Table of Contents  
ORIGINAL ARTICLE
Year : 2014  |  Volume : 7  |  Issue : 4  |  Page : 454-457  

Investıgatıon of malignancy in diabetic patients with anemia


1 Department of Internal Medicine, Findikli State Hospital, Rize, Turkey
2 Department of Internal Medicine, Taslišay State Hospital, Agri, Turkey
3 Department of Internal Medicine, Malatya State Hospital, Malatya, Turkey
4 Department of Internal Medicine, Faculty of Medicine, Sakarya University, Sakarya, Turkey
5 Department of Gastroenterology, Faculty of Medicine, Sakarya University, Sakarya, Turkey

Date of Web Publication25-Jun-2014

Correspondence Address:
Selcuk Yaylaci
Department of Internal Medicine, F?nd?kl? State Hospital, Rize
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0975-2870.135264

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  Abstract 

Introduction: The etiology of anemia is multifactorial in diabetes and covers inflammation, diabetes, nutritional deficiencies, autoimmune diseases, medications and hormonal changes, in addition to the kidney diseases or may be malignancy. In this study, it was aimed to study the profile of the malignancy in patients with type 2 diabetes mellitus (DM) and anemia. Materials and Methods: The files of the follow-up patients with type 2 diabetes were retrospectively reviewed and 103 patients with type 2 DM and anemia were included in the study. The demographic, hematological and biochemical analysis of the data was performed in the diabetic patients with anemia. The frequency of malignancy in diabetic patients with anemia, the etiology of malignancy, the relationship between the presence of malignancy and anemia type and depth, biochemical parameters in the determination of malignancy, the effects of endoscopic and imaging methods, the presence of anemia in patients without malignancy and the effect of in-depth glomerular filtration rate were investigated. Results: The iron deficiency anemia (69.9%) was the most common. Malignancy was found in 11 of the 103 patients (10.7%). 2 patients (1.9%) had stomach cancer, 4 patients (6.3%) had colon cancer in endoscopic procedures. In computerized tomography images, 5 patients were found to be malignant in addition to the stomach and colon cancer. The erythrocyte sedimentation rate was significantly higher in the group with malignancy. No correlation was found between malignancy and anemia type and depth. Conclusion: Screening for malignancy should be considered in diabetic patients with anemia, especially in patients with elevated erythrocyte sedimentation rate, regardless of the type and depth of the anemia. In addition, tomography should be recommended for malignancy screening in diabetic patients with anemia that have a normal gastrointestinal examination.

Keywords: Anemia, endoscopy, malignancy, type 2 diabetes


How to cite this article:
Yaylaci S, Genc AB, Demir MV, Cinemre H, Uslan M&, Tamer A. Investıgatıon of malignancy in diabetic patients with anemia. Med J DY Patil Univ 2014;7:454-7

How to cite this URL:
Yaylaci S, Genc AB, Demir MV, Cinemre H, Uslan M&, Tamer A. Investıgatıon of malignancy in diabetic patients with anemia. Med J DY Patil Univ [serial online] 2014 [cited 2021 Sep 29];7:454-7. Available from: https://www.mjdrdypu.org/text.asp?2014/7/4/454/135264


  Introduction Top


Diabetes mellitus (DM) is the most common endocrine disease in the world and the incidence of anemia in patients with diabetes is higher than other populations. There are some factors identified as the possible causes of anemia developed early in DM. Tubulointerstitial damage, autonomic dysfunction associated with diabetic nephropathy and the use of angiotensin-converting enzyme inhibitors in these patients are reported as the possible causes of anemia. [1],[2] In recent years, diabetes is accused of the development of solid organ malignancies (liver, pancreas, colorectal, breast, endometrium, uterus and bladder). [3] The potential risk factors that have been blamed in this regard include age, gender, obesity, sedentary life-style, diet, alcohol and smoking. [4],[5] Anemia can be seen in individuals with diabetes due to anti-platelet use due to an atherosclerotic condition, or due to the increased incidence of colorectal cancer, as well as the development of anemia in the early stages of nephropathy. [6] And approaches for an anemia-DM association are controversial. In this study, we investigated the relationship between malignancy and anemia type, depth and other factors in diabetic patients with anemia in order to clarify this issue.


