Effects of losartan on diabetic maculopathy in type 2 diabetic patients: a randomized,double-masked study

OBJECTIVE: Diabetic maculopathy (DMa) is a leading cause of visual loss in the western world. Preliminary studies have suggested that angiotensin converting enzyme inhibitors might be effective in preventing the progression of diabetic retinopathy, but no studies have quantitatively assessed the effect of this treatment on macular oedema in patients with DMa. We evaluated the effect of treatment with the angiotensin II receptor antagonist losartan on macular oedema and hard exudates in patients with an advanced stage of DMa. DESIGN: Randomized, placebo-controlled, double-masked and parallel-group trial. SETTING: Academic medical centre. SUBJECTS: Twenty-four type 2 diabetic patients with DMa. INTERVENTION: Subjects were randomly assigned to a 4-month treatment with either losartan (50 mg o.d.) or placebo. MAIN OUTCOME MEASURES: (i) Degree of macular oedema as estimated by optical coherence tomography scanning of the retina; (ii) fundus photography and flourescein angiography; (iii) 24-h ambulatory blood pressure (BP); (iv) urinary albumin excretion (UAE); and (v) transcapillary escape rate of albumin (TERalb). RESULTS: Central retinal thickness increased from 244 +/- 16 to 256 +/- 31 microm in the losartan group, whilst there was no change in the placebo group (245 +/- 36 microm vs. 242 +/- 30 microm), P = 0.017. Day BP were lowered in the losartan group (from 144/83 +/- 17/10 to 138/78 +/- 20/11 mmHg) compared with the placebo group (140/81 +/- 14/5 to 139/82 +/- 13/9 mmHg), P = 0.27 for systolic and P = 0.009 for diastolic BP. Importantly, there were no changes in night BP in any of the groups. We found no changes in the number of hard exudates, semiquantitative retinopathy grade, visual acuity, UAE, or TERalb in any of the groups. CONCLUSIONS: Type 2 diabetic patients with maculopathy do not seem to benefit from short-term treatment with losartan (50 mg once daily) as far as retinal thickness is concerned, as this dose may increase retinal thickness in the central macular area. Long-term studies are required to assess the clinical implications of these findings.     

Ⅱ型糖尿病患者的定量超声骨密度含量的研究

对１０５例Ⅱ型糖尿病患者的定量超声骨量（ＱＵＳ）进行了研究。结果表明，Ⅱ型糖尿病患者的超声导速度（ＳＯＳ）及其标准差（ｓ）均显著低于健康对照组，且Ⅱ型糖尿病患者的ＳＯＳ峰值比正常组ＳＯＳ峰值推迟一个年龄组，表明Ⅱ型糖尿病患者伴有不同程度骨钙、磷代谢异常，最终导致骨质疏松症。本结果还显示，女性患者显著低于男性患者ＳＯＳ，ｓ，表明女性Ⅱ型糖尿病患者更易受多种因素的影响，导致骨矿含量明显降低。因此，对Ⅱ     

Efficacy and safety of empagliflozin in combination with insulin in Chinese patients with type 2 diabetes and insufficient glycaemic control: A phase III,randomized, double-blind,placebo-controlled,parallel study

Aim

To evaluate the efficacy and safety of empagliflozin in combination with insulin ± oral antidiabetic drugs (OADs) over 24 weeks, in Chinese patients with type 2 diabetes (T2D) who had insufficient glycaemic control.

Materials and Methods

This was a randomized, double-blind, placebo-controlled, parallel group, multicentre phase III study. Adult patients with T2D and insufficient glycaemic control who received insulin ± up to two OADs were randomized (1:1:1) to receive empagliflozin 10 or 25 mg, or placebo for 24 weeks. The primary endpoint was change from baseline in HbA1c at week 24.

Results

Of 219 randomized patients, 73 patients were in each treatment group; baseline characteristics were comparable among the groups. There was a significantly larger decrease from baseline in HbA1c (adjusted mean treatment difference −0.99 and −0.98 for in the empagliflozin 10 and 25 mg groups, respectively; P < .0001) with both doses of empagliflozin than with placebo. There were also significantly larger decreases from baseline in fasting plasma glucose, 2-hour postprandial glucose and body weight with both empagliflozin doses than with placebo. Among patients in the empagliflozin 10 mg, 25 mg and placebo groups, 17.8%, 9.6% and 11.0% reported confirmed hypoglycaemic events, respectively (nominal P = .2422 and .7661 in the empagliflozin 10 and 25 mg groups, respectively), and no Clinical Events Committee-confirmed diabetic ketoacidosis events were reported.

