Abstract：Objective To investigate the correlation of plasma trimethylamine-N-oxide (TMAO) level with diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).Methods One hundred and one patients with T2DM admitted into the endocrinology department of Aerospace Center Hospital were enrolled in this study and divided into DR group (n=32) and without-DR group (n=69). Plasma TMAO level was measured by the ELISA method, and the Logistic regression and receiver operating characteristic (ROC) curve were used to analyze the relationship between plasma TMAO level and DR.Results The DR patients were older and showed higher duration of diabetes, systolic blood pressure and plasma TMAO level than without-DR group (P＜0.05), while serum albumin and triglycerides in DR group were lower (P＜0.05). Logistic regression analysis found that, after adjustment for confounding factor, the age (OR=1.070, 95%CI:1.011-1.133, P=0.019), serum albumin (OR=0.807, 95%CI:0.701-0.929, P=0.003), and plasma TMAO (OR=1.062, 95%CI:1.006-1.121,P=0.029) were independently associated with DR. Based on ROC analysis, the area under curve (AUC) of plasma TMAO alone was 0.650(P=0.024), and the AUC of age, serum albumin and plasma TMAO in combination was 0.789(P＜0.001).Conclusion DR patients show a higher plasma TMAO level. The combination of plasma TMAO, age and serum albumin is characterized by a higher predicting ability for DR.
王鸿, 李晓静, 刘佳, 王琳琳, 崔立芹, 董松. 2型糖尿病患者血浆氧化三甲胺与视网膜病变的相关性[J]. 武警医学, 2022, 33(8): 654-658.
WANG Hong, LI Xiaojing, LIU Jia, WANG Linin, CUI Liqin, DONG Song. Correlation between plasma TMAO level and DR in patients with T2DM. Med. J. Chin. Peop. Armed Poli. Forc., 2022, 33(8): 654-658.
Yau J W, Rogers S L, Kawasaki R, et al. Global prevalence and major risk factors of diabetic retinopathy [J]. Diabetes Care, 2012, 35(3):556-564.
[2]
Song P, Yu J, Chan K Y, et al. Prevalence, risk factors and burden of diabetic retinopathy in China: a systematic review and meta-analysis [J]. J Glob Health, 2018, 8(1):010803.
[3]
Ting D S, Cheung G C, Wong T Y. Diabetic retinopathy: global prevalence, major risk factors, screening practices and public health challenges: a review [J]. Clin Exp Ophthalmol,2016, 44(4): 260-277.
[4]
Liu Y, Dai M. Trimethylamine N-oxide generated by the gut microbiota is associated with vascular inflammation: new insights into atherosclerosis [J]. Mediators Inflamm, 2020, 2020:4634172.
[5]
Winther S A, Øllgaard J C, Tofte N, et al. Utility of plasma concentration of trimethylamine N-oxide in predicting cardiovascular and renal complications in individuals with type 1 diabetes [J]. Diabetes Care, 2019, 42(8):1512-1520.
[6]
Subramaniam S, Fletcher C. Trimethylamine N-oxide: breathe new life [J]. Br J Pharmacol, 2018, 175(8): 1344-1353.
[7]
Liu W, Wang C, Xia Y, et al. Elevated plasma trimethylamine-N-oxide levels are associated with diabetic retinopathy [J]. Acta Diabetol, 2021, 58(2):221-229.
[8]
Shan Z, Sun T, Huang H, et al. Association between microbiota-dependent metabolite trimethylamine-N-oxide and type 2 diabetes [J]. Am J Clin Nutr, 2017, 106(3): 888-894.
[9]
Lemaitre R N, Jensen P N, Wang Z, et al. Association of trimethylamine N-oxide and related metabolites in plasma and incident type 2 diabetes: The Cardiovascular Health Study [J]. JAMA Network Open, 2021, 4(8): e2122844.
[10]
Papandreou C, Bulló M, Zheng Y, et al. Plasma trimethylamine-N-oxide and related metabolites are associated with type 2 diabetes risk in the Prevención con Dieta Mediterránea (PREDIMED) trial [J]. Am J Clin Nutr, 2018, 108(1):163-173.
[11]
Lupachyk S, Watcho P, Stavniichuk R, et al. Endoplasmic reticulum stress plays a key role in the pathogenesis of diabetic peripheral neuropathy [J]. Diabetes, 2013, 62(3):944-952.
[12]
Alberti K G, Zimmet P Z. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation [J]. Diabet Med, 1998, 15(7):539-553.
Tanase D M, Gosav E M, Neculae E, et al. Role of gut microbiota on onset and progression of microvascular complications of type 2 diabetes (T2DM) [J]. Nutrients, 2020, 12(12):3719.
[15]
Gãtarek P, Kałuzna-Czaplińska J. Trimethylamine N-oxide (TMAO) in human health [J]. EXCLI J, 2021,20: 301-319.
[16]
Chen S, Henderson A, Petriello M C, et al. Trimethylamine N-oxide binds and activates PERK to promote metabolic dysfunction [J]. Cell Metab, 2019, 30(6):1141-1151.
[17]
Leustean A M, Ciocoiu M, Sava A, et al. Implications of the intestinal microbiota in diagnosing the progression of diabetes and the presence of cardiovascular complications [J]. J Diabetes Res, 2018, 2018:5205126.
[18]
Al-Obaide M A I, Singh R, Datta P, et al. Gut microbiota-dependent trimethylamine-N-oxide and serum biomarkers in patients with T2DM and advanced CKD [J]. J Clin Med, 2017, 6(9):86.
[19]
Loukovaara S, Piippo N, Kinnunen K, et al. NLRP3 inflammasome activation is associated with proliferative diabetic retinopathy[J]. Acta Ophthalmol, 2017, 95(8): 803-808.
[20]
Chen W, Zhao M, Zhao S, et al. Activation of the TXNIP/NLRP3 inflammasome pathway contributes to inflammation in diabetic retinopathy: a novel inhibitory effect of minocycline [J]. Inflamm Res, 2017, 66(2): 157-166.
[21]
Zhu Y, Cai X, Liu Y, et al. Serum albumin, but not bilirubin, is associated with diabetic chronic vascular complications in a Chinese type 2 diabetic population [J]. Sci Rep,2019, 9(1):12086.
[22]
Tan G S, Gan A, Sabanayagam C, et al. Ethnic differences in the prevalence and risk factors of diabetic retinopathy: the Singapore epidemiology of eye diseases study [J]. Ophthalmology, 2018, 125(4):529-536.
[23]
Jin G, Xiao W, Ding X, et al. Prevalence of and risk factors for diabetic retinopathy in a rural Chinese population: the Yangxi Eye Study [J]. Invest Ophthalmol Vis Sci, 2018, 59(12):5067-5073.
[24]
Iwasaki T, Togashi Y, Terauchi Y. Significant association of serum albumin with severity of retinopathy and neuropathy, in addition to that of nephropathy, in Japanese type 2 diabetic patients [J]. Endocr J,2008, 55(2):311-316.
[25]
Kuka J, Videja M, Makrecka-Kuka M, et al. Metformin decreases bacterial trimethylamine production and trimethylamine N-oxide levels in db/db mice[J]. Sci Rep, 2020, 10(1):14555.
[26]
de Vos W M, Tilg H, van Hul M, et al. Gut microbiome and health: mechanistic insights [J]. Gut, 2022, 71(5):1020-1032.
2022, Vol. 33 
