Multifactorial intervention in individuals with type 2 diabetes and microalbuminuria: the Microalbuminuria Education and Medication Optimisation (MEMO) study

Aims

To determine whether tighter cardiovascular risk factor control with structured education in individuals with type 2 diabetes (T2DM) and microalbuminuria benefits cardiovascular risk factors.

Methods

Participants from a multiethnic population, recruited from primary care and specialist clinics were randomised to intensive intervention with structured patient (DESMOND model) education (n = 94) or usual care by own health professional (n = 95). Primary outcome: change in HbA1c at 18 months. Secondary outcomes: changes in blood pressure (BP), cholesterol, albuminuria, proportion reaching risk factor targets, modelled cardiovascular risk scores.

Results

Mean (SD) age and diabetes duration of participants were 61.5 (10.5) and 11.5 (9.3) years, respectively. At 18 months, intensive intervention showed significant improvements in HbA1c (7.1(1.0) vs. 7.8(1.4)%, p < 0.0001), systolic BP (129(16) vs. 139(17) mmHg, p < 0.0001), diastolic BP (70(11) vs. 76(12) mmHg, p < 0.001), total cholesterol (3.7(0.8) vs. 4.1(0.9) mmol/l, p = 0.001). Moderate and severe hypoglycaemia was 11.2 vs. 29.0%; p = 0.001 and 0 vs. 6.3%; p = 0.07, respectively. More intensive participants achieved ≥3 risk factor targets with greater reductions in cardiovascular risk scores.

Conclusions

Intensive intervention showed greater improvements in metabolic control and cardiovascular risk profile with lower rates of moderate and severe hypoglycaemia. Intensive glycaemic interventions should be underpinned by structured education promoting self-management in T2DM.     

Effect of inhibition of the renin-angiotensin system on development of type 2 diabetes mellitus (meta-analysis of randomized trials)

The increasing prevalence and costs of type 2 diabetes mellitus (DM) make strategies to prevent its development vitally important. This analysis was conducted to determine if angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) prevent the development of DM. Medline and the Cochrane Central Register of Controlled Trials (1966 to May 2006) were queried for prospective, randomized, placebo-controlled or active-controlled trials of ACE inhibitor or ARB therapy in adults that reported rates of new-onset diabetes during follow-up. Meta-analyses of summary statistics from individual trials were performed using a random-effects model. Thirteen trials with a total of 93,451 patients were identified. Renin-angiotensin system antagonists reduced the incidence of DM from 9% in nontreated patients to 7.1% in those treated, a 26% reduction in odds (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.66 to 0.81, p<0.001). The effect sizes were similar in trials that randomized only hypertensive subjects (OR 0.73, 95% CI 0.66 to 0.82, p<0.001) and trials that studied the impact of renin-angiotensin system inhibition on outcomes of patients with vascular disease or heart failure (OR 0.67, 95% CI 0.50 to 0.90, p=0.008). ACE inhibitors and ARBs had comparable effects on the development of DM. In ACE inhibitor trials, the odds of developing DM were reduced by 28% (OR 0.72, 95% CI 0.63 to 0.84, p<0.001), and in the 5 ARB studies, there was a 27% reduction (OR 0.73, 95% CI 0.64 to 0.84, p<0.001) in the odds. In conclusion, evidence accumulated to date indicates that inhibition of the renin-angiotensin system may contribute to the prevention of DM.     

Efficacy of renin-angiotensin system (RAS) blockers on cardiovascular and renal outcomes in patients with type 2 diabetes

Cardiovascular disease is the predominant cause of morbidity in people with type 2 diabetes. Hypertension frequently coexists with diabetes and substantially increases the risk of developing end-organ damage. Controlling hypertension in patients with diabetes is therefore critical to reducing microvascular and macrovascular complications. Agents that block the renin-angiotensin system are increasingly used in patients with diabetes based on their cardiovascular and renoprotective effects, in addition to their direct effects on reducing blood pressure. Telmisartan, an angiotensin II receptor blocker (ARB), has a number of distinguishing pharmacological properties such as having the longest half-life and highest lipophilicity in its class. The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET(?)) trial showed that telmisartan reduces cardiovascular morbidity (including myocardial infarction and stroke) in subjects with a broad spectrum of cardiovascular risk factors, including type 2 diabetes. Telmisartan is the only ARB indicated for the reduction of cardiovascular morbidity in patients with diabetes and end-organ damage, as well as in patients without diabetes but with a history of coronary artery disease, peripheral artery disease, or previous stroke. Trials of telmisartan in patients with diabetes and varying degrees of nephropathy also suggest that this drug can slow the progression of renal disease, an effect that appears to be at least partly independent of reduction in blood pressure. Telmisartan is therefore an important therapeutic option for optimizing cardiovascular and renal protection in the type 2 diabetic population.     

