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ORIGINAL ARTICLE
Year : 2015  |  Volume : 52  |  Issue : 7  |  Page : 148-152
 

The correlation analysis of primary liver cancer with Type 2 diabetes


Department of Medical Oncology, Yishui Central Hospital, Linyi, China

Date of Web Publication20-Jul-2016

Correspondence Address:
Q Su
Department of Medical Oncology, Yishui Central Hospital, Linyi
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.186557

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 » Abstract 

OBJECTIVE: To explore the relationship between Type 2 diabetes and primary liver cancer. MATERIALS AND METHODS: In the period from December 2008 to December 2014, all blood sugar data of patients in our hospital was collected, and the total number is 18213. Except for repeatedly hospitalized diabetic person, newborn stress status, or venous transfusion blood glucose, gestational diabetes, etc., By retrieving the medical record information of patients in the hospital, and using telephone or letter follow-up the patients, we collected 127 people with type 1 diabetes and found no liver cancer patients; Type 2 diabetes, 10,794 cases of patient information, 59 with primary liver cancer. For data analysis, Stata11.0 ratio was used as the main analysis indicators, using Chi-square test and statistical analysis. RESULTS: About 10,794 Type 2 diabetes cases with 59 primary liver cancer, the incidence is 54.66/10,000, men liver cancer incidence (92.78/10,000) than women (27.13/10,000), with significant difference (χ2 = 26.621, P < 0.001). As the growth of the age, the possibility of liver cancer in patients with diabetes increased significantly (χ2 = 19.961, P = 0.001). The rate was highest for 50-60-year-old men, and the women at age 70, and older incidence is highest. Irrespective of men or women with diabetes as the growth of the age, the possibility of liver cancer had significantly increased (P = 0.001, P = 0.002). Hepatitis B or hepatitis C incidence was 2.94%, but diabetes incidence of hepatitis men (3.98%) and women (2.01%) did not find significant differences (χ2 = 0.3361, P = 0.562). Three hundred and seventeen cases of Type 2 diabetes with hepatitis, the incidence of primary liver cancer was 11.67%, the liver cancer incidence of diabetes patients with hepatitis men (17.78%) than women (3.97%), with significant difference (χ2 = 37.429, P < 0.001). With the growth of age, the overall risk of getting liver cancer (χ2 =15.023, P = 0.01) of diabetes and hepatitis patients is significantly increased, and with the growth of age, the risk of getting liver cancer of male patients showed significant (P < 0.05), but not the female patients. Without merge hepatitis, the morbility of primary liver cancer in 10477 cases of type2 diabetes incidence is 0.21%, the liver cancer incidence men (0.34%) than women (0.11%), with significant difference (χ2 = 6.471, P = 0.011).As the growth of age, the overall risk of getting liver cancer of diabetes patients without hepatits is significantly increased (χ2 =15.612, P = 0.008) ,and the risk of getting liver cancer of male patients showed significant (P < 0.05) as the growth of the age, but not the female patients. Diabetic persons according to the illness time can be divided into 0-5 years, 5-10 years, 10-20 years, and over 20 years of four stages, including 5-10 years and 10-20 years is liver cancer patients with diabetes incidence peak, male diabetic hepatitis in patients with liver cancer incidence than women, with significant difference (χ2 = 22.757, P < 0.001). The possibility of liver cancer in patients with diabetes increased significantly (χ2 = 15.023, P = 0.01) for longer duration of illness, but only the male patients with liver cancer incidence showed significant difference with longer duration of illness, women showed no significance. CONCLUSION: Diabetes was associated with the primary liver cancer, most likely is one of the causes of primary liver cancer.


Keywords: Correlation, incidence, primary liver cancer, Type 2 diabetes


How to cite this article:
Su Q, Sun F, Li J, Zhang H, Wang M, Zhou H, Qiao L. The correlation analysis of primary liver cancer with Type 2 diabetes. Indian J Cancer 2015;52, Suppl S3:148-52

How to cite this URL:
Su Q, Sun F, Li J, Zhang H, Wang M, Zhou H, Qiao L. The correlation analysis of primary liver cancer with Type 2 diabetes. Indian J Cancer [serial online] 2015 [cited 2019 Aug 24];52, Suppl S3:148-52. Available from: http://www.indianjcancer.com/text.asp?2015/52/7/148/186557



