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Objective To investigate the effect of dapagliflozin on metabolic markers, hepatic fat content, and autonomic nervous function in patients with type 2 diabetes mellitus (T2DM) and metabolic associated fatty liver disease (MAFLD). Methods A total of 90 patients with T2DM and MAFLD who were admitted to The Second Affiliated Hospital of Zhengzhou University from October 2019 to October 2020 were enrolled and randomly divided into control group and dapagliflozin group, with 45 patients in each group. All patients were given conventional treatment before enrollment; the patients in the control group were treated with the original hypoglycemic regimen, and those in the dapagliflozin group were given dapagliflozin in addition to the treatment in the control group. The treatment cycle was 24 weeks. General information was collected before and after treatment, and the two groups were compared in terms of the changes in body mass index (BMI), glycosylated hemoglobin (HbA1c), fasting blood glucose (FPG), blood lipids, serum uric acid (SUA), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), liver function, liver fat content, and heart rate variability after treatment. The paired t -test was used for comparison of normally distributed continuous data within each group, and the independent samples t -test was used for comparison between groups; the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data within each group, and the Mann-Whitney U test was used for comparison between groups. The Chi-square test was used for comparison of categorical data between two groups. Results A total of 43 patients in the dapagliflozin group and 40 patients in the control group completed the study. After 24 weeks of treatment, the dapagliflozin group had significant reductions in BMI, HbA1c, FBG, triglyceride (TG), SUA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), HOMA-IR, and liver fat content ( t =8.781, 8.765, 8.813, 3.485, 6.199, 5.694, 3.428, 6.492, and 4.925, all P < 0.05) and significant increases in high-density lipoprotein cholesterol, standard deviation of all normal R-R intervals (SDNN), standard deviation of average NN intervals (SDANN), root mean square of successive differences, percent of the number whose difference between adjacent NN interval are more than 50 ms (pNN50), high frequency (HF), and low frequency (LF) ( t =-2.055, -6.307, -7.696, -3.388, and -7.928, Z =-3.339 and -3.309, all P < 0.05), while the control group had significant reductions in HbA1c, FBG, and HOMA-IR ( t =9.220, 7.214, and 3.340, all P < 0.05). Compared with the control group after treatment, the dapagliflozin group had significantly lower levels of BMI, HbA1c, TG, SUA, HOMA-IR, ALT, AST, and liver fat content ( t =-4.055, -2.670, -2.056, -2.496, -3.976, -3.703, -2.123, and -5.184, all P < 0.05) and significantly higher levels of SDNN, SDANN, pNN50, LF, and HF ( t =4.136, 5.433, and 5.971, Z =-2.333 and -2.010, all P < 0.05). Conclusion For patients with T2DM and MAFLD, dapagliflozin can reduce BMI, HbA1c, TG, SUA, and liver fat content, improve insulin resistance and liver function, reduce the activity of sympathetic nerve, and regulate autonomic nerve function.
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@#The protective effect and mechanism of Oroxylin A, a naturally occurring compound in Scutellaria baicalensis Georgi, was investigated in this study. Isoproterenol administration to rats triggered classic cardiac failure, as demonstrated by objective parameters of cardiac dysfunction. Intragastric administration of oroxylin A at the dose of 25, 50 and 100 mg/(kg·d)significantly improved deranged cardiac parameters in the isoproterenol-induced heart failure model in a dose-dependent manner. At the same time, oroxylin A markedly ameliorated cardiac histological changes and down-regulated serum levels of various neuroendocrine factors including norepinephrine, aldosterone, brain natriuretic peptide, endothelin 1, angiotensin II and so on. Mechanistically, augmenting autophagy of myocardial cells via the inhibition of AKT1-RPS6KB1 signaling contributed to the improvement of isoproterenol-induced rat heart failure by oroxylin A. Taken together, these results suggest that oroxylin A ameliorates heart failure through promoting autophagy in myocardial cells.
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Cranial magnetic resonance imaging (MRI) examinations were performed in 419 patients with type 2 diabetes mellitus (T2DM) from June to December 2016.The brain white matter lesions were defined by white matter hyperintensity (WMH) in MRI,which was detected in 380 cases (WMH group) and not detected in 39 cases (non-WMH group).The Montreal Cognitive Assessment (MoCA) was used to evaluate the cognitive function.The study showed that there were significant differences in the duration of diabetes,the proportion of hypertension,total cholesterol (TC) and MoCA scores between the two groups (all P＜0.05).The age,duration of diabetes,hypertension and glyclated hemoglobin (HbA1c) were significantly correlated with white matter lesions(OR=1.157,1.116,5.184,1.128;P＜0.05);and the white matter lesions,age,and body mass index (BMI) were significantly correlated with cognitive dysfunction in diabetic patients (OR=2.137,1.175,1.247;P＜0.05).The study result indicates that control of white matter lesions may prevent and improve cognitive dysfunction in T2DM patients.
