Diabetes Mellitus Type 2 and Colorectal Cancer

Tessi Ananditya030.04.217

Faculty of MedicineTrisakti University

2008

PREFACE

Bismillaahir Rahmaanir Rahiim

First, I would like to express my gratitude for Allah SWT for His bless so I can finish my

task. Secondly, my beloved parents who accommodated me to finish all this task. Third, I

would like to give my gratitude to my supervisor, Prof. Dr. Julius E. Surjawidjaja,

Sp.MK, who has guiding me all along. Last but not least, I would like to thank to all of

my friends, thank you for your help and attention.

This paper title is “Diabetes Mellitus Type 2 and Colorectal Cancer”. This paper is made

to complete English assignment for subject Medical English 3 in the Faculty of Medicine,

Trisakti University.

I hope this paper can be useful for everyone generally and especially for everyone who

read this paper, I am sure my paper is not perfect, critics from you will be motivated me

to be better next day.

CONTENTS

Preface

i

Contents ii

Abstract iii

Chapter I : Introduction 1

Chapter II : Discussion 2

Chapter III : Conclusion 4

References 5

Abstract

Dietary and lifestyle factors related to insulin resistance and hyperinsulinemia,

including a westernized diet, physical inactivity, and obesity, have been linked to

increased colorectal cancer risk. These observations support the hypothesis that

hyperinsulinemia or factors associated with insulin resistance, such as hyperglycemia or

hypertriglyceridemia, may play a role in colorectal carcinogenesis. Epidemiologic studies

have observed an elevated risk of colorectal cancer associated with high circulating

insulin, IGF-1, and C-peptide (a marker of insulin secretion) concentrations.

CHAPTER I

INTRODUCTION

Recent studies shows that Diabetes Mellitus type 2 significantly elevates a

person’s lifetime risk of colorectal cancer. This association persisted even after

adjustment of other colorectal cancer risk factors including body mass index (BMI),

physical activity, screening patterns, and dietary factors. Although Diabetes Mellitus type

2 could influence colorectal carcinogenesis through several mechanisms, elevated levels

of both circulating postprandial insulin and C-peptide have been shown to increase

colorectal cancer risk.

In contrast, the influence of diabetes mellitus on the long-term outcome of patients

with established colon cancer remains uncertain. Moreover, because information

regarding cancer relapse was not available, it remained unclear whether the influence of

diabetes was directly related to a higher rate of cancer recurrence.

CHAPTER II

DISCUSSION

Diabetes Mellitus (DM) comprises a group of common metabolic disorders that

shares phenotype of hyperglycemia. DM is classified on the basis of pathogenic process

that leads to hyperglycemia. The two broad categories of DM are designated type 1 and

type 2.

Type 2 DM is a heterogeneous group of disorders characterized by variable

degrees of insulin resistance, impaired insulin secretion, and increased glucose

production. Insulin resistance impairs glucose utilization by insulin-sensitive tissues and

increase hepatic glucose output; both effects contribute to the hyperglycemia. Insulin

secretion and sensitivity are interrelated. In type 2 DM, insulin secretion initially

increases in response to insulin resistance to maintain normal glucose tolerance.

Colorectal cancer, also called colon cancer or large bowel cancer, includes

cancerous growths in the colon, rectum and appendix. Most colorectal cancer, regardless

of etiology, arise from adenomatous polyps.

The etiology for most cases of large-bowel cancer appears to be related to

environmental factors. The disease occurs more often in upper socioeconomic

populations who live in urban area. Mortality from colorectal cancer is directly correlated

with per capita consumption of calories, meat protein, and dietary fat and oil as well as

elevated serum cholesterol concentration and mortality from coronary disease.

