Tofogliflozin decreases body fat mass and improves peripheral insulin resistance

The impact of tofogliflozin, a sodium‐glucose co‐transporter‐2 inhibitor, on peripheral glucose uptake in patients with type 2 diabetes mellitus (T2DM) was investigated using the hyperinsulinaemic‐euglycaemic clamp method in a single‐arm, open‐label study. The following variables were compared between before and after tofogliflozin administration for 12 weeks in 16 patients with T2DM who were receiving dipeptidyl peptidase‐4 inhibitor treatment: body weight (BW); blood pressure; glucose metabolism; liver function; lipid profile; and body composition. Peripheral glucose uptake (M value and M/I ratio) was examined by the hyperinsulinaemic‐euglycaemic clamp method. After 12 weeks, there was a significant decrease (P < .001) in glycated haemoglobin, BW, body fat mass and lean body mass. Peripheral glucose uptake, which indicates insulin sensitivity, increased significantly (M value by 0.90 and M/I ratio by 0.49; both P < .05). The change in the M value after 12 weeks of tofogliflozin therapy was correlated with the change in body fat mass (P < .05). Tofogliflozin significantly improved insulin sensitivity and peripheral glucose uptake in patients with T2DM. These improvements were significantly correlated with reduction in body fat mass.     

血浆BNP对慢性阻塞性肺疾病有创机械通气撤机的指导价值

目的探讨撤机前后血浆BNP水平及其变化对慢性阻塞性肺疾病(简称慢阻肺)患者有创机械通气撤机的指导价值。方法回顾性调查满足条件的70例患者,测定患者开始有创机械通气时,自主呼吸试验(SBT)前、后的血浆BNP水平,分别标为(BNP 0、BNP 1、BNP 2),SBT前、后的血浆BNP水平差值(ΔBNP),并根据患者撤机结局分为撤机成功组与撤机失败组。绘制ROC曲线,分析血浆BNP水平对慢阻肺患者撤机结局的预测价值。结果 70例患者中,成功撤机52例,撤机失败18例。BNP 0、BNP 1、BNP 2预测慢阻肺患者撤机失败的AUC分别为0.6079、0.8568、0.9081,ΔBNP预测撤机失败的AUC为0.9466。结论血浆BNP水平对预测慢阻肺患者撤机结局有指导价值,其中ΔBNP预测慢阻肺患者撤机结局的价值最大。     

Post-initiation predictors of discontinuation of the sodium-glucose cotransporter-2 inhibitors: A comparative cohort study from the United Kingdom

Aims

To assess post-initiation predictors of discontinuation of sodium-glucose cotransporter-2 (SGLT2) inhibitors compared to dipeptidyl-peptidase-4 (DPP-4) inhibitors in the United Kingdom.

Materials and Methods

We conducted a comparative population-based retrospective cohort study using primary care data from the UK Clinical Practice Research Datalink (CPRD) with linked data to hospital and death records. We included new metformin users who initiated either SGLT2 inhibitors or DPP-4 inhibitors between January 2013 and October 2019. The main outcome was treatment discontinuation, defined as the first 90-day gap after the estimated treatment end date. We used a series of extended Cox models to assess which time-dependent predictors were associated with treatment discontinuation. To test if the hazard ratio of discontinuation for each predictor was statistically different between SGLT2 and DPP-4 inhibitors, an exposure-predictor interaction term was added to each model.

Results

There were 2550 new users of SGLT2 inhibitors and 8195 new users of DPP-4 inhibitors. Approximately 69% of SGLT2 inhibitor and 74% of DPP-4 inhibitor users had discontinued treatment by the end of follow-up. Occurrence of fractures after treatment initiation was a significant predictor of discontinuation of SGLT2 inhibitors (hazard ratio [HR] 4.13, 95% confidence interval [CI] 2.12-8.06) but not DPP-4 inhibitors (HR 0.93, 95% CI 0.79-1.11). The rate of treatment discontinuation was significantly higher for those with low estimated glomerular filtration rate and minimal contact with the healthcare system. Efficacy endpoints, such as heart failure and glycated haemoglobin level, were not associated with treatment discontinuation.

Conclusions

Our findings reflect some discrepancy between the available evidence and prescribing behaviour for SGLT2 inhibitors.     

