Background. Our study aimed to observe the effect of sodium glucose cotransporter-2 (SGLT2) inhibitor dapagliflozin on diabetic atherosclerosis and investigate the subsequent mechanism. Methods. Aortic atherosclerosis was induced in streptozotocin induced diabetic ApoE−/− mice by feeding with high-fat diet, and dapagliflozin was administrated intragastrically for 12 weeks as treatment. Effects of dapagliflozin on indices of glucose and fat metabolism, IL-1β, IL-18, NLRP3 protein levels, and the reactive oxygen species (ROS) were measured. The atherosclerosis was evaluated by oil red O and hematoxylin-eosin staining. The effects of dapagliflozin on the IL-1β production in culturing primary macrophages of wild type and NLRP3−/− knockout mice were investigated for mechanism analyses. Results. Dapagliflozin treatment showed favorable effects on glucose and fat metabolism, partially reversed the formation of atherosclerosis, inhibited macrophage infiltration, and enhanced the stability of lesion. Also, reduced production of IL-1β, IL-18, NLRP3 protein, and mitochondrial ROS in the aortic tissues was detected with dapagliflozin treatment. In vitro, NLRP3 inflammasome was activated by hyperglucose and hyperlipid through ROS pathway. Conclusions. Dapagliflozin may be of therapeutic potential for diabetic atherosclerosis induced by high-fat diet, and these benefits may depend on the inhibitory effect on the secretion of IL-1β by macrophages via the ROS-NLRP3-caspase-1 pathway.

Objective To investigate the microbial distribution and drug susceptibility among diabetic foot ulcers (DFUs) with different Wagner grades and between acute and chronic DFUs. Methods. We enrolled 428 DFU patients who were hospitalized and treated in the Southwest Hospital. We collected deep ulcer secretion for microbial culture and drug susceptibility tests and analyzed the results. We reexamined 67 patients with poor anti-infection efficacy and analyzed microbial species. Results: The 354 positive samples included 201 cases (56.8%) of single-pathogen infections and 153 cases (43.2%) of multiple-pathogen infections before antibiotic therapy. A total of 555 strains were cultivated, including 205 (36.9%) strains of gram-positive organisms (GPOs), 283 (51.0%) gram-negative bacilli (GNB), and 67 (12.1%) fungal strains. In terms of distribution, patients with different Wagner grades had different bacterial composition ratios (P < 0.01). Patients with Wagner grades 3–5 mainly had GNB. The specimens from chronic ulcer wounds were primarily GNB (54.2%), whereas fungi accounted for 14.4% of the infections; the distribution was significantly different from that of acute ulcers (P < 0.01). The susceptibility tests showed that the Staphylococcus genus was more susceptible to vancomycin, linezolid, and tigecycline. Tobramycin was the most effective drug (97%) for the treatment of Escherichia coli, followed by ertapenem (96.4%), imipenem (93.5%), and cefotetan (90%). Most of the remaining GNB were susceptible to antibiotics such as carbapenems, aminoglycosides, fluoroquinolones, ceftazidime, cefepime, and piperacillin-tazobactam (>63.2%). After antibiotic therapy, the positive rate of microbial culture was 52.2%, and the proportion of GNB and fungi increased to 68.9% and 20%. Conclusion The distribution and types of bacteria in diabetic foot infection (DFI) patients varied with the different Wagner classification grades, courses of the ulcers, and antibiotic therapy. Multidrug resistance were increased, and the clinical treatment of DFIs should select the most suitable antibiotics based on the pathogen culture and drug susceptibility test results.

