The endothelin receptor antagonist bosentan improves peripheral endothelial function in patients with type 2 diabetes mellitus and microalbuminuria: a randomised trial

Aims/hypothesis  

Endothelial dysfunction is important in the development of vascular complications in diabetes. Patients with type 2 diabetes have increased production of the vasoconstrictor and pro-inflammatory peptide, endothelin-1. Short-term intra-arterial administration of endothelin antagonists improves endothelium-dependent vasodilatation in patients with type 2 diabetes. We tested the hypothesis that oral administration of the dual endothelin receptor antagonist, bosentan, improves peripheral endothelial function in patients with type 2 diabetes and microalbuminuria.     

Effects of erythritol on endothelial function in patients with type 2 diabetes mellitus: a pilot study

Sugar substitutes are important in the dietary management of diabetes mellitus. Erythritol is a non-caloric dietary bulk sweetener that reverses endothelial dysfunction in diabetic rats. We completed a pilot study to examine the effects of erythritol on vascular function in patients with type 2 diabetes mellitus. Participants (n = 24) consumed erythritol 36 g/day as an orange-flavored beverage for 4 weeks and a single dose of 24 g during the baseline and final visits. We assessed vascular function before and after acute (2 h) and chronic (4 weeks) erythritol consumption. Acute erythritol improved endothelial function measured by fingertip peripheral arterial tonometry (0.52 ± 0.48 to 0.87 ± 0.29 au, P = 0.005). Chronic erythritol decreased central pulse pressure (47 ± 13 to 41 ± 9 mmHg, P = 0.02) and tended to decrease carotid-femoral pulse wave velocity (P = 0.06). Thus, erythritol consumption acutely improved small vessel endothelial function, and chronic treatment reduced central aortic stiffness. Erythritol may be a preferred sugar substitute for patients with diabetes mellitus.     

Effects of improved glycaemic control on endothelial function in patients with type 2 diabetes

Background: Patients with type 2 diabetes have abnormal endothelial function but it is not certain whether improvements in glycaemic control will improve endothelial function. Aims: To examine the effects of short‐term improved glycaemic control on endothelial function in patients with inadequately regulated type 2 diabetes mellitus. Methods: Forty‐three patients with type 2 diabetes and glycosylated haemoglobin (HbA_1c) > 8.9% were randomized to either improved glycaemic control (IC) n = 21 or usual glycaemic control (UC) n = 22 for 20 weeks. Using high‐resolution B‐mode ultrasound, brachial artery flow‐mediated dilatation (FMD) and glyceryl trinitrate‐mediated dilatation (GTN‐D) were measured at baseline and 20 weeks later. Results: After 20 weeks, HbA_1c was significantly lower in IC versus UC (IC 8.02 ± 0.25% versus UC 10.23 ± 0.23%, P < 0.0001) but changes in FMD and GTN‐D were not different between the groups (FMD at baseline and week 20 IC 5.1 ± 0.56% versus 4.9 ± 0.56% and UC 4.2 ± 0.51% versus 3.1 ± 0.51%; P = 0.23: GTN‐D IC 12.8 ± 1.34% versus 10.4 ± 1.32% and UC 13.7 ± 1.2% versus 12.7 ± 1.23%; P = 0.39). In the IC group weight increased by 3.2 ± 0.8 kg after 20 weeks compared to 0.02 ± 0.70 kg in UC (P = 0.003). Blood pressure and serum lipid concentrations did not change in either group. Conclusions: Short‐term reduction of HbA_1c levels did not appear to affect endothelial function in patients with type 2 diabetes and previously poorly regulated glycaemic control. (Intern Med J 2001; 31: 322–328)     

Effects of high dose aleglitazar on renal function in patients with type 2 diabetes

Background

Aleglitazar is a new, balanced dual peroxisome proliferator-activated receptor (PPAR)α/γ agonist designed to optimize lipid and glycemic benefits and minimize PPAR-related adverse effects.

Methods

SESTA R was a 26-week, randomized, double-blind, multicenter study comparing the effects of a supratherapeutic dosage of aleglitazar (600 μg/day) with pioglitazone (45 mg/day) on change in measured GFR (mGFR) in 174 patients with type 2 diabetes and normal to mildly impaired renal function (estimated GFR [eGFR] 60 to 120 ml/min/1.73 m²).

