|Year : 2015 | Volume
| Issue : 1 | Page : 4-6
Diabetes Mellitus and Oral Cancer: Are They Connected?
Manu Prasad Sen1, Nandita Shenoy1, Ashok K Shenoy2, Prabha Adhikari3, Junaid Ahmed1, Aruna Muralidhar Yadiyal4
1 Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore, Karnataka, India
2 Department of Pharmacology, Kasturba Medical College, Mangalore, Karnataka, India
3 Department of General Medicine, Kasturba Medical College, Mangalore, Karnataka, India
4 Department of Psychiatry, Father Muller Medical College, Mangalore, Karnataka, India
|Date of Web Publication||17-Jun-2015|
Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore, Affiliated to Manipal University, Manipal, Karnataka
Source of Support: None, Conflict of Interest: None
Introduction: Malignant neoplasm is a major cause of death in developed countries, and its incidence continues to grow, placing a heavy burden on the community. Diabetes mellitus is a serious and leading health problem. Recent studies demonstrated that glucose intolerance was associated with a higher risk of oral cancer death, beginning in the prediabetic range of glucose intolerance. However, few population-based studies, especially in Asian populations, have addressed these issues or have estimated glucose intolerance status. Aim: We undertook this study with the aim of finding out an association between impaired glucose tolerance (IGT) and oral cancer along with finding out prevalence of other risk factors for oral cancer. Materials and Methods: Forty-five cases and 45 controls were selected for the study. Oral glucose tolerance was performed on subjects who satisfied inclusion criteria and were willing to sign informed consent form. Results: Fifty-three percent of the cases had abnormal glucose tolerance when compared to 31% of the controls. Conclusion: To conclude, hyperglycemia (which includes impaired fasting glucose, IGT and diabetes) increases the risk of oral cancer two-fold, however IGT alone as defined by American Diabetes Association does not appear to play a role.
Keywords: Diabetes mellitus, impaired glucose tolerance, oral cancer
|How to cite this article:|
Sen MP, Shenoy N, Shenoy AK, Adhikari P, Ahmed J, Yadiyal AM. Diabetes Mellitus and Oral Cancer: Are They Connected?. Indian J Oral Health Res 2015;1:4-6
|How to cite this URL:|
Sen MP, Shenoy N, Shenoy AK, Adhikari P, Ahmed J, Yadiyal AM. Diabetes Mellitus and Oral Cancer: Are They Connected?. Indian J Oral Health Res [serial online] 2015 [cited 2020 Jan 18];1:4-6. Available from: http://www.ijohr.org/text.asp?2015/1/1/4/158901
| Introduction|| |
Noninsulin dependent diabetes mellitus (DM) is rapidly becoming a common chronic disease among the urban population. At the same time, the morbidity and mortality associated with oral cancer is increasing despite exhaustive research. Are they related? Is impaired glucose tolerance (IGT) a risk factor or a predisposing factor for oral cancer? There are studies on the inflammatory lesions of the periodontal tissues and oral mucosa in patients with DM;  these oral alterations are more serious in untreated or inadequately treated diabetic patients,  but there are hardly any studies on DM and its association with oral cancer.
Studies state that altered metabolism as in DM leads to break down in oxidation equilibrium leading to elevated glucose concentration, excessive formation of free radicals, leading to reduced activities of the antioxidant scavengers bringing out serious damages in the biological structures even at a molecular level. ,
Diabetes mellitus is associated with increased risk , as well as the worse outcome, of various malignancies, including endometrial, colon and pancreatic cancers.  The present study proposes a novel hypothesis for an etiological association between prediabetes, diabetes as a risk for cancers of the oral cavity. A large population of India is habituated to vices like tobacco and alcohol; hence we would also like to throw light on the relation between alcohol and tobacco in the causation of oral cancer.
