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01-04-2009 | Epidemiology

High insulin levels in newly diagnosed breast cancer patients reflect underlying insulin resistance and are associated with components of the insulin resistance syndrome

Authors: Pamela J. Goodwin, Marguerite Ennis, Mala Bahl, I. George Fantus, Kathleen I. Pritchard, Maureen E. Trudeau, Jarley Koo, Nicky Hood

Published in: Breast Cancer Research and Treatment | Issue 3/2009

Abstract

Background High insulin levels have been associated with poor outcomes in breast cancer. Our goal was to investigate whether hyperinsulinemia was associated with insulin resistance in a cohort of newly diagnosed locoregional breast cancer patients and to examine associations of hyperinsulinemia with the broader insulin resistance syndrome (IRS). Methods Five hundred and four women with T1-3, N0-1, M0 breast cancer provided fasting blood that was analyzed for glucose, insulin and lipids. They underwent anthropomorphic measurements and provided information on diet, exercise and sleep. Relationships of insulin with three validated indices of insulin resistance and with attributes of the IRS were examined. Results High insulin levels were strongly correlated with insulin resistance calculated using the three indices of insulin resistance/sensitivity (Spearman r = 0.83–0.98). Hyperinsulinemia was also associated with other components of the IRS (obesity, high waist–hip ratio, lipid profile). Conclusions High insulin levels in women with locoregional breast cancer reflect the presence of insulin resistance and are associated with other components of the IRS. These observations have implications for the development of therapies that target hyperinsulinemia in early stage breast cancer and for the long-term management of breast cancer survivors.

Seidell JC (2005) Epidemiology of obesity. Semin Vasc Med 5:3–14

Chlebowski RT, Aiello E, McTiernan A (2002) Weight loss in breast cancer patient management. J Clin Oncol 20:1128–1143PubMedCrossRef

Goodwin PJ (2006) Energy balance and cancer prognosis: breast cancer. In: McTiernan A (ed) Cancer prevention and management through exercise and weight control. CRC Press, Boca Raton, FL, pp 405–435

Goodwin PJ, Ennis M, Pritchard KI et al (2002) Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol 20:42–51PubMedCrossRef

Pasanisi P, Berrino F, De Petris M et al (2006) Metabolic syndrome as a prognostic factor for breast cancer recurrences. Int J Cancer 119:236–238PubMedCrossRef

Pollak MN, Chapman JW, Shepherd L et al (2006) Insulin resistance, estimated by serum C-peptide level, is associated with reduced event-free survival for postmenopausal women in NCIC CTG MA.14 adjuvant breast cancer trial. In: Grunberg SM (ed) Proceedings of the 42nd American society of clinical oncology annual meeting, Georgia, June 2006. Supplement to Journal of Clinical Oncology, vol 24. American Society of Clinical Oncology, Alexandria, VA, p 9s

Reaven GM (2005) The insulin resistance syndrome: definition and dietary approaches to treatment. Annu Rev Nutr 25:391–406PubMedCrossRef

Calle EE, Rodriguez C, Walker-Thurmond K et al (2003) Overweight, obesity and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 348:1625–1638PubMedCrossRef

Calle EE, Kaaks R (2004) Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 4:579–591PubMedCrossRef

10.

Morimoto LM, White E, Chen Z et al (2002) Obesity, body size, and risk of postmenopausal breast cancer: the Women’s Health Initiative (United States). Cancer Causes Control 13:741–751PubMedCrossRef

11.

Huang Z, Hankinson SE, Colditz GA et al (1997) Dual effects of weight and weight gain on breast cancer risk. JAMA 278:1407–1411PubMedCrossRef

12.

Lawlor DA, Smith GD, Ebrahim S (2004) Hyperinsulinaemia and increased risk of breast cancer: findings from the British Women’s Heart and Health Study. Cancer Causes Control 15:267–275PubMedCrossRef

13.

Yam D, Fink A, Mashiah A et al (1996) Hyperinsulinemia in colon, stomach and breast cancer patients. Cancer Lett 104:129–132PubMedCrossRef

14.

Del Giudice ME, Fantus IG, Ezzat S et al (1998) Insulin and related factors in premenopausal breast cancer risk. Breast Cancer Res Treat 47:111–120PubMedCrossRef

15.

Yang G, Lu G, Jin F et al (2001) Population-based, case–control study of blood C-peptide level and breast cancer risk. Cancer Epidemiol Biomarkers Prev 10:1207–1211PubMed

16.

Malin A, Dai Q, Yu H et al (2004) Evaluation of the synergistic effect of insulin resistance and insulin-like growth factors on the risk of breast carcinoma. Cancer 100:694–700PubMedCrossRef

17.

Bruning PF, Bonfrer JM, van Noord PA et al (1992) Insulin resistance and breast-cancer risk. Int J Cancer 52:511–516PubMedCrossRef

18.

American Diabetes Association (1998) Consensus Development Conference on Insulin Resistance. Diabetes Care 21:310–314

19.

Wallace TM, Matthews DR (2002) The assessment of insulin resistance in man. Diabet Med 19:527–534PubMedCrossRef

20.

Bonora E, Targher G, Alberiche M et al (2000) Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care 23:57–63PubMedCrossRef

21.

Katz A, Nambi SS, Mather K et al (2000) Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 85:2402–2410PubMedCrossRef

22.

McAuley KA, Williams SM, Mann JI et al (2001) Diagnosing insulin resistance in the general population. Diabetes Care 24:460–464PubMedCrossRef

23.

Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) (2001) Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 285:2486–2497

24.

Alberti KG, Zimmet PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 15:539–553PubMedCrossRef

25.

Block G, Hartman AM, Dresser CM et al (1986) A data-based approach to diet questionnaire design and testing. Am J Epidemiol 124:453–469PubMed

26.

