Risk factors associated with diabetes after liver transplant

Campos, Mariana Baldini; Riguetto, Cínthia Minatel; Boin, Ilka de Fátima Santana Ferreira; Moura Neto, Arnaldo

doi:10.20945/2359-3997000000447

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Original Article • Arch. Endocrinol. Metab. 66 (2) • Mar-Apr 2022 • https://doi.org/10.20945/2359-3997000000447 copy

Risk factors associated with diabetes after liver transplant

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Objective:

Post-transplant diabetes mellitus (PTDM) is a common metabolic complication after liver transplant that negatively affects a recipient's survival and graft function. This study aims to identify risk factors associated with diabetes after liver transplant.

Materials and methods:

This is a cross-sectional study conducted from September to November 2019. Data collection was performed by chart review, and patients were divided into 3 groups: patients without diabetes mellitus (DM), patients with pre-transplant diabetes mellitus, and patients with PTDM.

Results:

Two hundred and forty-seven patients’ medical charts were screened, and 207 patients were included: 107 without DM, 42 with pre-transplant DM, and 58 with PTDM. The leading cause for liver transplant was hepatitis C, followed by hepatocellular carcinoma secondary to alcohol. There was a higher exposure to tacrolimus in patients without DM ( P = 0.02) and to ciclosporin in patients with pre-transplant DM, compared to others ( P = 0.005). Microscopic interface inflammatory activity was more severe in patients without DM as well as those with PTDM ( P = 0.032). There was a higher prevalence of steatosis in recipients with pre-transplant DM than there was in others ( P < 0.001). Multivariate logistic regression identified the following independent risk factors for DM: cirrhosis due to alcohol, hepatitis C, and triglycerides. For PTDM, these independent risk factors were cirrhosis due to alcohol, hepatitis C, and prednisone exposure.

Conclusion:

Alcoholic cirrhosis is a risk factor for PTDM in liver recipients. Liver transplant recipients with a pre-transplant history of cirrhosis due to alcohol, hepatitis C, and prednisone exposure deserve more caution during PTDM screening.

Keywords
Post-transplant diabetes mellitus; liver transplantation; immunosuppressive drugs; insulin resistance; diabetes mellitus

Variables	Patients without DM n = 107	Pre-transplant DM n = 42	PTDM n = 58	p
Gender (male)	78 (72.9%)	27 (64.3%)	44 (75.9%)	0.425
Age (years)	56 (47-63)	62 (56.75-66.50)	60 (54-63.25)	0.001 ^a a Post hoc test difference between the group of patients without DM and pre-transplant DM.
Transplant duration (years)	4 (2-8)	2.5 (1.08-4.38)	6.5 (2.46-11.04)	0.001 ^c c Post hoc test difference between the group of patients with pre-transplant DM and PTDM.
Diabetes duration (years)	-	10 (8-19)	2.5 (1-4.25)	<0.001
Weight (kg)	75 (63.5-86.90)	71 (65-84.50)	74 (67.75-86)	0.670
Body mass index (kg/m2)	26.15 (23.15-28.09)	27.44 (24.54-30.46)	26.53 (24.46-28.72)	0.309
Cirrhosis due to alcohol	23 (21.5%)	12 (28.6%)	23 (41.8%)	0.025
Hepatocellular carcinoma secondary to alcohol intake	14 (13.1%)	8 (19%)	12 (20.7%)	0.397
Smoking	4 (7.7%)	4 (13.8%)	6 (19.4%)	0.290
Hypertension	38 (35.5%)	26 (61.9%)	30 (51.7%)	0.008
Hypertriglyceridemia	28 (26.2%)	24 (57.1%)	15 (25.9%)	0.001
Hypercholesterolemia	25 (23.4%)	22 (52.4%)	16 (27.6%)	0.002
Hepatitis B	14 (13.3%)	2 (4.9%)	3 (5.2%)	0.126
Hepatitis C	38 (35.8%)	15 (37.5%)	35 (60.3%)	0.007
HbA1c (%)	5.3 (4.7-5.45)	6.9 (6-7.75)	6.5 (5.6-7)	0.002 ^a a Post hoc test difference between the group of patients without DM and pre-transplant DM. , ^b b Post hoc test difference between the group of patients without DM and PTDM.
Glycemia (mg/dL)	93 (84-105)	127 (84.5-151)	117 (98-158)	<0.001 ^a a Post hoc test difference between the group of patients without DM and pre-transplant DM. , ^b b Post hoc test difference between the group of patients without DM and PTDM.
Creatinine (mg/dL)	1.1 (0.88-1.30)	1.25 (1.06-1.66)	1.08 (0.89-130)	0.013 ^a a Post hoc test difference between the group of patients without DM and pre-transplant DM. , ^c c Post hoc test difference between the group of patients with pre-transplant DM and PTDM.
GFR (mL/min)	78.72 (55.12-104.99)	60.43 (43.50-73.71)	75.63 (57.40-96.59)	0.002 ^a a Post hoc test difference between the group of patients without DM and pre-transplant DM. , ^c c Post hoc test difference between the group of patients with pre-transplant DM and PTDM.
Total cholesterol (mg/dL)	153 (134-179)	170 (126.5-209.50)	161 (130-183.5)	0.310
HDL (mg/dL)	42 (34-52.5)	39 (35-50)	44 (35.25-50)	0.558
LDL (mg/dL)	90.5 (67.25-108.75)	93.5 (65 – 118.9)	91.50 (66.75-110.5)	0.974
Triglycerides (mg/dL)	101 (75.5-150)	160 (106.5-256)	114 (88.5-169.5)	<0.001 ^a a Post hoc test difference between the group of patients without DM and pre-transplant DM.
TSH (μUI/mL)	2.37 (1.65-3.9)	2.54 (1.84-4.7)	2.74 (1.69-4.11)	0.779