 » Introduction Top


With improvement of living standards, changes in lifestyle and environmental pollution increasing, the incidence of diabetes is rising. [1],[2],[3] The clinical observation found that the incidence of primary liver cancer increases in persons with diabetes. [4] Liver cancer is a common malignant tumor which is seriously harmful to human health. [5] Most of late clinical patients lost surgery opportunity and lack effective treatment for liver cancer. It is the worst treatment effect in all kinds of cancer. At present, there are some definite causes of liver cancer, including hepatitis B and hepatitis C, liver cirrhosis, nonalcoholic liver cirrhosis, alcohol, and aflatoxin, but there are still some patients which etiology is not clear. Moreover, with the popularity of hepatitis B vaccination to prevent hepatitis B, the incidence of hepatitis B is remarkably decreasing, and hepatitis leads to liver cancer is weakening. Exploring and discovering the new causes of liver cancer has vital significance for early detection and early treatment of liver cancer, improve the cure rate and prolong survival time.


 » Materials and Methods Top


Investigation population

In the period from December 2008 when the database was established to December 2014, all blood sugar data of patients in our hospital was collected. During 6 years, it has 18,213 persons. Except for people with diabetes that had been hospitalized several times, newborn stress status, or intravenous fluids such as blood glucose increasing, gestational diabetes, 13,795 people diagnosed with diabetes, all included in the investigation object.

Investigation method

Patients who have telephone information register the telephone follow-up. Patients with no telephone information according to the specific address use follow-up letters. Then, statistical analysis was carried out for all the patients. Successful follow-up information was collected from 10,794 cases of patients with Type 2 diabetes. There are 64 cases of liver tumors, rotating all diagnosed with diabetes in the hospital medical record information metastatic liver tumors in 5 cases, 59 cases of primary liver cancer, and liver cancer are not found in 127 cases with Type 1 diabetes among them.

Diagnostic criteria

Diabetes according to the WHO diagnostic criteria in 1999, [6] which is fasting plasma glucose ≥7.0 mmol/L and/or oral glucose tolerance test-2 h blood glucose ≥11.1 mmol/L, and the medical institutions at or above the district level diagnosed with diabetes patients. Primary liver cancer and metastatic liver cancer were diagnosed according to the pathological examination.

Statistical analysis

As per the network platform for data entry provided by our information center, use STATA Version 11.0 software (Stata Corporation, Collage Station, TX, USA) as the main analysis tool and ratio as the main analysis indicators. If P < 0.05 when test by χ2, demonstrate it has statistical significance.


 » Results Top


Basic situation

By searching our information center database in December 2008 to December 2014 information of 10,794 patients with Type 2 diabetes, among them, 4497 cases of male, 6223 cases of female, accounted for 41.66% and 58.34% of patients surveyed; 10~, 30~, 40~, 50~,60~, 70~ age group number, respectively, accounted for 0.53%, 4.52%, 15.52%, 26.13%, 15.52%, and 23.73%.

The test result of incidence of liver cancer in the patients with Type 2 diabetes

In 10,794 cases of patients with Type 2 diabetes, there are 59 cases of primary liver cancer. Its incidence is 54.66/10,000 (male 92.78/10,000, female 27.13/10,000). This is 29 times the incidence of national standardization (18.8/100,000). The incidence of liver cancer in male diabetic patients was higher than that of female, and the difference was significant (χ2 = 26.621, P < 0.001). With increase in age, the possibility of liver cancer in diabetes patients was significantly improved (χ2 = 19.961, P = 0.001). The incidence of male was the highest in 50-60-year-old, and the female was the highest above the age of 70 years. Both male and female with diabetes, with age increase, the possibility of developing liver cancer was significantly increased (P = 0.001, P = 0.002). The results are shown in [Table 1].
Table 1: December 2008 to December 2014, the incidence of diabetes, hepatitis, and liver cancer


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The test result of incidence of hepatitis in the patients with Type 2 diabetes

In 10,794 patients with diabetes, 317 patients with hepatitis B or C, the incidence was 2.94% (male 3.98%; female 2.01%), but it is undifferentiated in men and women with diabetes (χ2 = 0.3361, P = 0.562). With increase in age, the possibility of hepatitis in patients with diabetes was significantly improved (χ2 = 26.3, P < 0.001). The incidence of hepatitis in male patients with diabetes showed significant difference (P < 0.001) with increase in age while female patients did not show any significant difference. The results are shown in [Table 1].

