Comparing the effects of empagliflozin and liraglutide on lipid metabolism and intestinal microflora in diabetic mice.

Background and Objectives: Recent studies have shown that the imbalance of intestinal flora is related to the occurrence and progression of diabetic nephropathy (DN) and can affect lipid metabolism. Sodium-dependent glucose transporters 2 (SGLT2) inhibitor and glucagon-like peptide-1 (GLP-1) receptor agonist are commonly used hypoglycemic drugs and have excellent renal safety. The purpose of this study was to compare the protective effects of empagliflozin and liraglutide on kidneys, lipid metabolism, and intestinal microbiota in diabetic mice. Methods: We established a mouse model of type two diabetes by feeding rats a high-fat diet (HFD) followed by an intraperitoneal injection of STZ. The mice were randomly divided into groups: normal control (NC), diabetic model (DM), liraglutide treatment (LirT), empagliflozin treatment (EmpT), and liraglutide combined with empagliflozin treatment (Emp&LirT) groups. Blood glucose, lipids, creatinine, and uric acid, as well as urinary nitrogen and albumin levels were measured. The renal tissues were subjected to HE, PAS and Masson's staining. These parameters were used to evaluate renal function and histopathological changes in mice. Mice feces were also collected for 16sRNA sequencing to analyze the composition of the intestinal flora. Results: All the indexes related to renal function were significantly improved after treatment with drugs. With respect to lipid metabolism, both drugs significantly decreased the serum triglyceride levels in diabetic mice, but the effect of liraglutide on reducing serum cholesterol was better than that of empagliflozin. However, empagliflozin had a better effect on the reduction of low-density lipoproteins (LDL). The two drugs had different effects on intestinal flora. At the phylum level, empagliflozin significantly reduced the ratio of Firmicutes to Bacteroidota, but no effect was seen with liraglutide. At the genus level, both of them decreased the number of Helicobacter and increased the number of Lactobacillus. Empagliflozin also significantly increased the abundance of Muribaculaceae, Muribaculum, Olsenella, and Odoribacter, while liraglutide significantly increased that of Ruminococcus. Conclusion: Liraglutide and empagliflozin were both able to improve diabetes-related renal injury. However, the ability of empagliflozin to reduce LDL was better compared to liraglutide. In addition, their effects on the intestine bacterial flora were significantly different.

The levels of hemoglobin are positively associated with arterial stiffness in community-dwelling Chinese adults.

BACKGROUND AND AIMS: Hemoglobin (Hb) concentrations are known to be related to cardiovascular diseases. This study investigated the association between Hb levels and arterial stiffness, as assessed by measurement of the brachial-ankle pulse wave velocity (baPWV). METHODS AND RESULTS: 3576 adults (2139 males and 1437 females) from the general Chinese population who had their physical check-ups in the health examination centers of Jiangmen Central Hospital were enrolled into the study. The anthropometrics and laboratory data as well as the baPWV and Hb levels were subsequently obtained. Age-adjusted partial correlation and multivariable stepwise linear regression analyses were used to evaluate the relationships between Hb and baPWV for men and women separately. In both sexes, Hb levels were positively associated with body mass index, total cholesterol, low-density lipoprotein cholesterol, triglycerides, glutamic-pyruvic transaminase, γ-glutamyltranspeptidase, uric acid and baPWV, but negatively correlated with the estimated glomerular filtration rate. Multivariable linear regression analysis showed that Hb was significantly and independently associated with arterial stiffness in men (ß = 0.043, 95% CI 0.010-0.077, p < 0.05) and women (ß = 0.035, 95% CI 0.001-0.069, P < 0.05), after adjustment for confounding factors. CONCLUSION: The data indicate that high Hb concentration significantly correlate with increased baPWV in general Chinese population.

Guava Leaf Extract Attenuates Insulin Resistance via the PI3K/Akt Signaling Pathway in a Type 2 Diabetic Mouse Model.

