Comparative efficacy of sodium glucose cotransporter-2 inhibitors in the management of type 2 diabetes mellitus:A real-world experience

BACKGROUND Sodium glucose cotransporter-2 inhibitors(SGLT-2i)are a class of drugs with modest antidiabetic efficacy,weight loss effect,and cardiovascular benefits as proven by multiple randomised controlled trials(RCTs).However,real-world data on the comparative efficacy and safety of individual SGLT-2i medications is sparse.AIM To study the comparative efficacy and safety of SGLT-2i using real-world clinical data.METHODS We evaluated the comparative efficacy data of 3 SGLT-2i drugs(dapagliflozin,canagliflozin,and empagliflozin)used for treating patients with type 2 diabetes mellitus.Data on the reduction of glycated hemoglobin(HbA1c),body weight,blood pressure(BP),urine albumin creatinine ratio(ACR),and adverse effects were recorded retrospectively.RESULTS Data from 467 patients with a median age of 64(14.8)years,294(62.96%)males and 375(80.5%)Caucasians were analysed.Median diabetes duration was 16.0(9.0)years,and the duration of SGLT-2i use was 3.6(2.1)years.SGLT-2i molecules used were dapagliflozin 10 mg(n=227;48.6%),canagliflozin 300 mg(n=160;34.3%),and empagliflozin 25 mg(n=80;17.1).Baseline median(interquartile range)HbA1c in mmol/mol were:dapagliflozin-78.0(25.3),canagliflozin-80.0(25.5),and empagliflozin-75.0(23.5)respectively.The respective median HbA1c reduction at 12 months and the latest review(just prior to the study)were:66.5(22.8)&69.0(24.0),67.0(16.3)&66.0(28.0),and 67.0(22.5)&66.5(25.8)respectively(P<0.001 for all comparisons from baseline).Significant improvements in body weight(in kilograms)from baseline to study end were noticed with dapagliflozin-101(29.5)to 92.2(25.6),and canagliflozin 100(28.3)to 95.3(27.5)only.Significant reductions in median systolic and diastolic BP,from 144(21)mmHg to 139(23)mmHg;(P=0.015),and from 82(16)mmHg to 78(19)mmHg;(P<0.001)respectively were also observed.A significant reduction of microalbuminuria was observed with canagliflozin only[ACR 14.6(42.6)at baseline to 8.9(23.7)at the study end;P=0.043].Adverse effects of SGLT-2i were as follows:genital thrush and urinary infection-20(8.8%)&17(7.5%)with dapagliflozin;9(5.6%)&5(3.13%)with canagliflozin;and 4(5%)&4(5%)with empagliflozin.Diabetic ketoacidosis was observed in 4(1.8%)with dapagliflozin and 1(0.63%)with canagliflozin.CONCLUSION Treatment of patients with SGLT-2i is associated with statistically significant reductions in HbA1c,body weight,and better than those reported in RCTs,with low side effect profiles.A review of large-scale real-world data is needed to inform better clinical practice decision making.

Sodium-dependent glucose transporter 2 inhibitors effects on myocardial function in patients with type 2 diabetes and asymptomatic heart failure

BACKGROUND Sodium-dependent glucose transporter 2 inhibitors(SGLT2i)have shown efficacy in reducing heart failure(HF)burden in a very heterogeneous groups of patients,raising doubts about some contemporary assumptions of their mechanism of action.We previously published a prospective observational study that evaluated mechanisms of action of SGLT2i in patients with type 2 diabetes who were in HF stages A and B on dual hypoglycemic therapy.Two groups of patients were included in the study:the ones receiving SGLT2i as an add-on agent to metformin and the others on dipeptidyl peptidase-4 inhibitors as an add-on to metformin due to suboptimal glycemic control.AIM To evaluate the outcomes regarding natriuretic peptide,oxidative stress,inflammation,blood pressure,heart rate,cardiac function,and body weight.METHODS The study outcomes were examined by dividing each treatment arm into two subgroups according to baseline parameters of global longitudinal strain(GLS),N-terminal pro-brain natriuretic peptide,myeloperoxidase(MPO),high-sensitivity C-reactive protein(hsCRP),and systolic and diastolic blood pressure.To evaluate the possible predictors of observed changes in the SGLT2i arm during follow-up,a rise in stroke volume index,body mass index(BMI)decrease,and lack of heart rate increase,linear regression analysis was performed.RESULTS There was a greater reduction of MPO,hsCRP,GLS,and blood pressure in the groups with higher baseline values of mentioned parameters irrespective of the therapeutic arm after 6 months of follow-up.Significant independent predictors of heart rate decrease were a reduction in early mitral inflow velocity to early diastolic mitral annular velocity at the interventricular septal annulus ratio and BMI,while the predictor of stroke volume index increase was SGLT2i therapy itself.CONCLUSION SGLT2i affect body composition,reduce cardiac load,improve diastolic/systolic function,and attenuate the sympathetic response.Glycemic control contributes to the improvement of heart function,blood pressure control,oxidative stress,and reduction in inflammation.

