Trimethylamine N-Oxide and Related Metabolites in the Serum and Risk of Type 2 Diabetes in the Chinese Population: A Case-Control Study

Figures & data

Figure 1 (a) Association between TMAO and the risk of T2DM from restricted cubic splines nested in logistic regression analyses. (b) Association between choline and the risk of T2DM from restricted cubic splines nested in logistic regression analyses.

Table 1 The Basic Characteristics of the Study

Variable	Non-T2DM (n=150)	T2DM (n=150)	P
Age^a, year	61.82±9.28	61.88±9.10	0.955
Male^b, n (%)	73(48.67)	73(48.67)	1.000
Education^b, n (%)			<0.001
Primary school or below	54(36.0)	85(56.7)
Junior high school	46(30.7)	36(24.0)
Senior high school or above	50(33.3)	29(19.3)
Physical activity^b, n (%)	133(88.67)	116(77.33)	0.013
Family history of diabetes^b, n (%)	1(0.67)	13(8.67)	0.001
Diet^c
Refined grains and their products, g/d	262.5(200.0,400.0)	353.4(257.1,444.7)	0.988
Whole grains and related products, g/d	64.3(32.5,100.0)	57.1(25.4,101.0)	0.353
Vegetables and fruit, g/d	250.0(150.0,400.0)	200.0(150.0,292.9)	0.139
Meats, g/d	48.2(18.5,80.4)	42.9(19.3,74.8)	0.554
Milk and its products, g/d	60.7(8.8,155.0)	24.6(0.0,152.3)	0.026
Aquatic products, g/d	4.2(1.0,14.3)	3.3(0.5,6.7)	0.011
Bean and its products, g/d	55.8(20.0,100.0)	27.6(7.1,54.4)	<0.001
BMI^a, kg/m²	24.72±3.28	26.71±4.56	<0.001
SBP^a, mmHg	129.53±18.39	136.90±21.76	0.002
DBP^a, mmHg	83.55±10.83	85.49±11.67	0.136
TG^a, mmol/L	1.87±1.53	2.41±2.06	0.010
TC^a, mmol/L,	3.97±0.72	3.94±0.75	0.734
HDL^a, mmol/L	1.07±0.25	1.00±0.24	0.014
LDL^a, mmol/L	2.83±0.69	2.76±0.68	0.345
TMAO^c, μmol/L	3.93(2.41,5.78)	5.79(3.08,8.93)	<0.001
Betaine^c, μmol/L	65.57(52.84,80.37)	55.52(48.37,69.37)	<0.001
L-carnitine^c, μmol/L	45.58(38.80,52.77)	42.09(35.41,50.41)	0.005
Choline^c, μmol/L	18.08(15.84,21.55)	19.20(16.54,23.01)	0.032
TMA^c, μmol/L	0.16(0.15,0.17)	0.16(0.15,0.18)	0.524

Notes: Quantitative variables are shown as mean ± SD and median (IQR), and qualitative variables are presented as numbers with the percentage. ^aThe significant difference were compared by using the Student ‘s t-test; ^bThe significant difference were compared by using the chi-square tests; ^cThe significant difference were compared by using the Wilcoxon-Mann–Whitney rank sum test.

Abbreviations: T2DM, type 2 diabetes mellitus; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; TG, triglyceride; TC, total cholesterol; LDL low-density lipoprotein; HDL, high-density lipoprotein; TMAO, Trimethylamine N-Oxide; TMA, trimethylamine.

Table 2 The Basic Characteristics of the Study and the Risk of T2DM

Variable	Model 1 OR (95% CI)	P	Model 2 OR (95% CI)	P	Model 3 OR (95% CI)	P
TMAO and its precursors
TMAO (ref.=TMAO≤2.85μmol/L)
TMAO1 (> 2.85μmol/L)	1.706(1.023,2.844)	0.041	–	–	1.718(0.938,3.149)	0.080
Choline (ref.=Choline≤15.31μmol/L)
Choline1 (15.32μmol/L ~)	0.887(0.465,1.691)	0.716	–	–	0.708(0.327,1.534)	0.382
Choline2 (19.41μmol/L ~)	1.284(0.613,2.691)	0.507	–	–	1.504(0.611,3.703)	0.374
Choline3 (> 22.62μmol/L)	1.949(0.940,4.039)	0.073	–	–	3.511(1.395,8.834)	0.008
Betaine	0.983(0.972,0.995)	0.005	–	–	0.978(0.964,0.992)	0.002
L-carnitine	0.966(0.943,0.988)	0.003	-	-	0.949(0.922,0.978)	0.001
TMA	5.507(0.052,580.627)	0.473	-	-	-	-
Traditional risk factors
Without diabetes history	-	-	0.062(0.007,0.544)	0.011	0.072(0.007,0.714)	0.025
Education (ref.=primary school and below)
Junior high school	-	-	0.584(0.316,1.078)	0.085	0.508(0.266,0.971)	0.040
Senior high school or above	-	-	0.399(0.213,0.747)	0.004	0.386(0.196,0.761)	0.006
Physical activity	-	-	0.503(0.252,1.004)	0.051	-	-
BMI	-	-	1.161(1.067,1.263)	0.001	1.152(1.052,1.261)	0.002
SBP	-	-	1.015(1.001,1.028)	0.029	1.019(1.004,1.033)	0.011
Bean and its product	-	-	0.993(0.988,0.997)	0.001	0.992(0.987,0.997)	0.001

Notes: Model 1, model of TMAO and its precursors on the risk of T2DM. Model 2, model of traditional risk factors on the risk of T2DM (adjusted for triglyceride, high-density lipoprotein, milk and its product, aquatic products, vegetables and fruit). Model 3, model of TMAO and its precursors and traditional risk factors on the risk of T2DM. (adjusted for triglyceride, high-density lipoprotein, milk and its product, aquatic products, vegetables and fruit).

Figure 2 Receiver operating characteristic curves of TMAO and its precursors (blue), traditional risk factors (grey), TMAO and precursors plus traditional risk factors (purple) for type 2 diabetes mellitus. The area under the operating characteristic curve (AUC) was 0.706 (95% CI: 0.647–0.765) for TMAO and its precursors model; 0.761 (95% CI: 0.707–0.816) for the traditional risk factors model; 0.816 (95% CI: 0.768–0.863) for the traditional risk factors plus TMAO and its precursors model. (P<0.05 for comparison of TMAO and its precursors plus traditional risk factors model with the other two models).