RESUMO
Obesity is a high-risk factor for such comorbidities as cardiovascular disease, several types of cancer, and type 2 diabetes; however not all individuals with obesity have such complications. Approximately 20% of individuals with obesity are metabolically healthy. This study focused on differences between obese individuals with and without type 2 diabetes (T2D+ and T2D-, respectively) on the transcriptome level. Subjects included were 35 T2D- patients with obesity and 35 T2D+ patients with obesity with the same body mass index (BMI). The study was based on the transcription analysis of mRNA and microRNAs (miRs) by RNAseq. In the first step, we performed RNAseq of miRs, in the second step, we analyzed only those mRNA, which appeared targets for significant miRs from the first step. All RNAseq results were validated by qPCR. There were seven miRs differently expressed with adjusted p-value <0.1, which were confirmed by qPCR. Five among them: miR-204-5p, miR125b-5p, miR-125a-5p, miR320a, miR-99b-were upregulated in T2D+ patients with obesity, while only two miRs, miR-23b-3p, and miR197-3p, were increased in T2D- patients with obesity. These seven miRs target two groups of genes: matrix metalloproteinases and TGFß signal pathway genes. According to the results of transcriptome analysis, the main difference between T2D+ and T2D- patients with obesity was in adipogenesis and fibrosis regulation by matrix metalloproteinases and SMAD4-RUNX2 signal cascade. Based on the data about transcription profiles of both groups, we suggested that the process of fibrosis in T2D+ patients with obesity is more pronounced than in T2D- patients with obesity.
RESUMO
AIMS: To compare glucose - lowering and weight reduction capacity of bypass operations (gastric bypass (GB), biliopancreatic diversion (BPD) vs GLP-1 agonist liraglutide 3.0 mg (models of maximum incretin effect) for 6 months. MATERIALS AND METHODS: 46 patients with type 2 diabetes and long history (≥10 years) of obesity were divided into 2 groups: surgery - group (n=23) and liraglutide - group (n=23), where liraglutide 3.0 mg in dose - escalation manner was added to baseline glucose - lowering therapy. Anthropometric parameters, HbA1c and insulin resistance (IR) by hyperinsulinemic euglycemic clamp (M-value) were measured before and 16 weeks after the intervention. With the stabilization of glycemia (≤6.5 mmol/l at fasting state, ≤8 mmol/l postprandial) the initial glucose - lowering therapy was canceled. RESULTS AND DISCUSSION: Both surgery and liraglutide 3.0 mg provided target HbA1c in 16 weeks. Bypass operations led to elimination of glucose - lowering therapy in 82.6% patients due to a more significant weight reduction and decrease in IR. In liraglutide - group previous glucose - lowering therapy was cancelled in 78.3% patients, mainly receiving baseline mono - and two - component therapy. The most significant difference between interventions was achieved in BMI (-8.9 kg in surgery group vs -3.8 kg in liraglutide group, p.