BACKGROUND AND OBJECTIVE: Insulin resistance is well known to exhibit essential effects on the progression of diabetes mellitus (DM). Guava leaf was also reported to exhibit anti-diabetic effects including decreasing blood glucose. Therefore, this present study aims to explore the role guava leaf extract (GLE) plays in insulin resistance and its mechanism of action via the PI3K/Akt signaling pathway. METHODS: KK-Ay mice is a spontaneous genetic type 2 diabetes mouse model induced by feeding a high fat and high sugar diet. Mice were randomly assigned into three groups: diabetic mice (DM), DM + MET (diabetic mice treated with metformin) and DM + GLE (diabetic mice treated with GLE) groups. After 8 weeks of treatment, body weight and levels of fasting plasma glucose (FPG), fasting insulin and lipids in plasma were measured. Mice were sacrificed and mRNA and protein expression of insulin receptor substrate1 (IRS1), phosphatidylinositol 3-kinase (PI3K) and serine/threonine kinase protein B (Akt) in livers were measured. RESULTS: GLE markedly reduced body weight, FPG, fasting insulin and insulin resistance index but increased the insulin sensitivity index of diabetic KK-Ay mice. Moreover, GLE upregulated the expression of IRS-1, PI3K and Akt mRNAs in livers of diabetic KK-Ay mice. In addition, GLE also elevated IRS-1, PI3K, Akt, p-PI3K and p-Akt protein expression in their livers. The results of the DM + MET group were similar to those of the DM + GLE group. CONCLUSION: GLE plays anti-diabetic roles by ameliorating insulin resistance in KK-Ay diabetic mice and this is related to the activation of PI3K/Akt signaling pathway.

Comparison of Hemoglobin Alc, Glycated Albumin and Fasting Plasma Glucose for Prediction of Arterial Stiffness in Chinese Adults.

OBJECTIVE: Although diabetes is closely related to cardiovascular disease, there are some disputes whether diabetes can promote arterial stiffness. Therefore, the objective of this study is to compare the predictive abilities of related-glycemic markers including fast plasma glucose (FPG), glycated hemoglobin (HbAlc) and glycated albumin (GA) for the arterial stiffness. METHODS: In the present study, 3640 subjects (2171 men, 1469 women) were enrolled, and anthropometrics, brachial ankle pulse wave velocity (baPWV) and other laboratory data were obtained. Spearman correlation and multivariate logistic regression analyses were used to evaluate the relationships between FPG, HbAlc, GA and baPWV. RESULTS: Age, BMI, blood pressure, blood lipids, γ-Glutamyl transpeptidase, uric acid, hypersensitive C-reactive protein, baPWV, FPG, HbAlc, GA, estimated glomerular filtration rate and the incidences of diabetes and hypertension in high baPWV group were much greater than those in control group. Moreover, these above three glycemic markers were positively related to baPWV, and the correlation coefficient of HbAlc was the highest. After adjusting the above factors, HbAlc and FPG, but not GA, were still positively associated with baPWV regardless of diabetes status. CONCLUSION: Our data demonstrated that, regardless of diabetes status, HbAlc and FPG were superior to GA for predicting arterial stiffness and HbAlc had the highest correlation with arterial stiffness, revealing that HbAlc may be regarded as an early diagnosis marker for atherosclerosis.

Effects of sevoflurane on NF-кB and TNF-α expression in renal ischemia-reperfusion diabetic rats.

BACKGROUND: Ischemia-reperfusion (I/R) injury is the main reason of acute renal failure. However, inflammatory response and cell apoptosis are important mechanisms implicated in I/R injury. Recent studies indicated that nuclear factor kappa B (NF-кB) and tumor necrosis factor α (TNF-α) are both involved in these mechanisms. Sevoflurane reduces NF-кB and TNF-α expression in rats' heart and decreases their renal I/R injury. However, few studies are available regarding the effect of sevoflurane on kidney of diabetic rats. Therefore, the aim of this study was to evaluate sevoflurane effect on NF-кB and TNF-α expression in diabetic rats to decrease renal I/R injury. METHODS: Male Sprague-Dawley rats were divided into five groups: Group A, non-diabetic rats underwent sham operation; Group B, non-diabetic rats with renal I/R injury; Group C, diabetic rats underwent sham operation; Group D, diabetic rats with renal I/R injury; Group E, diabetic rats with renal I/R injury after sevoflurane pretreatment. Rats of Group E were exposed to 2.5% sevoflurane for 30 min. After 24 h, creatinine (Cr), blood urea nitrogen (BUN), renal cell apoptosis, and NF-кB and TNF-α expression in kidney were assessed. RESULTS: Renal cell apoptosis, NF-кB, and TNF-α expression were significantly higher in diabetic rats with renal I/R injury group compared to diabetic rats that underwent sham operation (P < 0.01). These changes were significantly reduced by sevoflurane (P < 0.01). CONCLUSION: Sevoflurane exerted a protective effect against renal injury by lowering the expression of NF-кB and TNF-α in renal I/R diabetic rats.

Lipoprotein ratios are better than conventional lipid parameters in predicting arterial stiffness in young men.