Conclusions

In Chinese patients with T2D, empagliflozin combined with insulin ± OADs improved glycaemic control and was well tolerated, without an increased risk of hypoglycaemia.     

The efficacy of niacin supplementation in type 2 diabetes patients: Study protocol of a randomized controlled trial

Background:Dyslipidemia is a main risk factor of cardiovascular disease in the diabetic patients. Niacin was found acutely to decrease the plasma concentration of free fatty acids by inhibiting their mobilization from adipose tissue. This present study is a double blinded, randomized, and prospective trial to determine the effect of niacin during dyslipidemia in type 2 diabetic patients.Methods:This randomized controlled, double-blinded, single center trial is carried out according to the principles of Declaration of Helsinki. This present study was approved in institutional review committee of the Second Affiliated Hospital of Dalian Medical University. All the patients received the informed consent. Diabetic patients were randomized (1:1) to receive 3-month treatment with extended-release niacin or matching placebo. The major outcome of our present study was the change in the level of HbA1c from the baseline to week 12. Secondary outcome measures contained the levels of fasting blood glucose, the concentrations of serum transaminase, the other laboratory variables, and self-reported adverse events. The P < .05 was regarded as statistically significant.Results:We assumed that adding the niacin to the medication in patients with type 2 diabetes would reduce dyslipidemia and achieve target lipid levels.Trial registration:This study protocol was registered in Research Registry (researchregistry5925).     

随机、双盲、安慰剂对照评价盐酸吡格列酮并用磺酰脲类药物治疗2型糖尿病的有效性和安全性

目的 评价盐酸吡格列酮30 mg与磺酰脲类药物并用治疗2型糖尿病的有效性和安全性。方法 采用多中心、随机、双盲和安慰剂平行对照的研究方法。236例使用稳定剂量磺酰脲类药物治疗至少30 d而血糖控制不佳(空腹血糖7.5～ 13.0 mmol/L,糖化血红蛋白7.0％～12.0％)的2型糖尿病患者随机分入吡格列酮30 mg组与安慰剂组,磺酰脲类药物种类和剂量不变,治疗随访共16周。结果 16周时,吡格列酮组空腹血糖下降(1.48±2.08) mmol/L,安慰剂组则上升(0.17±1.92) mmol/L(P ＜0.05);吡格列酮组和安慰剂糖化血红蛋白分别下降(0.92±0.10)％和(0.28±0.11)％,空腹胰岛素下降(0.24±0.04) mU/L和(0.09±0.04) mU/L,稳态模型评价法计算的胰岛素抵抗指数下降1.42±2.90和0.46 ±3.52,TG平均下降0.36 mmol/L和0.14 mmol/L,HDL-C则平均上升0.17 mmol/L和0.05 mmol/L,两组间差异均有统计学意义(值均P＜0.05)。结论 为期16周的临床研究显示,2型糖尿病患者在单纯应用磺酰脲类血糖控制欠佳时加用吡格列酮30 mg/d,不仅可进一步改善血糖控制、增强胰岛素敏感性,还可降低TG、升高HDL-C水平,安全性和耐受性好。     

The efficacy and tolerability of fosinopril in Chinese type 2 diabetic patients with moderate renal insufficiency

BACKGROUND: The renoprotective effect of angiotensin II antagonists has been demonstrated in type 2 diabetic patients with nephropathy but similar data on angiotensin-converting enzyme (ACE) inhibitors are limited. We examined the efficacy and tolerability of fosinopril, an ACE inhibitor with dual hepatic and renal clearance, in 38 type 2 diabetic patients with moderate renal impairment (plasma creatinine 130-300 micromol/l) over a 2-year period. METHODS: This was a single-centre, randomized, double-blinded, placebo-controlled trial comparing fosinopril 20 mg daily vs. placebo in addition to conventional antihypertensive treatment over a 2-year period. The primary endpoints were the rate of change and the percentage change in both 24-h urinary albumin excretion (UAE) and creatinine clearance (CrCl). RESULTS: The mean age of the patients was 65 +/- 6 years (range 47-76 years, median 66 years) and plasma creatinine 190 +/- 49 micromol/l. For similar blood pressure control, the percentage change of UAE in patients with microalbuminuria was greater in the fosinopril than the placebo group (-24.2 +/- 28.8 vs. 11.6 +/- 42.1%, p = 0.003 after adjustment for baseline covariates). In the fosinopril group, the rate of change of endogenous CrCl was slower than the placebo group (-0.07 +/- 0.19 vs. -0.24 +/- 0.35 ml/min/week, p = 0.026). The incidence of adverse events was similar between the two groups. CONCLUSIONS: Fosinopril treatment reduced albuminuria and rate of decline in renal function in type 2 diabetic patients with moderate renal insufficiency and did not increase the incidence of adverse events.     

