The neutrophil-lymphocyte ratio as a risk factor for all-cause and cardiovascular mortality among individuals with diabetes: evidence from the NHANES 2003-2016.

BACKGROUND: Evidence regarding the neutrophil-lymphocyte ratio (NLR) and mortality risk in diabetes patients is scarce. This study investigated the relationship of the NLR with all-cause and cardiovascular mortality risk in diabetes patients. METHODS: Diabetes patients (n = 3251) from seven National Health and Nutrition Examination Survey (NHANES) cycles (2003-2016) were included in this study. The cause of death and mortality status of the participants were obtained from National Death Index records. Restricted cubic spline (RCS) was used to visualize the association of the NLR with mortality risk. The maximally selected rank statistics method (MSRSM) was used to determine the optimal NLR cutoff value corresponding to the most significant association with survival outcomes. Weighted multivariable Cox regression models and subgroup analyses were adopted to assess the association of the NLR with all-cause and cardiovascular mortality. Time-dependent receiver operating characteristic curve (ROC) analysis was conducted to evaluate the accuracy of the NLR in predicting survival outcomes. RESULTS: During a median follow-up of 91 months (interquartile range, 55-131 months), 896 (27.5%) of the 3251 diabetes patients died, including 261 (8.0%) with cardiovascular deaths and 635 (19.5%) with noncardiovascular deaths. The RCS regression analysis showed a positive linear association between the NLR and all-cause and cardiovascular mortality (both p > 0.05 for nonlinearity) in diabetes patients. Participants were divided into higher (> 3.48) and lower (≤ 3.48) NLR groups according to the MSRSM. In the multivariable-adjusted model, compared with participants with a lower NLR, those with a higher NLR had a significantly higher risk of both all-cause (HR 2.03, 95% confidence interval (CI) 1.64-2.51, p < 0.0001) and cardiovascular mortality (HR 2.76, 95% CI 1.84-4.14, p < 0.0001). The association was consistent in subgroup analyses based on age, sex, smoking status, drinking status, and hypertension, with no significant interaction between the aforementioned characteristics and the NLR (p interaction > 0.05). The time-dependent ROC curve showed that the areas under the curve of the 1-, 3-, 5-, and 10-year survival rates were 0.72, 0.66, 0.64, and 0.64 for all-cause mortality and 0.69, 0.71, 0.69 and 0.65, respectively, for cardiovascular mortality. CONCLUSION: An elevated NLR is independently associated with increased all-cause and cardiovascular mortality in diabetes patients.

A sensitive LC-MS/MS method for simultaneous determination of six flavonoids in rat plasma: application to a pharmacokinetic study of total flavonoids from mulberry leaves.

A simple and sensitive LC-MS/MS method has been developed and validated for the determination of rutin, isoquercitrin, astragalin, quercetin, kaempferol and isorhamnetin in rat plasma using naringin as the internal standard (IS). The plasma samples were pretreated and extracted by liquid-liquid extraction. Chromatographic separation was accomplished on a C18 column with a 10 min gradient elution using acetonitrile and 0.1% formic acid aqueous solution as mobile phase at a flow rate of 0.3 mL min(-1). A tandem mass spectrometric detection was conducted using multiple reaction monitoring (MRM) via an electrospray ionization (ESI) source and operating in the negative ionization mode. The lower limit of quantitation (LLOQ) of each analyte was lower than 1 ng mL(-1). Intra-day and inter-day precisions were less than 11.9%. The relative errors of accuracy were in the range of -9.2% to 6.1%. The mean recoveries of flavonoids and IS were higher than 53.8%. The proposed method was further applied to investigate the pharmacokinetics of all analytes after a single oral administration of total flavonoids from mulberry leaves to rats.