Glycated hemoglobin and antidiabetic strategies as risk factors for hepatocellular carcinoma

Table 1 Mean prevalence of HCV infection, HBV infection, alcohol abuse and DM2 in the free living population of the Pordenone area and controls in this study

	General population (%)		Control group of the study (%)
	Global	60-75 yr age interval
HCV positive	3.2	5.0	5.3
HBV positive	1.2	1.7	1.2
Alcohol abuse	4.5	5.0	4.7
DM2	4.8	12.4	12.6

HCV: Hepatitis C virus; HBV: Hepatitis B virus; DM2: Type 2 diabetes mellitus.

Table 2 Characteristics of patients in the HCC, LC and control groups n (%)

	HCC n = 465	LC n = 618	Controls n = 490	P
Sex, male	364 (78.3)	450 (72.8)	385 (78.6)	0.1706
Alcohol abuse	233 (51.2)	312 (50.6)	23 (4.7)	< 0.0001
DM2	145 (31.2)	144 (23.2)	62 (12.6)	< 0.0001
ALT ≥ 53 IU/L	113 (24.3)	150 (24.3)	N/A	0.9911
HBV positive	39 (8.4)	39 (6.3)	N/A	0.1908
HCV positive	268 (57.6)	285 (46.1)	N/A	0.0002

P-value of χ² test. HCC: Hepatocellular carcinoma; LC: Liver cirrhosis; N/A: Not available.

Table 3 Association of DM2 with HCC: results of multivariate analyses using controls and LC subjects as comparison groups

	OR	95% CI	P
Control group
Age ≥ 65 yr	0.873	0.606-1.259	0.4675
BMI ≥ 25 kg/m2	1.048	0.769-1.426	0.7681
Alcohol abuse	22.069	13.749-35.425	< 0.0001
DM2	2.507	1.703-3.692	< 0.0001
LC group
Age ≥ 65 yr	2.457	1.855-3.252	< 0.0001
BMI ≥ 25 kg/m2	1.560	1.197-2.032	0.0010
HBV positive	2.372	1.363-4.127	0.0022
HCV positive	2.783	1.896-4.084	< 0.0001
Alcohol abuse	1.937	1.318-2.845	0.0008
ALT ≥ 53 IU/L	0.919	0.672-1.256	0.5951
DM2	1.456	1.072-1.979	0.0162

BMI: Body mass index; OR: Odds ratio; 95% CI: 95% confidence interval; ALT: Alanine transaminase.

Table 4 Biochemical characteristics of diabetic HCC, LC patients and controls, DM2 duration and therapy (mean ± SD)

	HCC (n = 145)	LC (n = 144)	Controls (n = 62)	P
BMI (kg/m2) (median)	25.6 ± 2.9 (26.0)	25.8 ± 3.8 (25.0)	25.1 ± 2.4 (25.3)	0.3175a
Cholesterol (mg/dL) (median)	155.4 ± 47.4 (152)	155.9 ± 37.7 (155)	160.6 ± 45.4 (173.0)	0.6013a
Triglycerides (mg/dL) (median)	110.6 ± 60.7 (94.5)	108.0 ± 45.5 (101.5)	111.5 ± 67.9 (95.0)	0.8060a
Fasting plasma glucose (mg/dL) (median)	126.7 ± 47.3 (110.5)	109.3 ± 32.9 (100.0)	98.0 ± 20.6 (95.0)	< 0.0001a
Current HbA1c (%) (median)	7.5 ± 1.8 (7.3)	6.6 ± 1.5 (6.4)	6.8 ± 1.5 (6.5)	0.0001a
Average past HbA1c (%) (range)	7.7 ± 1.5 (4-13.5)	N/A	N/A
DM2 duration (mo) (median)	141.6 ± 81.0 (146)	135.4 ± 98.3 (117)	124.9 ± 100.5 (119)	0.2496a
Therapy, n (%)				< 0.0001b
Not reported	0 (0)	12 (8.3)	2 (3.2)
Metformin	13 (9.0)	39 (27.1)	15 (24.2)
Sulphonylureas	68 (46.9)	33 (22.9)	32 (51.6)
Insulin	64 (44.1)	60 (41.7)	13 (21.0)

^aP of Kruskal-Wallis test;

^bP of Fisher’s exact test. HbA1c: Glycated hemoglobin A1c.

Table 5 Association of antidiabetic therapy, metabolic control and DM2 duration with HCC among diabetic patients: results of multivariate analyses using controls and LC subjects as comparison groups

	OR1	95% CI	P
Control group
Sex, male	1.860	0.636-5.441	0.2574
Age ≥ 65 yr	0.225	0.071-0.715	0.0115
BMI ≥ 25 kg/m2	0.888	0.364-2.166	0.7936
Alcohol abuse	16.155	4.798-54.389	< 0.0001
Triglycerides (mg/dL, continuous)	1.001	0.994-1.008	0.8097
Cholesterol (mg/dL, continuous)	1.003	0.994-1.013	0.4890
Metformin vs sulphonylureas	0.149	0.039-0.507	0.0054
Insulin vs sulphonylureas	1.243	0.459-3.366	0.6686
DM2 duration (mo, continuous)	1.001	0.996-1.005	0.6740
HbA1c % (continuous)	1.265	0.943-1.699	0.1172
LC group
Sex, male	0.120	0.0051-0.278	< 0.0001
Age ≥ 65 yr	1.508	0.719-3.165	0.2774
BMI ≥ 25 kg/m2	1.473	0.716-3.029	0.2928
HBV+	3.535	0.428-29.184	0.2410
HCV+	2.870	1.129-7.293	0.0267
Alcohol abuse	1.455	0.567-3.732	0.4351
ALT ≥ 53 IU/L	0.808	0.394-1.675	0.5606
Triglycerides (mg/dL, continuous)	1.002	0.995-1.008	0.6366
Cholesterol (mg/dL, continuous)	1.003	0.995-1.011	0.4012
Metformin vs sulphonylureas	0.163	0.057-0.462	0.0006
Insulin vs sulphonylureas	0.428	0.203-0.901	0.0255
DM2 duration (mo, continuous)	1.001	0.997-1.005	0.6723
HbA1c % (continuous)	1.508	1.197-1.899	0.0005

¹Patients with unknown therapy not included in analysis.