The test result of incidence of liver cancer in patients with Type 2 diabetes and hepatitis

37 people of patients with diabetes and hepatitis in 317 cases got liver cancer, the incidence is 11.67% (male 17.78%, female 3.97%), of which female with diabetes and hepatitis patients with liver cancer rate is higher than the female. The difference is statistically significant (χ2 = 37.429, P < 0.001). With increase in age, the possibility of diabetes with hepatitis patients generally suffering from liver cancer increased significantly (χ2 = 15.023, P = 0.01). With increase in age, the incidence of liver cancer showed significant difference (P < 0.05) in male patients with diabetes and hepatitis, and female patients did not show any significant difference. The results are shown in [Table 1].

The test result of incidence of liver cancer in patients with Type 2 diabetes without hepatitis

In 10,477 patients with diabetes without hepatitis, 22 patients with liver cancer, the incidence was 0.21% (male 0.34%; female 0.11%), significantly lower than the incidence of liver cancer in patients with diabetes and hepatitis 11.67%. The incidence of the male is higher than female; the difference was statistically significant (χ2 = 6.471, P = 0.011). With increase in age, diabetes patients without hepatitis generally suffer from the possibility of liver cancer also increased significantly (χ2 = 15.612, P = 0.008), diabetic men without hepatitis incidence of hepatocellular carcinoma (HCC) along with the age growth showed significant difference (P < 0.05) while female patients did not show significant difference, and this gender difference and diabetic patients with hepatitis whose incidence of HCC were similar results. The results are shown in [Table 1].

Correlation between the duration of type 2 diabetes and the incidence of liver cancer [Table 2] According to the duration of diabetes of investigation objects, patients were divided into 0-5 years, 5-10 years, 10-20 years, and 20 years above 4 time periods. Five to 10 years and 10-20 years are diabetic patients with liver cancer incidence peak stage, male diabetic patients with hepatitis patients with liver cancer incidence is higher than female, and the difference is statistically significant (χ2 = 22.757, P < 0.001). However, the incidence of liver cancer in male patients was significantly increased with the increase of the duration of the disease, and the incidence of female patients was not significantly increased. The results are shown in [Table 2].
Table 2: The correlation results between diabetic duration and liver cancer incidence


Click here to view



 » Discussion Top


In recent decades, the incidence of diabetes increased significantly, especially in the Western developed countries, due to the influence of environmental pollution, obesity, lifestyle changes, aging, and other factors. The prevalence of adult diabetes in Chinese cities is 9.7%, and Type 2 diabetes mellitus is the total number of diabetes mellitus 90-95%. [7] The early stage of diabetes characterized by insulin resistance and hyperinsulinemia is developed to the late due to the islet cells decompensated cause diabetic disease, as a result of insufficient insulin secretion. Diabetes patients are a large social group, and the complication of diabetes mellitus, which leads to the formation of vascular occlusion, seriously harms the life quality and life of patients. Meanwhile, the clinical observation found that the incidence of primary liver cancer is increasing with the increase of the incidence of diabetes [4] and the majority of studies suggest that diabetes is closely related to liver disease, especially in primary liver cancer, and that diabetes can lead to liver cancer.