  Materials and Methods Top


The files of the follow-up patients with type 2 diabetes that have been admitted to the Department of Internal Medicine and Diabetes Outpatient Clinic, Ministry Of Health Sakarya University Training And Research Hospital, Sakarya-Turkey, between January 1, 2010 and December 31, 2011 were retrospectively reviewed and 103 patients with anemia were included in the study. The study was approved by the local Ethics Committee.

The Inclusion Criteria for the Study

Patients diagnosed as DM by ADA criteria or the patients that were still treated with a diagnosis of DM were accepted as diabetes. According to World Health Organization's criteria for anemia, values lower than 13 g/dl in males and 12 g/dl in females were accepted as anemia. Patients with type 2 diabetes and anemia were included in the study. The files were retrospectively reviewed.

Exclusion Criteria

Patients with type 1 DM, patients with missing data, patients with a diagnosis of malignancy and the patients smaller than 18 years of age were excluded from the study.

The imaging methods and endoscopic diagnoses were also recorded, in addition to demographic data, routine biochemical and hematological parameters. The detection rate of malignancy was determined by these methods.

The anemia types were classified as iron deficiency anemia, vitamin B12 deficiency and anemia of chronic disease. The patients with low levels of iron and ferritin and higher iron binding capacity and patients with transferrin saturation of lower than 20% were considered as patients with iron deficiency anemia. The patients with low levels of iron, lower iron binding capacity, normal or high ferritin and with normal transferrin saturation were considered as patients with anemia of chronic disease. And patients with B12 levels lower than 185 pg/ml were classified as patients with B12 deficiency. Patients with low level of mean corpuscular volume diagnosed as iron deficiency anemia together with B12 deficiency were included in the iron deficiency group. According to the depth of anemia, they were divided into two groups as the lower and greater than Hb 10 g/dl. Pathologically diagnosed patients and patients with malignant mass observed in the imaging were evaluated as the malignancy group. Glomerular filtration rate (GFR) was counted with Cockrfoft-Gault formula.

Statistical analysis was performed using the SPSS 17.0 software program. Categorical variables were expressed with numbers or percentages and the continuous variables were expressed as the mean ± standard deviation. Categorical variables were compared using the Chi-square test. The t-test for independent samples was used to compare the data that fit a normal distribution between the two groups. Statistically, P < 0.05 was considered to be significant.


  Results Top


The mean age of the 103 patients in the study was found as 63.3 ± 11.7 years (58 females, 45 males), mean diabetes duration 11 ± 7.7 years, mean Hb 9.49 ± 1.95 g/dl, mean HbA1c 8.09 ± 2, mean creatinine value 1.12 ± 0.5 mg/dl and the mean GFR value 74.2 ± 31 ml/min. In the evaluation according to the anemia panel, 72 patients had iron deficiency (69.9%), 16 patients had chronic disease (15.5%), 13 patients had iron deficiency and vitamin B12 deficiency (12.6%) and 2 had vitamin B12 and folate deficiency anemia (1.94%) respectively. No significant difference was found in terms of the age, duration of diabetes, level of creatinine, GFR and HbA1c parameters, when the patients were divided into two groups of iron deficiency anemia and anemia of chronic disease [Table 1] and [Table 2].
Table 1: The analysis of patients with anemia of chronic disease and iron deficiency

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Table 2: Demographic, hematological and biochemical data analysis between the malignancy group and the group of patient that had no malignancy

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A total of 102 patients underwent upper gastrointestinal endoscopy. Further examination of patients with esophageal varices, which was identified endoscopically, revealed hepatitis B in one patient, hepatitis C in another patient and three patients had cryptogenic cirrhosis of the liver. 2 patients had gastric adenocarcinoma. The incidence of cancer was found to be 1.9% in the upper gastrointestinal endoscopy. 64 patients underwent lower gastrointestinal endoscopy. 37 (35.9%) patients were rejected lower gastrointestinal endoscopy. Four of patients with polyps had hyperplastic polyps, two had tubular adenoma and another two had tubovillous adenomas. One patient had endocrine tumor and three patients had adenocarcinoma. Incidence of cancer was found to be 6.3% in lower gastrointestinal endoscopy. All patients had abdominal ultrasonography performed. The sign of malignancy was found by ultrasonography in 2 (1.8%) patients (1 patient had the liver mass and 1 patient had increased gastric wall thickness). 43 patients underwent thoracoabdominopelvic tomography. In the computed tomography (CT), mass lesion was observed in 11 (25.5%) patients (1 patient with prostate cancer, 1 patient with lung metastases of unknown primary, 1 patient with lung mass, 1 patient with intra-abdominal mass and 1 patient had a solid mass in the liver).