Tofogliflozin,a sodium/glucose cotransporter 2 inhibitor,attenuates body weight gain and fat accumulation in diabetic and obese animal models

Objective:

Tofogliflozin, a highly selective inhibitor of sodium/glucose cotransporter 2 (SGLT2), induces urinary glucose excretion (UGE), improves hyperglycemia and reduces body weight in patients with Type 2 diabetes (T2D). The mechanisms of tofogliflozin on body weight reduction were investigated in detail with obese and diabetic animal models.

Methods:

Diet-induced obese (DIO) rats and KKAy mice (a mouse model of diabetes with obesity) were fed diets containing tofogliflozin. Body weight, body composition, biochemical parameters and metabolic parameters were evaluated.

Results:

In DIO rats tofogliflozin was administered for 9 weeks, UGE was induced and body weight gain was attenuated. Body fat mass decreased without significant change in bone mass or lean body mass. Food consumption (FC) increased without change in energy expenditure, and deduced total calorie balance (deduced total calorie balance=FC−UGE−energy expenditure) decreased. Respiratory quotient (RQ) and plasma triglyceride (TG) level decreased, and plasma total ketone body (TKB) level increased. Moreover, plasma leptin level, adipocyte cell size and proportion of CD68-positive cells in mesenteric adipose tissue decreased. In KKAy mice, tofogliflozin was administered for 3 or 5 weeks, plasma glucose level and body weight gain decreased together with a reduction in liver weight and TG content without a reduction in body water content. Combination therapy with tofogliflozin and pioglitazone suppressed pioglitazone-induced body weight gain and reduced glycated hemoglobin level more effectively than monotherapy with either pioglitazone or tofogliflozin alone.

Conclusion:

Body weight reduction with tofogliflozin is mainly due to calorie loss with increased UGE. In addition, tofogliflozin also induces a metabolic shift from carbohydrate oxidation to fatty acid oxidation, which may lead to prevention of fat accumulation and inflammation in adipose tissue and liver. Tofogliflozin may have the potential to prevent obesity, hepatic steatosis and improve insulin resistance as well as hyperglycemia.     

Sodium–glucose cotransporter 2 inhibitor,tofogliflozin, shows better improvements of blood glucose and insulin secretion in patients with high insulin levels at baseline

Aims/Introduction

Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of drugs for the treatment of type 2 diabetes mellitus that improve control of plasma glucose and bodyweight, giving great hope for the clinical utility of these agents. However, it is unclear for which patients SGLT2 inhibitors will be useful.

Materials and Methods

We analyzed data from long‐term tofogliflozin monotherapy in an open‐label, randomized controlled trial in Japanese patients with type 2 diabetes mellitus. Patients were divided into tertiles by baseline insulin level: group low (L): insulin ≤5.6 μU/mL, group medium (M): 5.6< insulin ≤10 μU/mL and group high (H): insulin >10 μU/mL.

Results

Glycated hemoglobin and fasting plasma glucose levels, along with bodyweight, were significantly reduced from the baseline in all groups. The changes in levels of plasma glucose area under the curve for 2 h, C‐peptide index area under the curve for 2 h during the meal tolerance tests and the insulin secretion index were the largest in the H group. The incidence of drug‐related adverse events was not different among the three groups.

Discussion

Although tofogliflozin was effective regardless of baseline insulin level, it showed the highest efficacy in the H group.     

Comparisons of the effects of 12-week administration of miglitol and voglibose on the responses of plasma incretins after a mixed meal in Japanese type 2 diabetic patients

To compare the effects of miglitol [an alpha-glucosidase inhibitor (AGI) absorbed in the intestine] and voglibose (an AGI not absorbed) on plasma glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) levels, 26 and 24 Japanese type 2 diabetic patients were randomly assigned to receive miglitol or voglibose, respectively. After 12-week administration of both drugs, during 2-h meal tolerance test, plasma glucose, serum insulin and total GIP were significantly decreased and active GLP-1 was significantly increased. Miglitol group showed a significantly lower total GIP level than voglibose group. Miglitol, but not voglibose, significantly reduced body weight (BW). In all participants, the relative change in BW was positively correlated with that of insulin significantly and of GIP with a weak tendency, but not of GLP-1. In conclusion, both drugs can enhance postprandial GLP-1 responses and reduce GIP responses. The significant BW reduction by miglitol might be attributable to its strong GIP-reducing efficacy.     

