Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Cancer Causes & Control
Published in: Cancer Causes & Control 5/2010

01-05-2010 | Original paper

Insulin resistance-related biomarker clustering and subclinical inflammation as predictors of cancer mortality during 21.5 years of follow-up

Authors: Wann J. Loh, Bernard V. North, Desmond G. Johnston, Ian F. Godsland

Published in: Cancer Causes & Control | Issue 5/2010

Login to get access

Abstract

Objectives

Risk of cancer is increased in conditions associated with insulin resistance, but this could be secondary to subclinical inflammation. We evaluated whether insulinemia, indices of insulin resistance or a validated insulin resistance-related biomarker cluster, could predict cancer mortality independently of subclinical inflammation.

Methods

Fasting insulin and glucose concentrations and insulin-related metabolic variables were recorded in 1,016 white males, of whom 718 also had an oral glucose tolerance test (OGTT). Baseline measurements included the following: fasting insulin and the derived insulin resistance index, HOMA-IR; OGTT insulin and the derived insulin resistance index, Matsuda-IS; the factor score for a validated insulin resistance-related biomarker cluster; white blood cell count; erythrocyte sedimentation rate; and serum albumin and globulin concentrations.

Results

There were 105 deaths from cancer during the 21.5-year mean follow-up. Insulin concentrations and insulin resistance were not predictive. Insulin resistance-related biomarker clustering predicted cancer mortality (hazard ratio 1.65, 95% CI 1.26–2.17, p < 0.001). Subclinical inflammation markers were also predictive, but the insulin resistance-related biomarker cluster predicted cancer mortality independently of these and was particularly associated with death from colorectal cancer.