Accuracy of FreeStyle Libre flash glucose monitoring in patients with type 2 diabetes who migrated from highlands to plains

BACKGROUND The FreeStyle Libre flash glucose monitoring(FGM)system entered the Chinese market in 2017 to complement the self-monitoring of blood glucose.Due to its increased usage in clinics,the number of studies investigating its accuracy has increased.However,its accuracy has not been investigated in highland populations in China.AIM To evaluate measurements recorded using the FreeStyle Libre FGM system compared with capillary blood glucose measured using the enzyme electrode method in patients with type 2 diabetes(T2D)who had migrated within 3 mo from highlands to plains.METHODS Overall,68 patients with T2D,selected from those who had recently migrated from highlands to plains(within 3 mo),were hospitalized at the Department of Endocrinology from August to October 2017 and underwent continuous glucose monitoring(CGM)with the FreeStyle Libre FGM system for 14 d.Throughout the study period,fingertip capillary blood glucose was measured daily using the enzyme electrode method(Super GL,China),and blood glucose levels were read from the scanning probe during fasting and 2 h after all three meals.Moreover,the time interval between reading the data from the scanning probe and collecting fingertip capillary blood was controlled to<5 min.The accuracy of the FGM system was evaluated according to the CGM guidelines.Subsequently,the factors influencing the mean absolute relative difference(MARD)of this system were analyzed by a multiple linear regression method.RESULTS Pearson’s correlation analysis showed that the fingertip and scanned glucose levels were positively correlated(R=0.86,P=0.00).The aggregated MARD of scanned glucose was 14.28±13.40%.Parker's error analysis showed that 99.30%of the data pairs were located in areas A and B.According to the probe wear time of the FreeStyle Libre FGM system,MARD_(1 d) and MARD_(2-14 d) were 16.55%and 14.35%,respectively(t=1.23,P=0.22).Multiple stepwise regression analysis showed that MARD did not correlate with blood glucose when the largest amplitude of glycemic excursion(LAGE)was<5.80 mmol/L but negatively correlated with blood glucose when the LAGE was≥5.80 mmol/L.CONCLUSION The FreeStyle Libre FGM system has good accuracy in patients with T2D who had recently migrated from highlands to plains.This system might be ideal for avoiding the effects of high hematocrit on blood glucose monitoring in populations that recently migrated to plains.MARD is mainly influenced by glucose levels and fluctuations,and the accuracy of the system is higher when the blood glucose fluctuation is small.In case of higher blood glucose level fluctuations,deviation in the scanned glucose levels is the highest at extremely low blood glucose levels.

USP19 Stabilizes TAK1 to Regulate High Glucose/Free Fatty Acid-induced Dysfunction in HK-2 Cells

Objective Obesity-induced kidney injury contributes to the development of diabetic nephropathy(DN).Here,we identified the functions of ubiquitin-specific peptidase 19(USP19)in HK-2 cells exposed to a combination of high glucose(HG)and free fatty acid(FFA)and determined its association with TGF-beta-activated kinase 1(TAK1).Methods HK-2 cells were exposed to a combination of HG and FFA.USP19 mRNA expression was detected by quantitative RT-PCR(qRT-PCR),and protein analysis was performed by immunoblotting(IB).Cell growth was assessed by Cell Counting Kit-8(CCK-8)viability and 5-ethynyl-2′-deoxyuridine(EdU)proliferation assays.Cell cycle distribution and apoptosis were detected by flow cytometry.The USP19/TAK1 interaction and ubiquitinated TAK1 levels were assayed by coimmunoprecipitation(Co-IP)assays and IB.Results In HG+FFA-challenged HK-2 cells,USP19 was highly expressed.USP19 knockdown attenuated HG+FFA-triggered growth inhibition and apoptosis promotion in HK-2 cells.Moreover,USP19 knockdown alleviated HG+FFA-mediated PTEN-induced putative kinase 1(PINK1)/Parkin pathway inactivation and increased mitochondrial reactive oxygen species(ROS)generation in HK-2 cells.Mechanistically,USP19 stabilized the TAK1 protein through deubiquitination.Importantly,increased TAK1 expression reversed the USP19 knockdown-mediated phenotypic changes and PINK1/Parkin pathway activation in HG+FFA-challenged HK-2 cells.Conclusion The findings revealed that USP19 plays a crucial role in promoting HK-2 cell dysfunction induced by combined stimulation with HG and FFAs by stabilizing TAK1,providing a potential therapeutic strategy for combating DN.