Long‐term safety and efficacy of tofogliflozin as add‐on to insulin in patients with type 2 diabetes: Results from a 52‐week,multicentre, randomized,double‐blind,open‐label extension,Phase 4 study in Japan (J‐STEP/INS)

Aims

To evaluate the long‐term safety and efficacy of tofogliflozin as an add‐on treatment to insulin over 52 weeks.

Materials and methods

This 52‐week, multicentre, Phase 4 study consisted of a 16‐week, randomized, double‐blind, placebo‐controlled phase and a 36‐week open label extension phase (NCT02201004). Japanese patients with type 2 diabetes mellitus, aged 20 to 75 years, with suboptimal glycaemic control (7.5%‐10.5%) receiving insulin monotherapy (basal‐bolus, bolus, premix [low and high] and basal) or receiving combination therapy with basal insulin and dipeptidyl peptidase‐4 inhibitor were eligible for participation. Patients who received tofogliflozin throughout the study (52 weeks) were referred to as the ‘tofo‐tofo group’ and patients who received placebo and tofogliflozin (36 weeks) were referred to as the ‘pla‐tofo group’.

Results

A total of 210 patients received treatment per randomization. Hypoglycaemia was the most common treatment‐emergent adverse event (AE) (42.9% in the tofo‐tofo group and 29.4% in the pla‐tofo group). Patients reported genital infection, urinary tract infection, excessive urination and AEs related to volume depletion (2.1%, 2.1%, 7.1% and 10.0% of patients in the tofo‐tofo group, and 0%, 1.5%, 2.9% and 7.4% of patients in the pla‐tofo group, respectively). Mean HbA1c and body weight at baseline (mean changes ± standard error from baseline to Week 52) in the tofo‐tofo and pla‐tofo groups were 8.53% (?0.76% ± 0.077) and 8.40% (?0.73% ± 0.102); 68.84 kg (?1.52 kg ± 0.207) and 72.24 kg (?2.13 kg ± 0.313), respectively.

Conclusions

This study demonstrates the safety and efficacy of tofogliflozin as add‐on to insulin therapy in type 2 diabetes mellitus patients, offering a new therapeutic solution to diabetes management.     

Effects of sodium‐glucose co‐transporter 2 (SGLT2) inhibitors on serum uric acid level: A meta‐analysis of randomized controlled trials

The aim of this study was to describe the effects of sodium‐glucose co‐transporter 2 (SGLT2) inhibitors on serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM). PubMed, CENTRAL, EMBASE and ClinicalTrials.gov were searched for randomized controlled trials of SGLT2 inhibitors in patients with T2DM up to May 20, 2017. A total of 62 studies, comprising 34 941 patients, were included. Any of the SGLT2 inhibitors (empagliflozin, canagliflozin, dapagliflozin, tofogliflozin, luseogliflozin or ipragliflozin) significantly decreased SUA levels compared with control (total weighted mean difference [WMD] ?37.73 μmol/L, 95% CI [?40.51, ?34.95]). Treatment with empagliflozin resulted in a superior reduction in SUA (WMD ?45.83 μmol/L, 95% CI [?53.03, ?38.63]). The effect persisted during long‐term treatment. Dapagliflozin decreased SUA in a dose‐dependent manner (from 5 to 50 mg, P = .014). In subgroup analyses, greater reductions could be observed during the course of early diabetes and the SUA‐lowering effect was abolished in patients with chronic kidney disease (estimated glomerular filtration rate <60 mL/min per 1.73 m²). The effect of SGLT2 inhibitors on SUA reduction suggests that this class of drugs might be beneficial for diabetic patients with hyperuricaemia.     

Different effects on inhibition of cardiac hypertrophy in spontaneously hypertensive rats by monotherapy and combination therapy of adrenergic receptor antagonists and/or the angiotensin II type 1 receptor blocker under comparable blood pressure reduction.

