|Year : 2020 | Volume
| Issue : 2 | Page : 225-230
Association between hepatocellular carcinoma and type 2 diabetes in a sample of Egyptian patients
Mervat E El-Wakeel1, Zeinab A Hassan1, Aliaa A El-Naggar2, Marwa F El-Sayed1
1 Department of Endocrinology and Metabolism, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
2 Department of Diagnostic Radiology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
|Date of Submission||21-Feb-2020|
|Date of Decision||04-Mar-2020|
|Date of Acceptance||05-Mar-2020|
|Date of Web Publication||29-Jun-2020|
Mervat E El-Wakeel
Assistant Professor of Endocrinology and Metabolism, Faculty of Medicine for Girls, Al-Azhar University, Piece 377, Area D, Street 9, Mokattam, Cairo
Source of Support: None, Conflict of Interest: None
Background Studies have reported association between type 2 diabetes mellitus (T2DM) and hepatocellular carcinoma (HCC). T2DM may cause nonalcoholic fatty liver disease-related HCC, suggesting a role of T2DM in hepatocarcinogenesis.
Aim The aim was to study the association between HCC and some metabolic factors including insulin resistance and BMI in a sample of Egyptian patients with T2DM.
Patients and methods The present work is a case–control study, conducted on 50 patients recently diagnosed as having HCC, and 30 participants as control. Patients and control were classified into diabetic and nondiabetic subgroups. Patients with other primary malignancies, organ failure, ascites, and autoimmune hepatitis were excluded.
Results The study revealed that weight, BMI, waist circumference, fasting blood sugar, C peptide, homeostasis model assessment-insulin resistance, and glycosylated hemoglobin (HbA1c) were significantly higher in patients than control, and in diabetic and nondiabetic patients, than their controls. DM percent and duration were significantly higher in patients than control. In all patients, diabetic and nondiabetic, homeostasis model assessment-insulin resistance was significantly positively correlated with weight, BMI, waist circumference, fasting blood sugar, C peptide, and HbA1c. In diabetic patients, tumor size did not show significant correlation with the studied metabolic factors.
Conclusion The most predictive factors in diabetic patients with HCC were C peptide, BMI, and HbA1c %.
Keywords: hepatocellular carcinoma, insulin resistance, type 2 diabetes
|How to cite this article:|
El-Wakeel ME, Hassan ZA, El-Naggar AA, El-Sayed MF. Association between hepatocellular carcinoma and type 2 diabetes in a sample of Egyptian patients. Sci J Al-Azhar Med Fac Girls 2020;4:225-30
|How to cite this URL:|
El-Wakeel ME, Hassan ZA, El-Naggar AA, El-Sayed MF. Association between hepatocellular carcinoma and type 2 diabetes in a sample of Egyptian patients. Sci J Al-Azhar Med Fac Girls [serial online] 2020 [cited 2020 Jul 11];4:225-30. Available from: http://www.sjamf.eg.net/text.asp?2020/4/2/225/288275
| Introduction|| |
During the past two decades, the prevalence of type 2 diabetes mellitus (T2DM) has dramatically increased. Sedentary lifestyles, excessive food, and obesity are main causes of the current DM epidemic .
Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the third leading cause of cancer-related death .
Risk factors of HCC include hepatitis B virus, hepatitis C virus (HCV), cirrhosis, heavy alcohol consumption, nonalcoholic steatohepatitis, aflatoxin exposure, increasing age, male sex, and positive family history; however, in 15–50% of patients with HCC, no specific risk factor was found .
The liver plays a crucial role in glucose metabolism. DM is an epiphenomenon of many chronic liver diseases (CLDs) like chronic hepatitis, fatty liver, liver failure, and cirrhosis. Previous studies showed that T2DM is a cause of nonalcoholic fatty liver disease and that cirrhosis and HCV increase the susceptibility to DM .
Although such association could be related to the underlying CLD that preceded HCC development, there is evidence suggesting that diabetes is an independent risk factor for HCC .
Because DM is a complication of many CLD, detailed information about patients’ DM duration before HCC is crucial for properly studying this association .
| Aim of the work|| |
The aim was to study the association between HCC and some metabolic factors, including IR, anthropometry, C peptide, and glycosylated hemoglobin (HbA1c) in a sample of Egyptian patients with T2DM.
| Patients and methods|| |
The present work is a case–control study. It was conducted on 50 patients, comprising 10 females and 40 males, aged 40–60 years old, recently diagnosed to have HCC, selected from Arab Contractors Medical Center, in the period from December 2017 to October 2019.