Conclusions

Despite insulin concentrations or derived indices of insulin resistance failing to predict cancer mortality, insulin resistance-related biomarker clustering was highly predictive and predicted independently of simple measures of subclinical inflammation.
Literature
1.
2.
Giovannucci E, Colditz GA, Stampfer MJ, Willett WC (1996) Physical activity, obesity, and risk of colorectal adenoma in women (United States). Cancer Causes Control 7:253–263CrossRefPubMed
3.
Schoen RE, Tangen CM, Kuller LH, Burke GL, Cushman M, Tracy RP, Dobs A, Savage PJ (1999) Increased blood glucose and insulin, body size, and incident colorectal cancer. J Natl Cancer Inst 91:1147–1154CrossRefPubMed
4.
Coughlin SS, Calle EE, Teras LR, Petrelli J, Thun MJ (2004) Diabetes mellitus as a predictor of cancer mortality in a large cohort of US adults. Am J Epidemiol 159:1160–1167CrossRefPubMed
5.
Rapp K, Schroeder J, Klenk J, Ulmer H, Concin H, Diem G, Oberaigner W, Weiland SK (2006) Fasting blood glucose and cancer risk in a cohort of more than 140,000 adults in Austria. Diabetologia 49:945–952CrossRefPubMed
6.
Trevisan M, Liu J, Muti P, Misciagna G, Menotti A, Fucci F, Factors, and, Life, Expectancy, Research, Group (2001) Markers of insulin resistance and colorectal cancer mortality. Cancer Epidemiol Biomarkers Prev 10:937–941PubMed
7.
8.
Smith U, Gale EA (2009) Does diabetes therapy influence the risk of cancer? Diabetologia 52:1699–1708CrossRefPubMed
9.
Gliozzo B, Sung CK, Scalia P, Papa V, Frasca F, Sciacca L, Giorgino F, Milazzo G, Goldfine ID, Vigneri R, Pezzino V (1998) Insulin-stimulated cell growth in insulin receptor substrate-1-deficient ZR-75–1 cells is mediated by a phosphatidylinositol-3-kinase-independent pathway. J Cell Biochem 70:268–280CrossRefPubMed
10.
11.
Bailyes EM, Navé BT, Soos MA, Orr SR, Hayward AC, Siddle K (1997) Insulin receptor/IGF-I receptor hybrids are widely distributed in mammalian tissues: quantification of individual receptor species by selective immunoprecipitation and immunoblotting. Biochem J 327:209–215PubMed
12.
Snyder DK, Clemmons DR (1990) Insulin-dependent regulation of insulin-like growth factor-binding protein-1. J Clin Endocrinol Metab 71:1632–1636CrossRefPubMed
13.
Koohestani N, Chia MC, Pham NA, Tran TT, Minkin S, Wolever TM, Bruce WR (1998) Aberrant crypt focus promotion and glucose intolerance: correlation in the rat across diets differing in fat, n-3 fatty acids and energy. Carcinogenesis 19:1679–1684CrossRefPubMed
14.
Tran TT, Gupta N, Goh T, Naigamwalla D, Chia MC, Koohestani N, Mehrotra S, McKeown-Eyssen G, Giacca A, Bruce WR (2003) Direct measure of insulin sensitivity with the hyperinsulinemic-euglycemic clamp and surrogate measures of insulin sensitivity with the oral glucose tolerance test: correlations with aberrant crypt foci promotion in rats. Cancer Epidemiol Biomarkers Prev 12:47–56PubMed
15.
Pisani P (2008) Hyper-insulinaemia and cancer, meta-analyses of epidemiological studies. Arch Physiol Biochem 114:63–70CrossRefPubMed
16.
Gunter MJ, Hoover DR, Yu H, Wassertheil-Smoller S, Rohan TE, Manson JE, Li J, Ho GY, Xue X, Anderson GL, Kaplan RC, Harris TG, Howard BV, Wylie-Rosett J, Burk RD, Strickler HD (2009) Insulin, insulin-like growth factor-I, and risk of breast cancer in postmenopausal women. J Natl Cancer Inst 101:48–60PubMed
17.
Kabat GC, Kim M, Caan BJ, Chlebowski RT, Gunter MJ, Ho GY, Rodriguez BL, Shikany JM, Strickler HD, Vitolins MZ, Rohan TE (2009) Repeated measures of serum glucose and insulin in relation to postmenopausal breast cancer. Int J Cancer 125:2704–2710CrossRefPubMed
18.
Muniyappa R, Lee S, Chen H, Quon MJ (2008) Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab 294:E15–E26CrossRefPubMed
19.
Godsland IF (1985) Intra-individual variation: significant changes in parameters of lipid and carbohydrate metabolism in the individual and intra-individual variation in different test populations. Ann Clin Biochem 22:618–624PubMed
20.
Shoelson SE, Lee J, Goldfine AB (2006) Inflammation and insulin resistance. J Clin Invest 116:1793–1801CrossRefPubMed
21.
Hussain SP, Harris CC (2007) Inflammation and cancer: an ancient link with novel potentials. Int J Cancer 121:2373–2380CrossRefPubMed
22.
Godsland IF, Johnston DG (2008) Co-associations between insulin sensitivity and measures of liver function, subclinical inflammation and hematology. Metabolism 57:1190–1197CrossRefPubMed
23.