The erythrocyte sedimentation rate was significantly higher in the group with malignancy than the other group that had no malignancy. No relationship was found between malignancy and anemia type and depth, although there was a significant relationship between the depth of anemia and low GFR levels.


  Discussion Top


The common intersection points of diabetes and cancer are high-fat diet, sedentary lifestyle, obesity, inflammation, hyperglycemia and hyperinsulinemia. [4],[5] Diabetes has been recognized as a major factor contributing to the development of solid organ cancers, such as liver, pancreatic, colorectal, breast, endometrial, uterine and bladder cancers. [4],[7],[8],[9] In the studies, cancer risk and mortality were found to be increased in diabetic patients and higher HbA1c was found to be a crucial predictor. [7],[10],[11],[12]

In a study, where 9577 type-2 diabetic patients and 19,154 non-diabetic were examined, 661 (6.9%) cases of cancer were found in the diabetes group and 1364 (7.1%) cases of cancer were found in the non-diabetic group and the difference was not statistically significant. [13] In a study in which colorectal cancer was not included, the incidence of cancer was 4.6% among 7950 type-2 diabetic patients and the incidence of pancreatic cancer was significantly higher in type-2 diabetic patients. [14] Moreover in a study by Karlin et al., the prevalence of diabetes was 6.8% among the 15,951 cancer patients and in the study of Wideroff et al., the prevalence of diabetes was 8.05% among the 109,581 cancer patients. [15],[16] In our study, however, the malignancy rates were higher than those reported above. This is because we included selected patients with anemia in the study. Similar to the literature, in our study colon cancer was more common in diabetic patients (3.88%) and considering the 35.9% of patients who had reused colonoscopy, the rate of colorectal cancer was probably higher. In a study conducted by Ogunleye et al., stomach cancer (16 [0.2%]) and colon cancer (67 [0.7%]) was identified. According to this study, the rate of cancer was not increased in diabetic patients than non-diabetics, considering all cancers, but an increase in liver, colon and pancreatic cancers was observed in diabetic patients. [13] In our study, according to the relationship between malignancy and anemia types and depths, 9 (10.5%) patients with iron deficiency and 2 (12.5%) patients with anemia of chronic disease had malignancy and no significant difference was found in the malignancy ratio between iron deficiency anemia and anemia of chronic disease. According to the depth of anemia, there was no significant difference on the malignancy for lower or greater than Hb 10 g/dl.

In the studies, a relationship was found between DM and gastrointestinal cancers, such as liver, pancreas, colon and rectum cancers, [13] however, no relationship was found with the gastric cancer. [17]

There was no significant difference in terms of clinical and laboratory parameters, other than the erythrocyte sedimentation rate, between patients with and without malignancy. Although it was reported that the level of sedimentation is not a useful screening test in asymptomatic individuals and it is usually found to be normal in patients with cancer, [18] it is associated with poor prognosis in cancer patients with a high level of sedimentation. In patients with solid tumors, a sedimentation rate greater than 100 mm/h generally favors metastatic disease. [19] In our study, the erythrocyte sedimentation rate was significantly higher in patients with malignancy than the patients that had no malignancy. Therefore, the elevated erythrocyte sedimentation rate should not be regarded as a chronic disease in diabetics with anemia and an underlying malignancy should be investigated.

In our study, malignancy was found in 11 of the 103 type-2 diabetic patients (10.7%). The high rate of malignancy may be due to the inclusion of patients with colorectal cancer in our study. As the type of malignancy, colorectal cancer (6.3%), stomach cancer (1.9%), prostate cancer (0.97%), lung metastases of unknown primary (0.97%), lung cancer (0.97%), intra-abdominal mass (0.97%) and solid mass in the liver (0.97%) was identified respectively. The rate of colorectal cancer could be found higher, considering the fact that 35.9% of the patients have refused colonoscopy. According to analysis, the erythrocyte sedimentation rate was significantly higher in patients with malignancy than the patients that had no malignancy. No significant relationship was found between age, gender, duration of diabetes, HbA1c and GFR levels of the two groups.