Patients group (group 1) was classified into the following:
- Group 1a (diabetic group): 35 patients with DM 1 year or more before diagnosis of HCC.
- Group 1b (nondiabetic group): 15 nondiabetic patients with HCC.
- Group 2 (control group): 30 age-matched and sex-matched participants, who were divided into 12 diabetic patients (2a) and 18 nondiabetic patients (2b).
Patients with other malignancies, HCC treated by intervention within 15 days, autoimmune hepatitis, Wilson’s disease, primary biliary cirrhosis, other organ failure, decompensated liver cell failure, hepatorenal syndrome, and ascites were excluded.
All participants gave an informed consent. The study is approved by the Ethics Committee of Faculty of Medicine for Girls, Al-Azhar University.
All groups were subjected to the following:
- Full medical history (age, DM duration, and viral hepatitis) and complete clinical examination.
- Anthropometric measurements:
- Weight, height, BMI, and waist circumference (WC).
- Routine laboratory investigations: complete blood count, coagulation profile, liver function tests (serum albumin, serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, total bilirubin, and direct bilirubin), and kidney function tests.
- Hepatitis viral markers (HBsAg and HCV Antibodies) by ELISA.
- Glycemic profile: fasting blood sugar (FBS) and HbA1c.
- C peptide in pmol/l, using ELISA, after 8 h fasting. Reference range is 264.87–1026.39 pmol/l .
- Homeostasis model assessment-insulin resistance (HOMA-IR) calculation using C peptide as follows :
- Imaging studies:
- Abdominal ultrasonography was done for the patient group as one of the two confirming sets to diagnose HCC, as well as exclude other organ affection and ascites, and for control group to exclude hepatic focal lesions.
- Triphasic computed tomography or dynamic MRI was done for the patient group with full comment on the arterial phase and washout pattern to confirm diagnosis of HCC and to assess tumor maximal diameter.
Diagnosis of HCC is made by two sessions of imaging (ultrasound and triphasic computed tomography or dynamic MRI), or a single dynamic imaging plus elevated alpha fetoprotein greater than 400 ng/ml.
Data registration and statistical analysis
Results were statistically analyzed using a computer program SPSS version 23.0 (SPSS, Inc., Chicago, United States of America). Mean comparison was done by t-test and χ2 test. The sample mean, SD, and SEM as well as the range were obtained for numerical variables. For non-numerical variables, percentage were calculated.
The Student t-test was used to test the significance of the difference between two independent means. Correlation coefficient (r) was used to find out a correlation between two parameters where r value will be either +1 (positive correlation), 0 (no correlation), or −1 (negative correlation).
| Results|| |
The current study showed that anthropometry, DM percent and duration, FBS, C peptide, HOMA-IR, and HbA1c were significantly higher in patients with HCC than controls ([Table 1]).
|Table 1 Weight, BMI, waist circumference, DM percent, DM duration, fasting blood sugar, C-peptide, HOMA-IR, and HbA1C, in all studied groups|
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FBS, C-peptide, HOMA-IR, and HbA1c were significantly higher in diabetic than nondiabetic patients with HCC ([Table 2]).
|Table 2 Weight, height, BMI, Waist circumference, FBS, C peptide, HOMA-IR, HbA1c, and lipid profile in diabetic and non-diabetic patients with HCC|
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Age, anthropometry, FBS, C peptide HOMA-IR, and HbA1c were significantly higher in diabetic patients than control ([Table 3]), and in nondiabetic patients than control ([Table 4]).
|Table 3 Comparison between group 1a and group 2a regarding age, anthropometry, FBS, C peptide, HOMA-IR, and HbA1c|
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|Table 4 Comparison between group 1b and group 2b regarding age, anthropometry, FBS, C peptide, HOMA-IR, and HbA1c|
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HOMA-IR showed significant positive correlation with BW, BMI, WC, FBS, and C peptide, and HbA1c in patients with HCC and in diabetic patients with HCC, and nonsignificant negative correlation with age in nondiabetic patients with HCC and diabetic patients with HCC ([Table 5]).
|Table 5 Correlation between HOMA-IR and all parameters in group 1 and group 1a|
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The most predictive metabolic factors in diabetic patients with HCC were C peptide greater than 1125.71 pmol/l [odds ratio (OR): 26.2], BMI >28.6 kg/m2 (OR: 23.04), and HbA1c greater than 5.4% (OR: 21) ([Table 6]).
| Discussion|| |
In the current study, BW, WC, and BMI, were significantly higher in patients than control group. A nested case–control study by Schlesinger et al.  found that increased anthropometry was associated with higher HCC risk. The risk was significantly higher in both diabetic and nondiabetic patients.
