The role of trimethylamine-N-oxide level in the diagnosis of diabetic retinopathy and the differential diagnosis of diabetic and nondiabetic retinopathy

Yakar, Burkay; Onalan, Erhan; Kaymaz, Tugce; Donder, Emir; Gursu, Mehmet Ferit

doi:10.5935/0004-2749.2021-0527

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ORIGINAL ARTICLE • Arq. Bras. Oftalmol. 87 (2) • 2024 • https://doi.org/10.5935/0004-2749.2021-0527 copy

The role of trimethylamine-N-oxide level in the diagnosis of diabetic retinopathy and the differential diagnosis of diabetic and nondiabetic retinopathy

Papel do nível de N-óxido de trimetilamina no diagnóstico da retinopatia diabética e no diagnóstico diferencial da retinopatia diabética e não-diabética

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Purpose:

Trimethylamine N-oxide serum levels have been associated with type 2 diabetes mellitus and its complications. The current study aimed to find out if plasma trimethylamine N-oxide level may be a novel marker in the diagnosis of diabetic retinopathy and if it can be used in the differential diagnosis of diabetic and nondiabetic retinopathy.

Methods:

The study included 30 patients with diabetic retinopathy, 30 patients with nondiabetic retinopathy, 30 patients with type 2 diabetes mellitus without retinopathy, and 30 healthy control participants. Biochemical parameters, serum IL-6, TNF-α, and trimethylamine N-oxide levels were measured in all participants.

Results:

Trimethylamine N-oxide level was significantly higher in diabetic retinopathy than in the other groups (p<0.001). There was no significant difference in trimethylamine N-oxide levels between nondiabetic retinopathy and control or type 2 diabetes mellitus Groups. There was a significant positive correlation between trimethylamine N-oxide level and elevated FPG, BMI, HOMA-IR score, BUN, IL-6, and TNF-α levels.

Conclusion:

The current study showed that the trimethylamine N-oxide level is elevated in diabetic retinopathy. These findings suggest that serum trimethylamine N-oxide level might be a novel marker for diabetic retinopathy, and it might be used in the differential diagnosis of diabetic and nondiabetic retinopathy.

Keywords:
Biomarkers; Diabetic retinopathy; Differential diagnosis; Oxides; Type 2 diabetes mellitus; Trimethylamine-N-oxide; Trimethyloxamine

	DRP	Non-DRP	T2DM	Control	p value
Age (yr)	61.3 ± 6.1^* * p<0.05 DRP compared with control.	59.5 ± 9.2	55.3 ± 10.2	42.9 ± 8.2	<0.001
Male	18 (60.0)	14 (46.7)	14 (46.7)	19 (63.3)	0.426
FPG mg/dl	201.8 (107.5)^* * p<0.05 DRP compared with control. ⁺ + p<0.05 DRP compared with non-DRP.	92.3 (11.5)	184.2 (72.4)	85.5 (11.6)	<0.001
BMI (kg/m²)	28.2 (4.2)	27.2 (2.3)	29.2 (2.7)	26.5 (3.5)	0.009
HbA1c (%)	9.7 (2.4)^* * p<0.05 DRP compared with control. ⁺ + p<0.05 DRP compared with non-DRP.	5.5 (0.5)	9.3 (3.4)	5.1 (0.6)	<0.001
HOMA-IR	6.6 (4.1-18.1)^* * p<0.05 DRP compared with control. ⁺ + p<0.05 DRP compared with non-DRP.	1.5 (1.1-2.5)	6.0 (2.7-9.8)	1.9 (0.9-2.4)	<0.001
Triglyceride (mmol/L)	177.2 (85.0)^* * p<0.05 DRP compared with control.	135.3 (67.3)	164.1 (58.3)	128.6 (49.5)	0.015
TC (mmol/L)	187.7 (47.6)	174.5 (43.7)	193.8 (37.3)	184.7 (29.9)	0.312
LDL-C (mmol/L)	108.3 (36.1)	98.9 (28.9) ^¶ ¶ p<0.05 non-DRP compared with T2DM.	128.1 (30.6)	106.8 (20.9)	0.002
VLDL	28.8 (21.0-60.0)	24.5 (17.5-36.5)	31.0 (23.0-41.2)	25.4 (18.4-40.0)	0.141
D vit	12.2 (6.7-16.3)^* * p<0.05 DRP compared with control.	14.7 (8.1-19.2)	17.8 (10.5-22.9)	23.4 (16.8-29.6)	<0.001
ALT	18.0 (14.0-26.3)	24.5 (17.8-30.0)	25.0 (17.5-30.5)	17.0 (14.0-29.0)	0.114
AST	17.0 (15.8-19.8)	25.5 (18.3-29.5)	19.0 (16.8-23.8)	19.0 (17.0-23.0)	0.145
Hb	12.9 (1.7)^* * p<0.05 DRP compared with control.	12.8 (2.3)	13.7 (1.8)	14.8 (1.2)	<0.001
PLT	272.0 (193-331)	216.0 (178-251)	248.0 (218.7-397)	238.5 (215-257.8)	0.049
BUN	48.5 (34.5-57.0)^* * p<0.05 DRP compared with control. ^α α p<0.05 DRP compared with T2DM.	43.0 (33.0-66.0)	32.5 (25.0-41.0)	30.5 (25.5-34.3)	<0.001
Creatine (mg/dl)	1.1 (0.4)^* * p<0.05 DRP compared with control. ^α α p<0.05 DRP compared with T2DM.	1.3 (0.6)	0.8 (0.2)	0.8 (0.1)	<0.001
IL-6 (pg/ml)	457.0 (295.8-560.8)^* * p<0.05 DRP compared with control. ^α α p<0.05 DRP compared with T2DM.	358.0 (331.5-416.3)	352.5 (270.0-389.8)	319.0 (269.0-410.3)	<0.002
TNF-α (pg/ml)	1,495.8 (1,272.9-2122.0)^* * p<0.05 DRP compared with control.	1,788.4 (1,629.3-3149.6)^± ± p<0.05 non-DRP compared with control. ^¶ ¶ p<0.05 non-DRP compared with T2DM.	1,284.7 (996.6-1,498.2)	1,049.1 (816.9-1,168.7)	<0.001
TMAO µmol/L	1,899.5 (914.5-2,515.0)^* * p<0.05 DRP compared with control. ⁺ + p<0.05 DRP compared with non-DRP. ^α α p<0.05 DRP compared with T2DM.	757.7 (517.4-938.5)^a a p<0.05 non-DRP compared with control.	721.1 (538.2-1,215.3)^b b p<0.05 T2DM compared with control.	300.0 (206.2-403.3)	<0.001

Variable	TMAO µmol/L		Variable	TMAO µmol/L
Variable	r	p	Variable	r	p
Age/yr	0.386	<0.001	D vit	-0.228	0.012
FPG mg/dl	0.476	<0.001	ALT	0.045	0.628
BMI. kg/m²	0.220	0.016	AST	0.064	0.488
HbA1c. %	0.565	<0.001	Hb	-0.159	0.083
HOMA-IR	0.441	<0.001	PLT	-0.026	0.774
Triglyceride. mmol/L	0.114	0.214	BUN	0.320	<0.001
TC. mmol/L	0.073	0.430	Creatine mg/dl	0.177	0.053
LDL-C mmol/L	0.114	0.213	IL-6 (pg/ml)	0.305	0.001
VLDL	0.098	0.288	TNF-α (pg/ml)	0.230	0.012

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[1] Corresponding author: Burkay Yakar. E-mail: byakar@frat.edu.tr