Sallis JF, Haskell WL, Wood PD et al (1985) Physical activity assessment methodology in the Five-City Project. Am J Epidemiol 121:91–106PubMed

27.

National Institutes of Health (1982) Manual of laboratory operations, lipid research clinics program: I. Lipid and lipoprotein analysis. Bethesda, MD

28.

Meigs JB (2003) Epidemiology of the insulin resistance syndrome. Curr Diab Rep 3:73–79PubMedCrossRef

29.

Park YW, Zhu S, Palaniappan L et al (2003) The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988–1994. Arch Intern Med 163:427–436PubMedCrossRef

30.

Jorgensen ME, Bjerregaard P, Gyntelberg F et al (2004) Prevalence of the metabolic syndrome among the Inuit in Greenland. A comparison between two proposed definitions. Diabet Med 21:1237–1242PubMedCrossRef

31.

Ford ES, Giles WH (2003) A comparison of the prevalence of the metabolic syndrome using two proposed definitions. Diabetes Care 26:575–581PubMedCrossRef

32.

Marchesini G, Forlani G, Cerrelli F et al (2004) WHO and ATPIII proposals for the definition of the metabolic syndrome in patients with Type 2 diabetes. Diabet Med 21:383–387PubMedCrossRef

33.

Liao Y, Kwon S, Shaughnessy S et al (2004) Critical evaluation of adult treatment panel III criteria in identifying insulin resistance with dyslipidemia. Diabetes Care 27:978–983PubMedCrossRef

34.

Cheal KL, Abbasi F, Lamendola C et al (2004) Relationship to insulin resistance of the adult treatment panel III diagnostic criteria for identification of the metabolic syndrome. Diabetes 53:1195–1200PubMedCrossRef

35.

Ascaso JF, Pardo S, Real JT et al (2003) Diagnosing insulin resistance by simple quantitative methods in subjects with normal glucose metabolism. Diabetes Care 26:3320–3325PubMedCrossRef

36.

Ruderman N, Chisholm D, Pi-Sunyer X et al (1998) The metabolically obese, normal-weight individual revisited. Diabetes 47:699–713PubMedCrossRef

37.

Punjabi NM, Polotsky VY (2005) Disorders of glucose metabolism in sleep apnea. J Appl Physiol 99:1998–2007PubMedCrossRef

38.

Meisinger C, Heier M, Loewel H (2005) Sleep disturbance as a predictor of type 2 diabetes mellitus in men and women from the general population. Diabetologia 48:235–241PubMedCrossRef

39.

Spiegel K, Knutson K, Leproult R et al (2005) Sleep loss: a novel risk factor for insulin resistance and Type 2 diabetes. J Appl Physiol 99:2008–2019PubMedCrossRef

40.

Frasca F, Pandini G, Vigneri R et al (2003) Insulin and hybrid insulin/IGF receptors are major regulators of breast cancer cells. Breast Dis 17:73–89PubMed

41.

Sandhu MS, Dunger DB, Giovannucci EL (2002) Insulin, insulin-like growth factor-I (IGF-I), IGF binding proteins, their biologic interactions, and colorectal cancer. J Natl Cancer Inst 94:972–980PubMed

42.

Kaaks R (1996) Nutrition, hormones, and breast cancer: is insulin the missing link? Cancer Causes Control 7:605–625PubMedCrossRef

43.

Plymate SR, Matej LA, Jones RE et al (1988) Inhibition of sex hormone-binding globulin production in the human hepatoma (Hep G2) cell line by insulin and prolactin. J Clin Endocrinol Metab 67:460–464PubMedCrossRef

44.

Lee AV, Cui X, Oesterreich S (2001) Cross-talk among estrogen receptor, epidermal growth factor, and insulin-like growth factor signaling in breast cancer. Clin Cancer Res 7:4429s–4435sPubMed

45.

Yee D, Lee AV (2000) Crosstalk between the insulin-like growth factors and estrogens in breast cancer. J Mammary Gland Biol Neoplasia 5:107–115PubMedCrossRef

46.

Orchard TJ, Temprosa M, Goldberg R et al (2005) The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: the Diabetes Prevention Program randomized trial. Ann Intern Med 142:611–619PubMed

47.

Goodwin PJ, Pritchard KI, Fantus IG, Ennis M, Clemons M, Graham M (2006) Metformin lowers fasting insulin levels in hyperinsulinemia early stage breast cancer patients––results of a phase II study. Breast Cancer Res Treat 100(Suppl 1):A2085

48.

Ligibel JA, Campbell N, Partridge A et al (2008) Impact of a mixed strength and endurance exercise intervention on insulin levels in breast cancer survivors. J Clin Oncol 26:907–912PubMedCrossRef

49.

Goodwin PJ (2008) Insulin in the adjuvant breast cancer setting: a novel therapeutic target for lifestyle and pharmacologic intervention? J Clin Oncol 26:833–834PubMedCrossRef

50.

Chapman J-A, Meng D, Shepherd L et al (2008) Competing causes of death from a randomized trial of extended adjuvant endocrine therapy for breast cancer. J Natl Cancer Inst 200:252–260

51.

Schairer C, Mink PJ, Carroll L et al (2004) Probabilities of death from breast cancer and other causes among female breast cancer patients. J Natl Cancer Inst 96:1311–1321PubMedCrossRef

Title: High insulin levels in newly diagnosed breast cancer patients reflect underlying insulin resistance and are associated with components of the insulin resistance syndrome
Authors: Pamela J. Goodwin
Marguerite Ennis
Mala Bahl
I. George Fantus
Kathleen I. Pritchard
Maureen E. Trudeau
Jarley Koo
Nicky Hood
Publication date: 01-04-2009
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 3/2009
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-008-0019-0

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