C-peptide as a key risk factor for non-alcoholic fatty liver disease in the United States population

Table 1 Baseline characteristics of participants with non-alcoholic fatty liver disease and controls n (%)

	NAFLD, n = 817	Controls, n = 2418
Demographic
Age (yr)	48.47 ± 15.75	44.36 ± 16.20
Gender (male)	368 (45.04)	1004 (41.52)
Race/ethnicity
White (non-Hispanic)	308 (37.70)	1046 (43.13)
Black (non-Hispanic)	193 (23.62)	705 (29.16)
Mexican American	280 (34.27)	550 (22.75)
Others	36 (4.41)	120 (4.96)
Body measurement
Body mass index (kg/m2)	30.38 ± 6.95	26.56 ± 5.42
Waist circumference (cm)	101.73 ± 16.32	90.84 ± 13.45
Biochemistry tests
Iron (μg/dL)	75.35 ± 29.71	77.71 ± 32.75
TIBC (μg/dL)	364.79 ± 58.05	359.86 ± 56.59
Transferrin saturation (%)	21.13 ± 8.73	22.09 ± 9.65
Ferritin (ng/mL)	161.75 ± 152.55	110.16 ± 114.71
Cholesterol (mg/dL)	212.23 ± 44.95	202.73 ± 42.19
Triglyceride (mg/dL)	202.91 ± 137.97	136.58 ± 95.79
HDL cholesterol (mg/dL)	46.72 ± 16.80	52.10 ± 15.61
C-reactive protein (mg/dL)1	0.56 ± 0.80	0.45 ± 0.65
Uric acid (mg/dL)	5.62 ± 1.52	5.04 ± 1.42
Liver chemistry
AST (U/L)1	24.76 ± 19.62	20.72 ± 14.71
ALT(U/L)1	22.78 ± 17.86	15.96 ± 12.14
GGT (U/L)1	42.87 ± 66.68	28.14 ± 41.69
ALP (U/L)1	93.72 ± 33.61	86.04 ± 36.29
Total bilirubin (mg/dL)	0.55 ± 0.30	0.54 ± 0.28
Total protein (g/dL)	7.49 ± 0.46	7.37 ± 0.45
Albumin (g/dL)	4.11 ± 0.35	4.12 ± 0.36
Diabetes testing profile
HbA1c (%)1	6.02 ± 1.62	5.50 ± 1.09
FPG (mg/dL)1	114.50 ± 65.84	97.85 ± 35.68
Fasting C-peptide (pmol/mL)	1.11 ± 0.68	0.69 ± 0.53
Fasting insulin (μU/mL)1	21.85 ± 27.82	12.76 ± 19.24

¹The distribution is positively skewed with skewness > 3. ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; FPG: Fasting plasma glucose; GGT: Gamma glutamyl transferase; HbA1c: Glycated hemoglobin; TIBC: Total iron-binding capacity.

Table 2 Univariate analysis for predictors of non-alcoholic fatty liver disease

	Beta	Standard error	Odds ratio	P value
Demographic
Age (yr)	0.0157	0.0025	1.02	< 0.001a
Gender (male)	0.1435	0.0815	1.15	0.078
Race/ethnicity
White (non-Hispanic)	-0.226	0.0831	0.80	0.007a
Black (non-Hispanic)	-0.2857	0.0937	0.75	0.002a
Mexican American	0.5715	0.0882	1.77	< 0.001a
Others	-0.1248	0.1945	0.88	0.521
Body measurement
Body mass index (kg/m2)	0.1004	0.0069	1.11	< 0.001a
Waist circumference (cm)	0.0506	0.003	1.05	< 0.001a
Biochemistry tests
Iron (μg/dL)	-0.0024	0.0013	1.00	0.069
TIBC (μg/dL)	0.0015	0.0007	1.00	0.032a
Transferrin saturation (%)	-0.0111	0.0044	0.99	0.012a
Ferritin (ng/mL)	0.0029	0.0003	1.00	< 0.001a
Cholesterol (mg/dL)	0.005	0.0009	1.01	< 0.001a
Triglyceride (mg/dL)	0.0049	0.0004	1.00	< 0.001a
HDL cholesterol (mg/dL)	-0.0261	0.0031	0.97	< 0.001a
C-reactive protein (mg/dL)1	0.3398	0.0534	1.40	< 0.001a
Uric acid (mg/dL)	0.2649	0.0277	1.30	< 0.001a
Liver chemistry
AST (U/L)1	1.004	0.1153	1.02	< 0.001a
ALT (U/L)1	1.0274	0.0777	1.04	< 0.001a
GGT (U/L)1	0.7441	0.0612	1.01	< 0.001a
ALP (U/L)1	0.9011	0.1303	1.01	< 0.001a
Total bilirubin (mg/dL)	0.0914	0.1395	1.09	0.512
Total protein (g/dL)	0.581	0.0896	1.79	< 0.001a
Albumin (g/dL)	-0.0871	0.1141	0.92	0.445
Diabetes testing profile
HbA1c (%)1	2.2201	0.2184	1.34	< 0.001a
FPG (mg/dL)1	1.3125	0.1428	1.01	< 0.001a
Fasting C-peptide (pmol/mL)	1.1976	0.0753	3.31	< 0.001a
Fasting insulin (μU/mL)1	0.9646	0.059	1.02	< 0.001a

¹Log transformation was applied to this factor before including in regression model.

^aP < 0.05. ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; FPG: Fasting plasma glucose; GGT: Gamma glutamyl transferase; HbA1c: Glycated hemoglobin; TIBC: Total iron-binding capacity. ^aP < 0.05.

Table 3 Risk factors of non-alcoholic fatty liver disease from step-wise logistic regression

	Beta	Standard error	Odds ratio	Change in pseudo R2	P value
Demographic
Race/ethnicity
White (non-Hispanic)	0.2969	0.1162	1.35	0.18%	0.011
Mexican American	0.5495	0.1207	1.73	0.57%	0.020
Body measurement
Waist circumference (cm)	0.0308	0.0035	1.03	2.13%	< 0.001
Biochemistry tests
Ferritin (ng/mL)	0.0013	0.0004	1.00	0.15%	< 0.001
Triglyceride (mg/dL)	0.0008	0.0004	1.00	0.32%	< 0.001
Liver chemistry
ALT (U/L)1	0.5658	0.0875	1.76	1.16%	< 0.001
Total protein (g/dL)	0.5319	0.1045	1.70	0.72%	< 0.001
Diabetes testing profile
HbA1c (%)1	0.9266	0.2492	2.53	0.38%	< 0.001
Fasting C-peptide (pmol/mL)	0.6009	0.0877	1.82	1.33%	< 0.001

¹Log transformation was applied to this factor before including in regression model. Note: Pseudo R² = 16.68%; constant (Y-intercept) = 0.0000153; change in Pseudo R² is an incremental increase in Pseudo R² resulting from adding variable to model last. ALT: Alanine aminotransferase; HbA1c: Glycated hemoglobin.