Results

In 118 patients with evaluable GFR measurements, baseline mean (± SD) mGFR was 97.6 ± 17.5 ml/min/1.73 m² in the aleglitazar group and 101.9 ± 21.6 ml/min/1.73 m² in the pioglitazone group. Mean percent change from baseline mGFR was −16.9% (90% confidence interval −22.0 to −11.5) with aleglitazar and −4.6% (−10.15 to 1.35) with pioglitazone, a mean treatment difference of −13.0% (−19.0 to −6.5). The 17% decrease from baseline in mGFR was consistent with the 19% decrease in eGFR Modification of Diet in Renal Disease (MDRD) observed with aleglitazar, which reached a plateau after 4 weeks, with no further progression until treatment discontinuation. Following aleglitazar withdrawal, eGFR values returned to pretreatment levels within the 4-8-week follow-up, which suggests reversible hemodynamic changes in renal function.

Conclusions

Despite the increased incidence of expected, dose-dependent PPAR class side effects (e.g., peripheral edema, weight gain, and congestive heart failure) limiting further development of this supratherapeutic dosage of aleglitazar (600 μg/day), these data, together with the data from the dose-ranging SYNCHRONY study, suggest aleglitazar may be a potential new treatment for cardiovascular risk reduction in post-acute coronary syndrome patients at the therapeutic 150 μg daily dose.     

Preventing glycaemic relapse in recently controlled type 2 diabetes patients: a randomised controlled trial

Aims/hypothesis  

After achieving glycaemic control, many type 2 diabetic patients relapse to clinically significant levels of hyperglycaemia. We sought to determine the optimal frequency of telephone contact by nurse practitioners that was necessary to prevent glycaemic relapse.     

Oral glucose lowering with linagliptin and metformin compared with linagliptin alone as initial treatment in Asian patients with newly diagnosed type 2 diabetes and marked hyperglycemia: Subgroup analysis of a randomized clinical trial

Aims/Introduction

Type 2 diabetes mellitus is an epidemic in Asia, yet clinical trials of glucose‐lowering therapies often enroll predominantly Western populations. We explored the initial combination of metformin and linagliptin, a dipeptidyl peptidase‐4 inhibitor, in newly diagnosed type 2 diabetes mellitus patients in Asia with marked hyperglycemia.

Materials and Methods

This was a post‐hoc subgroup analysis of a multinational, parallel‐group clinical trial in which 316 newly diagnosed type 2 diabetes mellitus patients with glycated hemoglobin A1c (HbA1c) 8.5–12.0% were randomized to double‐blind oral treatment with linagliptin/metformin or linagliptin monotherapy. The primary end‐point was the change from baseline in HbA1c at week 24. We evaluated data for the 125 participants from Asian countries.

Results

After 24 weeks, the mean ± standard error reduction from baseline in HbA1c (mean 10.0%) was ?2.99 ± 0.18% with linagliptin/metformin and ?1.84 ± 0.18% with linagliptin; a treatment difference of ?1.15% (95% confidence interval ?1.65 to ?0.66, P < 0.0001). HbA1c <7.0% was achieved by 60% of participants receiving linagliptin/metformin. The mean bodyweight change after 24 weeks was ?0.45 ± 0.41 kg and 1.33 ± 0.45 kg in the linagliptin/metformin and linagliptin groups, respectively (treatment difference ?1.78 kg [95% confidence interval ?2.99 to ?0.57, P = 0.0043]). Drug‐related adverse events occurred in 9.7% of participants receiving linagliptin/metformin and 4.8% of those receiving linagliptin. Hypoglycemia occurred in 6.5% and 4.8% of the linagliptin/metformin and linagliptin groups, respectively, with no severe episodes. Gastrointestinal disorders occurred in 12.9% and 12.7% of the linagliptin/metformin and linagliptin groups, respectively, with no associated treatment discontinuations.

Conclusions

In people from Asia with newly diagnosed type 2 diabetes mellitus and marked hyperglycemia, the initial combination of linagliptin and metformin substantially improved glycemic control without weight gain and with infrequent hypoglycemia. Initial oral combination therapy might be a viable treatment for such individuals.

     

通心络对改善2型糖尿病患者血管内皮功能的临床观察

目的 探讨通心络胶囊对2型糖尿病患者血管内皮依赖性舒张功能的影响及相关机理.方法 80例2型糖尿病患者,随机分为对照组和通心络组,利用高分辨率超声观察治疗前后肱动脉舒张功能,以及血清一氧化氮(NO)、内皮素(ET)、6-酮-前列腺素F1α(6-keto-PGF1α)和血栓素B2(TXB2)浓度的变化.结果 经4周的治疗,通心络组血流介导的血管舒张(FMD)由治疗前的(8.19±0.71)%,上升为(12.47±0.98)%(P＜0.05).血清NO浓度也较治疗前显著升高[(47.65±4.38)pg/ml对(52.91±4.83)pg/ml,P＜0.001].ET浓度较治疗前显著降低[(31.23±2.46)pg/ml对(24.34±2.46)pg/ml;P＜0.001],而非内皮依赖性的血管舒张反应治疗前后无明显改变(P＞0.05).对照组上述参数治疗前后均无明显变化.结论 在4周的疗程中通心络可以调控NO/ET的平衡,改善2型糖尿病患者血管内皮依赖性的舒张功能,未发现明显的不良反应.     