To confirm that alpha1, beta adrenoceptor antagonists and angiotensin II type 1 receptor blockers (ARBs) have different abilities to attenuate progressive cardiac hypertrophy despite their comparable lowering of blood pressure, we compared the effect of these agents alone or in combination on hypertensive cardiac hypertrophy. Eight-week-old spontaneously hypertensive rats (SHR) were divided into 7 groups. Single administration of doxazosin, atenolol, or losartan, or half-dose combinations of these drugs were given orally for 6 weeks. The control group did not receive any drugs. The heart weight-to-body weight ratio (HW/BW), left ventricular mass index (LVMI), plasma brain natriuretic peptide (BNP) and left ventricular BNP mRNA expression were measured after 6-week administration. Blood pressure did not differ among the drug-treated groups, all of which showed lower blood pressure than the control group. The HW/BW and LVMI of the drug-treated groups, except the doxazosin group, were lower than in the control group. Moreover, the LVMI values of the groups receiving losartan were significantly lower than those in the groups without losartan (p < 0.05). Plasma BNP of the drug-treated groups was lower than that in the control group (p < 0.05). The left ventricular BNP mRNA expression of the drug-treated groups, except the doxazosin group, was lower than that in the control group. The atenolol group showed a higher level of BNP mRNA than the groups receiving losartan monotherapy or combination therapies (p < 0.05). In conclusion, the ARB had the strongest attenuating effect on the development of hypertensive cardiac hypertrophy, and the alpha1 and beta adrenergic receptor blockers were more effective in combination than as monotherapies in SHR.     

Serum retinol-binding protein 4 is associated with insulin secretion in Chinese people with normal glucose tolerance

Background:  Serum levels of retinol‐binding protein 4 (RBP4) are associated with insulin resistance and type 2 diabetes mellitus (T2DM) and may impact on β‐cell function. Thus, the present study investigated the relationship between serum RBP4 and insulin secretion in Chinese people with and without T2DM. Methods:  A 75 g oral glucose tolerance test was administered to all 867 subjects and serum RBP4 concentrations were determined. Insulin secretion was assessed by ΔI/ΔG (increment in plasma insulin concentration/plasma glucose concentration 30 min after the oral administration of 75 g glucose) and the total area under the curve for insulin over 180 min (AUC‐I). Magnetic resonance imaging was used to measure visceral fat area (VFA) at L4–L5; subjects with VFA ≥80 cm² were considered to have visceral obesity (VO). Results:  Serum RBP4 concentrations were significantly higher in subjects with VO than without, regardless of the presence of T2DM. In addition, in the entire group with normal glucose tolerance (NGT), serum RBP4 was positively correlated with ΔI/ΔG (r = 0.152; P < 0.01) and AUC‐I (r = 0.218; P < 0.01) after adjustment for gender. The correlation between RBP4 and ΔI/ΔG (r = 0.162; P < 0.05) and AUC‐I (r = 0.195; P < 0.01) remained in NGT non‐VO subjects. No correlation was found between serum RBP4 and ΔI/ΔG or AUC‐I in T2DM patients. Stepwise multiple regression analysis showed that serum RBP4 is an independent factor that contributes to ΔI/ΔG (β = 0.176) and AUC‐I (β = 0.204) in NGT non‐VO subjects. Conclusions:  Serum RBP4 is correlated with glucose‐stimulated insulin secretion in NGT non‐VO subjects, but not in NGT VO subjects and T2DM patients.     

Usefulness of plasma brain natriuretic peptide concentration for predicting subsequent left ventricular remodeling after coronary angioplasty in patients with acute myocardial infarction

To determine the relation between plasma brain natriuretic peptide (BNP) and remodeling in terms of infarct-related artery (IRA) patency, 106 patients with a first anterior wall acute myocardial infarction with a patent IRA at 1 month were studied. The IRA reoccluded at 6 months in 17 patients (reoccluded IRA) and was patent in 89 patients (patent IRA). The 2 groups did not differ with respect to clinical characteristics, hemodynamic variables, and left ventricular function at 1 month, except for left ventricular end-diastolic and systolic volumes, which were significantly greater in the reoccluded IRA group. Plasma BNP concentration in the reoccluded IRA group (336 +/- 288 pg/ml) was significantly higher than that in the patent IRA group (116 +/- 106 pg/ml) at 1 month. BNP concentration decreased significantly at 6 months in the 2 groups (reoccluded IRA vs patent IRA 152 +/- 162 vs 44 +/- 58 pg/ml, p <0.05). The increase in left ventricular volume from 1 to 6 months was significantly correlated with plasma BNP concentration at 1 month in the patent IRA group (r = 0.314, p < 0.01) and the reoccluded group (r = 0.634, p < 0.01). Linear regression analysis showed that the correlation between the 2 parameters in the 2 groups was similar. Based on stepwise multivariate linear regression analysis, only plasma BNP concentration was significantly correlated with the increase in left ventricular volume from 1 to 6 months in the 2 groups. In conclusion, these results suggest that plasma BNP concentration predicts left ventricular dilation independently of IRA patency.     