Godsland IF, Leyva F, Worthington M, Walton C, Stevenson JC (1998) Associations of smoking, alcohol and physical activity with risk factors for coronary heart disease and diabetes in the first follow-up cohort of the HDDRISC Study (HDDRISC-1). J Intern Med 244:33–41CrossRefPubMed
24.
Durnin J, Womersley J (1974) Body fat assessed from total body density and its estimation from skinfold thickness: measurements on 481 men and women aged from 16 to 72 years. Br J Nutr 32:77–97CrossRefPubMed
25.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and ß-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419CrossRefPubMed
26.
Matsuda M, DeFronzo RA (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing. Diabetes Care 22:1462–1470CrossRefPubMed
27.
Godsland IF, Rosankiewicz JR, Proudler AJ, Johnston DG (2001) Plasma total homocysteine concentrations are unrelated to insulin sensitivity and components of the metabolic syndrome in healthy men. J Clin Endocrinol Metab 86:719–723CrossRefPubMed
28.
Pintilie M (2006) Competing risks: a practical perspective. Wiley, Chichester
29.
Fine JP, Gray RJ (1999) A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94:496–509CrossRef
30.
31.
32.
Shankar A, Wang JJ, Rochtchina E, Yu MC, Kefford R, Mitchell P (2006) Association between circulating white blood cell count and cancer mortality: a population-based cohort study. Arch Intern Med 23:188–194CrossRef
33.
Phillips A, Shaper AG, Whincup PH (1989) Association between serum albumin and mortality from cardiovascular disease, cancer, and other causes. Lancet ii:1434–1436CrossRef
34.
Engel LW, Strauchen JA, Chiazze L Jr, Heid M (1980) Accuracy of death certification in an autopsied population with specific attention to malignant neoplasms and vascular diseases. Am J Epidemiol 111:99–112PubMed
35.
Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ (2006) Cancer statistics, 2006. CA Cancer J Clin 56:106–130CrossRefPubMed
36.
Colangelo LA, Gapstur SM, Gann PH, Dyer AR, Liu K (2002) Colorectal cancer mortality and factors related to the insulin resistance syndrome. Cancer Epidemiol Biomarkers Prev 11:385–391PubMed
37.
Ahmed RL, Schmitz KH, Anderson KE, Rosamond WD, Folsom AR (2006) The metabolic syndrome and risk of incident colorectal cancer. Cancer 107:28–36CrossRefPubMed
38.
Bowers K, Albanes D, Limburg P, Pietinen P, Taylor PR, Virtamo J, Stolzenberg-Solomon RZ (2006) A prospective study of anthropometric and clinical measurements associated with insulin resistance syndrome and colorectal cancer in male smokers. Am J Epidemiol 164:652–664CrossRefPubMed
39.
Stocks T, Lukanova A, Johansson M, Rinaldi S, Palmqvist R, Hallmans G, Kaaks R, Stattin P (2008) Components of the metabolic syndrome and colorectal cancer risk; a prospective study. Int J Obes (Lond) 32:304–314CrossRef
40.
Stürmer T, Buring JE, Lee IM, Gaziano JM, Glynn RJ (2006) Metabolic abnormalitities and risk for colorectal cancer in the Physicians’ Health Study. Cancer Epidemiol Biomarkers Prev 15:2391–2397CrossRefPubMed
41.
Hemkens LG, Grouven U, Bender R, Günster C, Gutschmidt S, Selke GW, Sawicki PT (2009) Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study. Diabetologia 52:1732–1744CrossRefPubMed
Metadata
Title
Insulin resistance-related biomarker clustering and subclinical inflammation as predictors of cancer mortality during 21.5 years of follow-up
Authors
Wann J. Loh
Bernard V. North
Desmond G. Johnston
Ian F. Godsland
Publication date
01-05-2010
Publisher
Springer Netherlands
Published in
Cancer Causes & Control / Issue 5/2010
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-009-9499-4

Other articles of this Issue 5/2010

Cancer Causes & Control 5/2010 Go to the issue

Original paper

Statin drugs, serum cholesterol, and prostate-specific antigen in the National Health and Nutrition Examination Survey 2001–2004

Original paper

Genetic variation in chromosomal translocation breakpoint and immune function genes and risk of non-Hodgkin lymphoma

Original paper

Prospective study of physical activity and risk of primary adenocarcinomas of the oesophagus and stomach in the EPIC (European Prospective Investigation into Cancer and nutrition) cohort

Original paper

Lifetime exposure to arsenic in drinking water and bladder cancer: a population-based case–control study in Michigan, USA

Original paper

Defining research priorities for pancreatic cancer in Australia: results of a consensus development process

Original paper

Birth weight, breast cancer susceptibility loci, and breast cancer risk
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
Image Credits