insulin, AUC insulin, and insulin resistance as measured by HOMA-IR. Beta cell function decreased as anticipated when insulin resistance improved. Additionally, leptin levels declined.

Conclusions

Breast cancer survivors who achieved ≥5% weight loss demonstrated significant improvements in indices of insulin resistance. Despite an exclusion criteria of diabetes at the time of enrolment, a high proportion met criteria for pre-diabetes or diabetes at baseline. Pre-diabetes appears to be under recognized in overweight breast cancer survivors. Behaviorally based weight loss interventions can result in weight loss and improvements in biomarkers related to breast cancer outcomes and additionally may decrease the chance of developing diabetes.

Trial registration

NCT01482702 4/12/2010 (retrospectively registered). https://clinicaltrials.gov/ct2/show/NCT01482702?term=Dittus&rank=4

Dawood S, Broglio K, Gonzalez-Angulo AM, Kau SW, Islam R, Hortobagyi GN, Cristofanilli M. Prognostic value of body mass index in locally advanced breast cancer. Clin Cancer Res. 2008;14(6):1718–25. https://doi.org/10.1158/1078-0432.ccr-07-1479.CrossRefPubMed

Protani M, Coory M, Martin JH. Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer Res Treat. 2010;123(3):627–35. https://doi.org/10.1007/s10549-010-0990-0.CrossRefPubMed

Chan DS, Vieira AR, Aune D, Bandera EV, Greenwood DC, McTiernan A, Navarro Rosenblatt D, Thune I, Vieira R, Norat T. Body mass index and survival in women with breast cancer-systematic literature review and meta-analysis of 82 follow-up studies. Ann Oncol. 2014;25(10):1901–14. https://doi.org/10.1093/annonc/mdu042.CrossRefPubMedPubMedCentral

Nichols HB, Trentham-Dietz A, Egan KM, Titus-Ernstoff L, Holmes MD, Bersch AJ, Holick CN, Hampton JM, Stampfer MJ, Willett WC, Newcomb PA. Body mass index before and after breast cancer diagnosis: associations with all-cause, breast cancer, and cardiovascular disease mortality. Cancer Epidemiol Biomarkers Prev. 2009;18(5):1403–9. https://doi.org/10.1158/1055-9965.epi-08-1094.CrossRefPubMedPubMedCentral

Goodwin PJ, Ennis M, Pritchard KI, Trudeau ME, Koo J, Madarnas Y, Hartwick W, Hoffman B, Hood N. Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol. 2002;20(1):42–51.CrossRefPubMed

Gallagher EJ, LeRoith D. Insulin, insulin resistance, obesity, and cancer. Curr Diab Rep. 2010;10(2):93–100. https://doi.org/10.1007/s11892-010-0101-y.CrossRefPubMed

Mantzoros C, Petridou E, Dessypris N, Chavelas C, Dalamaga M, Alexe DM, Papadiamantis Y, Markopoulos C, Spanos E, Chrousos G, Trichopoulos D. Adiponectin and breast cancer risk. J Clin Endocrinol Metab. 2004;89(3):1102–7. https://doi.org/10.1210/jc.2003-031804.CrossRefPubMed

Rose DP, Komninou D, Stephenson GD. Obesity, adipocytokines, and insulin resistance in breast cancer. Obes Rev. 2004;5(3):153–65. https://doi.org/10.1111/j.1467-789X.2004.00142.x.CrossRefPubMed

Kannel WB, Gordon T, Castelli WP. Obesity, lipids, and glucose intolerance. The Framingham study. Am J Clin Nutr. 1979;32(6):1238–45.CrossRefPubMed

10.

Mason C, Foster-Schubert KE, Imayama I, Kong A, Xiao L, Bain C, Campbell KL, Wang CY, Duggan CR, Ulrich CM, Alfano CM, Blackburn GL, McTiernan A. Dietary weight loss and exercise effects on insulin resistance in postmenopausal women. Am J Prev Med. 2011;41(4):366–75. https://doi.org/10.1016/j.amepre.2011.06.042.CrossRefPubMedPubMedCentral

11.

