Plasma acylcarnitine and diabetic retinopathy: A study from Eastern China.

Background and purpose: Acylcarnitines (ACars) are important for insulin resistance and type 2 diabetes (T2D). However, their roles in diabetic retinopathy (DR) remain controversial. In this study, we aimed to investigate the association of ACars with DR and their values in DR detection. Methods: This was a two-center case-control study based on the propensity score matching approach between August 2017 to June 2018 in Eastern China. Multivariable logistic regression models were applied to estimate the association of plasma ACars with DR. Differential ACars were screened by models of least absolute shrinkage and selection operator, elastic net, and weighted quantile sum regression, and their roles in DR identification were further evaluated by the area under the receiver operating curve (AUC). Results: Eight of twenty plasma ACars (8:0, 12:0, 12:1, 14:1, 16:2, 18:0, 18:2 and 18:3) were associated with DR, while only ACar 8:0 was selected by three variable selection methods. As compared to those with the 1st tertile of ACar 8:0, the adjusted odds ratio (OR) and 95% confidence interval (CI) of DR were 0.22 (0.08, 0.59) and 0.12 (0.04, 0.36) for subjects in the 2nd and 3rd tertiles, respectively (P for trend < 0.001). Consistent associations were also observed in both restricted cubic spline regression models and subgroup analyses. AUC (95% CI) were 0.74 (0.66, 0.82) for ACar 8:0 alone and 0.77 (0.70, 0.85) for ACar 8:0 combined with covariates. Conclusions: Our findings suggest higher ACar 8:0 is significantly associated with a decreased risk of DR, which provides a unique window for early identification of DR.

High-Coverage Serum Metabolomics Reveals Metabolic Pathway Dysregulation in Diabetic Retinopathy: A Propensity Score-Matched Study.

Background: Diabetic retinopathy (DR) is a major diabetes-related disease linked to metabolism. However, the cognition of metabolic pathway alterations in DR remains scarce. We aimed to corroborate alterations of metabolic pathways identified in prior studies and investigate novel metabolic dysregulations that may lead to new prevention and treatment strategies for DR. Methods: In this case-control study, we tested 613 serum metabolites in 69 pairs of type 2 diabetic patients (T2DM) with DR and propensity score-matched T2DM without DR via ultra-performance liquid chromatography-tandem mass spectrometry system. Metabolic pathway dysregulation in DR was thoroughly investigated by metabolic pathway analysis, chemical similarity enrichment analysis (ChemRICH), and integrated pathway analysis. The associations of ChemRICH-screened key metabolites with DR were further estimated with restricted cubic spline analyses. Results: A total of 89 differentially expressed metabolites were identified by paired univariate analysis and partial least squares discriminant analysis. We corroborated biosynthesis of unsaturated fatty acids, glycine, serine and threonine metabolism, glutamate and cysteine-related pathways, and nucleotide-related pathways were significantly perturbed in DR, which were identified in prior studies. We also found some novel metabolic alterations associated with DR, including the disturbance of thiamine metabolism and tryptophan metabolism, decreased trehalose, and increased choline and indole derivatives in DR. Conclusions: The results suggest that the metabolism disorder in DR can be better understood through integrating multiple biological knowledge databases. The progression of DR is associated with the disturbance of thiamine metabolism and tryptophan metabolism, decreased trehalose, and increased choline and indole derivatives.

Individual and joint effects of trehalose and glutamate on diabetic retinopathy: a propensity score-matched case-control study.

Although previous studies demonstrate that trehalose can help maintain glucose homeostasis in healthy humans, its role and joint effect with glutamate on diabetic retinopathy (DR) remain unclear. We aimed to comprehensively quantify the associations of trehalose and glutamate with DR. This study included 69 pairs of DR and matched type 2 diabetic (T2D) patients. Serum trehalose and glutamate were determined via ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry system. Covariates were collected by a standardized questionnaire, clinical examinations and laboratory assessments. Individual and joint association of trehalose and glutamate with DR were quantified by multiple conditional logistic regression models. The adjusted odds of DR averagely decreased by 86% (odds ratio (OR): 0.14; 95% CI: 0.06, 0.33) with per interquartile range increase of trehalose. Comparing with the lowest quartile, adjusted OR (95% CI) were 0.20 (0.05, 0.83), 0.14 (0.03, 0.63) and 0.01 (<0.01, 0.05) for participants in the second, third and fourth quartiles of trehalose, respectively. In addition, as compared to their counterparts, T2D patients with lower trehalose (

Whole-blood magnesium and blood lipids are individually and jointly associated with an elevated likelihood of youngsters being overweight or obese: A matched case-control study using the propensity score.