There are similar studies reported in the west but very few among Asians,  since there is considerable heterogeneity in the genetic background and lifestyle between Asian and Western populations, it is of value to review the influence of prediabetes on the risk of oral cancer.
| Materials and Methods|| |
Oral cancer subjects who visited for treatment to any of these three tertiary care hospitals of Manipal Hospital between October and December 2013. Expected sample size was calculated using following figures: Expected proportion of IGT in control group = 15%, anticipated odds ratio = 3, Calculated proportion of IGT among cancer patients = 35% and accordingly the power of study was calculated as 80%. The number of subjects recruited for the study was 45 subjects and 45 controls, the controls were people from the general population who were not known to be suffering from any illness. Ethics committee approval was obtained from Institutional Ethics Committee, and informed consents were taken from study participants.
Each participant completed a self-administered questionnaire covering medical history, family history of cancer, antidiabetic treatment, smoking habits, alcohol intake, and leisure-time physical activity. Smoking and alcohol intake were classified as either current use or not. At the baseline examination, we performed a 75-g oral glucose tolerance test between 8:00 am and 10:30 am after at least 8-h overnight fast. Plasma glucose levels were measured by means of the glucose oxidase method. Glucose tolerance was classified according to American Diabetes Association (ADA) diagnostic criteria 2002. 
The collected data were fed in the computer in MS excel and the analysis was performed using the statistical package SPSS version 11.5. The quantitative variables were analyzed using Student's t-test and ANOVA. The qualitative variables were analyzed using Chi-square test. A P < 0.05 was taken as statistically significant. The statistical significance of differences in the mean values and frequencies of risk factors was estimated by means of analysis of covariance and logistic regression analysis, respectively.
| Results|| |
Our study subjects and controls were age and gender matched. More than a third of the cases (36%) were in the fifth decade of their life, about 24% of them were in their 60's. 20% of the cases were between 40 and 50 years. Only 4% of the cases were in their 70's. 46% of our study subjects were diabetic, 54% of the cases were hyperglycemic as compared to 31% of the controls [Table 1] and [Table 2]. 71% of them were males. Majority of the cases (75.6%) did not have any family history of oral cancer. More than half of the cases (58%) consumed tobacco in the study population and among controls, 64% did not consume tobacco. Among those with habits in the study group, 65.3% of them were smokers, 34% of them were paan chewers, and 23% of them were paan chewers as well as smokers. Among the study population, half of the cases (53.33%) had a history of alcohol consumption, whereas 51% of controls did not consume alcohol.
| Discussion|| |
The present study clearly demonstrated that higher fasting plasma glucose and 2-h postprandal glucose levels were significantly associated with increased risks of oral cancer. These associations remained robust even after adjustment for other confounding factors, like consumption of tobacco and alcohol. Interestingly, we found that the risk of cancer death was increased significantly not only in diabetic subjects but also in subjects with IGT as compared with subjects with normal glucose tolerance. These findings highlight the clinical value of early management of hyperglycemia, even in the prediabetic range, to prevent cancer death.
Abnormal glucose was found in nearly half of the cases with oral cancer in comparison with control, while nearly quarter of the controls had abnormal glucose tolerance. This can be due to associated insulin resistance in type II DM. Chronically increased levels of insulin resulting in hyperinsulinemia, have been associated with colon cancer and cancer of breast, pancreas and endometrium. These tumourogenic effects of insulin could be directly mediated by insulin receptors in the preneoplastic target cells or might be due to related changes in endogenous hormone metabolism.  Recent studies say that insulin promotes the synthesis and biological activity of insulin like growth factors-1 (IGF-1), which act as a growth factor that promote cell proliferation and inhibits apoptosis. There is evidence that the effect of IGF-1 might be related to p53 mutations, which are quite common in head and neck malignancies. ,
Several prospective population-based studies have assessed the association between diabetes and cancer death, but laboratory parameters used were fasting plasma glucose levels , or postprandial glucose levels. ,
More than half of our study subjects were regular abusers of tobacco either in smoking form or smokeless form. Nearly half of them had a history of alcohol usage, this is consistent with the study done in Kerala. 