iGlarLixi effectively reduces residual hyperglycaemia in patients with type 2 diabetes on basal insulin: A post hoc analysis from the LixiLan-L study

Globally, nearly half of patients with type 2 diabetes (T2D) do not successfully achieve target HbA1c with basal insulin, despite meeting fasting plasma glucose (FPG) targets. In this post hoc analysis of the LixiLan-L study, we determined whether iGlarLixi, a fixed-ratio combination of insulin glargine Gla-100 (iGlar) and the glucagon-like peptide-1 receptor agonist lixisenatide (Lixi), addresses the challenge of reducing residual hyperglycaemia in patients with T2D. In LixiLan-L, a randomized, open-label study, 1018 patients with T2D on basal insulin for ≥6 months ± oral antidiabetes drugs entered a 6-week run-in period, during which they were switched to and/or optimized for a daily dose of iGlar while continuing only metformin. Following the run-in period, 736 patients were then randomized to receive iGlarLixi or were continued on iGlar for 30 weeks ± metformin. Residual hyperglycaemia was defined as HbA1c ≥ 7.0% despite FPG of <140 mg/dL. The proportion of patients with residual hyperglycaemia was similar in both treatment arms at screening (~~42%), and increased after the run-in period (~~62%). After 30 weeks, the proportion of patients with residual hyperglycaemia declined to 23.8% in the iGlarLixi versus 47.1% in the iGlar arm (P < .0001). The proportion of patients achieving both HbA1c (<7.0%) and FPG (<140 mg/dL) targets was higher in the iGlarLixi compared with the iGlar arm (50.3% vs. 27.4%, respectively; P < .0001). iGlarLixi effectively reduces residual hyperglycaemia in patients with T2D on basal insulin therapy.     

正常血压Ⅱ型糖尿病患者尿微量白蛋白多因素分析

应用多因素逐步回归的分析方法对７０例正常血压Ⅱ型糖尿病患者有关微量尿白蛋白排泄率（ＵＡＥＲ）的危险因素，包括年龄、体重指数（ＢＭＩ）、病程、收缩压、舒张压、空腹血糖（ＦＢＧ）、糖化血红蛋白（ＨｂＡ１ｃ）、红细胞山梨醇（ＲＢＣＳ）、血脂、血浆纤维蛋白原（Ｆｇ）、血浆镁、心血管交感神经活性（ＳＡ）和副交感神经活性（ＰＡ）等作了探讨。结果显示：糖尿病患者尿ＵＡＥＲ水平明显增高；多因素分析表明，在上述１７     

Correction of hypomagnesemia by dapagliflozin in patients with type 2 diabetes: A post hoc analysis of 10 randomized,placebo-controlled trials

AimsHypomagnesemia (serum magnesium [Mg] <0.74 mmol/L [<1.8 mg/dL]) is commonly observed in patients with type 2 diabetes (T2D). This study investigated the effect of treatment with dapagliflozin 10 mg on Mg concentrations in patients with T2D.MethodsIn this post hoc analysis, we used pooled data from 10 placebo-controlled studies of dapagliflozin over 24 weeks of treatment in patients with T2D. We evaluated the change in Mg in patients receiving dapagliflozin vs. placebo overall, and in subgroups with baseline hypomagnesemia and normal/hypermagnesemia (≥0.74 mmol/L [≥1.8 mg/dL]). We determined the proportion of patients with baseline hypomagnesemia who achieved Mg ≥0.74 mmol/L (≥1.8 mg/dL).ResultsA total of 4398 patients with T2D were included. The mean change from baseline to week 24 in Mg was significantly larger with dapagliflozin vs. placebo; difference, 0.06 mmol/L (95% confidence interval [CI]: 0.05, 0.06). The proportion of patients with Mg within the population reference range after 24 weeks of treatment was significantly higher with dapagliflozin vs. placebo; difference, 47.8% (95% CI: 41.4, 53.9). The proportion of patients displaying hypermagnesemia did not increase with dapagliflozin treatment.ConclusionsTreatment with dapagliflozin 10 mg resulted in correction of Mg concentrations in patients with T2D and hypomagnesemia.     