瑞舒伐他汀对2型糖尿病患者血管内皮功能的影响

目的观察瑞舒伐他汀对2型糖尿病患者血管内皮功能的影响。方法选择2型糖尿病（T2DM）患者并根据血脂水平分为血脂正常组21例和高脂血症组28例,两组均给予瑞舒伐他汀10mg/d口服,连续12周。测定治疗前、后患者的体重指数（BMI）、总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白-胆固醇（LDL-C）、高密度脂蛋白-胆固醇（HDL-C）、空腹血糖、空腹胰岛素、2h血糖、2h胰岛素、糖化血红蛋白（HbA1C）、高敏C反应蛋白（hs-CRP）、血管性血友病因子（vWF）,以及肱动脉内皮依赖性舒张功能（EDD）。结果①瑞舒伐他汀治疗可明显改善高脂血症组的血脂代谢;②血脂正常组及高脂血症组患者治疗后血清hs-CRP较治疗前均明显下降,分别为[（5.27±1.26）mg/Lvs.（6.66±1.37）mg/L,P〈0.01],[（5.31±1.34）mg/Lvs.（6.72±1.39）mg/L,P〈0.01];高脂血症组患者的vWF水平由（188.73±20.74）%降至（169.53±21.01）%,P〈0.05;③高脂血症组患者的肱动脉EDD治疗后较治疗前有明显改善[（6.12±1.02）%vs.（7.58±0.97）%,P〈0.01]。结论瑞舒伐他汀可改善2型糖尿病伴高脂血症患者的血管内皮功能,其机制与其调节血脂,减轻炎症反应有关。     

α-硫辛酸对2型糖尿病氧化应激状态和内皮功能的影响

目的观察α-硫辛酸对2型糖尿病患者氧化应激状态及血管内皮功能的影响。方法30例2型糖尿病患者每日给予α-硫辛酸600mg,治疗2周,检测治疗前后氧化还原系统指标、全血Na -K -ATP酶活力以及血流介导的内皮依赖性血管舒张功能。结果治疗后患者血清丙二醛含量降低、超氧化物歧化酶活力增高,差异有非常显著性(P<0.01),谷胱甘肽、维生素E含量增加,Na -K -ATP酶活力增强,血流介导的内皮依赖性的血管舒张功能增强,但差异无显著性(P>0.05),总体症状评分明显下降(P<0.01)。结论抗氧化剂α-硫辛酸治疗能改善2型糖尿病患者氧化应激状态及血管内皮功能,缓解临床症状。     

糖代谢异常对患者冠状动脉内皮功能影响的研究

目的探讨不同病程2型糖尿病患者冠脉血流速度储备（CFVR）功能的变化。方法我院59例门诊就诊患者分为3组：糖耐量正常组23例,新诊断2型糖尿病患者组21例,已诊断2型糖尿病患者组15例。对3组对象应用腺苷诱导的超声心动图检查,探测左前降支血流速度的改变,评估各组间CFVR功能的改变。结果糖耐量正常组、新发糖尿病患者组与已诊断糖尿病患者组CFVR功能逐渐下降,P〈0.01。结论糖尿病患者CFVR功能显著降低,在新诊断的糖尿病患者内皮功能就已受损,而且随着糖尿病病程的延长进一步恶化。     

Roux-en-Y gastric bypass vs sleeve gastrectomy for obese patients with type 2 diabetes: a randomised trial

Aims/hypothesis

Bariatric surgery is gaining acceptance as a ‘metabolic surgical intervention’ for patients with type 2 diabetes. The optimal form of surgery and the mechanism of action of these procedures are much debated. We compared two bariatric procedures for obese patients with type 2 diabetes and evaluated their effects on HbA_1c and glucose tolerance.

Methods

We performed a parallel un-blinded randomised trial of Roux-en-Y gastric bypass (RYGB) vs sleeve gastrectomy (SG) in 41 obese patients with type 2 diabetes, who were bariatric surgery candidates attending the obesity clinic. HbA_1c, body composition and glucose tolerance were evaluated at baseline, and at 3 and 12 months.

