Abstract Diabetic nephropathy (DN) is a common chronic complication of diabetes mellitus (DM), and dapagliflozin, a representative drug of sodium-glucose co-transport protein 2 inhibitors (SGLT2i), is a novel hypoglycemic agent for the treatment of type 2 diabetes mellitus (T2DM), which has been shown to reverse microalbuminuria in early type 2 diabetic nephropathy (T2DN), but the mechanism of action remains to be elucidated. In this study, five patients with early T2DN treated in our hospital from October 2020 to May 2021 were selected for the study and were treated with insulin combined with dapagliflozin to lower glucose, and the initial insulin treatment was named as DN group, and the addition of dapagliflozin was named as DN-DAPA group, and another five patients with a healthy physical examination at the same period were selected as the blank control group (NC group). Patients' morning urine samples were collected and processed using iTRAQ unlabeled quantitative proteomics technology. Bioinformatics analysis was performed to obtain 193 differentially expressed proteins. 91 expressions were up-regulated and 72 expressions were down-regulated in the DN group compared with the NC group, and 11 expressions were up-regulated and 26 expressions were down-regulated in the DN-DAPA group compared with the DN group. Five significantly co-expressed protein molecules were screened at P < 0.05 and [logFC] >1.5: SOD1, SLC25A6, S100A13, PPP2R2A, CXCL12. Therefore, these differential proteins are associated with early T2DN injury. Molecularly, dapagliflozin improves mitochondrial oxidative stress and reduces urinary microalbumin excretion in early T2DN patients by inhibiting PPP2R2A and CXCL12/ S100A13 pathways to reverse early T2DN.

维生素D对机体钙磷代谢、细胞生长和分化方面具有十分重要的作用.近几十年来研究证实糖脂代谢、炎症反应及免疫调节等生物过程均有维生素D的参与.机体几乎所有细胞均具有维生素 D 受体(Vitamin D receptor,VDR),如:心肌细胞、胰腺细胞、脂肪细胞等,维生素 D通过与 VDR结合,在机体中发挥调节作用.维生素 D介导了多种疾病的发病.大量研究证实,维生素 D在糖代谢疾病的发病中具有重要作用.维生素 D 对胰岛β细胞还有保护作用,是胰岛β细胞的保护因子之一,对机体血糖平衡和胰岛素的合成分泌过程具有重要作用.

An 82-year-old female patient received monotherapy with nivolumab (240 mg by an IV infusion on the firsr day, 14 days as a cycle) because of multiple metastases of central adenocarcinoma in the right upper lobe of the lung. After 8 cycles of immunotherapy (about 4 months), the patient developed severe nausea and vomiting. Laboratory tests showed random blood glucose 43.2 mmol/L and β-hydroxybutyric acid 5.3 mmol/L. Blood gas analysis showed pH 7.01, bicarbonate root 4.0 mmol/L, alkali residual -22.4 mmol/L, serum potassium 6.1 mmol/L, and lactic acid 2.9 mmol/L. The patient had no previous history of diabetes mellitus. Fulminant type 1 diabetes mellitus due to nivolimab was considered. Nivolumab was stopped and rehydration, hypoglycemia, acidosis correction, and other symptomatic treatments were given. Two days later, her symptoms were improved obviously. Laboratory tests showed fasting plasma glucose 15.8 mmol/L and β-hydroxybutyric acid 0.2 mmol/L. Blood gas analysis showed pH 7.39, bicarbonate root 21.2 mmol/L, alkali residual -3.8 mmol/L, serum potassium 4.3 mmol/L, and lactic acid 1.0 mmol/L.