Rock CL, Pande C, Flatt SW, Ying C, Pakiz B, Parker BA, Williams K, Bardwell WA, Heath DD, Nichols JF. Favorable changes in serum estrogens and other biologic factors after weight loss in breast cancer survivors who are overweight or obese. Clin Breast Cancer. 2013;13(3):188–95. https://doi.org/10.1016/j.clbc.2012.12.002.CrossRefPubMedPubMedCentral

12.

Campbell KL, Van Patten CL, Neil SE, Kirkham AA, Gotay CC, Gelmon KA, McKenzie DC. Feasibility of a lifestyle intervention on body weight and serum biomarkers in breast cancer survivors with overweight and obesity. J Acad Nutr Diet. 2012;112(4):559–67. https://doi.org/10.1016/j.jada.2011.10.022.CrossRefPubMed

13.

Dittus K, Bunn J, Kokinda N, Wilson K, Howard A. Effectiveness of an internet delivered behavioral weight loss intervention delivered to breast Cancer survivors. Adv Obes Weight Manag Control. 2015;2(3):00027.

14.

Harvey-Berino J, West D, Krukowski R, Prewitt E, VanBiervliet A, Ashikaga T, Skelly J. Internet delivered behavioral obesity treatment. Prev Med. 2010;51(2):123–8. https://doi.org/10.1016/j.ypmed.2010.04.018.CrossRefPubMedPubMedCentral

15.

Jen KL, Djuric Z, DiLaura NM, Buison A, Redd JN, Maranci V, Hryniuk WM. Improvement of metabolism among obese breast cancer survivors in differing weight loss regimens. Obes Res. 2004;12(2):306–12. https://doi.org/10.1038/oby.2004.38.CrossRefPubMed

16.

Look ARG, Wadden TA, West DS, Delahanty L, Jakicic J, Rejeski J, Williamson D, Berkowitz RI, Kelley DE, Tomchee C, Hill JO, Kumanyika S. The look AHEAD study: a description of the lifestyle intervention and the evidence supporting it. Obesity (Silver Spring, Md). 2006;14(5):737–52. https://doi.org/10.1038/oby.2006.84.CrossRef

17.

Diabetes Prevention Program Research G. The diabetes prevention program (DPP): description of lifestyle intervention. Diabetes Care. 2002;25(12):2165–71.CrossRef

18.

Jeffery RW, Wing RR, Thorson C, Burton LR, Raether C, Harvey J, Mullen M. Strengthening behavioral interventions for weight loss: a randomized trial of food provision and monetary incentives. J Consult Clin Psychol. 1993;61(6):1038–45.CrossRefPubMed

19.

Jakicic JM, Winters C, Lang W, Wing RR. Effects of intermittent exercise and use of home exercise equipment on adherence, weight loss, and fitness in overweight women: a randomized trial. JAMA. 1999;282(16):1554–60.CrossRefPubMed

20.

Jakicic JM, Marcus BH, Gallagher KI, Napolitano M, Lang W. Effect of exercise duration and intensity on weight loss in overweight, sedentary women: a randomized trial. JAMA. 2003;290(10):1323–30. https://doi.org/10.1001/jama.290.10.1323.CrossRefPubMed

21.

American Diabetes Association. Classification and diagnosis of diabetes. Diabetes Care. 2015;38(Suppl):S8–S16.

22.

Allison DB, Paultre F, Maggio C, Mezzitis N, Pi-Sunyer FX. The use of areas under curves in diabetes research. Diabetes Care. 1995;18(2):245–50.CrossRefPubMed

23.

Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999;22(9):1462–70.CrossRefPubMed

24.

Muniyappa R, Lee S, Chen H, Quon MJ. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab. 2008;294(1):E15–26. https://doi.org/10.1152/ajpendo.00645.2007.CrossRefPubMed

25.