The evaluation of noninferiority for renal composite outcomes between sodium–glucose cotransporter inhibitors in Japan

BackgroundIn Japan, six types of sodium–glucose cotransporter inhibitors (SGLT2Is) are currently in use. Here, we evaluated differences in renal composite outcomes between SGLT2Is with or without evidence of cardio vascular outcome trials (CVOTs).MethodsWe retrospectively surveyed 536 Japanese patients with type 2 diabetes mellitus with chronic kidney disease who received SGLT2Is for more than 1 year. Patients were classified as having received empagliflozin, canagliflozin, or dapagliflozin (n = 270, Evidence (+) group) or as having received ipragliflozin, tofogliflozin, or luseogliflozin (n = 266, Evidence (−) group). The propensity score matching method was performed.ResultOn matched cohort model including 205 cases in each group, there were no significant differences in the incidence of renal composite outcomes (n = 28 [14%] in the Evidence (+) group, n = 21 [10%] in the Evidence (−) group for the matched model; p = 0.29) between groups. Cox hazard analyses in the matched cohort model showed that the risk ratio for renal composite outcomes in the Evidence (−) group was 0.73 (95% confidence interval: 0.40–1.32), which was greater than the noninferiority margin of 1.22.ConclusionThree SGLT2Is with no CVOT’s evidence did not show noninferiority compared with other SGLT2Is with evidences.     

Responses of plasma concentrations of A type natriuretic peptide and B type natriuretic peptide to alacepril, an angiotensin-converting enzyme inhibitor, in patients with congestive heart failure.

BACKGROUND--Plasma concentrations of A type or atrial natriuretic peptide (ANP) and B type or brain natriuretic peptide (BNP) are increased in patients with congestive heart failure (CHF). OBJECTIVE--To examine the haemodynamic and hormonal responses, especially of ANP and BNP, to oral administration of an angiotensin-converting enzyme (ACE) inhibitor in patients with CHF and in controls. PATIENTS--12 patients with CHF and 11 controls. METHODS--Haemodynamic variables and plasma concentrations of ANP, BNP, and other hormones were serially measured for 24 hours after alacepril (37.5 mg) was given by mouth. RESULTS--Pulmonary capillary wedge pressure and systemic vascular resistance decreased significantly in both groups. The cardiac index increased only in the CHF group. In patients with CHF pulmonary capillary wedge pressure, systemic vascular resistance, and cardiac index were significantly changed from 1 to 12 hours after alacepril administration. Plasma ANP and BNP decreased significantly after alacepril was given to the CHF group: neither concentration changed in the control group. In the CHF group plasma ANP was significantly lower between 1 and 6 hours and was highly significantly correlated with pulmonary capillary wedge pressure. Plasma BNP, however, was significantly lower between 6 and 24 hours after alacepril and was not correlated with pulmonary capillary wedge pressure. CONCLUSIONS--The response of plasma BNP after alacepril administration occurred later and lasted longer than the plasma ANP response. This may indicate that the mechanisms of synthesis, secretion, or degradation of the two peptides are different.     

