Skip to main content
Top
Published in: Digestive Diseases and Sciences 9/2008

01-09-2008 | Original Paper

Elevated HbA1c Is an Independent Predictor of Aggressive Clinical Behavior in Patients with Colorectal Cancer: A Case-Control Study

Authors: Ali A. Siddiqui, Stuart J. Spechler, Sergio Huerta, Serag Dredar, Bertis B. Little, Byron Cryer

Published in: Digestive Diseases and Sciences | Issue 9/2008

Login to get access

Abstract

Aim The aim of this study was to seek an association between the control of type 2 diabetes mellitus (T2DM), as determined by hemoglobin A1c (HbA1c) levels, and the outcome of colorectal cancer (CRC). Methods We performed a retrospective review of patients with T2DM who had CRC diagnosed between 1997 and 2001. We defined well-controlled T2DM as HbA1c < 7.5% and poorly controlled T2DM as HbA1c ≥ 7.5%. A group of age- and gender-matched patients who had CRC without T2DM were used as controls. Forty clinical factors were reviewed, and those associated with poor clinical outcome in each group were examined by univariate analysis (UA) and by the maximum likelihood analysis of logistic regression to determine the independent predictors of cancer outcome. Results We identified 155 patients with T2DM and CRC, and 114 control patients who had CRC without T2DM. We found no significant differences in any clinical factor by UA between the patients with well-controlled T2DM and the patients who had CRC without T2DM. Compared to both of those patients groups, in contrast, the patients with poorly controlled T2DM had more right-sided CRCs (P = 0.04, OR = 2, 95% CI = 1–4.1), more advanced CRCs (P = 0.02, OR = 2.1, 95% CI = 1–4.4), a younger age of presentation (P = 0.05), greater use of exogenous insulin (P = 0.002), and a poorer 5-year survival (P = 0.001) by UA. Logistic regression showed that poorly controlled T2DM independently predicted the early onset of CRC, a more advanced stage at the time of presentation, poorer 5-year survival, and an increased incidence of right-sided CRCs. Conclusions In patients with T2DM who have CRC, poor glycemic control is associated with a clinically aggressive course for the cancer.
Literature
1.
go back to reference Engelgau MM, Geiss LS, Saaddine JB, Boyle JP, Benjamin SM, Gregg EW, Tierney EF, Rios-Burrows N, Mokdad AH, Ford ES, Imperatore G, Narayan KM (2004) The evolving diabetes burden in the United States. Ann Intern Med 140:945–950PubMed Engelgau MM, Geiss LS, Saaddine JB, Boyle JP, Benjamin SM, Gregg EW, Tierney EF, Rios-Burrows N, Mokdad AH, Ford ES, Imperatore G, Narayan KM (2004) The evolving diabetes burden in the United States. Ann Intern Med 140:945–950PubMed
2.
go back to reference Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ (2006) Cancer statistics, 2006. CA Cancer J Clin 56:106–130PubMedCrossRef Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ (2006) Cancer statistics, 2006. CA Cancer J Clin 56:106–130PubMedCrossRef
6.
go back to reference Will JC, Galuska DA, Vinicor F, Calle EE (1998) Colorectal cancer: another complication of diabetes mellitus? Am J Epidemiol 147:816–825PubMed Will JC, Galuska DA, Vinicor F, Calle EE (1998) Colorectal cancer: another complication of diabetes mellitus? Am J Epidemiol 147:816–825PubMed
7.
go back to reference Hu FB, Manson JE, Liu S, Hunter D, Colditz GA, Michels KB, Speizer FE, Giovannucci E (1999) Prospective study of adult onset diabetes mellitus (type 2) and risk of colorectal cancer in women. J Natl Cancer Inst 91:542–547. doi:10.1093/jnci/91.6.542 PubMedCrossRef Hu FB, Manson JE, Liu S, Hunter D, Colditz GA, Michels KB, Speizer FE, Giovannucci E (1999) Prospective study of adult onset diabetes mellitus (type 2) and risk of colorectal cancer in women. J Natl Cancer Inst 91:542–547. doi:10.​1093/​jnci/​91.​6.​542 PubMedCrossRef
8.
