ObjectiveThis study aimed to explore the relationship between short-term (≤12 months) changes in the estimated glomerular filtration rate (eGFR) and hemoglobin A1c (HbA1c) in patients with type 2 diabetes (T2D).MethodA total of 2,599 patients with T2D were enrolled if they were registered in the Diabetes Sharecare Information System, were aged 18–75 years, and had 2–3 HbA1c and eGFR measurements within the preceding 12 months. The studied patients were categorized into five groups based on eGFR, i.e., the relatively stable (RS), fast decline (FD), modest decline (MD), modest increase (MI), and fast increase (FI) groups.ResultsThe median eGFR changes from baseline were −22.14, −6.44, 0.00, 6.32, and 20.00 ml/min per 1.73 m2 for patients in the FD, MD, RS, MI, and FI groups, respectively. Up to 1,153 (44.4%) subjects experienced an eGFR decline of ≥3.5 ml/min per 1.73 m2, including 821 (31.6%) FD subjects and 332 (12.8%) MD subjects. A decreased trend was found between the eGFR change and HbA1c decrease category, even after multivariable adjustment. In general, an eGFR FD was frequently found in patients who had an HbA1c reduction of ≥3.00% and a baseline HbA1c ≥8.0%; alternatively, such a result was also observed for a urinary albumin-to-creatinine ratio (UACR) of 30.0–300.0 mg/g, regardless of a diabetes duration of <10.0 or ≥10.0 years, or in patients who had an HbA1c reduction of ≥1.00% accompanied by hyperfiltration.ConclusionsSome patients with T2D experienced an eGFR FD or MD during the ≤12-month follow-up period. A significant downward trend in eGFR change was demonstrated alongside an HbA1c reduction, independent of UACR stage, diabetes duration, and hyperfiltration. Sustained monitoring and cautious interpretation of the HbA1c and eGFR changes will be needed in clinical practice.

Gastric cancer (GC) ranks as the most common gastrointestinal cancer and is among the leading causes of cancer death worldwide. Glaucocalyxin A (GLA), an entkauranoid diterpene isolated from Rab-dosia japonica var., possesses various bioactivities. To date, the data on the effect of GLA on GC are still minimal, and the molecular mechanisms remain largely unknown. Herein, we found that GLA could significantly inhibit the proliferation, cell adhesion, and invasion of HGT-1, SNU-1, SNU-6, and NCI-N87 GC cells in a dose-dependent manner. GLA enhanced the apoptosis of the GC cells as evidenced by the increased caspase-3 activity and the elevated levels of cleaved caspase-3 and cleaved PARP in GC cells in the presence of GLA. We then showed that the downregulation of Murine Double Minute Clone 2 (MDM2) and Ring Finger Protein 6 (RNF6) by GLA was implicated in the GLA-induced inhibition of the GC cells. Furthermore, MDM2 and RNF6 were identified as the targets of miR-3658 that was downregulated in the GC cells and upregulated by GLA. Moreover, it was shown that miR-3658 was hypermethylated in the GC cells, and GLA could rescue the expression of miR-3658 via demethylation by abrogating EZH2-mediated epigenetic silencing. In addition to the miR-3658-MDM2/RNF6 regulatory axis, activation of the SMG1-UPF mRNA decay pathway contributed to the downregulation of MDM2 and RNF6 by GLA in the GC cells. The inhibitory effect of GLA on gastric cancer and the expression of MDM2 and RNF6 was also validated in in vivo study. Our findings suggest that has the therapeutic potential for GC by downregulating oncogenes via posttranscriptional regulation.