Sodium glucose cotransporter2 inhibitors for type 1 diabetes mellitus: A meta-analysis of randomized controlled trials.

AIMS: Sodium glucose cotransporter2 (SGLT2) inhibitors are controversial in the treatment of type 1 diabetes mellitus (T1DM). This study is a systematic evaluation of the safety of SGLT2 inhibitors usage in T1DM. METHODS: Comprehensive literature search in six databases from inception to September 2022. Randomized controlled trials (RCTs) of T1DM treated with SGLT2 inhibitor vs. placebo were included. Data were extracted from the literature that met the inclusion criteria. After quality evaluation by the Cochrane risk bias assessment tool, meta-analysis was performed using Revman 5.4 and Stata 17.1. RESULTS: The study consisted of 16 RCTs with 7192 patients. The results indicated that SGLT2inhibitors reduce glycated hemoglobin (HbA1c, Mean difference (MD)- 0.29%, P < 0.05), fasting plasma glucose (FPG, MD-0.85 mmol/L, P < 0.05), mean amplitude of glucose excursions (MAGE, 15.75 mg/dL, P < 0.05), body weight (MD-3.49 kg, P < 0.05), and total insulin dosage (MD-7.14 IU/day, P < 0.05). Furthermore, cautious SGLT2 inhibitors did not induce the risk of hypoglycemia (RR1.00, P = 0.86), urinary tract infections (RR1.02, P = 0.085), and diarrhea (RR1.34, P = 0.523). CONCLUSION: Based on this meta-analysis, SGLT22 inhibitors reduce insulin dosage without increasing the risk of hypoglycemia and diabetic ketoacidosis for type 1 diabetes mellitus in 1month.

Identifying key genes for diabetic kidney disease by bioinformatics analysis.

BACKGROUND: There are no reliable molecular targets for early diagnosis and effective treatment in the clinical management of diabetic kidney disease (DKD). To identify novel gene factors underlying the progression of DKD. METHODS: The public transcriptomic datasets of the alloxan-induced DKD model and the streptozotocin-induced DKD model were retrieved to perform an integrative bioinformatic analysis of differentially expressed genes (DEGs) shared by two experimental animal models. The dominant biological processes and pathways associated with DEGs were identified through enrichment analysis. The expression changes of the key DEGs were validated in the classic db/db DKD mouse model. RESULTS: The downregulated and upregulated genes in DKD models were uncovered from GSE139317 and GSE131221 microarray datasets. Enrichment analysis revealed that metabolic process, extracellular exosomes, and hydrolase activity are shared biological processes and molecular activity is altered in the DEGs. Importantly, Hmgcs2, angptl4, and Slco1a1 displayed a consistent expression pattern across the two DKD models. In the classic db/db DKD mice, Hmgcs2 and angptl4 were also found to be upregulated while Slco1a1 was downregulated in comparison to the control animals. CONCLUSIONS: In summary, we identified the common biological processes and molecular activity being altered in two DKD experimental models, as well as the novel gene factors (Hmgcs2, Angptl4, and Slco1a1) which may be implicated in DKD. Future works are warranted to decipher the biological role of these genes in the pathogenesis of DKD.

miR-223-3p mediates the diabetic kidney disease progression by targeting IL6ST/STAT3 pathway.

Diabetic kidney disease (DKD), the most pervasive complication in diabetic patients, has become a major health threat to the aging population. Our previous miRNA profiling identified hsa-miR-223-3p as a dysregulated miRNA in the DKD samples, which may serve as a biomarker for DKD diagnosis. However, the specific mechanism of miR-223-3p in the pathogenesis of DKD remains to be elucidated. In this study, we first verified that miR-223-3p level was significantly decreased in the in vitro cell model and in vivo db/db DKD model, accompanied with endothelial cell damage. Importantly, inhibiting the expression of miR-223-3p exacerbated high-glucose induced damages in Human Umbilical Vein Endothelial Cells (HUVECs) and Human Renal Glomerular Endothelial Cells (HRGECs), while miR-223-3p overexpression showed the opposite effect. We further demonstrated that miR-223-3p associated with IL6T mRNA and attenuated the progression of DKD by suppressing the downstream STAT3 activation, indicative of the implication of miR-223-3p/IL6T/STAT3 axis in the pathogenesis of DKD.