go back to reference Limburg PJ, Vierkant RA, Fredericksen ZS, Leibson CL, Rizza RA, Gupta AK, Ahlquist DA, Melton LJ 3rd, Sellers TA, Cerhan JR (2006) Clinically confirmed type 2 diabetes mellitus and colorectal cancer risk: a population-based, retrospective cohort study. Am J Gastroenterol 101:1872–1879. doi:10.1111/j.1572-0241.2006.00725.x PubMedCrossRef Limburg PJ, Vierkant RA, Fredericksen ZS, Leibson CL, Rizza RA, Gupta AK, Ahlquist DA, Melton LJ 3rd, Sellers TA, Cerhan JR (2006) Clinically confirmed type 2 diabetes mellitus and colorectal cancer risk: a population-based, retrospective cohort study. Am J Gastroenterol 101:1872–1879. doi:10.​1111/​j.​1572-0241.​2006.​00725.​x PubMedCrossRef
9.
go back to reference Khaw KT, Wareham N, Bingham S, Luben R, Welch A, Day N (2004) 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 13:915–919PubMed Khaw KT, Wareham N, Bingham S, Luben R, Welch A, Day N (2004) 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 13:915–919PubMed
10.
go back to reference Wei EK, Ma J, Pollak MN, Rifai N, Fuchs CS, Hankinson SE, Giovannucci E (2005) A prospective study of C-peptide, insulin-like growth factor-I, insulin-like growth factor binding protein-1, and the risk of colorectal cancer in women. Cancer Epidemiol Biomarkers Prev 14:850–855. doi:10.1158/1055-9965.EPI-04-0661 PubMedCrossRef Wei EK, Ma J, Pollak MN, Rifai N, Fuchs CS, Hankinson SE, Giovannucci E (2005) A prospective study of C-peptide, insulin-like growth factor-I, insulin-like growth factor binding protein-1, and the risk of colorectal cancer in women. Cancer Epidemiol Biomarkers Prev 14:850–855. doi:10.​1158/​1055-9965.​EPI-04-0661 PubMedCrossRef
12.
go back to reference Tran TT, Medline A, Bruce WR (1996) Insulin promotion of colon tumors in rats. Cancer Epidemiol Biomarkers Prev 5:1013–1015PubMed Tran TT, Medline A, Bruce WR (1996) Insulin promotion of colon tumors in rats. Cancer Epidemiol Biomarkers Prev 5:1013–1015PubMed
13.
go back to reference Wu X, Fan Z, Masui H, Rosen N, Mendelsohn J (1995) Apoptosis induced by an anti-epidermal growth factor receptor monoclonal antibody in a human colorectal carcinoma cell line and its delay by insulin. J Clin Invest 95:1897–1905. doi:10.1172/JCI117871 PubMedCrossRef Wu X, Fan Z, Masui H, Rosen N, Mendelsohn J (1995) Apoptosis induced by an anti-epidermal growth factor receptor monoclonal antibody in a human colorectal carcinoma cell line and its delay by insulin. J Clin Invest 95:1897–1905. doi:10.​1172/​JCI117871 PubMedCrossRef
14.
go back to reference Corpet DE, Jacquinet C, Peiffer G, Taché S (1997) Insulin injections promote the growth of aberrant crypt foci in the colon of rats. Nutr Cancer 27:316–320PubMed Corpet DE, Jacquinet C, Peiffer G, Taché S (1997) Insulin injections promote the growth of aberrant crypt foci in the colon of rats. Nutr Cancer 27:316–320PubMed
15.
go back to reference Koenuma M, Yamori T, Tsuruo T (1989) Insulin and insulin-like growth factor 1 stimulate proliferation of metastatic variants of colon carcinoma 26. Jpn J Cancer Res 80:51–58PubMed Koenuma M, Yamori T, Tsuruo T (1989) Insulin and insulin-like growth factor 1 stimulate proliferation of metastatic variants of colon carcinoma 26. Jpn J Cancer Res 80:51–58PubMed
16.
17.
go back to reference Saydah SH, Platz EA, Rifai N, Pollak MN, Brancati FL, Helzlsouer KJ (2003) Association of markers of insulin and glucose control with subsequent colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 12:412–418PubMed Saydah SH, Platz EA, Rifai N, Pollak MN, Brancati FL, Helzlsouer KJ (2003) Association of markers of insulin and glucose control with subsequent colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 12:412–418PubMed
20.
go back to reference Goldstein DE, Little RR, Wiedmeyer HM, England JD, McKenzie EM (1986) Glycated hemoglobin: methodologies and clinical applications. Clin Chem 32:B64–B70PubMed Goldstein DE, Little RR, Wiedmeyer HM, England JD, McKenzie EM (1986) Glycated hemoglobin: methodologies and clinical applications. Clin Chem 32:B64–B70PubMed