Influence of blood glucose fluctuations on chemotherapy efficacy and safety in type 2 diabetes mellitus patients complicated with lung carcinoma

BACKGROUND Patients with type 2 diabetes mellitus(T2DM)have large fluctuations in blood glucose(BG),abnormal metabolic function and low immunity to varying degrees,which increases the risk of malignant tumor diseases and affects the efficacy of tumor chemotherapy.Controlling hyperglycemia may have important therapeutic implications for cancer patients.AIM To clarify the influence of BG fluctuations on chemotherapy efficacy and safety in T2DM patients complicated with lung carcinoma(LC).METHODS The clinical data of 60 T2DM+LC patients who presented to the First Affiliated Hospital of Ningbo University between January 2019 and January 2021 were retrospectively analyzed.All patients underwent chemotherapy and were grouped as a control group(CG;normal BG fluctuation with a mean fluctuation<3.9 mmol/L)and an observation group(OG;high BG fluctuation with a mean fluctuation≥3.9 mmol/L)based on their BG fluctuations,with 30 cases each.BGrelated indices,tumor markers,serum inflammatory cytokines and adverse reactions were comparatively analyzed.Pearson correlation analysis was performed to analyze the correlation between BG fluctuations and tumor markers.RESULTS The fasting blood glucose and 2-hour postprandial blood glucose levels in the OG were notably elevated compared with those in the CG,together with markedly higher mean amplitude of glycemic excursions(MAGE),mean of daily differences,largest amplitude of glycemic excursions and standard deviation of blood glucose(P<0.05).In addition,the OG exhibited evidently higher levels of carbohydrate antigen 19-9,carbohydrate antigen 125,carcinoembryonic antigen,neuron-specific enolase,cytokeratin 19,tumor necrosis factor-α,interleukin-6,and highsensitivity C-reactive protein than the CG(P<0.05).Pearson analysis revealed a positive association of MAGE with serum tumor markers.The incidence of adverse reactions was significantly higher in the OG than in the CG(P<0.05).CONCLUSION The greater the BG fluctuation in LC patients after chemotherapy,the more unfavorable the therapeutic effect of chemotherapy;the higher the level of tumor markers and inflammatory cytokines,the more adverse reactions the patient experiences.

Effects of sodium-dependent glucose transporter 2 inhibitors in patients with type 2 diabetes mellitus and asymptomatic heart failure

Sodium-dependent glucose transporter 2 inhibitors(SGLT2i)have been increa-singly used with proven efficacy in patients with heart failure(HF),regardless of diabetes status.GrubićRotkvićet al recently published an observational study on SGLT2i therapy in patients with type 2 diabetes mellitus and asymptomatic HF.They found that the use of SGLT2i led to reduced cardiac load and improved cardiovascular performance,reinforcing the evolving paradigm that SGLT2i are not merely glucose-lowering agents but are integral to the broader management of cardiovascular risk in patients with type 2 diabetes mellitus.The study by GrubićRotkvićet al contributes to the growing body of literature supporting the early use of SGLT2i in patients with diabetic cardiomyopathy,offering a potential strategy to mitigate the progression of HF.Future larger studies should be con-ducted to confirm these findings,and explore the long-term cardiovascular bene-fits of SGLT2i,particularly in asymptomatic patients at risk of developing HF.

Effectiveness and mechanisms of sodium-dependent glucose transporter 2 inhibitors in type 2 diabetes and heart failure patients

We comment on an article by GrubićRotkvićet al published in the recent issue of the World Journal of Cardiology.We specifically focused on possible factors affecting the therapeutic effectiveness of sodium-dependent glucose transporter inhibitors(SGLT2i)in patients with type 2 diabetes mellitus(T2DM)and their impact on comorbidities.SGLT2i inhibits SGLT2 in the proximal tubules of the kidneys,lowering blood glucose levels by inhibiting glucose reabsorption by the kidneys and causing excess glucose to be excreted in the urine.Previous studies have demonstrated a role of SGLT2i in cardiovascular function in patients with diabetes who take metformin but still have poor glycemic control.In addition,SGLT2i has been shown to be effective in anti-apoptosis,weight loss,and cardiovascular protection.Accordingly,it is feasible to treat patients with T2DM with cardiovascular or renal diseases using SGLT2i.

