Insulin, Glucose, Insulin Resistance, and Incident Colorectal Cancer in Male Smokers

Overview

Journal Clin Gastroenterol Hepatol

Specialty Gastroenterology

Date 2006 Dec 13

PMID 17162243

Citations 49

Authors

Paul J Limburg

Rachael Z Stolzenberg-Solomon

Robert A Vierkant

Katherine Roberts

Thomas A Sellers

Philip R Taylor

Jarmo Virtamo

James R Cerhan

Demetrius Albanes

Affiliations

Soon will be listed here.

Abstract

Background & Aims: Hyperinsulinemia is a putative colorectal cancer (CRC) risk factor. Insulin resistance (IR) commonly precedes hyperinsulinemia and can be quantitatively measured by using the homeostasis model assessment-insulin resistance (HOMA-IR) index. To date, few studies have directly examined serum insulin as an indicator of CRC risk, and none have reported associations on the basis of HOMA-IR.

Methods: We performed a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study (n=29,133). Baseline exposure and fasting serum biomarker data were available for 134 incident CRC case and 399 non-case subjects. HOMA-IR was derived as fasting insulin x fasting glucose/22.5. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by using age-adjusted and multivariable-adjusted Cox proportional hazards regression models.

Results: Median (interquartile range) values for serum insulin, glucose, and HOMA-IR were 4.1 (2.9-7.2) mIU/L, 101 (94-108) mg/dL, and 0.99 (0.69-1.98) for case subjects and 4.1 (2.7-6.1) mIU/L, 99 (93-107) mg/dL, and 1.02 (0.69-1.53) for non-case subjects, respectively. On the basis of comparison of the highest versus lowest quartiles for each biomarker, insulin (HR, 1.84; 95% CI, 1.03-3.30) and HOMA-IR (HR, 1.85; 95% CI, 1.06-3.24) were significantly associated with incident CRC, whereas glucose was marginally associated with incident CRC (HR, 1.70; 95% CI, 0.92-3.13) in age-adjusted risk models. However, trends across biomarker quartiles were somewhat inconsistent (P trend=.12, .04, and .12, respectively), and multivariable adjustment generally attenuated the observed risk estimates.

Conclusions: Data from this prospective study of male smokers provide limited support for hyperinsulinemia, hyperglycemia, and/or insulin resistance as CRC risk factors.

Citing Articles

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Li W, Liu T, Qian L, Wang Y, Ma X, Cao L Front Endocrinol (Lausanne). 2022; 13:983160.

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References

Colangelo L, Gapstur S, Gann P, Dyer A, Liu K . Colorectal cancer mortality and factors related to the insulin resistance syndrome. Cancer Epidemiol Biomarkers Prev. 2002; 11(4):385-91. View

Hedblad B, Nilsson P, Engstrom G, Berglund G, Janzon L . Insulin resistance in non-diabetic subjects is associated with increased incidence of myocardial infarction and death. Diabet Med. 2002; 19(6):470-5. DOI: 10.1046/j.1464-5491.2002.00719.x. View

Bonora E, Formentini G, Calcaterra F, Lombardi S, Marini F, Zenari L . HOMA-estimated insulin resistance is an independent predictor of cardiovascular disease in type 2 diabetic subjects: prospective data from the Verona Diabetes Complications Study. Diabetes Care. 2002; 25(7):1135-41. DOI: 10.2337/diacare.25.7.1135. View

Hanley A, Williams K, Stern M, Haffner S . Homeostasis model assessment of insulin resistance in relation to the incidence of cardiovascular disease: the San Antonio Heart Study. Diabetes Care. 2002; 25(7):1177-84. DOI: 10.2337/diacare.25.7.1177. View

Wallace T, Matthews D . The assessment of insulin resistance in man. Diabet Med. 2002; 19(7):527-34. DOI: 10.1046/j.1464-5491.2002.00745.x. View

Korhonen P, Malila N, Pukkala E, Teppo L, Albanes D, Virtamo J . The Finnish Cancer Registry as follow-up source of a large trial cohort--accuracy and delay. Acta Oncol. 2002; 41(4):381-8. DOI: 10.1080/028418602760169442. View

