Minimizing tacrolimus decreases the risk of new-onset diabetes mellitus after liver transplantation

Table 1 Demographic and clinical characteristics of recipients with and without new-onset diabetes millitus after liver transplantation (n = 528) n (%)

Characteristics	Total (n = 528)	NODM group (n = 131)	Non-NODM group (n = 397)	P value
Recipient characteristics
Age (yr)	44.93 ± 9.41	46.24 ± 9.54	44.50 ± 9.34	0.068
Gender (male)	446 (84.5)	144 (87.0)	332 (83.6)	0.352
Child-Pugh (A/B/C)	136/223/169	39/44/48	97/179/121	0.069
MELD Score	13 (6-40)	15 (6-40)	13 (6-40)	0.010
BMI ≥ 25 pre-LT	110 (20.8)	36 (27.5)	74 (18.6)	0.006
Hypertension pre-LT	12 (2.3)	7 (5.3)	5 (1.3)	0.017
Dyslipidemia pre-LT	41 (8.2)	15 (11.5)	26 (6.5)	0.069
Indications for LT
Hepatitis B virus disease	420 (79.5)	102 (77.9)	318 (80.1)	0.582
Hepatitis C virus disease	6 (1.1)	1 (0.8)	5 (1.3)	> 0.990
Alcoholic cirrhosis	16 (3.0)	7 (5.3)	9 (2.3)	0.137
Tumors	269 (50.9)	56 (42.7)	213 (53.7)	0.030
Mean cTAC (ng/mL)	5.26 ± 2.91	7.66 ± 3.41	4.47 ± 2.22	< 0.001
Rapamycin administration	129 (24.4)	30 (22.9)	99 (24.9)	0.638
MMF administration	322 (61.0)	78 (59.5)	244 (61.5)	0.696
Complications post-LT
BMI ≥ 25 post-LT	128 (24.2)	40 (30.5)	88 (22.2)	0.053
Hypertension post-LT	67 (12.7)	22 (16.8)	45 (11.3)	0.104
Dyslipidaemia post-LT	175 (33.1)	63 (48.1)	112 (28.2)	< 0.001
Cardio-cerebral events post-LT	18 (3.4)	10 (7.6)	8 (2.0)	0.005
CKD post-LT	91 (17.2)	28 (21.4)	63 (15.9)	0.148
AR post-LT	58 (11.0)	20 (15.3)	38 (9.6)	0.071
CR post-LT	20 (3.8)	9 (6.9)	11 (2.8)	0.062
Infection post-LT	165 (28.7)	65 (36.7)	100 (25.2)	0.042
Graft failure	52 (9.8)	20 (15.3)	32 ( 8.1)	0.016
Donor characteristics
Age (yr)	34.01 ± 8.75	33.62 ± 8.33	34.13 ± 8.89	0.559
Gender (male)	443 (84.5)	108 (82.4)	335 (84.4)	0.600
Donor type (LDLT)	158 (29.9)	34 (26.0)	124 (31.2)	0.252

NODM: New-onset diabetes mellitus; Age: Age at transplantation; MELD: Model for end-stage liver disease; BMI: Body mass index; LT: Liver transplantation; cTAC: Tacrolimus trough concentration; MMF: Mycophenolate mofetil; CKD: Chronic kidney disease; AR: Acute rejection; CR: Chronic rejection; LDLT: Living donor liver transplantation.

Table 2 Clinical complications associated with mean tacrolimus trough concentration n (%)

Complications post-LT	Low-cTAC group (n = 356)	High-cTAC group (n = 172)	P value
Overweight/obesity (BMI ≥ 25)	76 (21.3)	52 (30.2)	0.026
Hypertension	48 (13.5)	19 (11.0)	0.431
Dyslipidaemia	98 (27.5)	77 (44.8)	< 0.001
Cardio-cerebral events	12 (3.4)	6 (3.5)	0.944
CKD	52 (14.6)	39 (22.7)	0.021
AR	34 (9.6)	24 (14.0)	0.129
CR	10 (2.8)	10 (5.8)	0.090
Infection	88 (24.7)	57 (33.1)	0.042
New-onset malignance	8 (2.2)	1 (0.6)	0.304

cTAC: Tacrolimus trough concentration; BMI: Body mass index; LT: Liver transplantation; CKD: Chronic kidney disease; AR: Acute rejection; CR: Chronic rejection.

Table 3 Univariate analysis of risk factors for new-onset diabetes mellitus after liver transplantation

Clinical factor	HR	95%CI	P value
Recipient characteristics
Elder recipient (age > 50 yr)	1.568	1.096-2.245	0.014
Male recipient gender	0.690	0.414-1.150	0.155
Child-Pugh (A/B/C)	0.985	0.788-1.232	0.895
MELD Score	1.107	0.997-1.037	0.088
BMI ≥ 25 pre-LT	1.616	1.100-2.373	0.014
Hypertension pre-LT	4.458	2.058-9.659	< 0.001
Dyslipidaemia pre-LT	2.064	1.201-3.549	0.009
Hepatitis B virus disease	0.955	0.632-1.443	0.828
Hepatitis C virus disease	0.699	0.098-5.007	0.722
Alcoholic cirrhosis	2.307	1.076-4.948	0.032
Tumors	0.961	0.676-1.304	0.822
With Rapamycin	1.168	0.744-1.761	0.459
With MMF	0.979	0.690-1.387	0.903
High mean cTAC (cTAC ≥ 5.89 ng/mL)	8.709	5.873-12.915	< 0.001
BMI ≥ 25 post-LT	1.345	0.927-1.951	0.119
Hypertension post-LT	1.278	0.808-2.021	0.294
Dyslipidaemia post-LT	2.014	1.429-2.838	< 0.001
CKD post-LT	1.140	0.925-1.405	0.218
AR post-LT	1.701	1.056-2.742	0.029
CR post-LT	2.068	1.050-4.074	0.036
Donor characteristics
Donor age at LT (per year)	0.994	0.975-1.015	0.590
Male donor gender	1.202	0.766-1.886	0.423
Donor type (LDLT)	0.859	0.581-1.270	0.446

LT: Liver transplantation; MELD: Model for end-stage liver disease; MMF: Mycophenolate mofetil; cTAC: Tacrolimus trough concentration; CKD: Chronic kidney disease; AR: Acute rejection; CR: Chronic rejection; BMI: Body mass index; LDLT: Living donor liver transplantation.

Table 4 Multivariate analysis of risk factors for new-onset diabetes mellitus after liver transplantation

Clinical factor	HR	95%CI	P value
Elder recipient (age > 50 yr)	1.925	1.335-2.776	< 0.001
Hypertension pre-LT	4.220	1.931-9.226	< 0.001
High mean cTAC (cTAC ≥ 5.89 ng/mL)	9.474	6.357-14.119	< 0.001

cTAC: Tacrolimus trough concentration; LT: Liver transplantation.