Demographic and clinical characteristics
The study enrolled 232 patients with HCC, of which 67 (28.9%) were in the hypoglycemia group and 165 (71.1%) in the non-hypoglycemia group. The median age was 56 (range: 28–84) years. Most of the patients were men (207 [89.2%]). In total, 54 (23.3%), 143 (61.6%), and 35 (15.1%) patients had educational levels of primary, secondary, and university education, respectively. There was no significant difference between the two groups in terms of sex and age (p>0.05), but the difference in the composition ratio of educational level was statistically significant (χ2=7.22, p=0.027). The proportion of patients in the hypoglycemia group with secondary education was higher than that of patients in the non-hypoglycemia group. The proportion of patients with Child-Pugh grades A, B, and C in the hypoglycemia group were 20.9%, 26.9%, and 50.7%, respectively. In the non-hypoglycemia group, the proportions were 32.1%, 28.5%, and 39.4%, respectively. There was a significant difference in the Child-Pugh stage between the two groups (χ2=35.93, p<0.001). The incidence rates of mild, moderate, and severe ascites in the two groups were 14.9%, 20.9%, 17.9% and 7.3%, 10.9%, and 9.7%, respectively, and the difference was statistically significant. In addition, the incidence rates of diarrhea (17.9% and 7.3%, χ2=5.82, p=0.016) and lower extremity edema (34.3% and 13.9%, χ2= 12.46, p<0.001) and the patient’s diet (χ2=19.20, p<0.001) were significantly different between the two groups. However, there were no significant differences in diabetes history, Barcelona staging, hepatic encephalopathy, persistent vomiting, or use of somatostatin between the two groups (p>0.05). Detailed information is shown in Table1.
Table 1 Demographic and clinical characteristics of patients with hepatocellular carcinoma
|
Hypoglycemia group (n=67)
|
Non-hypoglycemia group (n=165)
|
/Z
|
P
|
Sex
|
|
|
|
|
Male
|
60 (89.6%)
|
147 (89.1%)
|
0.01
|
0.918
|
Female
|
7 (10.4%)
|
18 (10.9%)
|
|
|
Age (year, median [min–max])
|
55 (31–76)
|
57 (28–84)
|
1.60
|
0.110
|
Educational levels
|
|
|
|
|
Primary school education
|
8 (11.9%)
|
46 (27.9%)
|
7.22
|
0.027
|
High school education
|
49 (73.1%)
|
94 (57.0%)
|
|
|
College degree
|
10 (14.9%)
|
25 (15.2%)
|
|
|
Diabetes history
|
|
|
|
|
No
|
60 (89.6%)
|
132 (80.0%)
|
3.05
|
0.081
|
Yes
|
7 (10.4%)
|
33 (20.0%)
|
|
|
Barcelona staging
|
|
|
|
|
A
|
14 (20.9%)
|
53 (32.1%)
|
5.76
|
0.098
|
B
|
18 (26.9%)
|
47 (28.5%)
|
|
|
C
|
34 (50.7%)
|
65 (39.4%)
|
|
|
D
|
1 (1.5%)
|
0 (0)
|
|
|
Child-Pugh grades
|
|
|
|
|
A
|
25 (37.3%)
|
113 (68.5%)
|
35.93
|
<0.001
|
B
|
24 (35.8%)
|
47 (28.5%)
|
|
|
C
|
18 (26.9%)
|
5 (3.0%)
|
|
|
Hepatic encephalopathy*
|
|
|
|
|
No
|
64 (95.5%)
|
163 (98.8%)
|
-
|
0.146
|
Yes
|
3 (4.5%)
|
2 (1.2%)
|
|
|
Ascites
|
|
|
|
|
No
|
31 (46.3%)
|
119 (72.1%)
|
13.98
|
0.003
|
Mild
|
10 (14.9%)
|
12 (7.3%)
|
|
|
Moderate
|
14 (20.9%)
|
18 (10.9%)
|
|
|
Severe
|
12 (17.9%)
|
16 (9.7%)
|
|
|
Diarrhea
|
|
|
|
|
No
|
55 (82.1%)
|
153 (92.7%)
|
5.82
|
0.016
|
Yes
|
12 (17.9%)
|
12 (7.3%)
|
|
|
Persistent vomiting*
|
|
|
|
|
No
|
64 (95.5%)
|
163 (98.8%)
|
-
|
0.146
|
Yes
|
3 (4.5%)
|
2 (1.2%)
|
|
|
Lower extremity edema
|
|
|
|
|
No
|
44 (65.7%)
|
142 (86.1%)
|
12.46
|
<0.001
|
Yes
|
23 (34.3%)
|
23 (13.9%)
|
|
|
Whether to use somatostatin*
|
|
|
|
|
No
|
64 (95.5%)
|
163 (98.8%)
|
-
|
0.146
|
Yes
|
3 (4.5%)
|
2 (1.2%)
|
|
|
The patient’s diet
|
|
|
|
|
Fasting
|
3 (4.5%)
|
2 (1.2%)
|
19.20
|
<0.001
|
Poor
|
3 (4.5%)
|
1 (0.6%)
|
|
|
General
|
24 (35.8%)
|
26 (15.8%)
|
|
|
Good
|
37 (55.2%)
|
136 (82.4%)
|
|
|
*Fisher’s exact probability method.