There are some risk factors for development of colorectal cancer. One of it is

insulin resistance. The number of calories inherent in westernized diets coupled with

physical inactivity have been associated with higher prevalence of obesity. Persons with

such excess weight gain develop insulin resistance with increasing circulating level of

insulin, leading to higher circulating concentration of insulin-like growth factors type I

(IGF-1). This factors appears to stimulate proliferation of the intestinal mucosa.

IGF-1 is a polypeptide protein hormone similar in molecular structure to insulin.

It plays an important role in childhood growth and continues to have anabolic effects in

adults

The effects of diabetes mellitus on colorectal cancer may be mediated through

mechanisms ranging from increased colonic transit time to hyperinsulinaemia. In relation

to the latter, at least in the early phase of development, type 2 diabetes mellitus is

associated with increased circulating insulin concentrations. Insulin may stimulate cell

proliferation through two pathways: a minor pathway that entails direct activation of the

insulin receptor or insulin-like growth factor (IGF)-I receptor, and a major pathway via

inhibition of IGF binding proteins (in particular, IGFBP-1 and IGFBP-2), resulting

theoretically in increased bioavailability of IGF-I to the IGF-I receptor. Clinical studies

also independently link high circulating concentrations of C-peptide, as a marker of

insulin production, with increased colorectal cancer risk.

Insulin and insulin-like growth factor (IGF) axes are major determinants of

proliferation and apoptosis and thus may influence carcinogenesis. In various animal

models, modulation of insulin and IGF-1 levels through various means, including direct

infusion, energy excess or restriction, genetically induced obesity, dietary quality

including fatty acid and sucrose content, inhibition of normal insulin secretion and

pharmacologic inhibition of IGF-1, influences colonic carcinogenesis. Human evidence

also associates high levels of insulin and IGF-1 with increased risk of colon cancer.

Clinical conditions associated with high levels of insulin (noninsulin-dependent

diabetes mellitus and hypertriglyceridemia) and IGF-1 are related to increased risk of

colon cancer, and increased circulating concentrations of insulin and IGF-1 are related to

a higher risk of colonic neoplasia. Determinants and markers of hyperinsulinemia

(physical inactivity, high body mass index, central adiposity) and high IGF-1 levels are

also related to higher risk. Many studies indicate that dietary patterns that stimulate

insulin resistance or secretion, including high consumption of sucrose, various sources of

starch, a high glycemic index and high saturated fatty acid intake, are associated with a

higher risk of colon cancer.

CHAPTER III

CONCLUSION

Changing lifestyle of westernized diet, physical inactivity, and obesity, leads to

hyperglycemia which leads to higher secretion of insulin. On long term effect it will

caused Type 2 Diabetes Mellitus.

Type 2 DM is characterized by insulin resistance and impaired insulin secretion. This

will caused higher insulin and IGF-1 circulation in blood.

Insulin and insulin-like growth factor (IGF) axes are major determinants of

proliferation and apoptosis and thus may influence carcinogenesis.

REFERENCES

1. Asplin, John R., Fredric L. Coe, Murray J. Favus. In Kasper, Braunwald, Fauci, Hauser, Longo, Jameson. Harrison’s Principles of Internal Medicine 16 th Edition, 2005

2. Will JC, Galuska DA, Vinicor F, Calle EE. Colorectal cancer: another complication of diabetes mellitus? Am J Epidemiol 1998;147: 816-25

3. Meyerhardt JA, Catalano PJ, Haller DG, Mayer RJ, Macdonald JS, Benson AB 3rd, et al. Impact of diabetes mellitus on outcomes in patients with colon cancer. J Clin Oncol 2003;21: 433-40

4. Ma J, Giovannucci E, Pollak M, Leavitt A, Tao Y, Gaziano JM, et al. A prospective study of plasma C-peptide and colorectal cancer risk in men. J Natl Cancer Inst 2004;96: 546-53

5. Yang YX, Hennessy S, Lewis JD. Insulin therapy and colorectal cancer risk among type 2 diabetes mellitus patients. Gastroenterology 2004;127: 1044-50