Wallace TM, Matthews DR. The assessment of insulin resistance in man. Diabet Med. 2002;19(7):527–34.CrossRefPubMed

26.

Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care. 2004;27(6):1487–95.CrossRefPubMed

27.

Weyer C, Hanson K, Bogardus C, Pratley RE. Long-term changes in insulin action and insulin secretion associated with gain, loss, regain and maintenance of body weight. Diabetologia. 2000;43(1):36–46. https://doi.org/10.1007/s001250050005.CrossRefPubMed

28.

Goldstein DJ, Rampey AH Jr, Roback PJ, Wilson MG, Hamilton SH, Sayler ME, Tollefson GD. Efficacy and safety of long-term fluoxetine treatment of obesity--maximizing success. Obes Res. 1995;3 Suppl 4:481s–90s.CrossRefPubMed

29.

Goodwin PJ. Insulin in the adjuvant breast cancer setting: a novel therapeutic target for lifestyle and pharmacologic interventions? J Clin Oncol. 2008;26(6):833–4. https://doi.org/10.1200/jco.2007.14.7132.CrossRefPubMed

30.

Pi-Sunyer X, Kris-Etherton PM. Improving health outcomes: future directions in the field. J Am Diet Assoc. 2005;105(5 Suppl 1):S14–6. https://doi.org/10.1016/j.jada.2005.02.027.CrossRefPubMed

31.

Arcidiacono B, Iiritano S, Nocera A, Possidente K, Nevolo MT, Ventura V, Foti D, Chiefari E, Brunetti A. Insulin resistance and cancer risk: an overview of the pathogenetic mechanisms. Exp Diabetes Res. 2012;2012:789174. https://doi.org/10.1155/2012/789174.CrossRefPubMedPubMedCentral

32.

Befort CA, Klemp JR, Austin HL, Perri MG, Schmitz KH, Sullivan DK, Fabian CJ. Outcomes of a weight loss intervention among rural breast cancer survivors. Breast Cancer Res Treat. 2012;132(2):631–9. https://doi.org/10.1007/s10549-011-1922-3.CrossRefPubMed

33.

Facchini FS, Hua N, Abbasi F, Reaven GM. Insulin resistance as a predictor of age-related diseases. J Clin Endocrinol Metab. 2001;86(8):3574–8. https://doi.org/10.1210/jcem.86.8.7763.CrossRefPubMed

34.

Cowey S, Hardy RW. The metabolic syndrome: A high-risk state for cancer? Am J Pathol. 169(5):2006, 1505–1522. https://doi.org/10.2353/ajpath.2006.051090.

35.

Thomson CA, Stopeck AT, Bea JW, Cussler E, Nardi E, Frey G, Thompson PA. Changes in body weight and metabolic indexes in overweight breast cancer survivors enrolled in a randomized trial of low-fat vs. reduced carbohydrate diets. Nutr Cancer. 2010;62(8):1142–52. https://doi.org/10.1080/01635581.2010.513803.CrossRefPubMed

36.

Goodwin PJ. Obesity, insulin resistance and breast cancer outcomes. Breast. 2015; https://doi.org/10.1016/j.breast.2015.07.014.

37.

Trayhurn P, Bing C, Wood IS. Adipose tissue and adipokines--energy regulation from the human perspective. J Nutr. 2006;136(7 Suppl):1935S–9S.CrossRefPubMed

38.

Vona-Davis L, Rose DP. Angiogenesis, adipokines and breast cancer. Cytokine Growth Factor Rev. 2009;20(3):193–201. https://doi.org/10.1016/j.cytogfr.2009.05.007.CrossRefPubMed

39.

Guo S, Liu M, Wang G, Torroella-Kouri M, Gonzalez-Perez RR. Oncogenic role and therapeutic target of leptin signaling in breast cancer and cancer stem cells. Biochim Biophys Acta. 2012;1825(2):207–22. https://doi.org/10.1016/j.bbcan.2012.01.002.PubMedPubMedCentral

40.