Sodium-Glucose Cotransporter-2 Inhibitors: Who, When & How? Guidance for Use from a Multidisciplinary Practical Approach

Sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitors) have transformed diabetes management by targeting renal glucose reabsorption. Designed initially as antidiabetic agents, their ability to lower blood glucose levels independently of insulin is well-documented. Beyond glycemic control, emerging research has unveiled their profound cardiorenal benefits. By inhibiting SGLT-2 protein, these drugs enhance glucose excretion in urine, reducing blood glucose levels. This mechanism has translated into significant cardiovascular and renal protection, establishing SGLT-2 inhibitors as pivotal in managing not only diabetes but also cardiovascular and renal diseases. Recent studies have illuminated the broader therapeutic potential of SGLT-2 inhibitors beyond diabetes. Evidence indicates their efficacy in managing heart failure, chronic kidney disease (CKD), and cardiovascular complications in individuals with or without diabetes. This expanded therapeutic landscape has catalyzed a paradigm shift in SGLT-2 inhibitor use, positioning them as key agents in the cardiorenal metabolic continuum. Moreover, their role in the secondary prevention of cardiovascular events and slowing CKD progression in T2DM patients has garnered considerable attention. This consensus-based review aims to offer practical guidance in an algorithmic approach to primary care healthcare professionals to optimize SGLT-2 inhibitors utilization and maximize their benefits. The review seeks to empower clinicians to effectively manage patients who may benefit from SGLT-2 inhibitor therapy by addressing common initiation barriers and optimizing treatment strategies. Additionally, it aims to raise awareness among primary care physicians regarding the multifaceted benefits of these medications and overcome clinical inertia in their adoption into routine clinical practice.

Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance

BACKGROUND Type 2 diabetes mellitus(T2DM)is a chronic metabolic disease featured by insulin resistance(IR)and decreased insulin secretion.Currently,vitamin D deficiency is found in most patients with T2DM,but the relationship between vitamin D and IR in T2DM patients requires further investigation.AIM To explore the risk factors of IR and the effects of vitamin D supplementation on glucose and lipid metabolism in patients with T2DM.METHODS Clinical data of 162 T2DM patients treated in First Affiliated Hospital of Harbin Medical University between January 2019 and February 2022 were retrospectively analyzed.Based on the diagnostic criteria of IR,the patients were divided into a resistance group(n=100)and a non-resistance group(n=62).Subsequently,patients in the resistance group were subdivided to a conventional group(n=44)or a joint group(n=56)according to the treatment regimens.Logistic regression was carried out to analyze the risk factors of IR in T2DM patients.The changes in glucose and lipid metabolism indexes in T2DM patients with vitamin D deficiency were evaluated after the treatment.RESULTS Notable differences were observed in age and body mass index(BMI)between the resistance group and the non-resistance group(both P<0.05).The resistance group exhibited a lower 25-hydroxyvitamin D_(3)(25(OH)D_(3))level,as well as notably higher levels of 2-h postprandial blood glucose(2hPG),fasting blood glucose(FBG),and glycosylated hemoglobin(HbA1c)than the non-resistance group(all P<0.0001).Additionally,the resistance group demonstrated a higher triglyceride(TG)level but a lower high-density lipoprotein-cholesterol(HDL-C)level than the non-resistance group(all P<0.0001).The BMI,TG,HDL-C,25(OH)D_(3),2hPG,and HbA1c were found to be risk factors of IR.Moreover,the posttreatment changes in levels of 25(OH)D_(3),2hPG,FBG and HbA1c,as well as TG,total cholesterol,and HDL-C in the joint group were more significant than those in the conventional group(all P<0.05).CONCLUSION Patients with IR exhibit significant abnormalities in glucose and lipid metabolism parameters compared to the noninsulin resistant group.Logistic regression analysis revealed that 25(OH)D_(3)is an independent risk factor influencing IR.Supplementation of vitamin D has been shown to improve glucose and lipid metabolism in patients with IR and T2DM.

Dual-functional marigold-like Zn_(x)Cd_(1-x)S homojunction for selective glucose photoreforming with remarkable H_(2)coproduction

The global commitment to pivoting to sustainable energy and products calls for technology development to utilize solar energy for hydrogen(H_(2))and value-added chemicals production by biomass photoreforming.Herein,a novel dual-functional marigold-like Zn_(x)Cd_(1-x)S homojunction has been the production of lactic acid with high-yield and H_(2)with high-efficiency by selective glucose photoreforming.The optimized Zn_(0.3)Cd_(0.7)S exhibits outstanding H_(2)generation(13.64 mmol h^(-1)g^(-1)),glucose conversion(96.40%),and lactic acid yield(76.80%),over 272.80 and 19.21 times higher than that of bare ZnS(0.05 mmol h^(-1)g^(-1))and CdS(0.71 mmol h^(-1)g^(-1))in H_(2)generation,respectively.The marigold-like morphology provides abundant active sites and sufficient substrates accessibility for the photocatalyst,while the specific role of the homojunction formed by hexagonal wurtzite(WZ)and cubic zinc blende(ZB)in photoreforming biomass has been demonstrated by density functional theory(DFT)calculations.Glucose is converted to lactic acid on the WZ surface of Zn_(0.3)Cd_(0.7)S via the photoactive species·O_(2)^(-),while the H_(2)is evolved from protons(H^(+))in H_(2)O on the ZB surface of Zn_(0.3)Cd_(0.7)S.This work paves a promising road for the production of sustainable energy and products by integrating photocatalysis and biorefine.