Although dyslipidemia is associated with cardiovascular disease, there are conflicting data about the role of serum lipids and their ratios in promoting arterial stiffness. The authors aimed to compare serum lipid profiles to predict arterial stiffness, which was assessed by brachial-ankle pulse wave velocity in young Chinese men. A total of 1015 participants aged 18 to 44 years without serious comorbidities were recruited for conventional detection. Anthropometrics, brachial-ankle pulse wave velocity, serum lipids, and other laboratory data were measured. Univariate analysis and multivariate logistic regression were performed to examine the relationship between serum lipid profiles and brachial-ankle pulse wave velocity. Participants with high brachial-ankle pulse wave velocity exhibited higher levels of total cholesterol, triglyceride (TG), low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (HDL-C), total cholesterol/HDL-C, TG/HDL-C, low-density lipoprotein cholesterol/HDL-C, and non-HDL-C/HDL-C. The subsequent multivariable logistic regression showed that TG/HDL-C, total cholesterol/HDL-C, non-HDL-C/HDL-C, and TG significantly increased the risk for arterial stiffness after adjustment for confounding factors. Results indicate that lipid ratios are superior to conventional lipid parameters for predicting arterial stiffness in young men and that the TG/HDL-C ratio has the strongest association with arterial stiffness.

Triglyceride to HDL-C ratio and increased arterial stiffness in apparently healthy individuals.

OBJECTIVES: High triglycerides and low high density lipoprotein cholesterol are important cardiovascular risk factors. Triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) has been reported to be useful in predicting cardiovascular disease. Brachial-ankle pulse wave velocity (baPWV) is a valid and reproducible measurement by which to assess arterial stiffness and a surrogate marker of atherosclerosis. However, there is limited evidence about the relationship between them. Therefore, we tested the hypotheses that TG/HDL-C is associated with baPWV in healthy individuals. METHODS: Fasting lipid profiles, baPWV and clinical data were measured in 1498 apparently healthy, medication-free subjects (926 men, 572 women) who participated in a routine health screening from 2011 to 2013. Participants were stratified into quartiles of TG/HDL-C ratio. BaPWV > 1400 cm/s was defined as abnormal baPWV, Multivariable logistic regression was used to identify associations of TG/HDL-C quartiles and baPWV, after adjusting for the presence of conventional cardiovascular risk factors. RESULTS: In both genders, we observed positive relationships between TG/HDL-C quartiles and BMI, systolic BP, diastolic BP, fasting glucose, total cholesterol, LDL-C, triglycerides, uric acid, and percentages of high baPWV. Multivariable logistic regression revealed that baPWV abnormality OR value of the highest TG/HDL-C quartiles was 1.91 (95% CI: 1.11-3.30, P < 0.05) and 2.91 (95% CI: 1.02-8.30, P < 0.05) in male and female after adjusting for age, systolic BP, diastolic BP, BMI, fasting plasma glucose, LDL-C, uric acid and estimated glomerular filtration rate when compared with the lowest TG/HDL-C quartiles. CONCLUSION: Increased TG/HDL-C was independently associated with baPWV abnormality in apparently healthy individuals.

[Effect of TIEG-siRNA on Smad2, p-smad2 and collagen IV in diabetic nephropathy].

OBJECTIVE: To investigate the effect of TIEG-siRNA on Smad2, p-smad2 and collagen IV in diabetic nephropathy rats induced by streptozotocin (STZ). METHODS: Ten Sprague-Dawley rats injected with STZ were randomly divided into TIEG-siRNA and Control groups. Other five normal rats were used as control. Each of the TIEG-siRNA and Control groups were injected with TIEG-siRNA and Control 0.5 ml via tail vein at 0 and 72 hours respectively. All rats were sacrificed at week 4 after a successful modeling. To confirmed the efficacy of TIEG-siRNA in rat kidney, the TIEG levels were determined by fluorescence quantitative PCR. The expressions of Smad2, p-smad2 and collagen IV protein were detected by immunohistochemical method while Smad2 and p-smad2 examined by Western blot. RESULTS: The TIEG levels were greatly down-regulated in the TIEG-siRNA treated group (0.0636 ± 0.0066) versus the empty vector treated group (0.1054 ± 0.0111) (P < 0.05). The immunohistochemical semi-quantitative method indicated that there was a decrease in the TIEG-siRNA treated group versus the empty vector treated group: (2.13 ± 0.19)% vs (2.53 ± 0.34)% in Smad2, (21.77 ± 2.00)% vs (27.03 ± 2.51)% in p-smad2 and (3.67 ± 0.42)% vs (4.85 ± 0.43)% in collagen IV. Western blot also showed that smad2 in the TIEG-siRNA treated group (0.32 ± 0.09) was much lower than that in the empty vector treated group (0.50 ± 0.04). And p-smad2 in the TIEG-siRNA treated group (0.16 ± 0.01) was much lower than that in the empty vector treated group (0.32 ± 0.02) (P < 0.05). CONCLUSION: TIEG-siRNA may be useful in preventing the progression of diabetic nephropathy through influencing the expression of Smad2 and its activation and down-regulating collagen IV.