Elevated TPOAb is a Strong Predictor of Autoimmune Development in Patients of Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease: A Case–Control Study

Figures & data

Table 1 Comparison of Clinical Baseline Data Between T2DM with NAFLD and T2DM Patients

Variables	T2DM with NAFLD Group (n = 212)	T2DM Group (n = 188)	p value
Age, year	63 (53~73)	58 (50.25~65)	<0.001
Female, n (%)	107 (50.5%)	108 (57.4%)	0.16
Duration of T2DM, year	7.5 (4~10)	6 (3~9)	0.01
Smoking history, n (%)	61 (28.8%)	40 (21.3%)	0.09
Systolic blood pressure, mmHg	112 (103~128)	112 (99~120)	0.18
Diastolic blood pressure, mmHg	76 (67~83)	75 (69~83)	0.94
BMI, kg/m^2	22.83±3.48	22.96±3.17	0.70
Waist circumference	87.5 (84.33~90.08)	87.1 (84.53~89.6)	0.39
Fasting glucose, mmol/L	11 (7.9~13.2)	9.85 (7.3~12.7)	0.06
Fasting insulin, mU/L	16.46 (11.1~20.14)	12.79 (7.62~17.15)	<0.001
Fasting C-peptide, ng/mL	2.68 (1.98~3.24)	2.5 (1.76~3.29)	0.14
Insulin resistance index, molU/L^2	6.85 (4.6~10.01)	5.01 (3.39~7.55)	<0.001
HbA1c, %	11.4 (8.8~13.3)	10 (8~12.2)	<0.001
AST, U/L	31 (17~42)	27 (16~36)	<0.001
ALT, U/L	27 (20~34)	22 (17~28)	<0.001
GGT, U/L	43.45 (26.33~59.2)	41.9 (24.85~60.98)	0.95
Hyperlipidemia, n (%)	71 (33.5%)	5 (2.7%)	<0.001
HCY, µmol/L	16.5(12.83~20.2)	16.25(12.3~20.38)	0.57

Table 2 Comparison of Thyroid Function Between T2DM with NAFLD and T2DM Patients

Variables	T2DM with NAFLD Group (n = 212)	T2DM Group (n = 188)	p value
TPOAb(+), n (%)	36 (17%)	13 (6.9%)	<0.01
TGAb(+), n (%)	17 (8%)	9 (4.8%)	0.19
TPOAb and TGAb(+), n (%)	14 (6.6%)	7 (3.7%)	0.20
FT4, ng/dL	0.89 (0.71~1)	1.08 (0.87~1.29)	<0.001
TSH, uIU/mL	2.85 (1.52~3.74)	2.28 (1.37~3.41)	0.02
TPOAb/TGAb	1.56 (0.82~3.12)	1.28 (0.6~2.7)	0.02

Table 3 Comparison of the General Conditions of Patients with T2DM and NAFLD According to Thyroid Antibody

Variables	Thyroid Autoimmunity Positive (n = 38)	Thyroid Autoimmune Negative (n = 174)	p value
Age, year	70.5 (62.75~76.25)	60 (52~70)	<0.001
Female, n (%)	27 (71.1%)	80 (46.0%)	<0.01
Duration of T2DM, year	12.5 (9~17)	6.5 (3~10)	<0.001
Smoking history, n (%)	12 (31.6%)	49 (28.2%)	0.67
Systolic blood pressure, mmHg	114 (100.75~129)	112 (103~128.25)	0.92
Diastolic blood pressure, mmHg	76.5 (68.75~86.25)	76 (67~82.25)	0.19
BMI, kg/m^2	22.26 (19.7~24.71)	22.73 (20.57~25.48)	0.19
Total leukocyte count, ×10^9/L	6.34 (5.54~7.86)	6.21 (5~7.65)	0.54
Lymphocyte percentage, %	38 (34.85~41.1)	32.2 (26.4~39.53)	<0.001
Total lymphocytes, 10^9/L	2.34 (2.01~2.92)	1.96 (1.59~2.6)	<0.01
Fasting glucose, mmol/L	12.4 (11.33~13.6)	10.2 (7.48~13.03)	<0.01
Fasting insulin, mU/L	17.78 (15.09~20.95)	15.58 (9.89~19.64)	<0.01
Fasting C-peptide, ng/mL	2.9 (2.6~3.18)	2.59 (1.82~3.24)	0.04
Insulin resistance index, molU/L^2	9.62 (7.74~11.67)	6.14 (4.22~9.08)	<0.001
HbA1c, %	11.85 (11.2~13.15)	11.05 (8.38~13.4)	0.02
AST, U/L	25 (14.25~36)	33 (19~43)	<0.01
ALT, U/L	31.5 (24.25~46)	26 (19~31)	<0.01
GGT, U/L	43.2 (23.48~63.58)	43.95 (26.38~58.58)	0.63
TC, mmol/L	5.64 (5.29~5.88)	4.72 (4.25~5.27)	<0.001
TG, mmol/L	1.7 (1.27~2.09)	1.41 (1.06~1.76)	<0.001
HDL-C, mmol/L	0.79 (0.67~1.01)	1 (0.77~1.27)	<0.01
LDL-C, mmol/L	2.89 (2.41~3.32)	2.55 (2.03~3.12)	0.02
HCY, µmol/L	14.4 (11.7~19.38)	17 (13.18~20.65)	0.05
FT4, ng/dL	0.59 (0.53~0.7)	0.92 (0.78~1.03)	<0.001
TSH, uIU/mL	3.65 (2.5~4.99)	2.67 (1.32~3.64)	<0.001
TPOAb/TGAb	6.8 (1.09~50.59)	1.46 (0.79~2.49)	<0.001
Fatty liver (mild), n (%)	13 (34.2%)	103 (59.2%)	<0.01
Fatty liver (moderate), n(%)	9 (23.7%)	51 (29.3%)	0.49
Fatty liver (severe), n(%)	16 (42.1%)	20 (11.5%)	<0.001