23.
go back to reference [No authors listed] (1998) Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 352:837–853. doi:10.1016/S0140-6736(98)07019-6 CrossRef [No authors listed] (1998) Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 352:837–853. doi:10.​1016/​S0140-6736(98)07019-6 CrossRef
24.
go back to reference Delmas-Beauvieux MC, Peuchant E, Thomas MJ, Dubourg L, Pinto AP, Clerc M, Gin H (1998) The place of electron spin resonance methods in the detection of oxidative stress in type 2 diabetes with poor glycemic control. Clin Biochem 31:221–228. doi:10.1016/S0009-9120(98)00019-8 PubMedCrossRef Delmas-Beauvieux MC, Peuchant E, Thomas MJ, Dubourg L, Pinto AP, Clerc M, Gin H (1998) The place of electron spin resonance methods in the detection of oxidative stress in type 2 diabetes with poor glycemic control. Clin Biochem 31:221–228. doi:10.​1016/​S0009-9120(98)00019-8 PubMedCrossRef
27.
go back to reference Bird CL, Ingles SA, Frankl HD, Lee ER, Longnecker MP, Haile RW (1996) Serum lipids and adenomas of the left colon and rectum. Cancer Epidemiol Biomarkers Prev 5:607–612PubMed Bird CL, Ingles SA, Frankl HD, Lee ER, Longnecker MP, Haile RW (1996) Serum lipids and adenomas of the left colon and rectum. Cancer Epidemiol Biomarkers Prev 5:607–612PubMed
28.
go back to reference Trevisan M, Liu J, Muti P, Misciagna G, Menotti A, Fucci F, Risk Factors and Life Expectancy Research Group (2001) Markers of insulin resistance and colorectal cancer mortality. Cancer Epidemiol Biomarkers Prev 10:937–941PubMed Trevisan M, Liu J, Muti P, Misciagna G, Menotti A, Fucci F, Risk Factors and Life Expectancy Research Group (2001) Markers of insulin resistance and colorectal cancer mortality. Cancer Epidemiol Biomarkers Prev 10:937–941PubMed
29.
go back to reference Yamada K, Araki S, Tamura M, Sakai I, Takahashi Y, Kashihara H, Kono S (1998) Relation of serum total cholesterol, serum triglycerides and fasting plasma glucose to colorectal carcinoma in situ. Int J Epidemiol 27:794–798. doi:10.1093/ije/27.5.794 PubMedCrossRef Yamada K, Araki S, Tamura M, Sakai I, Takahashi Y, Kashihara H, Kono S (1998) Relation of serum total cholesterol, serum triglycerides and fasting plasma glucose to colorectal carcinoma in situ. Int J Epidemiol 27:794–798. doi:10.​1093/​ije/​27.​5.​794 PubMedCrossRef
30.
go back to reference McKeown-Eyssen G (1994) Epidemiology of colorectal cancer revisited: are serum triglycerides and/or plasma glucose associated with risk? Cancer Epidemiol Biomarkers Prev 3:687–695PubMed McKeown-Eyssen G (1994) Epidemiology of colorectal cancer revisited: are serum triglycerides and/or plasma glucose associated with risk? Cancer Epidemiol Biomarkers Prev 3:687–695PubMed
32.
go back to reference Giovannucci E (2001) Insulin, insulin-like growth factors and colon cancer: a review of the evidence. J Nutr 131:3109S–3120SPubMed Giovannucci E (2001) Insulin, insulin-like growth factors and colon cancer: a review of the evidence. J Nutr 131:3109S–3120SPubMed
33.
go back to reference 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 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
34.
35.
36.
go back to reference Ma J, Pollak MN, Giovannucci E, Chan JM, Tao Y, Hennekens CH, Stampfer MJ (1999) Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. J Natl Cancer Inst 91:620–625. doi:10.1093/jnci/91.7.620 PubMedCrossRef Ma J, Pollak MN, Giovannucci E, Chan JM, Tao Y, Hennekens CH, Stampfer MJ (1999) Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. J Natl Cancer Inst 91:620–625. doi:10.​1093/​jnci/​91.​7.​620 PubMedCrossRef
37.