Sodium-glucose cotransporter-2 inhibitor use in kidney transplant recipients

Sodium-glucose cotransporter-2 inhibitors(SGLT2i)are novel oral hypoglycemic agents garnering much attention for their substantial benefits.These recent data have positioned SGLT2i at the forefront of diabetic chronic kidney disease(CKD)and heart failure management.SGLT2i use post-kidney transplant is an emerging area of research.Highlights from this mini review include the following:Empagliflozin is the most prescribed SGLT2i in kidney transplant recipients(KTRs),median time from transplant to initiation was 3 years(range:0.88-9.6 years).Median baseline estimated glomerular filtration rate(eGFR)was 66.7 mL/min/1.73 m2(range:50.4-75.8).Median glycohemoglobin(HgbA1c)at initiation was 7.7%(range:6.9-9.3).SGLT2i were demonstrated to be effective short-term impacting HgbA1c,eGFR,hemoglobin/hematocrit,serum uric acid,and serum magnesium levels.They are shown to be safe in KTRs with low rates of infections,hypoglycemia,euglycemic diabetic ketoacidosis,and stable tacrolimus levels.More data is needed to demonstrate long-term outcomes.SGLT2i appear to be safe,effective medications for select KTRs.Our present literature,though limited,is founded on precedent robust research in CKD patients with diabetes.Concurrent research/utilization of SGLT2i is vital to not only identify long-term patient,graft and cardiovascular outcomes of these agents,but also to augment management in KTRs.

Effects of glucagon-like peptide-1 receptor agonists on glucose excursion and inflammation in overweight or obese type 2 diabetic patients

BACKGROUND Currently,the lack of comparative studies between weekly and daily formulations of glucagon-like peptide-1 receptor agonists(GLP-1RAs)for glucose excursion is worth investigation.AIM To investigate the effects of weekly and daily formulations of GLP-1RA on glucose excursion and inflammation in overweight and obese patients with type 2 diabetes.METHODS Seventy patients with type 2 diabetes mellitus who were treated at our hospital between January 2019 and January 2022 were enrolled in this retrospective analysis.All patients were treated with metformin.We evaluated changes in blood glucose levels and a series of important indicators in patients before and after treatment with either a weekly or daily preparation of GLP-1RA(group A;n=33 and group B;n=37).RESULTS The degree of decrease in the levels of fasting blood glucose,mean blood glucose,mean amplitude of glycemic excursions,total cholesterol,triglycerides,tumor necrosis factor-α,interleukin-6,and high-sensitivity C-reactive protein after treatment in group A was higher than that in group B(P<0.05),whereas the 2-h postprandial blood glucose levels decreased more so in group B than in group A(P<0.001).However,there were no statistically significant differences in the levels of glycated hemoglobin,standard deviation of blood glucose,coefficient of variation,absolute mean of daily differences,percentage of time with 3.9 mmol/L<glucose<10 mmol/L,and high-and low-density lipoproteins between the two groups(P>0.05).The incidence of adverse reactions was significantly lower in group A than in group B(P<0.05).CONCLUSION The effect of the weekly preparation of GLP-1RA in controlling blood glucose levels in the patients,suppressing inflammation,and reducing adverse reactions was significantly higher than that of the daily preparations,which is worthy of clinical promotion.

Effect of miR-27b-3p and Nrf2 in human retinal pigment epithelial cell induced by high-glucose