The differences in albumin (t = 3.38, p = 0.001), total bilirubin (TBIL) (Z = 4.44, p < 0.001), and direct bilirubin (DBIL) levels (Z = 4.89, p < 0.001), prothrombin time (PT) (Z = 3.26, p = 0.001), glycated hemoglobin (HbA1c) level (Z = 5.28, p < 0.001), body weight loss index (Z = 2.71, p = 0.007), and alpha-fetoprotein (AFP) (Z = 2.50, p = 0.012) and aspartate transaminase (AST) levels (Z = 3.69, p < 0.001) were statistically significant, but those in platelet count and alanine aminotransferase level were not (p > 0.05) (Table 2). The TBIL, DBIL, PT, AFP, and AST levels of patients in the hypoglycemia group were higher than those in the non-hypoglycemia group.
Table 2
The difference of hematology test indexes between the hypoglycemia and non-hypoglycemia groups
|
Hypoglycemia group (n = 67)
|
Non-hypoglycemia group (n = 165)
|
t/Z
|
P
|
Albumin
|
32.4 ± 5.3
|
35.0 ± 5.3
|
3.38
|
0.001
|
TBIL
|
22.5 (14.3–48.1)
|
15.0 (10.1–20.8)
|
4.44
|
< 0.001
|
DBIL
|
6.9 (4.1–24.1)
|
3.6 (2.4–6.3)
|
4.89
|
< 0.001
|
Plasma prothrombin time
|
14.6 (13.4–17.0)
|
13.8 (13.2–14.6)
|
3.26
|
0.001
|
PLT
|
138.0(93.0–199.0)
|
133.0 (88.0–188.0)
|
0.75
|
0.451
|
HbA1c
|
4.9 (4.2–5.4)
|
5.4 (5.0–6.1)
|
5.28
|
< 0.001
|
AFP
|
64.8 (6.1–913.7)
|
12.0 (3.2–318.6)
|
2.50
|
0.012
|
ALT
|
26.0 (16.0–59.0)
|
25.0 (17.0–40.5)
|
0.75
|
0.456
|
AST
|
52.0 (32.0–103.0)
|
38.0 (26.0–54.0)
|
3.69
|
< 0.001
|
Body weight loss index
|
−0.02 (− 0.08–0)
|
0 (− 0.04–0.02)
|
2.71
|
0.007
|
* |
TBIL, total bilirubin; DBIL, direct bilirubin; PLT, platelet; HbA1c, glycated hemoglobin; AFP, alpha-fetoprotein; ALT, alanine aminotransferase; AST, aspartate transaminase |
Multivariate regression analysis to determine the factors for hypoglycemia in hepatocellular carcinoma
We further performed a multivariate logistic regression analysis on the statistically significant variables in the univariate analysis. The specific variable assignments are listed in Table 3. The regression analysis results showed that Child-Pugh grade C (odds ratio [OR] = 7.3, 95% confidence interval [CI] 2.28–23.31, p = 0.008), HbA1c level (OR = 0.46, 95% CI 0.29–0.73, p = 0.001), and AFP level (OR = 1.000035, 95% CI 1.000007–1.000063, p = 0.015) were significantly associated with hypoglycemia in patients with HCC. Patients with Child-Pugh grade C had a 7.3 times higher risk of hypoglycemia than grade A. Every percent increase in HbA1c was associated with a 0.56 decrease in the risk of hypoglycemia.
Table 3
Multivariate logistic regression model odds ratios (95% confidence interval [CI], p-value) analysis of the hypoglycemia versus non-hypoglycemia group
Variables
|
Β coefficient
|
Standard error
|
Wald
|
P
|
Odds ratio (OR) (95% CI)
|
Child-Pugh grades
|
|
|
11.247
|
0.004
|
|
A
|
-
|
-
|
-
|
-
|
1.00
|
B
|
0.42
|
0.36
|
1.34
|
0.246
|
1.52 (0.75–3.09)
|
C
|
1.99
|
0.59
|
11.23
|
0.008
|
7.3 (2.28–23.31)
|
HbA1c
|
−0.77
|
0.23
|
10.81
|
0.001
|
0.46 (0.29–0.73)
|
AFP
|
0.4×10− 4
|
0.2×10− 4
|
5.91
|
0.015
|
1.35×10− 4 (1.7×10− 5–1.63×10− 4)
|
Constant
|
4.67
|
1.21
|
14.74
|
0.000
|
106.96
|
HbA1c, glycated hemoglobin; AFP, alpha-fetoprotein |