Sodium‐glucose co‐transporter 2 inhibitors in addition to insulin therapy for management of type 2 diabetes mellitus: A meta‐analysis of randomized controlled trials

Given inconsistent trial results of sodium‐glucose cotransporter 2 (SGLT2) inhibitors in addition to insulin therapy for treating type 2 diabetes mellitus (T2DM), a meta‐analysis was performed to evaluate the efficacy and safety of this combination for T2DM by searching available randomized trials from PubMed, Embase, CENTRAL and ClinicalTrials.gov . Our meta‐analysis included seven eligible placebo‐controlled trials involving 4235 patients. Compared with placebo, SGLT2 inhibitor treatment was significantly associated with a mean reduction in HbA1c of ?0.56%, fasting plasma glucose of ?0.95 mmol/L, body weight of ?2.63 kg and insulin dose of ?8.79 IU, but an increased risk of drug‐related adverse events by 36%, urinary tract infections by 29% and genital infections by 357%. No significant increase was observed in risk of overall adverse events [risk ratio (RR), 1.00], serious adverse events (RR, 0.90), adverse events leading to discontinuation (RR, 1.16), hypoglycaemia events (RR, 1.07) and severe hypoglycaemia events (RR, 1.24). No diabetic ketoacidosis events were reported. Further studies are needed to establish optimal combination type and dose.     

Septal rebound stretch is a strong predictor of outcome after cardiac resynchronization therapy

BackgroundSeptal rebound stretch (SRSsept) is a distinctive characteristic of discoordination-related mechanical inefficiency. We assessed how intermediate- and long-term outcome after cardiac resynchronization therapy (CRT) relate to baseline SRSsept.Methods and ResultsA total of 101 patients (age 65 ± 11 years, 69 men, 18 New York Heart Association (NYHA) class IV, QRS 173 ± 23 ms) scheduled for CRT underwent clinical assessment, echocardiography, and brain-type natriuretic peptide (BNP) measurements before and 6.4 ± 2.3 months after CRT. Baseline SRSsept (all systolic stretch after initial shortening in the septum) was quantified by speckle tracking echocardiography. Primary composite end point was death, urgent cardiac transplantation, or left ventricular assist device implantation at the end of the study. Secondary end points were intermediate-term (6 months) response, quantified as decreases in left ventricular end-systolic volume (ΔLVESV) and BNP (ΔBNP). After a mean clinical follow-up of 15.6 ± 9.0 months; 23 patients had reached the primary end point. Baseline SRSsept (hazard ratio [HR] 0.742; 95% confidence intervals [CI] 0.601–0.916, P < .01]) was independently associated with a better outcome and NYHA class (HR 5.786: 95% CI 2.341–14.299, P < .001) with a worse outcome. Contrary to baseline NYHA class, baseline SRSsept was an independent predictor of both ΔLVESV (beta 0.53; P < .001) and ΔBNP (beta 0.29; P < .01). Intermediate-term ΔLVESV and ΔBNP were associated with a favorable long-term outcome.ConclusionsSRSsept at baseline is a strong, independent predictor of long-term prognosis after CRT and of improvements in left ventricular remodeling and neurohormonal activation at intermediate term.     

Carotid-radial pulse wave velocity responses following hyperemia in patients with congestive heart failure

Carotid-radial pulse wave velocity (PWV) normally decreases following hyperemia and is an indicator of vasodilator reserve. This response is impaired in patients with congestive heart failure (CHF). To identify specific factors related to an impaired response, we studied 50 patients (60 ± 14 years, 67% male) with chronic CHF. Baseline PWV was measured using applanation tonometry and repeated 1 minute after release of upper arm occlusion for 5 minutes. Percentage changes (Δ) of PWV were normally distributed and mean ΔPWV was −2.2 ± 15.3%. On univariate analyses, ΔPWV correlated with New York Heart Association class, mean arterial pressure, log brain natriuretic peptide (BNP) levels, and baseline PWV, but not with left ventricular ejection fraction. Multivariate linear regression analysis demonstrated log BNP levels, mean arterial pressure, and baseline PWV (all P < .05) as independent predictors of ΔPWV. Hyperemia increased PWV in 42% of patients. On logistic regression, higher BNP levels and lower baseline PWV were independent predictors of a PWV increase. Higher BNP levels and lower baseline PWV are independent predictors of an abnormal hyperemic PWV response in patients with CHF. Higher BNP levels may reflect abnormal vasodilator reserve. Forty-two percent of heart failure patients showed an increase in PWV following hyperemia, which may reflect more severe arterial vasodilator impairment.     