X-ray, ultrasound, CT, Endoscopy and Colonoscopy methods are frequently used on the etiology of anemia. [20] In our study, all patients were examined by ultrasonography. Nearly 1.9% of the malignancies were detected by ultrasonography. Tomographic examination was performed on 43 patients. In the CT, 11 (25.5%) of the patients had 18 different malignancies. All of the 6 patients with gastric and colon cancer according to the endoscopic procedures, had also gastric and colonic mass or wall thickening, in the tomographic examination. Furthermore, malignancy was detected in 5 patients, who had no pathological results according to endoscopic examination. Tomography was found to have an important role in the differential diagnosis of anemia, since it increases the diagnostic efficiency of the gastrointestinal endoscopic procedures, as well as locating lesions in other organs.


  Conclusion Top


In the light of the studies conducted, it can be said that there is no need for a general cancer screening in diabetic patients. However, since the rate of cancer in diabetic patients with anemia was found as high as 10.7% in line with our study, it should be suggested that the malignancy must be sought irrespective of the presence of iron deficiency anemia and/or anemia of chronic disease in diabetic patients with anemia. Especially the high level of sedimentation requires being more careful in this regard.

 
  References Top

1.Bilous R. Anaemia - A diabetologist's dilemma? Acta Diabetol 2002;39 (Suppl 1):S15-9.  Back to cited text no. 1
    
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3.Suh S, Kim KW. Diabetes and cancer: Is diabetes causally related to cancer? Diabetes Metab J 2011;35:193-8.  Back to cited text no. 3
    
4.Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, et al. Diabetes and cancer: A consensus report. CA Cancer J Clin 2010;60:207-21.  Back to cited text no. 4
    
5.Sun G, Kashyap SR. Cancer risk in type 2 diabetes mellitus: Metabolic links and therapeutic considerations. J Nutr Metab 2011;2011:708183.  Back to cited text no. 5
    
6.Luo W, Cao Y, Liao C, Gao F. Diabetes mellitus and the incidence and mortality of colorectal cancer: A meta-analysis of 24 cohort studies. Colorectal Dis 2012;14:1307-12.  Back to cited text no. 6
    
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8.Weiderpass E, Gridley G, Persson I, Nyrén O, Ekbom A, Adami HO. Risk of endometrial and breast cancer in patients with diabetes mellitus. Int J Cancer 1997;71:360-3.  Back to cited text no. 8
    
9.Sun L, Yu S. Diabetes mellitus is an independent risk factor for colorectal cancer. Dig Dis Sci 2012;57:1586-97.  Back to cited text no. 9
    
10.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.  Back to cited text no. 10
    
11.Yang X, Ko GT, So WY, Ma RC, Yu LW, Kong AP, et al. Associations of hyperglycemia and insulin usage with the risk of cancer in type 2 diabetes: The Hong Kong diabetes registry. Diabetes 2010;59:1254-60.  Back to cited text no. 11
    
12.Barone BB, Yeh HC, Snyder CF, Peairs KS, Stein KB, Derr RL, et al. Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: A systematic review and meta-analysis. JAMA 2008;300:2754-64.  Back to cited text no. 12
    
13.Ogunleye AA, Ogston SA, Morris AD, Evans JM. A cohort study of the risk of cancer associated with type 2 diabetes. Br J Cancer 2009;101:1199-201.  Back to cited text no. 13
    
14.Zhang PH, Chen ZW, Lv D, Xu YY, Gu WL, Zhang XH, et al. Increased risk of cancer in patients with type 2 diabetes mellitus: A retrospective cohort study in China. BMC Public Health 2012;12:567.  Back to cited text no. 14
    
15.Karlin NJ, Dueck AC, Cook CB. Cancer with diabetes: Prevalence, metabolic control, and survival in an academic oncology practice. Endocr Pract 2012;18:898-905.  Back to cited text no. 15
    
16.Wideroff L, Gridley G, Mellemkjaer L, Chow WH, Linet M, Keehn S, et al. Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark. J Natl Cancer Inst 1997;89:1360-5.  Back to cited text no. 16
    
17.Marimuthu SP, Vijayaragavan P, Moysich KB, Jayaprakash V. Diabetes mellitus and gastric carcinoma: Is there an association? J Carcinog 2011;10:30.  Back to cited text no. 17
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18.Sox HC Jr, Liang MH. The erythrocyte sedimentation rate. Guidelines for rational use. Ann Intern Med 1986;104:515-23.  Back to cited text no. 18
    
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20.Available from: http://www.mayoclinic.org/diseases-conditions/anemia/basics/tests-diagnosis/con-20026209 [Last accessed on 2014 Jan 20].  Back to cited text no. 20
    



 
 
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