Increased Serum Trimethylamine N-Oxide Level in Type 2 Diabetic Patients with Mild Cognitive Impairment

Figures & data

Table 1 Demographic and Clinical Characteristics of Type 2 Diabetic (T2DM) Patients

Variables	Non-MCI (n = 179)	MCI (n = 74)	Z or χ2	P value
Age (year)	59 (55–66)	64 (57.8–69)	2.930	0.003
Male [n (%)]	96 (53.6%)	35 (47.3%)	0.841	0.359
Education (years)	9 (9–12)	9 (9–9.75)	3.655	<0.001
BMI	24.7 (23.6–25.7)	25.1 (24.4–26.0)	2.289	0.022
Smoking	51 (28.5%)	26 (35.1%)	1.091	0.296
Drinking	39 (21.8%)	23 (31.1%)	2.444	0.118
Diabetes duration (years)	9.2 (8.4–9.9)	9.9 (9.1–10.5)	4.120	<0.001
CVD	74 (41.3%)	39 (52.7%)	2.735	0.098
Hypertension	44 (24.6%)	31 (41.9%)	7.523	0.006
Hyperlipidemia	43 (24.0%)	30 (40.5%)	6.959	0.008
Retinopathy	32 (17.9%)	22 (29.7%)	4.381	0.036
Nephropathy	39 (21.8%)	25 (33.8%)	3.987	0.046
Neuropathy	19 (10.6%)	13 (17.6%)	2.291	0.130
FBG (mmol/L)	8.3 (7.9–8.5)	8.3 (8.0–8.6)	0.733	0.464
HbA1c (%)	8.8 (8.5–9.2)	8.9 (8.6–9.3)	1.319	0.187
TG (mmol/L)	2.8 (2.4–3.0)	2.9 (2.6–3.2)	2.745	0.006
TC (mmol/L)	6.4 (6.1–6.7)	6.5 (6.3–6.8)	1.801	0.072
LDL-C (mmol/L)	3.7 (3.4–3.9)	3.8 (3.5–4.1)	1.944	0.052
HDL-C (mmol/L)	1.6 (1.6–2.1)	1.8 (1.6–1.9)	2.091	0.037
Creatinine (μmol/L)	82.7 (75.1–88.0)	84.3 (81.3–88.1)	2.440	0.015
Hs-CRP (ng/mL)	2.5 (2.2–2.9)	2.8 (2.5–3.0)	3.966	<0.001
BDNF (ng/mL)	8.9 (7.8–10.1)	8.2 (7.7–9.0)	2.974	0.003
MoCA	28 (27–29)	23 (22–24)	12.616	<0.001

Notes: Data are expressed as medians and inter-quartile ranges (IQR) for quantitative variables, and expressed as cases and percentage for category variables. Mann–Whitney U-test (Z), or χ2 test was used to test for significant differences.

Abbreviations: BMI, body mass index; CVD, cardiovascular disease; FBG, fasting blood glucose; HbAlc, glycosylated hemoglobin; TG, triglyceride; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; hs-CRP, high sensitivity C-reactive protein; BDNF, brain-derived neurotrophic factor; MoCA, Montreal Cognitive Assessment.

Figure 1 Serum levels of TMAO in diabetic patients (a) without and (b) with MCI. All data are expressed as medians and inter-quartile ranges (IQR). Mann–Whitney U-tests were performed to compare the differences between groups. ***P<0.001 vs healthy control group.

Abbreviation: MCI, mild cognitive impairment.

Table 2 The Correlations of Serum TMAO Level with Clinical Indicators in T2DM Patients

Variables	TMAO (μmol/L)
	r	P value
Age (year)	0.147	0.019
Education (years)	−0.017	0.790
BMI	0.153	0.015
Diabetes duration (years)	0.160	0.011
FBG (mmol/L)	0.056	0.371
HbA1c (%)	0.138	0.029
TG (mmol/L)	0.138	0.029
TC (mmol/L)	0.109	0.084
LDL-C (mmol/L)	0.115	0.067
HDL-C (mmol/L)	−0.144	0.022
Creatinine (μmol/L)	0.184	0.003
Hs-CRP (ng/mL)	0.243	<0.001
BDNF (ng/mL)	−0.165	0.009
MoCA	−0.386	<0.001

Notes: Spearman correlation was performed in 253 patients.

Abbreviations: BMI, body mass index; FBG, fasting blood glucose; HbAlc, glycosylated hemoglobin; TG, triglyceride; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; hs-CRP, high sensitivity C-reactive protein; BDNF, brain-derived neurotrophic factor; MoCA, Montreal Cognitive Assessment.

Table 3 Multivariate Logistic Regression Evaluates the Risk of MCI in T2DM Patients

Variables	β	SE of β	P value	OR	95% CI
Education (years)	−0.282	0.087	0.001	0.754	0.636–0.895
Diabetes duration (years)	0.369	0.143	0.010	1.446	1.092–1.914
Hyperlipidemia	1.063	0.371	0.004	2.894	1.398–5.991
Hs-CRP (ng/mL)	1.072	0.399	0.007	2.920	1.336–6.384
TMAO (μmol/L)	0.339	0.057	<0.001	1.404	1.255–1.571

Abbreviations: MCI, mild cognitive impairment; β, regression coefficient; SE, standard error; OR, odds ratio; CI, confidence interval for odds ratio; hs-CRP, high sensitivity C-reactive protein.

Figure 2 Receiver operator characteristic (ROC) curve of serum TMAO. The ROC curve was plotted to determine the cut-off point for serum TMAO that distinguishes the MCI and non-MCI in diabetic patients.

Abbreviation: MCI, mild cognitive impairment.