Carter S, Caron A, Richard D, Picard F. Role of leptin resistance in the development of obesity in older patients. Clin Interv Aging. 2013;8:829–44. https://doi.org/10.2147/CIA.S36367.PubMedPubMedCentral

41.

Harrigan M, Cartmel B, Loftfield E, Sanft T, Chagpar AB, Zhou Y, Playdon M, Li F, Irwin ML. Randomized trial comparing telephone versus in-person weight loss counseling on body composition and circulating biomarkers in women treated for breast Cancer: the lifestyle, exercise, and nutrition (LEAN) study. J Clin Oncol. 2016;34(7):669–76. https://doi.org/10.1200/JCO.2015.61.6375.CrossRefPubMed

42.

Thompson HJ, Sedlacek SM, Wolfe P, Paul D, Lakoski SG, Playdon MC, McGinley JN, Matthews SB. Impact of weight loss on plasma leptin and adiponectin in overweight-to-obese post menopausal breast Cancer survivors. Nutrients. 2015;7(7):5156–76. https://doi.org/10.3390/nu7075156.CrossRefPubMedPubMedCentral

43.

Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996;334(5):292–5. https://doi.org/10.1056/NEJM199602013340503.CrossRefPubMed

44.

Ligibel JA, Campbell N, Partridge A, Chen WY, Salinardi T, Chen H, Adloff K, Keshaviah A, Winer EP. Impact of a mixed strength and endurance exercise intervention on insulin levels in breast cancer survivors. J Clin Oncol. 2008;26(6):907–12. https://doi.org/10.1200/JCO.2007.12.7357.CrossRefPubMed

45.

Irwin ML, Varma K, Alvarez-Reeves M, Cadmus L, Wiley A, Chung GG, Dipietro L, Mayne ST, Yu H. Randomized controlled trial of aerobic exercise on insulin and insulin-like growth factors in breast cancer survivors: the Yale exercise and survivorship study. Cancer Epidemiol Biomark Prev. 2009;18(1):306–13. https://doi.org/10.1158/1055-9965.EPI-08-0531.CrossRef

46.

Miller JP, Pratley RE, Goldberg AP, Gordon P, Rubin M, Treuth MS, Ryan AS, Hurley BF. Strength training increases insulin action in healthy 50- to 65-yr-old men. J Appl Physiol (1985). 1994;77(3):1122–7.CrossRef

47.

Mann S, Beedie C, Balducci S, Zanuso S, Allgrove J, Bertiato F, Jimenez A. Changes in insulin sensitivity in response to different modalities of exercise: a review of the evidence. Diabetes Metab Res Rev. 2014;30(4):257–68. https://doi.org/10.1002/dmrr.2488.CrossRefPubMed

Title: Impact of a behaviorally-based weight loss intervention on parameters of insulin resistance in breast cancer survivors
Authors: Kim L. Dittus
Jean R. Harvey
Janice Y. Bunn
Nathan D. Kokinda
Karen M. Wilson
Jeff Priest
Richard E. Pratley
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-018-4272-2

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

ACC 2024 Congress

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2018

Human mesenchymal stem cells in the tumour microenvironment promote ovarian cancer progression: the role of platelet-activating factor

Elevated expression of hyaluronan synthase 2 associates with decreased survival in diffusely infiltrating astrocytomas

Impact of renal impairment on outcomes after autologous stem cell transplantation in multiple myeloma: a multi-center, retrospective cohort study

The predictive powers of plasma trefoil factor 3 or its related micro RNAs for patients with hepatocellular carcinoma

Prognostic value of differentiation status in gastric cancer

Relationship between the extent of resection and the survival of patients with low-grade gliomas: a systematic review and meta-analysis

Keynote webinar | Spotlight on antibody–drug conjugates in cancer