Effect of pramlintide on A1C and body weight in insulin-treated African Americans and Hispanics with type 2 diabetes: a pooled post hoc analysis

An unresolved problem in the management of type 2 diabetes is that improvement of glycemic control with insulin, insulin secretagogues, and insulin sensitizers is often accompanied by undesired weight gain. This problem is of particular concern in ethnic groups with a high propensity for diabetes and obesity, such as African Americans and Hispanics. Two 1-year, randomized, double-blind, placebo-controlled clinical trials in insulin-treated patients with type 2 diabetes have shown that adjunctive therapy with pramlintide, an analog of the human beta-cell hormone amylin, reduces A(1C) with concomitant weight loss, rather than weight gain. To assess the effect of pramlintide in various ethnic groups with type 2 diabetes using insulin, we conducted a pooled post hoc analysis of the 2 trials, which included all Caucasian (n = 315), African American (n = 47), and Hispanic (n = 48) patients (age 57 years, A(1C) 9.1%, body mass index [BMI] 33 kg/m(2), mean values) who completed 52 weeks of treatment with either pramlintide (120 microg twice daily or 150 microg 3 times a day) or placebo. Primary endpoints included changes from baseline to week 52 in A(1C) and body weight. Collectively, pramlintide-treated patients achieved significant reductions from baseline in both A(1C) and body weight (placebo-corrected treatment effects at week 52: -0.5% and -2.6 kg, respectively, both P <.0001). The simultaneous reduction in A(1C) and body weight at week 52 was evident across all 3 ethnic groups and appeared to be most pronounced in African Americans (-0.7%, -4.1 kg), followed by Caucasians (-0.5%, -2.4 kg) and Hispanics (-0.3%, -2.3 kg). The glycemic improvement with pramlintide was not associated with an increased incidence of hypoglycemia over the entire study period (43% pramlintide v 40% placebo). Nausea, the most common adverse event associated with pramlintide treatment, was mostly mild and confined to the first 4 weeks of therapy (25% pramlintide v 16% placebo) with comparable patterns in the 3 ethnic groups. Thus, pending further experience, the combined improvement in glycemic and weight control with pramlintide treatment appears to be generalizable to a broad population of mixed ethnicity.     

关注利拉鲁肽在2型糖尿病治疗中的心血管益处

[提要]2型糖尿病常伴随超重或肥胖、高血压、高血脂等代谢异常状态,并与心血管风险的增加密不可分.目前大多数降糖药以降糖为主要机制,难以兼顾多种代谢异常状态并降低心血管风险.本文对利拉鲁肽在降低血糖的同时,对体重、血压、血脂的有益影响,以及对心血管系统可能的保护作用的临床研究进展作一综述.     

微量白蛋白尿:2型糖尿病慢性并发症的关键标志

微量白蛋白尿的出现是肾小球滤过膜损伤的结果,是糖尿病肾损害的最早临床征象;伴微量白蛋白尿的糖尿病患者其心血管病变的发生率及病死率明显增高.对糖尿病微量白蛋白尿期患者进行针对可能导致病情加重的多个危险因素的强化治疗,包括改变生活方式、严格控制血糖、RAS系统阻断、严格降压、他汀类调脂及抗凝等能延缓或阻止病变的进展.     