Table 4 Relationship Between Different TPOAb Titer and Severity of Fatty Liver

Severity of Fatty Liver	TPOAb in Normal Range	Upper Limit of Normal < TPOAb < 10 Times the Upper Limit of Normal	10 Times the Upper Limit of Normal < TPOAb < 50 Times the Upper Limit of Normal	TPOAb > 50 Times the Upper Normal Limit	p value
Fatty liver (mild)	104 (59.1%)	12 (75.0%)	0 (0.0%)	0 (0.0%)	< 0.001
Fatty liver (moderate)	51 (29.0%)	3 (18.8%)	5 (41.7%)	1 (12.5%)
Fatty liver (severe)	21 (11.9%)	1 (6.3%)	7 (58.3%)	7 (87.5%)

Table 5 Relationship Between Different TPOAb Titer and Multiple Possible Influencing Factors

Variables	Group 1	Group 2	Group 3	Group 4
	TPOAb in Normal Range	Upper Limit of Normal < TPOAb < 10 Times the Upper Limit of Normal	10 Times the Upper Limit of Normal < TPOAb < 50 Times the Upper Limit of Normal	TPOAb > 50 Times the Upper Normal Limit
HbA1c	11.1 (8.4~13.38)	11.75 (10.98~12.7)	12.15 (10.98~13.33)	13.25 (12~14.6)
Cholesterol	4.75 (4.25~5.28)	5.34 (4.92~5.69)*	5.69 (5.46~5.91)*	5.88 (5.79~6.08)*
Triglyceride	1.41 (1.07~1.77)	1.55 (1.25~1.96)	1.56 (1.25~2.29)	1.97 (1.74~2.13)*
AST	33 (19~42.75)	16 (10~29)*	35 (16~44.5)	24 (17~33.75)
ALT	26 (19~31)	31.5 (27~42.25)*	32.5 (22~46.75)	42 (26.75~46.75)
FT4	0.92 (0.77~1.03)	0.57 (0.51~0.62)*	0.59 (0.51~0.87)*	0.63 (0.56~1.13)
TSH	2.69 (1.32~3.67)	3.9 (2.61~5.15)*	3.27 (2.32~4.88)	3.41 (2.41~4.66)

Note: *p<0.05 when compared to Group 1 (group with TPOAb in the normal range).

Table 6 Binary Logistic Regression Analysis of Thyroid Autoimmunity in T2DM and NAFLD Patients

Variables	B	p value	OR	95% Confidence Interval
				Lower Limit	Upper Limit
Age	−0.003	0.913	0.997	0.952	1.045
Sex	−1.252	0.018	0.286	0.102	0.803
Duration of T2DM	0.169	0.002	1.185	1.066	1.316
FT4	−3.135	0.006	0.044	0.005	0.415
TSH	0.899	<0.01	2.456	1.600	3.77
HbA1c	0.272	0.011	1.312	1.065	1.617
TC	1.457	0.001	4.294	1.769	10.422
TG	1.169	0.016	3.217	1.241	8.341
TPOAb/TGAb	0.235	<0.01	1.265	1.153	1.387
Fatty liver		0.021
Fatty liver (mild)	−1.357	0.065	0.258	0.061	1.088
Fatty liver (moderate)	−2.828	0.002	0.059	0.01	0.358
Fatty liver (severe)	−1.463	0.121	0.232	0.036	1.469

Table 7 Multivariate Logistic Regression Analysis of Different Levels of TPOAb with Patients

Variables	OR	Chi-Square	p value	95% Confidence Interval
				Lower Limit	Upper Limit
Age	1.011	0.031	0.860	0.893	1.146
HbA1c	1.111	0.084	0.772	0.547	2.252
Cholesterol	0.174	1.067	0.302	0.006	4.811
Triglyceride	2.309	0.539	0.463	0.247	21.628
TSH	1.616	1.678	0.195	0.782	3.337
FT4	6.713	1.006	0.316	0.163	277.272
NAFLD	0.045	4.359	0.037*	0.002	0.827

Note: *P<0.05.