血浆B型利钠肽水平对老年腹膜透析患者心功能的评估价值

目的初步观察不同心功能状态下的老年CAPD患者血浆BNP变化，并判断其对心脏组织结构及功能改变的影响。方法收集2006年1月至2007年3月在我院腹膜透析门诊随访的90例老年腹膜透析患者的血浆标本，采用免疫荧光法检测其BNP的水平，以彩色多普勒超声心动图测定患者的左室射血分数（LVEF）、左心室心肌质量指数（LVMl）等指标。依据NYHA分级方案对心衰患者进行心功能分级。探讨BNP水平与心功能LVEF、LVMI等之间的关系。结果（1）腹膜透析患者C组的BNP巾位数（908pg／ml）高于B组（290pg／ml）和A组（195.5pg／ml），（P〈0.05）。（2）相关性分析提示BNP与LVMI呈正相关（r=0.3153，P〈0.05），BNP与LVEF呈负相关（r=-0.4756，P〈0.05）。（3）ROC曲线分析发现BNP诊断CAPD患者心衰的诊断界值（cutoff值）为224pg／ml，其诊断心衰的灵敏度和特异度分别为84.6％和78.9％。结论老年腹膜透析患者的血浆BNP水平随着心功能的减退逐渐增高，血浆BNP的浓度与心室重塑以及左心室功能密切相关，其心衰诊断的灵敏度和特异度较高，作为初步评价老年腹膜透析患者心功能，客观性预测临床心衰发生的实验室指标有其临床应用价值。     

康复治疗对急性心肌梗塞患者血浆脑钠肽水平的影响

目的:观察早期康复治疗对急性心肌梗塞(AMI)患者左室收缩功能及血浆脑钠肽(BNP)水平变化的影响。方法:以超声心动图检测80例AMI患者以及20例健康对照者的左室舒张末内径(LVEDd)、左室射血分数(LVEF)及左室短轴缩短率(LVFS),应用酶联免疫吸附法(ELISA)测定两组脑钠肽(BNP)的浓度;AMI患者被随机分为传统治疗组(38例)和早期康复组(42例),3周和3月时再测定上述指标。结果:AMI患者在治疗后3周LVEDd、LVEF及LVFS与治疗前比较均无统计学差异(P>0.05),3个月时的上述指标与治疗前比较改善显著(P<0.01),但早期康复治疗组LVEF水平较传统治疗组升高更明显(P<0.05)。AMI患者在梗塞后24h血浆BNP水平均高于正常对照组,治疗3周和3月时血浆BNP水平均明显下降(P<0.01),但早期康复组较传统治疗组下降更明显(P<0.05)。两组患者血浆BNP水平与LVEF呈负相关(P<0.01)。结论:早期康复治疗可以改善AMI患者心功能和降低血浆BNP水平;AMI患者血浆BNP水平的改变早于心脏结构的变化,可作为观察AMI病情的一个灵敏指标。     

Efficacy and safety of canagliflozin as add‐on therapy to a glucagon‐like peptide‐1 receptor agonist in Japanese patients with type 2 diabetes mellitus: A 52‐week,open‐label,phase IV study

Sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors and glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) are antihyperglycaemic agents with weight‐lowering effects. The efficacy and safety of the SGLT2 inhibitor canagliflozin as add‐on therapy in Japanese patients with type 2 diabetes mellitus (T2DM) and inadequate glycaemic control with a GLP‐1RA (≥12 weeks) were evaluated in this phase IV study. Patients received canagliflozin 100 mg once daily for 52 weeks. Efficacy endpoints included change in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), body weight, systolic blood pressure (SBP) and HDL cholesterol from baseline to week 52. Safety endpoints included adverse events (AEs), hypoglycaemia and laboratory tests. Of the 71 patients treated with canagliflozin, 63 completed the study. At 52 weeks, HbA1c was significantly reduced from baseline (?0.70%; paired t test, P < .001). Significant changes were also observed in FPG (?34.7 mg/dL), body weight (?4.46%), SBP (?7.90 mm Hg), and HDL cholesterol (7.60%; all P < .001). The incidence of AEs, adverse drug reactions and hypoglycaemia was 71.8%, 32.4% and 9.9%, respectively. All hypoglycaemic events were mild. These findings suggest that the long‐term combination of canagliflozin with a GLP‐1RA is effective and well tolerated in Japanese patients with T2DM.