Background: Diabetes mellitus (DM) is considered as a risk factor for the progress of liver diseases.After tissue damage, there is the highest amplitude of ubiquitously sterile inflammatory response in the liver, resulting in a major clinical consequence concerning a high prevalence of steatohepatitis in DM patients. This study aimed to investigate the inhibitory efficacy of dapagliflozin (DAPA), a sodium glucose cotransporter-2 (SGLT2) inhibitor, on experimental steatohepatitis with DM.Methods: DM-steatohepatitis model was established by dual intraperitoneal injection of streptozotocin (STZ) and feeding with the high-fat diet (HFD) in apolipoprotein E-deficient (ApoE -/-) mice (n=40). The mice were concurrently treated with DAPA (1 mg/kg/d) by gavage for 12 weeks.Results: In ApoE -/mice, dual HFD/STZ dramatically induced hepatic damage and inflammation as compared with HFD alone. DAPA treatment was effective to protect from hepatic damage and inflammation in dual HFD/STZ treated ApoE -/mice. DAPA also significantly the probability decreased the blood glucose, hepatic lipid accumulation, liver steatosis, and fibrotic response in dual HFD/STZ treated ApoE -/mice. Further mechanistic investigations indicated that the protection of DAPA on diabetic liver injury was associated with the suppressed production of hepatic reactive oxygen species (ROS) and malondialdehyde (MDA) and the inhibited activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome.Conclusions: These data demonstrate the efficacy of DAPA for protecting liver damage, inflammation and steatosis from experimental steatohepatitis with DM, and indicate a possible involvement of the inhibited activity of ROS-NLRP3 inflammasome.

Malignant tumors are a major cause of death, and their incidence is increasing worldwide. Although the survival rate for some cancers has improved, treatments for other malignant tumors are limited, and their mortality rate continues to increase. People with type 2 diabetes have a higher risk of malignant tumors and a higher mortality rate than those without diabetes. Metformin is a commonly used hypoglycemic drug. In recent years, a growing number of studies have indicated that metformin has antitumor effects and increases the sensitivity of malignant tumors to chemotherapy. However, the effect of metformin on different tumors is currently controversial, and the mechanism of metformin’s antitumor action is not fully understood. Insights into the effect of metformin on malignant tumors and the possible mechanism may contribute to the development of antitumor drugs.

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The aims of this study were to use cardiovascular magnetic resonance (CMR) cine to assess left atrium (LA) and left ventricle (LV) function and structure in normotensive type 2 diabetes mellitus (T2DM) patients and to identify the most sensitive index of those T2DM-related cardiac changes. Fifty T2DM patients with normotension (25 males, age 54.7 ± 8.7 years, duration of diabetes: 7.5 ± 5.1 years) and 35 controls (16 males, age: 52.2 ± 13.2 years) were prospectively enrolled. All patients were scanned using CMR four- and two-chamber long-axis cine to assess LA and LV structure and function. Normotensive T2DM patients were associated with decreased LA total ejection fraction (EF), passive EF and LV end diastolic volume, normal LA active EF and LV myocardial mass and increased LV mass/volume (M/V). LA total EF and passive EF correlated with body mass index, duration of diabetes and M/V. To differentiate between diabetic patients and healthy controls, area under the receiver operating characteristic (ROC) curve (AUC) values were calculated to be 0.763, 0.706, 0.647 and 0.649 for LA passive EF, total EF, LVEDV and M/V, respectively. The addition of LA total EF, LVEDV, M/V and the combination thereof did not significantly improve AUC values in a model containing LA passive EF. Normotensive T2DM patients were associated with LA decreased total ejection fraction, decreased passive EF and LV concentric remodeling. Among these indices, LA passive EF was the most sensitive to T2DM-related LA function changes.

Background. Diabetic cardiomyopathy (DCM) is always accompanied with alteration of left ventricular structure and function. The aims of this study were to assess the structural remodelling in patients with DCM by cardiovascular magnetic resonance (CMR) and correlation of structural remodelling with severity of DCM. Methods. Twenty-five patients (53.8 ± 8.8 years, 52.0% males) with DCM and thirty-one normal healthy controls (51.9 ± 13.6 years, 45.2% males) were scanned by CMR cine to assess function and structure of left ventricular. Length of diabetic history and results of cardiac echocardiography (E′, A′, and E′/A′) were also measured. Results. Compared with normal controls group, DCM group was associated with significantly increased ratio of left ventricular mass at end diastole to end-diastolic volume (MVR) (P < 0.05) and no significant difference was in mass at end diastole (P > 0.05). The ratio correlated with both length of diabetic history and echocardiographic Doppler tissue imaging E′ (all P < 0.05). Conclusions. CMR can be a powerful technique to assess LV remodelling, and MVR may be considered as an imaging marker to evaluate the severity of LV remodelling in patients with DCM.