Triglyceride Glucose Index for the Detection of Diabetic Kidney Disease and Diabetic Peripheral Neuropathy in Hospitalized Patients with Type 2 Diabetes.

INTRODUCTION: The triglyceride-glucose index (TyG) has been identified as a dependable and simple indicator marker of insulin resistance (IR). Research has demonstrated a correlation between macrovascular complications and TyG. However, limited research exists regarding the relationship between TyG and diabetic microvascular complications. Consequently, the objective of this study is to investigate the association between TyG and diabetic kidney disease (DKD) and diabetic peripheral neuropathy (DPN). METHODS: This is a cross-sectional, observational study. A total of 2048 patients from Tongren Hospital, Shanghai Jiao Tong University School of Medicine were enrolled. The primary outcomes are DKD and DPN. Quantile regression analysis was employed to investigate the implicit factors of TyG quartiles. Subsequently, based on implicit factors, logistic regression models were constructed to further examine the relationship between TyG and DKD and DPN. RESULTS: In the baseline, TyG exhibited higher values across patients with DKD, DPN, and co-existence of DKD and DPN (DKD + DPN) in type 2 diabetes (T2D). Univariate logistic regressions demonstrated a significant association between an elevated TyG and an increased risk of DKD (OR = 1.842, [95% CI] 1.317-2.578, P for trend < 0.01), DPN (OR = 1.516, [95% CI] 1.114-2.288, P for trend < 0.05), DKD + DPN (OR = 2.088, [95% CI] 1.429-3.052, P for trend < 0.05). Multivariable logistic regression models suggested a statistically significant increase in the risk of DKD (OR = 1.581, [95% CI] 1.031-2.424, p < 0.05), DKD + DPN (OR = 1.779, [95% CI] 1.091-2.903, p < 0.05) after adjusting the implicit factors of TyG quartiles. However, no significant relationship was observed between TyG and DPN in the multivariable regression analysis. CONCLUSIONS: Elevated TyG was significantly associated with an increased risk of DKD in T2D, but no significant relationship was shown with DPN. This finding provided further evidence for the clinical significance of integrating TyG into the initial assessment of diabetic microvascular complications.

MicroRNA-214-5p aggravates sepsis-related acute kidney injury in mice.

Acute kidney injury (AKI) is a devastating comorbidity in sepsis and correlates with a very poor prognosis and increased mortality. Currently, we use lipopolysaccharide (LPS) to establish sepsis-related AKI and try to demonstrate the pathophysiological role of microRNA-214-5p (miR-214-5p) in this process. Mice were intravenously injected with the miR-214-5p agomir, antagomir or negative controls for three consecutive days and then received a single intraperitoneal injection of LPS (10 mg/kg) for 24 h to induce AKI. Besides, the Boston University mouse proximal tubular cell lines were stimulated with LPS (10 µg/ml) for 8 h to investigate the role of miR-214-5p in vitro. To inhibit adenosine monophosphate-activated protein kinase (AMPK), compound C (CpC) was used in vivo. For glucagon-like peptide-1 receptor (GLP-1R) silence, cells were transfected with the small interfering RNA against GLP-1R. miR-214-5p level was upregulated in LPS-treated kidneys and proximal tubular cell lines. The miR-214-5p antagomir reduced LPS-induced renal inflammation and oxidative stress, thereby preventing renal damage and dysfunction. In contrast, the miR-214-5p agomir aggravated LPS-induced inflammation, oxidative stress and AKI in vivo and in vitro. Mechanistically, we found that the miR-214-5p antagomir prevented septic AKI via activating AMPK and that CpC treatment completely abrogated its renoprotective effect in mice. Further detection showed that miR-214-5p directly bound to the 3'-untranslational region of GLP-1R to inhibit GLP-1R/AMPK axis. Our data identify miR-214-5p as a promising therapeutic candidate to treat sepsis-related AKI.

Isotopic Effect in Double Proton Transfer Process of Porphycene Investigated by Enhanced QM/MM Method.

The single deuterium substitution in porphycene leads to an asymmetric molecular geometry, which may affect the double proton transfer process in the porphycene molecule. In this study, we applied an enhanced QM/MM method called SITS-QM/MM to investigate hydrogen/deuterium (H/D) isotope effects on the double proton transfer in porphycene. Distance changes in SITS-QM/MM molecular dynamics simulations suggested that the deuterium substituted porphycene adopted the stepwise double proton transfer mechanism. The structural analysis and the free energy shifts of double proton transfer process indicated that the asymmetric isotopic substitution subtly compressed the covalent hydrogen bonds and may alter the original transition state location.