Advanced glycation end product: A potential biomarker for risk stratification of non-alcoholic fatty liver disease in ELSA-Brasil study

Table 1 Clinical characteristics according to non-alcoholic fatty liver disease-associated steatosis severity

	Mild (n = 182)	Moderate/severe (n = 123)	P value1
Age (yr)	50 (44-54)	52 (45-57)	0.002
Gender
Male	99 (54)	72 (59)	0.503
Female	83 (46)	51 (41)
Race
Black	17 (9)	15 (12)	0.383
Brown	52 (29)	41 (34)
White	109 (61)	61 (50)
Asian	2 (1)	3 (2)
Indigenous	0 (0)	2 (2)
Use of alcohol
Never used	15 (8)	10 (8)	0.144
Ex-user	46 (25)	22 (18)
User	121 (67)	91 (74)
Smoking habit
Non smoker	102 (56)	62 (50)	0.261
Smoker	80 (44)	61 (50)
Metabolic syndrome (NCEP ATP III)
Presence	62 (34)	78 (63)	< 0.001
Absence	120 (66)	45 (37)
Diabetes mellitus
Presence	25 (14)	45 (37)	< 0.001
Absence	157 (86)	78 (63)
High cholesterol
Presence	59 (33)	62 (51)	< 0.001
Absence	122 (67)	61 (49)
Body mass index (kg/m2)	26.6 (24.6-29.6)	29.2 (27.2-32.3)	< 0.001
Waist circumference (cm)	94.1 (87.5-100.0)	101.5 (94.1-107.5)	< 0.001
Systolic blood pressure (mmHg)	117 (108-127.5)	121.5 (113.5-131.2)	0.001
Diastolic blood pressure (mmHg)	75.5 (69.6-81.5)	79.5 (74.0-86.0)	< 0.001
Laboratory
Fasting glucose (mg/dL)	99.28 (93.33-105.84)	104.24 (97.79-116.14)	< 0.001
HbA1c (mg/dL)	5.40 (5.1-5.8)	5.76 (5.3-6.2)	< 0.001
Insulin (mcUI/mL)	9.91 (7.1-13.9)	13.71 (10.5-19.32)	< 0.001
Total cholesterol (mg/dL)	199.6 (176.8-227.6)	196.2 (175.3-222.8)	0.636
Triglycerides (mg/dL)	107.8 (79.0-152.4)	137.15 (99.6-225.0)	< 0.001
HDL (mg/dL)	50.1 (42.9-60.1)	47.45 (42.0-54.2)	0.007
ALT (mg/dL)	25 (19-33)	30 (22.5-40)	0.001
AST (mg/dL)	24 (21-28)	24 (21-29.5)	0.276
GGT (mg/dL)	24 (18-35)	33 (23-51)	< 0.001
hs-CRP (mg/dL)	1.6 (0.8-3.5)	2.2 (1.4-4.7)	< 0.001
Uric acid (mg/dL)	5.4 (4.5-6.6)	6 (5.2-6.9)	< 0.001
Microalbuminuria (mg/dL)	0.50 (0.33-0.82)	0.51 (0.31-1.05)	0.265
Creatinine (mg/dL)	0.87 (0.77-0.97)	0.87 (0.77-0.97)	0.324
Sodium (mg/dL)	143 (141-144)	143 (141-144)	0.200
Potassium (mg/dL)	4.5 (4.2-4.7)	4.4 (4.2-4.7)	0.820

Data were presented as median (interquartile range) or count (percentage).

¹Jonckheere-Terpstra for continuous variables and Cox-Mantel-Haenszel for categorical ones for trend between categories.

HbA1c: Hemoglobin A1c; HDL: High-density lipoprotein; ALT: alanine aminotransferase; AST: aspartate aminotransferase; GGT: Gamma-glutamyl transferase; hs-CRP: High sensitivity C-reactive protein.

Table 2 Non-alcoholic fatty liver disease-associated steatosis stratification accordingly to fatty liver serum biomarkers

	Mild (n = 182)	Moderate/severe (n = 123)	P value1
Fatty liver index	44.65 (26.71-67.91)	74.50 (54.08-88.16)	< 0.001
Hepatic steatosis index	36.66 (33.63-40.89)	41.22 (37.75-45.47)	< 0.001
Atherogenic index	0.35 (0.16-0.50)	0.44 (0.29-0.70)	< 0.001

Data were presented as median (interquartile range).

¹Jonckheere-Terpstra test for trend between categories.

Table 3 Effect of high advanced glycation end product levels on the non-alcoholic fatty liver disease-associated steatosis severity

Variable	SE	OR (95%CI)	Sensitivity	Specificity	Accuracy
Crude model	0.47	2.64 (1.04-6.92)	0.62	0.61	0.61
Model 1	0.52	3.38 (1.24-9.98)	0.60	0.73	0.64
Model 2	0.55	3.34 (1.17-10.40)	0.71	0.68	0.69
Model 3	0.61	4.52 (1.44-16.28)	0.78	0.72	0.75
Model 4	0.62	4.66 (1.45-17.16)	0.77	0.77	0.77

Model 1: Adjusted for gender; Model 2: Additionally adjusted for gamma-glutamyl transferase; Model 3: Additionally adjusted for altered blood glucose (categorical ≥ 126, 110 ≤ 125); Model 4: Additionally adjusted for high cholesterol. High cholesterol was defined as use of medication to treat dyslipidemia or low-density lipoprotein cholesterol ≥ 130. OR: Odds ratio; CI: Confidence interval.