Majority of the cases were males, and there is a statistically significant association in men for the development of oral cancer. It is possible that males and females reported history of diabetes differently and due to social reasons females report to doctors quite late. Men are likely to represent patients with poorer metabolic control, leading to higher levels of insulin, and probably more oxidative damage to DNA. It has been proposed that poor diabetic control is associated with an increased cancer risk due to enhanced oxidative damage to DNA. ,
| Conclusions|| |
The following conclusions were drawn, hyperglycemia (which includes impaired fasting glucose, IGT and diabetes) increase the risk of oral cancer two-folds, and however IGT alone as defined by ADA does not appear to play a role. Several potential confounders of the association between DM and cancer incidence were accounted for in the analysis, although the possibility of residual confounding factors cannot be denied. However, numerous potential confounders were controlled in the present study. We did not obtain information about the use of some antidiabetic drugs that could improve insulin resistance and reduce the risk of cancer.
In summary, the current study suggests preexisting DM is positively associated with the incidence of oral cancer. Given the increasing epidemic of DM in recent years, it is time to be on the move and start preventive programs aimed at those with DM, so as to prevent cancer.
The strength of the present study is its prospective design, which prevents recall bias.
In our study, serum insulin level estimation was not done, which is the most appropriate test to determine the insulin resistance, this was due to financial constraints.
| References|| |
Oliver RC, Tervonen T. Diabetes - A risk factor for periodontitis in adults? J Periodontol 1994;65:530-8.
Taylor GW, Burt BA, Becker MP, Genco RJ, Shlossman M, Knowler WC, et al.
Severe periodontitis and risk for poor glycemic control in patients with non-insulin-dependent diabetes mellitus. J Periodontol 1996;67:1085-93.
Soskolne WA. Epidemiological and clinical aspects of periodontal diseases in diabetics. Ann Periodontol 1998;3:3-12.
Baynes JW, Thorpe SR. Role of oxidative stress in diabetic complications: A new perspective on an old paradigm. Diabetes 1999;48:1-9.
Adami HO, McLaughlin J, Ekbom A, Berne C, Silverman D, Hacker D, et al.
Cancer risk in patients with diabetes mellitus. Cancer Causes Control 1991;2:307-14.
Chan JC, Malik V, Jia W, Kadowaki T, Yajnik CS, Yoon KH, et al.
Diabetes in Asia: Epidemiology, risk factors, and pathophysiology. JAMA 2009;301:2129-40.
Hogan P, Dall T, Nikolov P, American Diabetes Association. Economic costs of diabetes in the US in 2002. Diabetes Care 2003;26:917-32.
Calle EE, Kaaks R. Overweight, obesity and cancer: Epidemiological evidence and proposed mechanisms. Nat Rev Cancer 2004;4:579-91.
Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, et al.
Diabetes and cancer: A consensus report. Diabetes Care 2010;33:1674-85.
Dikshit RP, Ramadas K, Hashibe M, Thomas G, Somanathan T, Sankaranarayanan R. Association between diabetes mellitus and pre-malignant oral diseases: A cross sectional study in Kerala, India. Int J Cancer 2006;118:453-7.
Pollak M. Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer 2008;8:915-28.
Jee SH, Ohrr H, Sull JW, Yun JE, Ji M, Samet JM. Fasting serum glucose level and cancer risk in Korean men and women. JAMA 2005;293:194-202.
Lam EK, Batty GD, Huxley RR, Martiniuk AL, Barzi F, Lam TH, et al.
Associations of diabetes mellitus with site-specific cancer mortality in the Asia-Pacific region. Ann Oncol 2011;22:730-8.
Smith GD, Egger M, Shipley MJ, Marmot MG. Post-challenge glucose concentration, impaired glucose tolerance, diabetes, and cancer mortality in men. Am J Epidemiol 1992;136:1110-4.
Saydah SH, Loria CM, Eberhardt MS, Brancati FL. Abnormal glucose tolerance and the risk of cancer death in the United States. Am J Epidemiol 2003;157:1092-100.
Sankaranarayanan R, Mathew B, Jacob BJ, Thomas G, Somanathan T, Pisani P, et al.
Early findings from a community-based, cluster-randomized, controlled oral cancer screening trial in Kerala, India. The Trivandrum Oral Cancer Screening Study Group. Cancer 2000;88:664-73.
Dandona P, Thusu K, Cook S, Snyder B, Makowski J, Armstrong D, et al
. Oxidative damage to DNA in diabetes mellitus. Lancet 1996;347:444-5.
[Table 1], [Table 2]