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Objective To observe the influence of insulin resistance(IR) and isosorbide mononitrate(ISMN) on myocardial cellular apoptosis in spontaneously hypertensive rats (SHR) .Methods Forty male 14‐week old Wistar(W) rats and SHR(S) each were respectively or jointly fed with normal diet (ND) ,high fat and high glucose(HFHG) diet ,normal saline(NS)and ISMN by ga‐vage .Then they were randomly divided into the normal and NS group (normal W and normal S ) ,HFHG and NS group(HFHG W and HFHG S) ,normal and ISMN group(ISMN W and ISMN S) ,HFHG and ISMN group(HI W and HI S) ,with 10 rats in each group .After 12‐week feeding ,carotid arterial blood was collected for detecting blood glucose concentration and insulin level and cal‐culating insulin resistance index (HOMA‐IR);4 myocardial tissue samples were taken for respectively observing the morphology under microscope ,and detecting the NO level ,myocardial Bcl‐2 ,Bax gene and their protein expression levels in myocardial tissue . Results Myocardial NO level ,Bax gene mRNA and related protein levels in the HFHG and ISMN intervention groups were higher than those in the normal group ,while the bcl‐2 gene mRNA and related protein expression were on the contrary ;myocardial tissue NO level ,Bax gene mRNA and related protein expression in the S groups were increased compared with the corresponding W groups ,while the bcl‐2 gene mRNA and related protein expression were on the contrary ;in the HFHG W group ,the myocardial tis‐sue NO level had significantly positive correlation with HOMA‐IR ,and in the ISMN W group ,HOMA‐IR was positively correlated with the NO level in the myocardial tissue .Conclusion Myocardial cellular apoptosis of SHR is increased compared with Wistar rats ;both IR and ISMN can aggravate the apoptosis of SHR myocardial cells ,moreover IR has a mutual induction and reciprocal causation with ISMN .
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Objective To observe the clinical effect of compound danshen dropping pills on the early diabetic kidney disease.Methods A total of 850 type 2 diabetes mellitus (T2DM) patients with diabetic nephropathy (DN) at stage Ⅲ who met the criteria for DN from January 2012 to July 2012,aged 60 to 75 years [mean age (66.6±4.8) years],were retrospectively analyzed and randomized into the treatment group (n=601) and the control group (n=249).All patients received rational hypoglycemic,antihypertensive,lipids-adjusting treatment and the treatment group received compound danshen drop pill (15 pills,tid),additionally.Laboratory indexes such as urine albumin (UA) and urine creatinine (UCR) were examined 24 weeks after treatment.Results The levels of UA and UCR,and the UA/UCR ratio (ACR) in the treatment group were decreased after versus before treatment.The decreases of UA and UCR had significant differences between the treatment and control group [(39.1±78.7) mg/L vs.(14.7±77.1) mg/L,(1.1±4.5) mmol/L vs.(-0.3± 3.6) mmol/L,t=4.15 and 4.86,both P＜0.01].Conclusions The comprehensive treatment combined with compound danshen dropping pills for 24 weeks can more effectively reduce UA and ACR,thereby it has effects in treating DN and delaying the progression of DN.
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Objective To investigate the effect of phosphoinositide-3-kinase inhibitor LY294002 on the differentiation of human embryonic stem cells (HESC) into more mature insulin-producing cells. Methods HESCs were induced to differentiate into insulin-producing cells through five stages. Nicotinamide and B27 (group B27), nicotinamide and LY294002 (group LY) were used to induce the nesting positive cells into mature insulin-producing cells. The morphological change of each stage was observed under microscope , and expressions of insulin, c-peptide, somatostatin and glucagon were identified by immunofluorescence staining. Results After 14 days in stage 5 , there was no significant difference in rate of insulin positive cells between group LY and group B27 (P﹥0.05), but rates of somatostatin and glucagon positive cells in group LY were lower than those in group B27(P﹤0.05). Furthermore, the co-stained rate of somatostatin and insulin in group LY was also lower than that in group B27 (P﹤0.05). Conclusion HESCs can be induced to differentiate into more mature insulin-producing cells by phosphoinositide-3-kinase inhibitor LY294002 in serum-free culture medium.