Traditional Chinese medicine body constitution predicts new-onset diabetic albuminuria in patients with type 2 diabetes: Taichung diabetic body constitution prospective cohort study

This prospective cohort study explored whether body constitution (BC) independently predicts new-onset albuminuria in persons with type 2 diabetes mellitus (T2DM) enrolled in the diabetes care management program (DCMP) of a medical center, providing evidence of integrating traditional Chinese medicine into DCMP for improving care quality. Persons with T2DM (n = 426) originally without albuminuria enrolled in DCMP were recruited in 2010 and were then followed up to 2015 for detecting new-onset albuminuria. The participants received urinalysis and blood test annually. Albuminuria was determined by an elevated urinary albumin/creatinine ratio (≥ 30 µg/mg), and poor glucose control was defined as Glycosylated hemoglobin above or equal to 7%. BC type (Yin deficiency, Yang deficiency, and phlegm stasis) was assessed using a well-validated body constitution questionnaire at baseline. Risk factors for albuminuria (sociodemographic factors, diabetes history, lifestyle behaviors, lipid profile, blood pressure, and kidney function) were also recorded. Hazard ratios (HR) of albuminuria for BC were estimated using multivariate Cox proportional hazards model. During the 4-year follow-up period, albuminuria occurred in 30.5% of participants (n = 130). The HR indicated that Yin deficiency was significantly associated with an increased risk of new-onset albuminuria in persons with T2DM and good glucose control after adjustment for other risk factors (HR = 2.09; 95% confidence interval = 1.05–4.17, P = .04), but not in those with poor glucose control. In persons with T2DM and poor glucose control, phlegm stasis was also significantly associated with a higher risk of albuminuria (2.26; 1.03–4.94, P = .04) after multivariate adjustment, but not in those with good glucose control. In addition to already-known risk factors, BC is an independent and significant factor associated with new-onset albuminuria in persons with T2DM. Our results imply Yin deficiency and phlegm stasis interacting with glucose control status may affect new-onset albuminuria in persons with T2DM.     

The efficacy of self-monitoring of blood glucose in the management of patients with type 2 diabetes treated with a gliclazide modified release-based regimen. A multicentre, randomized, parallel-group, 6-month evaluation (DINAMIC 1 study)

Aim: To determine if therapeutic management programmes for type 2 diabetes that include self‐monitoring of blood glucose (SMBG) result in greater reductions in glycated haemoglobin (HbA1c) compared with programmes without SMBG in non‐insulin requiring patients. Methods: Multicentre, randomized, parallel‐group trial. A total of 610 patients were randomized to SMBG or non‐SMBG groups. Patients in both groups received the same oral antidiabetic therapy using a gliclazide modified release (MR)–based regimen for 27 weeks. The primary efficacy end‐point was the difference between groups in HbA1c at the end of observation. Results: A total of 610 patients were randomized: 311 to the SMBG group and 299 to the non‐SMBG group. HbA1c decreased from 8.12 to 6.95% in the SMBG group and from 8.12 to 7.20% in the non‐SMBG group; between‐group difference was 0.25% (95% CI: 0.06, 1.03; p = 0.0097). Symptoms suggestive of mild to moderate hypoglycaemia was the most commonly reported adverse event, reported by 27 (8.7%) and 21 (7.0%) patients in the SMBG and non‐SMBG groups, respectively; the incidence of symptomatic hypoglycaemia was lower in the SMBG group. Conclusion: In patients with type 2 diabetes, the application of SMBG as an adjunct to oral antidiabetic agent therapy results in further reductions in HbA1c.     