The results of this paper were collected from 10,794 patients with Type 2 diabetes and 59 patients with primary liver cancer. Survey results reveal that male diabetic patients with liver cancer were reported to have incidence rate (92.78/million) than female patients (27.13/million). The difference is statistically significant (χ2 = 26.621, P < 0.001). This is similar with previous reports. With increase in age, diabetic patients suffering from the possibility of liver cancer increased significantly (χ2 = 19.961, P = 0.001), in accordance with the laws of nature. In patients with Type 2 diabetes and hepatitis, incidence rate of liver cancer is 12.09%, as well as the hepatitis B is one of the causes of liver cancer, hepatitis B and hepatitis C can lead to liver cancer, diabetes, but it is statistically insignificant. The incidence of HCC of male patients with diabetes mellitus complicated with hepatitis is reported to be higher (17.78%) compared to the incidence in women (3.97%), and the difference is statistically significant (χ2 = 37.429, P < 0.001). With increasing age, diabetes and hepatitis patients generally suffering from the possibility of liver cancer increased significantly (χ2 = 15.023, P = 0.01). It is indisputable that hepatitis B and C are closely related to the incidence of primary liver cancer. This is similar to previous research. After exclusion of hepatitis cause liver cancer, Type 2 diabetes mellitus patients without hepatitis incidence rate was 0.21%, of which the male liver cancer incidence (0.34%) was higher than in women (0.11%), and the difference is statistically significant (χ2 = 6.471, P = 0.011). With increase in age, diabetic patients without hepatitis generally had the possibility of HCC increased significantly (χ2 = 15.612, P = 0.008), diabetic men without hepatitis incidence of HCC along with the growth of age showed significant difference (P < 0.05), but female patients did not show any significant difference. Moreover, the investigation showed that the duration time of diabetes was correlated with the incidence of liver cancer, patients with diabetes generally suffering from the possibility of liver cancer increased significantly with prolonged illness (χ2 = 15.023, P = 0.01). However, the incidence of liver cancer in male patients is significantly increased with increase in time. Whether the incidence of primary liver cancer in the patients with Type 2 diabetes and hepatitis was 11.67%, and the incidence of without hepatitis was 0.21%, and the incidence of HCC in China was 18.80/100,000, [8] and the incidence of liver cancer significantly increased . According to the analysis of the GLOBOCAN 2012 years data and global annual new primary liver cancer, nearly 800,000, China new onset and mortality of primary HCC accounted for about half, ranking first in the world, calculated according to the China's population of 130 million new HCC of 200,000, liver cancer incidence is 15.38/100,000. This topic ignored hepatitis leads to primary HCC, the incidence is 0.21%. This is 13.65 times than liver cancer incidence"change to: "According to the data analysis of GLOBOCAN2012, the number of new primar liver cancer people is nearly 800 thousand every year in global,the primary hepatocellular carcinoma patients of neopathy in China accounted for about half of it and ranks first in the world, If there is 400 thousand new HCC in 130 million in China,the incidence of primary liver cancer is 0.03%. This study shows that the incidence of type 2 diabetes is 0.21%, it is 7 times the incidence of primary liver cancer. Early studies about the relationship between diabetes and liver cancer are not clear, and various studies in recent years have indicated that diabetes has a close relationship with liver cancer. Chen et al. [9] found that the incidence of HCC was statistically significant. Most studies suggest that Type 2 diabetes is not only related to primary liver cancer but also related with the digestive system tumors, lung cancer, blood system tumors, urinary system tumors, breast cancer, head and neck cancer, gynecological cancer, and other related tumors. Recently, some scholars have confirmed that diabetes can increase the risk of malignant tumor, and it is obvious that breast cancer, colon cancer, liver cancer, and so on are some of these. [10] The first large-scale controlled study of diabetes and HCC was carried out in the United States. A total of 2061 patients with HCC and 6183 non cancer patients were analyzed, and the other major factors, associated with HCC, have not been ruled out for such as hepatitis, hemochromatosis, alcoholic liver disease cases, such as diabetes are at increased risk of HCC 3 times than the result. Exclusion of hepatitis, hemochromatosis, and cases of alcoholic liver disease was analyzed. Patients with diabetes or value, despite the decline, have a significant difference (odds ratio, 2.87; 95% confidence interval [CI], 2.49-3.30). [11] The conclusions of the study are that diabetes is an independent cause of HCC. A study of patients aged 30 or older showed a significant increase in the risk of liver cancer in patients with diabetes mellitus. [12] Taiwan scholars [13] followed up 50899 patients, found that diabetes is an important cause to liver cancer; diabetes increased the risk of suffering from liver cancer for those people who have not been infected with hepatitis virus (Hazard Ratio, HR, 5.4) and hepatitis C antibody positive population (HR, 3.1) but no special effect of hepatitis B surface antigen positive populations. The risk of developing HCC with hepatitis C virus infection (HR, 18.8) was significantly higher than that of hepatitis B virus (HR, 12.6). There is only 3 patients with chronic hepatitis C got hepatocellular carcinoma in the subject, and didn't compare with the morbility of hepatitis B and C. Gao Shan et al. (1)carried out cohort study and Meta analysis for diabetes and primary liver cancer, collected 28 articles, with 