Rajala U, Laakso M, Paivansalo M, Pelkonen O, Suramo I, Keinanen-Kiukaanniemi S . Low insulin sensitivity measured by both quantitative insulin sensitivity check index and homeostasis model assessment method as a risk factor of increased intima-media thickness of the carotid artery. J Clin Endocrinol Metab. 2002; 87(11):5092-7. DOI: 10.1210/jc.2002-020703. View

Vanhala P, Vanhala M, Kumpusalo E, Keinanen-Kiukaanniemi S . The quantitative insulin sensitivity check index QUICKI predicts the onset of type 2 diabetes better than fasting plasma insulin in obese subjects: a 5-year follow-up study. J Clin Endocrinol Metab. 2002; 87(12):5834-7. DOI: 10.1210/jc.2002-020591. View

Marugame T, Lee K, Eguchi H, Oda T, Shinchi K, Kono S . Relation of impaired glucose tolerance and diabetes mellitus to colorectal adenomas in Japan. Cancer Causes Control. 2003; 13(10):917-21. DOI: 10.1023/a:1021967301138. View

10.

Saydah S, Platz E, Rifai N, Pollak M, Brancati F, Helzlsouer K . Association of markers of insulin and glucose control with subsequent colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 2003; 12(5):412-8. View

11.

Saydah S, Loria C, Eberhardt M, Brancati F . Abnormal glucose tolerance and the risk of cancer death in the United States. Am J Epidemiol. 2003; 157(12):1092-100. DOI: 10.1093/aje/kwg100. View

12.

Chang C, Ulrich C . Hyperinsulinaemia and hyperglycaemia: possible risk factors of colorectal cancer among diabetic patients. Diabetologia. 2003; 46(5):595-607. DOI: 10.1007/s00125-003-1109-5. View

13.

Reaven G . The insulin resistance syndrome. Curr Atheroscler Rep. 2003; 5(5):364-71. DOI: 10.1007/s11883-003-0007-0. View

14.

Einhorn D, Reaven G, Cobin R, Ford E, Ganda O, Handelsman Y . American College of Endocrinology position statement on the insulin resistance syndrome. Endocr Pract. 2003; 9(3):237-52. View

15.

Palmqvist R, Stattin P, Rinaldi S, Biessy C, Stenling R, Riboli E . Plasma insulin, IGF-binding proteins-1 and -2 and risk of colorectal cancer: a prospective study in northern Sweden. Int J Cancer. 2003; 107(1):89-93. DOI: 10.1002/ijc.11362. View

16.

Monzillo L, Hamdy O . Evaluation of insulin sensitivity in clinical practice and in research settings. Nutr Rev. 2004; 61(12):397-412. DOI: 10.1301/nr.2003.dec.397-412. View

17.

Ma J, Giovannucci E, Pollak M, Leavitt A, Tao Y, Gaziano J . A prospective study of plasma C-peptide and colorectal cancer risk in men. J Natl Cancer Inst. 2004; 96(7):546-53. DOI: 10.1093/jnci/djh082. View

18.

Lawlor D, Davey Smith G, Ebrahim S . Hyperinsulinaemia and increased risk of breast cancer: findings from the British Women's Heart and Health Study. Cancer Causes Control. 2004; 15(3):267-75. DOI: 10.1023/B:CACO.0000024225.14618.a8. View

19.

Renehan A, Zwahlen M, Minder C, ODwyer S, Shalet S, Egger M . Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet. 2004; 363(9418):1346-53. DOI: 10.1016/S0140-6736(04)16044-3. View

20.

Khaw K, Wareham N, Bingham S, Luben R, Welch A, Day N . Preliminary communication: glycated hemoglobin, diabetes, and incident colorectal cancer in men and women: a prospective analysis from the European prospective investigation into cancer-Norfolk study. Cancer Epidemiol Biomarkers Prev. 2004; 13(6):915-9. View