AIM:To determine whether the microRNA-27b-3p(miR-27b-3p)/NF-E2-related factor 2(Nrf2)pathway plays a role in human retinal pigment epithelial(hRPE)cell response to high glucose,how miR-27b-3p and Nrf2 expression are regulated,and whether this pathway could be specifically targeted.METHODS:hRPE cells were cultured in normal glucose or high glucose for 1,3,or 6d before measuring cellular proliferation rates using cell counting kit-8 and reactive oxygen species(ROS)levels using a dihydroethidium kit.miR-27b-3p,Nrf2,NAD(P)H quinone oxidoreductase 1(NQO1)and heme oxygenase-1(HO-1)mRNA and protein levels were analyzed using reverse transcription quantitative polymerase chain reaction(RT-qPCR)and immunocytofluorescence(ICF),respectively.Western blot analyses were performed to determine nuclear and total Nrf2 protein levels.Nrf2,NQO1,and HO-1 expression levels by RT-qPCR,ICF,or Western blot were further tested after miR-27b-3p overexpression or inhibitor lentiviral transfection.Finally,the expression level of those target genes was analyzed after treating hRPE cells with pyridoxamine.RESULTS:Persistent exposure to high glucose gradually suppressed hRPE Nrf2,NQO1,and HO-1 mRNA and protein levels and increased miR-27b-3p mRNA levels.High glucose also promoted ROS release and inhibited cellular proliferation.Nrf2,NQO1,and HO-1 mRNA levels decreased after miR-27b-3p overexpression and,conversely,both mRNA and protein levels increased after expressing a miR-27b-3p inhibitor.After treating hRPE cells exposed to high glucose with pyridoxamine,ROS levels tended to decreased,proliferation rate increased,Nrf2,NQO1,and HO-1 mRNA and protein levels were upregulated,and miR-27b-3p mRNA levels were suppressed.CONCLUSION:Nrf2 is a downstream target of miR-27b-3p.Furthermore,the miR-27b-3p inhibitor pyridoxamine can alleviate high glucose injury by regulating the miR-27b-3p/Nrf2 axis.

Heterogeneity in cardiorenal protection by Sodium glucose cotransporter 2 inhibitors in heart failure across the ejection fraction strata:Systematic review and meta-analysis

BACKGROUND Gliflozins or Sodium glucose cotransporter 2 inhibitors(SGLT2i)are relatively novel antidiabetic medications that have recently been shown to represent favorable effects on patients’cardiorenal outcomes.However,there is shortage of data on potential disparities in this therapeutic effect across different patient subpopulations.AIM To investigate differential effects of SGLT2i on the cardiorenal outcomes of heart failure patients across left ventricular ejection fraction(LVEF)levels.METHODS Literature was searched systematically for the large randomized double-blind controlled trials with long enough follow up periods reporting cardiovascular and renal outcomes in their patients regarding heart failure status and LVEF levels.Data were then meta-analyzed after stratification of the pooled data across the LVEF strata and New York Heart Associations(NYHA)classifications for heart failure using Stata software version 17.0.RESULTS The literature search returned 13 Large clinical trials and 13 post hoc analysis reports.Meta-analysis of the effects of gliflozins on the primary composite outcome showed no significant difference in efficacy across the heart failure subtypes,but higher efficacy were detected in patient groups at lower NYHA classifications(I2=46%,P=0.02).Meta-analyses across the LVEF stratums revealed that a baseline LVEF lower than 30%was associated with enhanced improvement in the primary composite outcome compared to patients with higher LVEF levels at the borderline statistical significance(HR:0.70,95%CI:0.60 to 0.79 vs 0.81,95%CI:0.75 to 0.87;respectively,P=0.06).Composite renal outcome was improved significantly higher in patients with no heart failure than in heart failure patients with preserved ejection fraction(HFpEF)(HR:0.60,95%CI:0.49 to 0.72 vs 0.94,95%CI:0.74 to 1.13;P=0.04).Acute renal injury occurred significantly less frequently in heart failure patients with reduced ejection fraction who received gliflozins than in HFpEF(HR:0.67,95%CI:51 to 0.82 vs 0.94,95%CI:0.82 to 1.06;P=0.01).Volume depletion was consistently increased in response to SGLT2i in all the subgroups.CONCLUSION Heart failure patients with lower LVEF and lower NYHA sub-classifications were found to be generally more likely to benefit from therapy with gliflozins.Further research are required to identify patient subgroups representing the highest benefits or adverse events in response to SGLT2i.

Relationship Between Postprandial Blood Glucose,Fasting Insulin,and Glycated Hemoglobin Levels and Early Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus

Objective:To investigate the relationship between postprandial blood glucose(PBG),fasting insulin(FINS),and glycated hemoglobin(HbA1c)levels and early diabetic nephropathy in patients with type 2 diabetes.Methods:96 cases of type 2 diabetes mellitus treated in our hospital from May 2021 to May 2022 were selected as the research subjects.The patients were divided into two groups according to the urinary albumin excretion rate(UAER),with 53 cases in the type 2 diabetes group(UAER<30μg/min)and 43 cases in the early diabetic nephropathy group(30μg/min≤UAER<300μg/min).PBG,FINS,and HbA1c levels were detected in 87 healthy patients.Results:The levels of PBG,FINS,and HbA1c in the early diabetic nephropathy group were higher than those in the control group(P<0.01)and the type 2 diabetes group(P<0.01).Conclusion:PBG,FINS,and HbA1c are factors affecting the occurrence of diabetic nephropathy in patients with type 2 diabetes;thus,controlling the levels of PBG,FINS,and HbA1c can effectively prevent the occurrence of diabetic nephropathy in type 2 diabetes mellitus.