14 involved Meta analysis, followed up 3672248 cases, with 3800 cases of patients with liver cancer, compared with those without diabetes by Meta analysis, found that the RR value of the incidence of patients with diabetic is 3.33 (95% CI: 1.82-1.82). It is suggested that there is a close relationship between diabetes and liver cancer, and it may be one of the risk factors of primary liver cancer. Hu et al., [14] using stratified cluster sampling method, retrospective survey 10,079 cases of equal to or more than 40-year-old residents of diabetes and malignant tumor incidence Jiashan county, Zhejiang province, analyzed different levels of glucose metabolism and the incidence cancer, and the trend used was Chi-square statistical inspection. In the past, a lot of men have a higher incidence than women, its prevalence of malignant tumors in patients with diabetes mellitus (268.79/million) higher than men (124.31/million). With the decrease of blood glucose adjustment ability, the incidence of malignant tumor is increasing, and the risk of malignant tumor is increased by 1.67 times in male patients and 2.62 times in female patients. The highest proportion of malignant tumors in patients with diabetes mellitus is breast cancer and colorectal cancer, and the incidence of glucose metabolism in the patients has a certain correlation with the risk of malignant tumor. It is regrettable that there is no statistical data on liver cancer. It is also indicated that the size of the correlation between diabetes and liver cancer depends on the duration of diabetes and the choice of treatment options. It is worth noting that the application of thiourea can increase the probability of HCC about more than 7 times. Donadon et al. [15] suggest that the risk of developing HCC in diabetic patients with insulin and thiourea is significantly higher while the risk of using metformin is significantly lower. Some researchers also found that the risk of HCC in patients with diabetes who use insulin was higher than those patients without insulin. Contrasted with the insulin or sulfonylurea group, the risk of hepatocellular carcinoma in metformin or thiazolidinedione group, and used insulin or sulfonylurea in the experimental group, the risk of HCC had significantly reduced. The oral dose of metformin and the course of treatment is correlation with reduced incidence of liver cancer. The above research conclusions agree with previous consultation. The total incidence of diabetes mellitus in patients with liver cancer was 54.66/million, which is 29 times more than the national standard, and the cause of the disease is more and the interaction, as many clinical studies suggest that diabetes may be the cause of primary liver cancer, the actual incidence is high. And the increased opportunity of treatment for diabetic population make it easier to find and diagnose liver cancer, and increase the chances of making it into the study object. The obesity and eating habits, as the interference factors, have not been effectively ruled out as some potential causes of liver cancer. Many studies have focused on diabetes and hepatitis virus, the synergistic effect of alcohol for HCC, besides hemochromatosis, immune liver disease, nonspecific cirrhosis of the liver, obesity, and nonalcoholic cirrhosis of the liver is also noteworthy. Most of the existing research supports diabetes can be a collaborative cause of liver cancer, the authors also agree with this view. The mechanism of diabetes may lead to liver cancer, which may be related to high levels of insulin, hyperglycemia, and chronic inflammation. Among them, insulin/insulin-like growth factor (IGF-1), has been in vitro experiments, animal experiments and epidemiological studies show that high concentrations of insulin and IGF through the/IGF axis to promote the development of cancer. [16] Under normal physiological conditions, the majority of cells obtain energy by the aerobic oxidation of sugar and the cancer cells were mainly expressed in aerobic fermentation. The active glycolysis of cancer cells improve its affinity with glucose, experimental studies have shown that glucose can reduce possibility of cancer cells apoptosis and high level of glucose can promote the proliferation of cancer cells, [17] elevated blood glucose increased the risk of various types of cancer. Many scholars believe that diabetes is a chronic low-grade inflammatory disease. The humoral and cellular immune function was damaged in patients with diabetes mellitus. Some basic studies have found that diabetic patients with weak immune system, decreased immunity, insulin resistance, high blood glucose, and insulin IGF-1 levels were higher and these factors cause liver cancer cell apoptosis and increase the incidence of liver cancer. [18] In addition, the potential risk factors include age, gender, race, obesity, diet, physical exercise, smoking and alcohol, and other factors affecting the incidence of liver cancer. More detailed clinical studies are needed to explore these factors and confirm it.


 » Conclusion Top


In summary, diabetes is likely to lead to the onset of primary liver cancer, as the conclusions of subject and many clinical researches on diabetes have become the cause of primary liver cancer and these conclusions are gradually clear. Prevention and control of diabetes is also very important for prevention and control of primary liver cancer. It will be helpful to reduce the risk of primary liver cancer. It is important to strengthen the follow-up and screening of diabetic patients, detect disease at earlier stage and take treatment for improve the cure rate of liver cancer patients.

Financial support and sponsorship

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Conflicts of interest

There are no conflicts of interest.

 
 » References Top

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  [Table 1], [Table 2]



 

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