阿卡波糖治疗在日常临床工作中的有效性、安全性和被接受程度——对中国2型糖尿病患者的阿卡波糖上市后监测

此项上市后监测的目的是为了评价中国的2型糖尿病患者日常实际使用阿卡波糖的有效性、安全性和接受程度。中国共有231位临床医师招募了2480例2型糖尿病患者参加了本次开放性、前瞻性，非对照、非随机的多中心研究。主要的疗效参数是阿卡波糖治疗后空腹和餐后血糖水平的变化以及HbA1c水平的变化。大部分患者入组之前曾接受其他口服降糖药或胰岛素的治疗，并且在平均为13．5周的观察期内接受了降糖药物联合治疗。大部分患者阿卡波糖的起始剂量为50mg，3次／日。在整个研究期间，阿卡波糖使空腹血糖浓度下降了56．1mg／d（18mg／d葡萄糖=1mmol／L葡萄糖），餐后2h血糖下降了111．3mg／d，HbA。c下降了1．9％，体重下降0．9kg。研究期间出现了76次阿卡波糖相关的不良事件，两例患者出现严重不良事件。主治医师对90．1％的患者做出“非常好”或“较好”的评价，患者对阿卡波糖的耐受性为89．1％，接受程度为87．1％。无论作为单药治疗还是和其他降糖药物合用，每天常规使用阿卡波糖对于中国的2型糖尿病患者是有效、安全和接受程度较好的。     

国产瑞格列奈的有效性和安全性再观察

采用多中心、开放性临床试验,观察国产瑞格列奈上市后治疗2型糖尿病的有效性和安全性。瑞格列奈治疗12周可显著降低空腹血糖、餐后2小时血糖和糖化血红蛋白水平,副作用轻微。     

Gliclazide modified release: results of a 2-year study in patients with type 2 diabetes

AIM: To evaluate the efficacy and safety of gliclazide modified release (MR), alone or combined with other oral antidiabetic drug(s) over 2 years in type 2 diabetic patients. METHODS: Two consecutive periods: (i) a 10-month, double-blind comparative study, where 800 type 2 diabetic patients were randomized either to gliclazide MR (30-120 mg) once daily or to gliclazide (80-320 mg) twice daily. All the patients were then treated with gliclazide MR for a 2-month switch period; (ii) 549 patients were subsequently enrolled in a 12-month, open-label period on gliclazide MR alone or in combination according to glycaemic control, 507 of whom completed the study. RESULTS: Glycated haemoglobin (HbA1c) significantly decreased from baseline over 2 years by -0.46 +/- 1.08% in the whole cohort of 2-year completed patients, -0.95% in the subgroup of diet-failed patients and by -0.34% in the subgroup of patients pretreated with one oral antidiabetic drug. HbA1c was reduced by -0.43 +/- 1.02% and by -0.51 +/- 1.16%, when gliclazide MR was used in monotherapy and in combination therapy, respectively. The overall incidence of symptoms suggestive of hypoglycaemia was 4.8 episodes/100 patient-year, with no severe episode. This incidence was similarly low in elderly patients and patients with impaired renal function. CONCLUSION: Gliclazide MR alone or in combination with another oral antidiabetic drug significantly improved glycaemic control in type 2 diabetic patients over 2 years with a very good safety profile, notably in the elderly and in patients with impaired renal function.     

Association of homocysteine with peripheral neuropathy in Chinese patients with type 2 diabetes

Aim

To explore the relationship between plasma total homocysteine concentration and diabetic neuropathy in Chinese patients with type 2 diabetes.

Methods

Chinese patients with type 2 diabetes (n = 249) were enrolled in a cross-sectional hospital based study. Diabetic neuropathy status was documented by presence of clinical signs and confirmed by electromyography. Plasma total homocysteine concentration was measured using fluorescence polarization immunoassay. Traditional risk factors for diabetic neuropathy were obtained from fasting blood samples and interviewer-questionnaire.

Results

Plasma total homocysteine levels were higher in subjects with diabetic neuropathy than without (12.8 (9.2-14.8) μmol/l vs. 8.0 (7.7-9.1) μmol/l, p = 0.005). The association of homocysteine with diabetic neuropathy was independent of major traditional risk factors for diabetic neuropathy (duration of diabetes, HbA1c) and determinants of higher homocysteine concentration (age, gender, serum folate and vitamin B12, renal status, and Biguanide use) (OR: 1.12 (1.00-1.25), p = 0.042). Furthermore, per increase of 4.0 μmol/l plasma homocysteine was related to neuropathy, after controlling for per unit increase of other factors (OR: 1.17 (0.94-1.33), p = 0.045).

Conclusion

Plasma total homocysteine concentration was independently associated with occurrence of diabetic neuropathy in Chinese people. Future prospective studies are warranted to clarify the relationship.     