go back to reference Kaaks R, Toniolo P, Akhmedkhanov A, Lukanova A, Biessy C, Dechaud H, Rinaldi S, Zeleniuch-Jacquotte A, Shore RE, Riboli E (2000) Serum C-peptide, insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women. J Natl Cancer Inst 92:1592–1600. doi:10.1093/jnci/92.19.1592 PubMedCrossRef Kaaks R, Toniolo P, Akhmedkhanov A, Lukanova A, Biessy C, Dechaud H, Rinaldi S, Zeleniuch-Jacquotte A, Shore RE, Riboli E (2000) Serum C-peptide, insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women. J Natl Cancer Inst 92:1592–1600. doi:10.​1093/​jnci/​92.​19.​1592 PubMedCrossRef
38.
go back to reference Ma J, Giovannucci E, Pollak M, Leavitt A, Tao Y, Gaziano JM, Stampfer MJ (2004) A prospective study of plasma C-peptide and colorectal cancer risk in men. J Natl Cancer Inst 96:546–553PubMed Ma J, Giovannucci E, Pollak M, Leavitt A, Tao Y, Gaziano JM, Stampfer MJ (2004) A prospective study of plasma C-peptide and colorectal cancer risk in men. J Natl Cancer Inst 96:546–553PubMed
39.
go back to reference Lyons TJ, Neel RL, Simpson CG, Moore VA, Van Syoc DL, Knowles JR, Salamanca VP (1997) East meets West: a comparison of eastern block/western aeromedical practices. Aviat Space Environ Med 68:1150–1153PubMed Lyons TJ, Neel RL, Simpson CG, Moore VA, Van Syoc DL, Knowles JR, Salamanca VP (1997) East meets West: a comparison of eastern block/western aeromedical practices. Aviat Space Environ Med 68:1150–1153PubMed
41.
go back to reference Stadler J, Yeung KS, Furrer R, Marcon N, Himal HS, Bruce WR (1988) Proliferative activity of rectal mucosa and soluble fecal bile acids in patients with normal colons and in patients with colonic polyps or cancer. Cancer Lett 38:315–320. doi:10.1016/0304-3835(88)90023-7 PubMedCrossRef Stadler J, Yeung KS, Furrer R, Marcon N, Himal HS, Bruce WR (1988) Proliferative activity of rectal mucosa and soluble fecal bile acids in patients with normal colons and in patients with colonic polyps or cancer. Cancer Lett 38:315–320. doi:10.​1016/​0304-3835(88)90023-7 PubMedCrossRef
43.
44.
go back to reference Liu LU, Holt PR, Krivosheyev V, Moss SF (1999) Human right and left colon differ in epithelial cell apoptosis and in expression of Bak, a pro-apoptotic Bcl-2 homologue. Gut 45:45–50PubMedCrossRef Liu LU, Holt PR, Krivosheyev V, Moss SF (1999) Human right and left colon differ in epithelial cell apoptosis and in expression of Bak, a pro-apoptotic Bcl-2 homologue. Gut 45:45–50PubMedCrossRef
45.
go back to reference Yoshida I, Suzuki A, Vallée M, Matano Y, Masunaga T, Zenda T, Shinozaki K, Okada T (2006) Serum insulin levels and the prevalence of adenomatous and hyperplastic polyps in the proximal colon. Clin Gastroenterol Hepatol 4:1225–1231. doi:10.1016/j.cgh.2006.07.002 PubMedCrossRef Yoshida I, Suzuki A, Vallée M, Matano Y, Masunaga T, Zenda T, Shinozaki K, Okada T (2006) Serum insulin levels and the prevalence of adenomatous and hyperplastic polyps in the proximal colon. Clin Gastroenterol Hepatol 4:1225–1231. doi:10.​1016/​j.​cgh.​2006.​07.​002 PubMedCrossRef
48.
go back to reference Singh SM, Paszat LF, Li C, He J, Vinden C, Rabeneck L (2004) Association of socioeconomic status and receipt of colorectal cancer investigations: a population-based retrospective cohort study. CMAJ 171:461–465. doi:10.1503/cmaj.1031921 PubMed Singh SM, Paszat LF, Li C, He J, Vinden C, Rabeneck L (2004) Association of socioeconomic status and receipt of colorectal cancer investigations: a population-based retrospective cohort study. CMAJ 171:461–465. doi:10.​1503/​cmaj.​1031921 PubMed
Metadata
Title
Elevated HbA1c Is an Independent Predictor of Aggressive Clinical Behavior in Patients with Colorectal Cancer: A Case-Control Study
Authors
Ali A. Siddiqui
Stuart J. Spechler
Sergio Huerta
Serag Dredar
Bertis B. Little
Byron Cryer
Publication date
01-09-2008
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 9/2008
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-008-0264-4

Other articles of this Issue 9/2008

Digestive Diseases and Sciences 9/2008 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.