Risks of liver cirrhosis, hepatocellular carcinoma, hepatic-related complications, and mortality in patients with type 2 diabetes in Taiwan

Table 1 General characteristics of the study subjects

Variables1	Nondiabetic group		Type 2 diabetic group
	n	%	n	%
Demographics
Age (years)
< 50	433720	66.86	13991	42.16
≥ 50	215026	33.14	19193	57.84
mean ± SD	49.56	7.79	55.34	10.16
Sex
Women	391920	60.41	14853	44.76
Men	256826	39.59	18331	55.24
SBP (mmHg)
< 130	408227	62.93	14018	42.24
≥ 130	240519	37.07	19166	57.76
mean ± SD	125.00	18.65	133.50	18.67
DBP (mmHg)
< 85	465778	71.80	21673	65.31
≥ 85	182968	28.20	11511	34.69
mean ± SD	78.44	12.71	80.98	11.98
Medications
Anti-diabetic agents	0	0.00	33184	100.00
Antihypertensive agents	142453	21.96	21489	64.76
Antilipid agents	35626	5.49	19710	59.40
Laboratory results
FPG (mg/dL)
< 126	648746	100.00	8319	25.07
≥ 126	0	0	24865	74.93
mean ± SD	91.94	10.85	170.00	70.75
TC (mg/dL)
< 200	348098	53.66	22169	66.81
≥ 200	300648	46.34	11015	33.19
mean ± SD	199.00	37.63	187.00	45.14
HDL-C (mg/dL)
M: > 40; F > 50	471424	72.67	17571	52.95
M: ≤ 40; F ≤ 50	177322	27.33	15613	47.05
mean ± SD	56.04	16.69	47.73	15.91
TG (mg/dL)
< 150	470029	72.45	17411	52.47
≥ 150	178717	27.55	15773	47.53
mean ± SD	134.60	126.40	196.20	223.70
ALT (IU/L)
Normal	539660	83.19	24258	73.10
Above normal	109086	16.81	8.926	26.90
mean ± SD	25.86	31.40	31.76	34.01
AST (IU/L)
Normal	579562	89.34	27350	82.42
Above normal	69184	10.66	5834	17.58
mean ± SD	24.51	23.81	26.88	25.83
Metabolic dysfunctions
Obesity, kg/m2
BMI ≤ 30	600060	92.50	26247	79.10
BMI > 30	48686	7.5	6937	20.90
Hypertension
No	370062	57.04	12457	37.54
Yes	278684	42.96	20727	62.46
Dyslipidemia
No	207416	31.97	8227	24.79
Yes	441330	68.03	24957	75.21
Personal history
Regular exercise
No	359624	55.43	17272	52.05
Yes	289122	44.57	15912	47.95
Outcomes
Cirrhosis of liver	2697	0.42	385	1.16
Hepatic complications	1436	0.22	207	0.62
HCC	803	0.12	183	0.55
Hepatic mortality	517	0.08	134	0.40
Mean follow-up period (years) (± SD)	6.59	2.36	6.78	2.45
Total	648746	100.00	33184	100.00

¹The inconsistency between the total population and the population summed for individual variables was due to missing information.

ALT: Alanine transaminase; AST: Aspartate transaminase; BMI: Body mass index; DBP: Diastolic blood pressure; FPG: Fasting plasma glucose; HCC: Hepatocellular carcinoma; HDL-C: High-density lipoprotein cholesterol; SBP: Systolic blood pressure; TC: Total cholesterol; TG: Triglyceride; M: Male; F: Female.

Table 2 Overall incidence densities and relative hazards of cirrhosis of the liver, hepatocellular carcinoma, hepatic-related complications, and mortality in patients with type 2 diabetes and nondiabetic subjects

Variables	Non-diabetic group			Patients with T2D			Model 1 crude HR (95%CI)	Model 2 adjusted HR (95%CI)2
	No. of patients	No. of events	Incidence densities (per 10000 person-years) (95%CI)1	No. of patients	No. of events	Incidence densities (per 10000 person-years) (95%CI)1
Cirrhosis of the liver	648746	2697	6.32 (6.08-6.56)	33184	385	17.20 (15.48-18.92)	2.71 (2.43-3.01)	1.45 (1.30-1.62)
Hepatocellular carcinoma	648746	803	1.88 (1.75-2.01)	33184	183	8.15 (6.97-9.33)	4.33 (3.69-5.09)	1.81 (1.52-2.15)
Hepatic complications	648746	1436	3.36 (3.19-3.54)	33184	207	9.22 (7.96-10.48)	2.75 (2.37-3.18)	1.87 (1.60-2.19)
Hepatic mortality	648746	517	1.21 (1.11-1.31)	33184	134	5.96 (4.95-6.97)	4.73 (3.91-5.72)	2.08 (1.70-2.54)

¹Based on the Poisson assumption.