Results

Of the 41 patients, 37 completed the follow-up (19 RYGB, 18 SG). Both groups had similar baseline anthropometric and biochemical measures, and showed comparable weight loss and fat:fat-free mass ratio changes at 12 months. A similar normalisation of HbA_1c levels was observed as early as 3 months post-surgery (6.37?±?0.71% vs 6.23?±?0.69% for RYGB vs SG respectively, p?<?0.001 in both groups for baseline vs follow-up).

Conclusions/interpretation

In this study, RYGB did not have a superior effect in comparison to SG with regard to HbA_1c levels or weight loss during 12 months of follow-up.

Trial registration

ClinicalTrials.gov NCT00667706

Funding

This work was supported by grant no. 3-000-8480 from the Israel Ministry of Health Chief Scientist, the Stephen Morse Diabetes Research Foundation and by Johnson & Johnson.     

Efficacy of a self-management education programme on patients with type 2 diabetes in primary care: A randomised controlled trial

Aim

The purpose of this study was to assess the efficacy of the Spanish Diabetes Self-Management Program (SDSMP) versus usual care in adults with type 2 diabetes mellitus (T2DM) residing in a Spanish region.

Pioglitazone restores endothelial function in patients with type 2 diabetes treated with insulin

The primary aim of this study was to evaluate the effect of pioglitazone on endothelial function, as assessed by flow-mediated dilatation (FMD) nitroglycerine-induced dilatation (NID) in patients with type 2 diabetes mellitus treated with insulin. A randomized double-blind placebo-controlled trial involved 20 patients with insulin-treated type 2 diabetes. Patients received either pioglitazone 30 mg or placebo for 4 months. FMD, NID, and HbA1c were measured before and after 4 months of treatment. HbA1c decreased from 10.0 (+/- 2.3) to 8.4 (+/- 2.0) in the pioglitazone group, a statistically significant improvement in glycemic control (p = 0.018). HbA1c was unchanged in the placebo group (p = 0.477). Endothelial function as assessed by FMD significantly improved from 10.1 (+/- 4.0)% to 14.6 (+/- 6.2)% in the pioglitazone group (p = 0.036) as compared to the placebo group (p = 0.705). There was a trend towards improvement in the NID in the pioglitazone group (from 13.3 +/- 8.0% to 18.9 +/- 5.4%; p = 0.056). In insulin-treated patients with type 2 diabetes, the addition of pioglitazone improves endothelial function, as measured by FMD. Addition of pioglitazone to insulin in type 2 diabetes patients may favorably impact vascular function in diabetes, even after many years of insulin resistance and hyperglycemia.     

Effects of carvedilol versus metoprolol on endothelial function and oxidative stress in patients with type 2 diabetes mellitus

BACKGROUND: Data suggest that carvedilol possesses antioxidant properties that might provide vascular protection. We sought to compare the effects of carvedilol and metoprolol tartrate on endothelial function and oxidative stress in a head-to-head trial. METHODS: Thirty-four patients with type 2 diabetes mellitus (T2DM) and hypertension were randomized to receive either carvedilol (n = 16) or metoprolol (n = 18) in addition to their current antihypertensive medications for 5 months. The following variables were measured pre- and posttreatment: blood pressure, fasting glucose and insulin, insulin resistance by homeostasis-model assessment, hemoglobin A1c, lipids, C-reactive protein (CRP), 8-isoprostane, asymmetric dimethylarginine, oxidized LDL cholesterol, ultrasound assessment of brachial-artery flow-mediated dilation (FMD), nitroglycerin-induced endothelium-independent dilation (EID), brachial and carotid artery distension, distensibility and compliance, and carotid artery intima-media thickness (cIMT). RESULTS: Both carvedilol and metoprolol treatment resulted in significant and similar decreases in systolic (P < .05) and diastolic (P < .0001) blood pressure. Compared with metoprolol, carvedilol significantly improved FMD (P < .001). No differences between groups were noted for any of the glycemic or lipid variables except for HDL cholesterol, which significantly decreased (P < .05) in the metoprolol group compared with the carvedilol group. No differences were observed between groups for CRP, the markers of oxidative stress, EID, arterial stiffness, or cIMT. CONCLUSIONS: Compared with metoprolol, carvedilol significantly improves endothelial function in patients with T2DM. Changes in glycemic control and oxidative stress do not seem to explain the observed improvements in FMD, which suggests that other mechanisms may be involved.