Variables	Patients without DM	Pre-transplant DM	PTDM	p
Mycophenolate	81 (75.7%)	33 (80.5%)	36 (62.1%)	0.080
Dose of mycophenolate (mg)	720 (720-720)	720 (720-720)	720 (720-720)	0.401
Prednisone	27 (25.2%)	15 (36.6%)	22 (39.3%)	0.134
Tacrolimus	93 (86.9%)	28 (68.3%)	49 (84.5%)	0.025
Dose of tacrolimus (mg)	4 (2-6)	5 (2-7)	2 (2-4)	<0.001 ^a a Post hoc test difference between the group of patients without DM and pre-transplant DM. , ^b b Post hoc test difference between the group of patients without DM and PTDM.
Maximum dose of tacrolimus (mg)	8 (6-10.5)	8 (6-10)	7 (5-8)	0.038 ^b b Post hoc test difference between the group of patients without DM and PTDM.
Everolimus	20 (18.7%)	13 (31.7%)	12 (20.7%)	0.223
Dose of everolimus (mg)	1 (1-2)	1.5 (0.69-1.81)	0.88 (0.5-1.5)	0.226
Cyclosporine	6 (5.6%)	10 (24.4%)	9 (15.5%)	0.005
Dose of cyclosporine (mg)	150 (75-175)	150 (125-200)	100 (87.50-150)	0.497
Maximum dose of cyclosporine (mg)	150 (150-225)	262.5 (187.5-325)	175 (118.75-325)	0.368
Azathioprine	9 (8.4%)	5 (12.2%)	6 (10.5%)	0.765
Dose of azathioprine (mg)	50 (50-100)	50 (50-75)	100 (50-100)	0.451
Sirolimus	2 (1.9%)	2 (4.9%)	3 (5.3%)	0.442
Dose of sirolimus ^* * Less than three patients were on sirolimus in each group. (mg)	1.5 (1.0)	1.0 (1.0)	0.75 (0.5)	0.368

Model 1 – All patients included (no DM versus all DM)
Risk factors	Odds Ratio	95% CI	p
Cirrhosis due to alcohol	2.90	1.47-5.7	0.002
Hepatitis C	2.02	1.08-3.75	0.027
Triglycerides	1.00	1.0-1.01	<0.001

Model 2 – patients without DM versus PTDM
Risk factors	Odds Ratio	95% CI	p
Cirrhosis due to alcohol	3.77	1.69-8.4	0.001
Hepatitis C	3.35	1.57-7.09	0.002
Prednisone	2.77	1.26-6.08	0.011

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[1] Correspondence to: Arnaldo Moura Neto, Faculdade de Ciências Médicas, Universidade Estadual de Campinas Rua Tessália Vieira de Camargo, 126 13084-971 – Campinas, SP, Brasil. arnaldo.mouraneto@gmail.com