This study showed that DM percent and duration were significantly higher in patients with HCC than control. Epidemiologic studies showed that higher rates of diabetes were found to be associated with HCC by different investigators in different locations using different study designs. Because diabetes is common and potentially modifiable risk factor, this association cannot be ignored .
Hassan et al.  suggest that association between diabetes and HCC increased as the duration of diabetes increased. Conversely, Donadon et al.  did not find a significant difference between HCC and non-HCC cases regarding DM duration.
In this study, C peptide and HOMA-IR were significantly higher in patients with HCC than control group. Khattab et al.  found that FBS, fasting insulin, and HOMA-IR were significantly higher in patients with HCC than control.
FBS and HbA1c were significantly higher in patients than control. These findings were consistent with Donadon et al. , who demonstrated that both were significantly higher in patients with HCC than liver cirrhosis (LC). High HbA1c levels were associated with significantly increased risk of HCC.
In this study, FBS, C peptide, HOMA-IR, and HbA1c were significantly higher in diabetic than non-diabetic patients with HCC.
Visceral fat has a high metabolic activity . In this study, age and anthropometry were significantly higher in nondiabetic patients with HCC than control. FBS, C peptide level, HOMA-IR, and HbA1c were significantly higher in nondiabetic patients with HCC than control. This may be attributed to prediabetes and IR, which were more prevalent in nondiabetic patients with HCC than control.
In this study, anthropometry, C peptide, and HbA1c were significantly higher in diabetic patients with HCC than diabetic controls. Khattab et al.  compared between HCC, chronic hepatiis C (CHC), and healthy participants regarding metabolic factors and found that BMI, FBS, insulin level, and HOMA-IR were significantly higher in patients with HCC than healthy participants. They reported that IR is an independent risk factor for HCC development.
Donadon et al.  evaluated HOMA-IR in HCC, LC, CHC, and healthy participants and found that percentage were similar in LC and nondiabetic patients with HCC but higher than CHC. The diabetic HCC had the greatest percentages.
In this study, FBS and HbA1c were significantly higher in diabetic patients with HCC than controls. This is in agreement with Donadon et al.  who found that in patients with preexisting T2DM, the risk of HCC is positively associated with poor glycemic control.
In patients with HCC and in diabetic HCC subgroup, HOMA-IR showed significant positive correlation with anthropometry, HbA1c, FBS, and C peptide. Similarly, Zhao et al. , found a significant positive correlation between HOMA-IR and FBS, C peptide, and BMI in hepatitis B virus-related patients with HCC.
Khattab et al.  reported a significant positive correlation between HOMA-IR and BMI, FBS, and insulin level in patients with HCC.
The this study showed that metabolic predictors with highest ORs were C peptide, BMI, and HbA1c. Konishi et al.  reported that IR has been recognized as an independent risk factor for HCC. Calle et al.  reported significant increase in HCC among those with the highest BMI compared with the lowest BMI.
Current data suggest that uncontrolled DM is related to increased HCC risk. However, this is limited by absence of data about previous HbA1c levels in the studied participants. Donadon et al.  reported that increased HbA1c% is associated with increased HCC risk.
This study suggests that T2DM and longer duration of DM are associated with increased risk of HCC. It also confirms that IR and obesity are independent risk factor for HCC, as HOMA-IR and BMI were significantly higher in both diabetic and nondiabetic patients with HCC than diabetic and nondiabetic control. In diabetic patients with CLD, chronic poor glycemic control may increase the risk of developing HCC.
| Conclusion|| |
T2DM is associated with increased HCC risk. The most predictive metabolic factors in diabetic patients with HCC were C peptide, BMI, and HbA1c.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]