OBJECTIVES: Youngsters who are overweight or obese (YOO) have become an important global health concern. Some micronutrients may be modifiable influential factors. This study aimed to investigate the individual and joint association of whole-blood magnesium (WBMg) and total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), or high-density lipoprotein cholesterol (HDL-C) in YOO. METHODS: This is a propensity score matching-based case-control study. YOO was defined depending on age- and sex-specific body mass index z-score, calculated with SAS macros (%group_standard and %WHO2007) from the World Health Organization website. WBMg, blood lipids, and covariates were carefully measured by trained technicians using a whole-blood, five-element, basic analyzer and atomic absorption spectrometer or automatic biochemical analyzer. Locally weighted scattered plot smoothing and multivariable conditional logistic regression models were applied to estimate the associations of WBMg and blood lipids in YOO. RESULTS: WBMg was positively associated with YOO. The adjusted likelihood of YOO significantly increased by 21% (odds ratio: 1.21; 95% confidence interval [CI], 1.10-1.33) with per-interquartile range elevation of WBMg. Compared with the 1st quartile, adjusted odds ratios among youngsters in the 2nd, 3rd, and 4th quartiles of WBMg were 1.11 (95% CI, 0.92-1.35), 1.29 (95% CI, 1.06-1.57), and 1.47 (95% CI, 1.18-1.83), respectively. Furthermore, the relationship between WBMg and YOO was moderated by lipid profiles. Compared with those having lower (< median) WBMg and TC, TG, LDL-C, or higher (≥ median) HDL-C, youngsters with both higher WBMg and TC, TG, LDL-C, or lower HDL-C had higher YOO odds, which averagely increased by 188%, 250%, 339%, and 369%, respectively. CONCLUSIONS: WBMg was an independent risk factor of YOO, and the associations were stronger among those with unhealthy blood lipids. Our findings can help to guide clinical and public health policies on the relevance of magnesium nutritional status.

Serum ω-6/ω-3 polyunsaturated fatty acids ratio and diabetic retinopathy: A propensity score matching based case-control study in China.

BACKGROUND: Optimal ω-6/ω-3 polyunsaturated fatty acids ratio (PUFAR) is reported to exert protective effects against chronic diseases. However, data on PUFAR and diabetic retinopathy (DR) remains scarce. We aimed to thoroughly quantify whether and how PUFAR was related to DR as well as its role in DR detection. METHODS: This two-centre case-control study was conducted from August 2017 to June 2018 in China, participants were matched using a propensity score matching algorithm. We adopted multivariable logistic regression models and restricted cubic spline analyses to estimate the independent association of PUFAR with DR, adjusting for confounders identified using a directed acyclic graph. The value of PUFAR as a biomarker for DR identification was further evaluated by receiver operating characteristic analyses and Hosmer-Lemeshow tests. FINDINGS: An apparent negative relationship between PUFAR and DR was observed. Adjusted odds of DR decreased by 79% (OR: 0·21, 95% CI: 0·10-0·40) with an interquartile range increase in PUFAR. Similar results were also obtained in tertile analysis. As compared to those in the 1st tertile of PUFAR, the adjusted odds of DR decreased by 76% (OR: 0·24, 95% CI: 0·08-0·66) and 93% (OR: 0·07, 95% CI: 0·03-0·22) for subjects in the 2nd and 3rd tertiles, respectively. Good calibration and discrimination of the PUFAR associated predictive model were detected and PUFAR = 35 would be an ideal cut-off value for DR identification. INTERPRETATION: Our results suggest that serum PUAFR is inversely associated with DR. Although PUFAR-alteration is not observed amongst different stages of DR, it can serve as an ideal biomarker in distinguishing patients with DR from those without DR. FUNDING: This study was funded by Natural Science Foundation of Zhejiang Province, Zhejiang Basic Public Welfare Research Project, the Major Project of the Eye Hospital of Wenzhou Medical University, and the Academician's Science and Technology Innovation Program in Zhejiang province. Part of this work was also funded by the National Nature Science Foundation of China, and Research Project for College Students in Wenzhou Medical University.