2型糖尿病微量白蛋白尿与氧化应激的关系

目的探讨2型糖尿病患者微量白蛋白尿与氧化应激状态的关系。方法将72例2型糖尿病患者分为无微量白蛋白尿的糖尿病组（DM组）和伴有微量白蛋白尿的糖尿病肾病组（DN组）,选择30例无糖尿病患者作正常对照组（NGT组）,测定三组的血清丙二醛（MDA）水平、生化指标及年龄、身高、体质量指数。结果DN组MDA水平明显高于NGT组及DM组,MDA水平与尿微量白蛋白排泄率（UAER）有显著相关性。结论与无微量白蛋白尿的糖尿病患者相比,糖尿病肾病患者存在着严重的氧化应激状态,这可能与UAER的严重程度相关。     

马来酸罗格列酮对2型糖尿病患者的长期疗效与安全性的观察

目的观察罗格列酮对2型糖尿病（T2DM）患者的长期疗效及安全性。方法采用自身治疗前后对照的方法，42例合用磺脲类、双胍类和α糖苷酶抑制剂药物治疗3个月以上血糖控制不良的T2DM患者加服马来酸罗格列酮，随访36个月，观察治疗前后血糖、HbA1c、FIns、HOMAIR、ISI、血清高敏C反应蛋白（hsC-RP）、Hb、谷丙转氨酶（GPT）、谷草转氨酶（GOT）、谷氨酰转移酶（γ-GT）等的变化。结果马来酸罗格列酮治疗组FPG、2hPG、HbA1c、FIns、hsCRP均较治疗前明显下降（P〈0．01），且与时间成正比，约治疗9个月后疗效趋于稳定，GPT、GOT、γ-GT较治疗前明显下降（P〈0．05）；所见的不良反应为下肢水肿，发生率为4．8％，经对症处理后消失。结论马来酸罗格列酮能有效降低长期口服降糖药物控制不佳的T2DM患者的血糖水平，对因脂肪肝而致的肝脏酶谱的增高有治疗作用，有良好的安全性。     

国产格列齐特缓释片治疗2型糖尿病的疗效及安全性

目的评价国产格列齐特缓释片治疗2型糖尿病(T2DM)的疗效和安全性。方法234例T2DM患者随机分为两组:对照组117例,口服格列齐特片,每次80 mg,每日2次;试验组117例,口服格列齐特缓释片,每次60 mg,每日1次。疗程12周。结果225例完成了试验。两组均可有效降低空腹血糖(FBG)、餐后2 h血糖(2 hBG)和糖化血红蛋白(HbA1c),差异无统计学意义。格列齐特缓释片组降低FBG的显效率与总有效率分别为51.26%和93.16%,格列齐特片组的显效率与总有效率分别为44.44%与94.02%。格列齐特缓释片组降低2 hBG的显效率与总有效率分别为29.91%和92.31%,格列齐特片组的显效率与总有效率分别为23.08%与89.74%。两组不良反应发生率均为7.69%。未见严重不良反应及实验室证实的低血糖(血糖≤2.78 mmol/L),个别病例谷丙转氨酶轻度升高。结论国产格列齐特缓释片能有效地降低FBG、2 hBG以及HbA1c水平。患者耐受性好,不良反应轻微。     

2型糖尿病患者勃起功能障碍患病率及西地那非的疗效和安全性评价

目的调查内分泌门诊中糖尿病患者阴茎勃起功能障碍(ED)患病率,并评价西地那非(万艾可)在糖尿病合并ED患者中的疗效和安全性。方法多中心收集2型糖尿病男性患者6193例,入选6178例,患者签署知情同意书后,根据国际勃起功能指数表(IIEF5)患者进行自我评分。对3个月内服用3剂万艾可的患者除要求填写治疗前的IIEF5表评分外,还要求填写治疗后的总体疗效问题回答表,以评价万艾可治疗的疗效,并记录患者服药后的不良事件以评价其安全性。结果国内42家医院内分泌门诊2型糖尿病患者中ED的患病率为75.2%,其中重度、中度和轻度ED分别为9.1%、17.2%、48.9%。该受检人群中ED的知晓率为85.0%,但治疗率仅为9.4%。多因素回归分析显示患者年龄、糖尿病病程、血糖控制不佳(HbA1C>6.5%)与糖尿病患者ED的发生独立相关。共有389例患者服用万艾可治疗,治疗后患者IIEF5总评分和各问题的评分均显著高于治疗前(P<0.01);根据IIEF5评分,治疗后重、中度ED患者例数明显少于治疗前(P<0.01)。根据总体疗效评估问题的回答,给予万艾可治疗后勃起功能改善率达86.4%。对安全性评价显示服用万艾可后出现的与药物有关的不良事件主要是颜面潮红、头痛、心悸和口干等,大多为轻度。结论在2型糖尿病患者中ED是常见的合并症,万艾可治疗糖尿病合并ED疗效确切,并有良好的安全性。