²Based on the Cox proportional hazard regression model adjusted for age, body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride, high-density lipoprotein cholesterol, alanine transaminase, and aspartate transaminase as continuous variables, with sex and regular exercise as categorical variables.

T2D: Type 2 diabetes; HR: Hazard ratio.

Table 3 Effects of age, sex, the metabolic profile, and exercise on the relative risks of cirrhosis of the liver, hepatocellular carcinoma, hepatic complications, and mortality in patients with type 2 diabetes and nondiabetic subjects

Variables	Cirrhosis of the liver, HR (95%CI)1	HCC, HR (95%CI)1	Hepatic complications, HR (95%CI)1	Hepatic mortality, HR (95%CI)1
Age
Nondiabetic group
< 50 years	1.0	1.0	1.0	1.0
≥ 50 years	2.29 (2.12-2.48)	5.49 (4.67-6.45)	1.59 (1.43-1.78)	4.32 (3.57-5.24)
T2D patients
< 50 years	1.78 (1.46-2.17)	2.05 (1.30-3.23)	2.11 (1.64-2.71)	2.22 (1.37-3.59)
≥ 50 years	3.41 (2.98-3.91)	11.91 (9.61-14.77)	3.10 (2.56-3.74)	10.29 (7.99-13.26)
Sex
Nondiabetic group
Women	1.0	1.0	1.0	1.0
Men	2.11 (1.94-2.28)	2.67 (2.29-3.12)	1.53 (1.37-1.71)	2.56 (2.11-3.11)
T2D patients
Women	1.82 (1.53-2.18)	1.78 (1.30-2.43)	2.34 (1.87-2.94)	2.28 (1.61-3.23)
Men	2.70 (2.33-3.14)	4.86 (3.87-6.09)	2.45 (1.98-3.03)	5.10 (3.89-6.71)
Obesity (BMI ≤ 30 kg/m2vs > 30 kg/m2)
Nondiabetic group
No	1.0	1.0	1.0	1.0
Yes	1.30 (1.15-1.48)	1.51 (1.20-1.91)	0.89 (0.72-1.09)	1.55 (1.18-2.05)
T2D patients
No	1.43 (1.27-1.63)	1.87 (1.55-2.25)	1.65 (1.39-1.97)	2.04 (1.63-2.55)
Yes	1.98 (1.60-2.45)	2.47 (1.74-3.49)	2.25 (1.69-3.00)	3.25 (2.25-4.71)
Hypertension
Nondiabetic group
No	1.0	1.0	1.0	1.0
Yes	1.19 (1.09-1.29)	1.08 (0.94-1.25)	0.96 (0.59-1.54)	1.26 (1.05-1.52)
T2D patients
No	1.55 (1.28-1.87)	1.52 (1.11-2.07)	1.74 (1.48-2.04)	1.88 (1.30-2.73)
Yes	1.70 (1.47-1.96)	2.07 (1.66-2.57)	2.80 (1.65-4.77)	2.70 (2.08-3.51)
Dyslipidemia
Nondiabetic group
No	1.0	1.0	1.0	1.0
Yes	1.26 (1.17-1.37)	0.87 (0.75-1.00)	1.43 (1.29-1.60)	1.23 (1.03-1.47)
T2D patients
No	1.55 (1.29-1.85)	1.48 (1.13-1.93)	2.06 (1.59-2.67)	1.97 (1.42-2.74)
Yes	1.83 (1.59-2.11)	1.92 (1.56-2.37)	2.69 (2.22-3.26)	2.78 (2.16-3.57)
Regular exercise
Nondiabetic group
No	1.0	1.0	1.0	1.0
Yes	0.71 (0.66-0.77)	0.71 (0.62-0.82)	0.77 (0.69-0.85)	0.63 (0.53-0.75)
T2D patients
No	1.56 (1.35-1.80)	1.71 (1.35-2.17)	2.06 (1.69-2.51)	2.12 (1.63-2.75)
Yes	0.94 (0.79-1.11)	1.36 (1.08-1.71)	1.26 (0.99-1.59)	1.27 (0.95-1.71)

¹Based on the Cox proportional hazard regression model adjusted for age, body mass index, systolic blood pressure, diastolic blood pressure, high-density lipoprotein cholesterol, total cholesterol, triglyceride, alanine transaminase, and aspartate transaminase as continuous variables, with sex and regular exercise as categorical variables.

BMI: Body mass index; T2D: Type 2 diabetes; HR: Hazard ratio.