RESUMO
INTRODUCTION: We aim to evaluate the efficacy and safety of pioglitazone/metformin fixed-dose combination (FDC) versus uptitrated metformin in patients with type 2 diabetes mellitus (T2DM) without adequate glycemic control. METHODS: A total of 304 patients were recruited from 15 hospitals in China and randomly assigned (1:1) to the test group (pioglitazone/metformin FDC, 15/500 mg) or the control group (uptitrated metformin, 2000-2500 mg/day). The primary endpoint was the proportion of patients with glycated hemoglobin A1c (HbA1c) ≤ 6.5% and ≤ 7.0% at week 16. The secondary outcomes included the change from baseline in glucose, serum lipids, and liver function. Full analysis set (FAS) and per-protocol set (PPS) were used for analyses. RESULTS: In the test group, 103 (69.59%) patients reached HbA1c ≤ 7.0% (FAS, P = 0.009), with 68 (45.95%) patients achieved HbA1c ≤ 6.5 (FAS, P = 0.043). More reduction in HbA1c, homeostatic model assessment for insulin resistance, and diastolic pressure was found. Bodyweight, body mass index, and high-density lipoprotein cholesterol increased markedly. The changes of triglycerides, alanine transaminase, aspartate aminotransferase, and high-sensitivity C-reactive protein decreased noticeably. There were no significant differences in rates of adverse events between the two groups. CONCLUSIONS: Pioglitazone/metformin FDC was superior to uptitrated metformin among patients with T2DM without adequate glycemic control. TRIAL REGISTRATION NUMBER: This trial is registered with the Chinese Clinical Trial Registry (ChiCTR1900028606).
RESUMO
BACKGROUND: Baduanjin, a traditional Chinese exercise therapy, has been widely used in China to treat type 2 diabetes (T2DM) with depression (DD). However, the underlying mechanism of Baduanjin in anti-DD is unclear. This study was focused on investigating the effects of Baduanjin on symptoms of depression and blood glucose in patients with DD and the underlying mechanism. METHODS: We performed a 12-week Baduanjin intervention on patients with DD and longitudinally compared the differential expressions of lncRNAs, circRNAs, and mRNAs between pre- (BDD) and post- (ADD) Baduanjin intervention in the same group. Subsequently, Gene Ontology (GO) and pathway analysis was performed to investigate the function of differentially expressed mRNAs. Finally, Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was used to verify the sequencing result and the mRNA-lncRNA regulatory network was constructed. RESULTS: The blood glucose level, depression index scores, and PHQ9 scores of the patients with DD were significantly decreased (P < 0.05) after Baduanjin intervention. Compared to BDD, 207 lncRNAs, 266 circRNAs, and 610 differentially expressed mRNAs were identified in ADD. Kyoto Encyclopedia of Genes and Genomes (KEGG) and GO showed that the significantly dysregulated mRNAs were mainly involved in immune function and inflammatory response pathways, and various signaling pathways including IL-17 and TNF. In addition, we selected five differentially expressed lncRNAs to construct an lncRNA-mRNA regulatory network, and found a total of 1045 mRNAs associated with them. CONCLUSIONS: Our research is the first systematic profiling of mRNA, lncRNA, and circRNA in patients of ADD and BDD, and provides valuable insights in the potential mechanism of Baduanjin in anti-DD. Further, it was confirmed that Baduanjin is a safe and effective intervention for patients with DD because it can effectively ameliorate the symptoms of depression and blood glucose levels in patients with DD by regulating the dysregulated expression of lncRNA, mRNA, and circRNA.
RESUMO
This study sought to identify sources of the reduced fertility of men with type 2 diabetes mellitus. Significant reductions in semen volume, sperm concentration, and total sperm count were observed in diabetic individuals, while transmission electron microscopy revealed that the structure of mitochondria in the tail of sperm from diabetic patients was damaged. Proteins potentially associated with these sperm defects were identified using proteomics. Isobaric tagging for relative and absolute quantitation labeling and high-performance liquid chromatography-tandem mass spectrometry allowed us to identify 357 proteins significantly differentially expressed in diabetic versus control semen (>1.2 or <0.83). According to gene ontology enrichment and pathway analyses, many of these differentially expressed proteins are associated with sperm function, including binding of sperm to the zona pellucida and proteasome function; of particular interest, half of these proteins were related to mitochondrial metabolism. Protein-interaction networks revealed that a decrease in Cystatin C and Dipeptidyl peptidase 4 in the mitochondria may be sources of the decreased motility of sperm from diabetic patients.