Saudi Consensus on the Usage of Sodium-Glucose Cotransporter-2 Inhibitors on the Management of Chronic Kidney Diseases

According to recent epidemiological data, chronic kidney diseases (CKDs) affect approximately 10% of the global population. Like many countries, CKD is a significant public health issue in Saudi Arabia. The prevalence of CKD in Saudi Arabia is estimated to be around 4.5% of the adult population, with a higher prevalence in older age groups. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are a class of oral medications used to treat type 2 diabetes mellitus (T2DM). In addition to their glucose-lowering effects, SGLT2i have been shown to have beneficial effects on kidney function in patients with or without T2DM. Therefore, a Saudi task force gathered to develop an explicit, evidence-based consensus on SGLT2i use in CKD Saudi patients. A panel of 14 experts made up a task force. An initial concept proposal was obtained. The proposal was divided into several topics discussed on 24 May 2023. A literature review was carried out. The literature search was completed on 3rd June 2023. A drafted report was distributed to the entire panel. Approval of the recommendations required consensus, defined as a majority approval (i.e. above 75%). The recommendations were revised to accommodate any differences of opinion until a consensus was reached. Recommendations were finally formulated on 21st June 2023. Subsequently, the panel reviewed and discussed the supporting rationale of the revised recommendations. This article presents these practical recommendations.

姜酮通过激活Nrf2/HO-1信号通路减轻OGD/R后氧化应激损伤对HT22细胞凋亡的抑制作用

目的:探讨姜酮对氧糖剥夺/复糖复氧(OGD/R)后小鼠海马神经元HT22细胞的保护作用,阐明其相关作用机制。方法:培养HT22细胞,设置不同OGD/R时间梯度,建立OGD/R细胞损伤模型。HT22细胞分为对照组、OGD/R组、OGD/R+1μmol·L^(-1)姜酮组、OGD/R+10μmol·L^(-1)姜酮、OGD/R+100μmol·L^(-1)姜酮组和OGD/R+0.2%二甲亚枫(DMSO)组,CCK-8法检测各组细胞活性并计算各组细胞存活率,确定姜酮最适药物浓度。细胞分为对照组、OGD/R组、OGD/R+姜酮组和OGD/R+姜酮+核因子E2相关因子2(Nrf2)抑制剂(ML385)组,OGD/R+姜酮组细胞经姜酮给药处理4 h后予以OGD 8 h和复糖复氧8 h处理,OGD/R+姜酮+ML385组细胞在姜酮给药前予以10μmol·L^(-1)ML385预处理6 h,CCK-8法检测各组细胞活性,Western blotting法检测各组细胞中Nrf2、血红素加氧酶1(HO-1)、B细胞淋巴瘤2(Bcl-2)和Bcl-2相关X蛋白(Bax)蛋白表达水平,酶联免疫吸附试验(ELISA)法检测各组细胞培养上清中超氧化物歧化酶(SOD)活性和丙二醛(MDA)水平。结果:与对照组比较,HT22细胞经OGD 8 h和复糖复糖8 h处理后细胞存活率低于50%,以OGD 8 h和复糖复糖8 h建立HT22细胞OGD/R模型。与OGD/R组比较,OGD/R+不同剂量姜酮组细胞存活率均不同程度升高,其中OGD/R+100μmol·L^(-1)姜酮组细胞存活率升高最明显(P<0.01),故选用100μmol·L^(-1)姜酮用于后续实验。与对照组比较,OGD/R组细胞活性明显降低(P<0.01),细胞中Nrf2、HO-1和Bax蛋白表达水平明显升高(P<0.01),Bcl-2蛋白表达水平明显降低(P<0.05),细胞培养上清中SOD活性明显降低(P<0.01),MDA水平明显升高(P<0.01);与OGD/R组比较,OGD/R+姜酮组细胞活性明显升高(P<0.01),细胞中Nrf2、HO-1和Bcl-2蛋白表达水平明显升高(P<0.05或P<0.01),Bax蛋白表达水平明显降低(P<0.05),细胞培养上清中SOD活性明显升高(P<0.01),MDA水平明显降低(P<0.01);与OGD/R+姜酮组比较,OGD/R+姜酮+ML385组细胞活性明显降低(P<0.01),细胞中Nrf2、HO-1和Bcl-2蛋白表达水平明显降低(P<0.01),Bax蛋白表达水平明显升高(P<0.01),细胞培养上清中SOD活性明显降低(P<0.01),MDA水平明显升高(P<0.05)。结论:姜酮可通过激活Nrf2/HO-1信号通路减轻OGD/R后氧化应激损伤对HT22细胞凋亡的抑制作用。

