Association between hepatocellular carcinoma and type 2 diabetes mellitus in Italy: Potential role of insulin

Table 1 Frequency of DM2 in HCC patients and in controls

	Number of subjects	DM2 absent (%)	DM2 present (%)	OR (95% CI)	P	RR
HCC	465	320 (68.8)	145 (31.2)	3.12 (2.22-4.43)	< 0.001	2.46
Controls	490	428 (87.3)	62 (12.7)
Males				3.14 (2.14-4.63)	< 0.001	2.45
HCC	364	246 (67.6)	118 (32.4)
Controls	385	334 (86.7)	51 (13.3)
Females				3.11 (1.38-7.4)	0.002	2.55
HCC	101	74 (73.3)	27 (26.7)
Controls	105	94 (89.5)	11 (10.5)

HCC: Hepatocellular carcinoma; DM2: Type 2 diabetes mellitus; OR: Odds ratio; CI: Confidence interval; RR: Relative risk.

Table 2 Multivariate analysis of variables associated with HCC

	Odds ratio (95% CI)	P
Diabetes
Absent	1	0.01
Present	2.2 (1.2-4)
HBV
Absent	1	≤ 0.001
Present	252.1 (53.7-1183.9)
HCV
Absent	1	≤ 0.001
Present	106.5 (58.2-194.9)
Alcohol
Absent	1	≤ 0.001
Present	121.2 (61.9-233.7)

Table 3 Etiology in the 465 HCC patients and prevalence of DM2 [mean  ±  SD, n (%)]

Etiology	N° HCC (%)	Age (yr)	Prevalence of DM2 (%)
HBV	20 (4.3)	63.3 ± 10.31	3 (15.0)
HCV	177 (38.1)	71.5 ± 7.31	47 (26.6)2
Alcohol	141 (30.4)	66.7 ± 8.51	52 (36.9) 2
HBV + HCV	8 (1.7)	60.8 ± 12.81	2 (25.0)
HBV + alcohol	9 (1.9)	62.9 ± 9.31	2 (22.2)
HCV + alcohol	81 (17.4)	67.7 ± 9.31	27 (33.3)
HBV + HCV + alcohol	2 (0.4)	68.4 ± 10.3	0
Cryptogenetic	27 (5.8)	68.6 ± 9.3	11 (40.7)

¹HCV vs HBV + HCV, P < 0.001; HCV vs HBV, P < 0.001; HCV vs HBV + alcohol, P < 0.001; HCV vs HCV + alcohol; HCV vs alcohol, P < 0.001;

²HCV vs alcohol, P = 0.048.

Table 4 Type of therapy with oral antidiabetic agents in HCC patients and controls with DM2

	Number of subjects	Diet with or without metformin N° cases (%)	Sulfonylureas with or without metformin N° cases (%)	P
Total
HCC	88	14 (15.9)	74 (84.1)	0.04
Controls	48	15 (31.2)	33 (68.8)
Males
HCC	75	12 (16.0)	63 (84.0)	0.049
Controls	41	13 (31.7)	28 (68.3)
Females
HCC	13	2 (15.4)	11 (84.6)	0.5
Controls	7	2 (28.6)	5 (71.4)

Table 5 Clinical features of DM2 in HCC patients of the FU and CO groups (%)

	FU group	CO group	P
Prevalence of DM2	92 (30.2)	53 (33.1)	0.51
HbA1c (mean% ± SD)	8.2 ± 2.78	7.1 ± 2.12	0.1
Insulin therapy	45 (48.9)	15 (28.3)	0.01
Antidiabetic oral agents	47 (51.1)	38 (71.7)	0.01
Diet with/without metformin	7 (14.9)	4 (10.5)	0.55
Sulfonylureas with/without metformin	40 (85.1)	34 (89.5)	0.55
Duration of DM2 (mean ± SD, mo)	127.8 ± 80.1	167.1 ± 114.3	0.03
Duration of insulin therapy (mean ± SD, mo)	50.0 ± 50.5	77.8 ± 86.4	0.12

FU: Follow-up group; CO: Clinically overt group; HbA1c: Glycated haemoglobin.