Objective. The objective of this study is to investigate the relationship between time in range (TIR), a new metric of continuous glucose monitoring (CGM) and cardiovascular autonomic neuropathy (CAN) in individuals with type 2 diabetes mellitus (T2DM). Methods. A total of 349 individuals with T2DM were enrolled in this study. Evaluating by the standard cardiac autonomic reflex tests (CARTs), there were 228 diabetic individuals without cardiovascular autonomic neuropathy (without confirmed CAN) including absent CAN (n=83 cases) and early CAN (n=145 cases) and 121 diabetic individuals complicated with cardiovascular autonomic neuropathy (CAN) including definite CAN (n=109 cases) and severe CAN (n=12 cases). All patients underwent 3-day CGM. TIR is defined as the time percent during a 24-hour period when the glucose is in the range of 3.9-10 mmol/L. The Spearman analysis was used to analyze the correlation between TIR and CART parameters, total CAN score. The logistic regression was applied to analyze the relationship between TIR and CAN by adjusting for the age, duration of diabetes, sex, lipid situation, serum creatinine, body mass index, blood pressure, HbA1c (%), and other glycemic variability (GV) metrics. Results. The total presence of CAN was 34.67% (definite CAN 31.23% and severe CAN 3.44%). Patients with more severe CAN had lower TIR (P<0.001). With increasing quartiles of TIR, the presence of CAN by severity declined (P<0.05). TIR is inversely correlated with total score of CAN (P<0.001) and positively associated with heart rate variation during the lying to standing, Valsalva maneuver, and deep breathing (P<0.05). The logistic regression found a robust association between TIR and CAN independent of HbA1c and GV metrics. Conclusion. TIR is associated with the presence of CAN independent of HbA1c and GV metrics in Chinese type 2 diabetes.

BACKGROUND Time in range (TIR), as a novel metric for glycemic control, has robust relevance with diabetic complications. Diabetic peripheral neuropathy (DPN) is characterized by sudomotor dysfunction. AIM To explore the relationship between TIR obtained from continuous glucose monitoring (CGM) and sudomotor function detected by SUDOSCAN in subjects with type 2 diabetes. METHODS The research enrolled 466 inpatients with type 2 diabetes. All subjects underwent 3-d CGM and SUDOSCAN. SUDOSCAN was assessed with electrochemical skin conductance in hands (HESC) and feet (FESC). Average feet ESC < 60 µS was defined as sudomotor dysfunction (+), otherwise it was sudomotor dysfunction (-). TIR refers to the percentage of time when blood glucose is between 3.9-10 mmol/L during 1 d period. RESULTS Among the enrolled subjects, 135 (28.97%) presented with sudomotor dysfunction. Patients with sudomotor dysfunction (+) showed a decreased level of TIR ( P < 0.001). Compared to the lowest tertile of TIR, the middle and the highest tertiles of TIR was associated with an obviously lower prevalence of sudomotor dysfunction (20.51% and 21.94% vs 44.52%) ( P < 0.001). In addition, with the increase of TIR, HESC and FESC increased ( P < 0.001). Regression analysis demonstrated that TIR was inversely and independently linked with the prevalence of sudomotor dysfunction after adjusting for confounding values (odds ratio = 0.979, 95%CI: 0.971-0.987, P < 0.001). CONCLUSION The tight glycemic control assessed by TIR is of vitally protective value for sudomotor dysfunction in type 2 diabetes mellitus.

Adipose tissue macrophage (ATM) inflammation is involved with meta-inflammation and pathology of metabolic complications. Here we report that in adipocytes, elevated lactate production, previously regarded as the waste product of glycolysis, serves as a danger signal to promote ATM polarization to an inflammatory state in the context of obesity. Adipocyte-selective deletion of lactate dehydrogenase A (Ldha), the enzyme converting pyruvate to lactate, protects mice from obesity-associated glucose intolerance and insulin resistance, accompanied by a lower percentage of inflammatory ATM and reduced production of pro-inflammatory cytokines such as interleukin 1β (IL-1β). Mechanistically, lactate, at its physiological concentration, fosters the activation of inflammatory macrophages by directly binding to the catalytic domain of prolyl hydroxylase domain-containing 2 (PHD2) in a competitive manner with α-ketoglutarate and stabilizes hypoxia inducible factor (HIF-1α). Lactate-induced IL-1β was abolished in PHD2-deficient macrophages. Human adipose lactate level is positively linked with local inflammatory features and insulin resistance index independent of the body mass index (BMI). Our study shows a critical function of adipocyte-derived lactate in promoting the pro-inflammatory microenvironment in adipose and identifies PHD2 as a direct sensor of lactate, which functions to connect chronic inflammation and energy metabolism.

The RNA-binding motif (RBM) proteins are a class of RNA-binding proteins named, containing RNA-recognition motifs (RRMs), RNA-binding domains, and ribonucleoprotein motifs. RBM proteins are involved in RNA metabolism, including splicing, transport, translation, and stability. Many studies have found that aberrant expression and dysregulated function of RBM proteins family members are closely related to the occurrence and development of cancers. This review summarizes the role of RBM proteins family genes in cancers, including their roles in cancer occurrence and cell proliferation, migration, and apoptosis. It is essential to understand the mechanisms of these proteins in tumorigenesis and development, and to identify new therapeutic targets and prognostic markers.