钠-葡萄糖协同转运蛋白2抑制剂对急性心肌梗死合并2型糖尿病患者临床指标及预后的影响

目的观察钠-葡萄糖协同转运蛋白2抑制剂(SGLT-2i)对急性心肌梗死(AMI)合并2型糖尿病(T2DM)患者临床指标及预后的影响。方法回顾性选取2020年1月至2022年6月于安徽医科大学第二附属医院胸痛中心就诊后确诊AMI合并T2DM患者180例,根据入院后降糖方案分为对照组(79例,给予磺脲类、α-糖苷酶抑制剂、二甲双胍等药物)和观察组(101例,给予达格列净或恩格列净)。患者出院后定期随访,比较2组患者临床指标及主要不良心血管事件(MACE)发生情况。结果所有患者随访6~12个月,结果显示观察组白细胞计数小于对照组[(7.4±1.6)×10^(9)/L比(8.7±1.6)×10^(9)/L],左心室舒张末期内径改善优于对照组[(-0.527±1.462)mm比(1.359±2.111)mm](均P<0.05)。观察组MACE发生率低于对照组[5.4%(2/37)比25.0%(8/32)],差异有统计学意义(P=0.020)。结论SGLT-2i较其他降糖药物12个月内能改善AMI合并T2DM患者的心脏功能及预后,且能减轻该类患者的全身炎症反应。

互联网自我管理模式对2型糖尿病患者血糖控制和自我管理水平的影响

目的探讨基于互联网的自我管理模式对2型糖尿病(T2DM)患者血糖控制和自我管理水平的影响。方法选取我院2021年6月至2022年12月收治的138例T2DM患者,经随机数字表法分为试验组(n=69)及对照组(n=69),对照组予以常规健康管理,试验组予以基于互联网的自我管理模式。比较两组血糖、血压及体重控制情况、干预前后代谢指标、自我管理水平[采用中文版糖尿病自我管理活动问卷(SDSCA)]及生活质量[采用糖尿病生存质量量表(DSQL)]。结果干预后,两组糖化血红蛋白、空腹血糖(FPG)、餐后2 h血糖、舒张压、收缩压、体质量指数均低于干预前,且试验组低于对照组(P<0.05);两组低密度脂蛋白胆固醇、总胆固醇及甘油三酯均低于干预前,且试验组低于对照组(P<0.05);两组足部护理、血糖监测、运动及饮食等维度评分均高于干预前,且试验组高于对照组(P<0.05);两组治疗、社会关系、心理、生理功能等维度评分均低于干预前,且试验组低于对照组(P<0.05)。结论基于互联网的自我管理模式有利于T2DM患者控制血糖、血压及体重控制,能改善患者代谢指标,提高管理水平及生活质量。

糖肝煎丸联合腹部推拿对二甲双胍治疗肥胖2型糖尿病患者糖脂代谢和炎症因子的影响

目的 探究糖肝煎丸(TGJW)联合腹部推拿(AM)对二甲双胍治疗肥胖2型糖尿病(OT2DM)患者糖脂代谢和炎症因子的影响。方法 纳入2021年6月至2023年6月在武汉市中医医院诊治的OT2DM患者为研究对象,根据随机数字表法分为AM组(二甲双胍联合AM)和TGJW组(二甲双胍联合AM+TGJW)。连续干预3个月,评估治疗疗效和安全性。比较TGJW组和AM组治疗前后肥胖相关指标[腰臀比(WHR)和体重指数(BMI)]、糖脂代谢指标[糖化血红蛋白(HbA1c)、空腹血糖(FBG)、餐后2 h血糖(P2hG)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)]、胰岛素敏感性指标[稳态模型胰岛素抵抗指数(HOMA-IR)和稳态模型胰岛β细胞功能指数(HOMA-β)]和炎症指标[白细胞介素-6(IL-6)、肿瘤坏死因子α(TNF-α)和C-反应蛋白(CRP)]变化情况。结果研究共纳入OT2DM患者100例,TGJW组和AM组各50例。干预后,TGJW组治疗有效率明显高于AM组(P <0.05),且治疗期间未发生恶性不良反应事件。与治疗前比较,两组WHR、BMI、FBG、P2hG、HbA1c、TC、TG、LDL-C、HOMA-IR、IL-6、TNF-α和CRP水平均下降(P <0.05),而HDL-C和HOMA-β水平显著上升(P <0.05)。干预后,TGJW组WHR、BMI、FBG、P2hG、HbA1c、TC、TG、LDL-C、HOMA-IR、IL-6、TNF-α和CRP水平低于AM组(P <0.05),而HDL-C和HOMA-β水平高于AM组(P <0.05)。结论 与单纯AM治疗比较,TGJW联合AM可改善OT2DM患者糖脂代谢、胰岛素敏感性和炎症指标,提升二甲双胍治疗OT2DM患者治疗效果,且安全性高,有一定的临床推广意义。