Safety and efficacy of empagliflozin in elderly Japanese patients with type 2 diabetes mellitus: A post hoc analysis of data from the SACRA study

Elderly diabetic patients are likely to have uncontrolled nocturnal hypertension, which confers higher risks of cardiovascular events and heart failure. To investigate the efficacy and safety of empagliflozin in elderly patients with type 2 diabetes (T2DM), a sub‐analysis was performed of data from the SGLT2 inhibitor and Angiotensin receptor blocker Combination theRapy in pAtients with diabetes and uncontrolled nocturnal hypertension (SACRA) study, a multi‐center, double‐blind, randomized, parallel study of T2DM patients who were treated with empagliflozin for 12 weeks. In the present analysis, we compared efficacy and safety outcomes in participants aged <75 and ≥75 years. At baseline, 44 participants were ≥75 years and 87 were <75 years. Nighttime ambulatory systolic blood pressure (SBP) decreased by 4.2 mm Hg in the ≥75‐year‐old group and by 7.9 mm Hg in the <75‐year‐old group (p = .884 for the between‐age group difference in the change between baseline and week 12) [primary endpoint]. Empagliflozin, but not placebo, significantly reduced mean 24‐h SBP (−8.7 mm Hg in ≥75‐year‐olds vs. −11.0 mm Hg in <75‐year‐olds) and daytime SBP (−10.8 mm Hg in ≥ 75‐year‐olds vs. −12.3 mm Hg in <75‐year‐olds) between baseline and week 12, with no significant differences between the groups. In addition, there were significant reductions in glycated hemoglobin, body weight, and uric acid during 12 weeks of empagliflozin treatment in the two age groups. The incidences of hypoglycemic episodes, hypotension, and metabolic adverse events were similar in the two groups. Thus, empagliflozin was effective and well tolerated in elderly diabetic patients with uncontrolled nocturnal hypertension when administered for 12 weeks.     

Microalbuminuria as a marker of cardiovascular risk in patients with type 2 diabetes

Diabetes is a major risk factor for coronary artery disease and most patients with diabetes die of cardiovascular complications. Reduction of cardiovascular risk is therefore a high priority in the management of patients with diabetes. Microalbuminuria is an important predictor of cardiovascular events and forms one of the components of the insulin resistance/metabolic syndrome, which confers a particularly high risk of cardiovascular death. The currently available glucose-lowering agents vary considerably in their ability to reduce microalbuminuria. The sulfonylureas and metformin appear to have little effect on microalbuminuria expressed as urinary albumin/creatinine ratio, while the thiazolidinediones have unique effects on this risk factor, in parallel with their effects on insulin resistance. In two 1-year European multicenter, randomized, double-blind monotherapy trials (n=2444), pioglitazone produced similar reductions in urinary albumin/creatinine ratio to gliclazide and greater reductions than metformin (P<0.001). Similarly, two further 1-year European multicenter, randomized, double-blind trials assessed the effects of add-on therapy (n=1269) on urinary albumin/creatinine ratio. In the first study, urinary albumin/creatinine ratio was reduced by pioglitazone add-on to sulfonylurea (-15%), but was largely unaffected by metformin add-on to sulfonylurea (2%; P<0.05). In the second, urinary albumin/creatinine ratio was also reduced by pioglitazone add-on to metformin (-10%), but increased by gliclazide add-on to metformin (6%, P<0.05). The results of these studies indicated that compared with metformin or gliclazide, pioglitazone may provide therapeutic benefits, over and above those due to improved glycemic control. These include significant reductions in urinary albumin/creatinine ratio, a known cardiovascular risk marker.     

Preventing microalbuminuria in patients with diabetes: rationale and design of the Randomised Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study

Diabetic nephropathy has developed into a worldwide epidemic and is responsible for the majority of end-stage renal disease in most countries. Antihypertensive treatment slows the progression of the disease. In addition, blockade of the renin-angiotensin system reduces the degree of albuminuria and angiotensin II receptor blockers (ARBs) have been shown to delay the progression from microalbuminuria to overt proteinuria in patients with diabetes. However, few studies have examined whether the initial stage of diabetic nephropathy (i.e. the development of microalbuminuria) in patients with type 2 diabetes can be slowed or prevented by ARB treatment. The Randomised Olmesartan And Diabetes MicroAlbuminuria Prevention (ROADMAP) study is a placebo-controlled, multicentre, double-blind, parallel group study investigating the effect of the ARB, olmesartan medoxomil, on the incidence of microalbuminuria. A total of 4400 type 2 diabetes patients with normoalbuminuria will be randomized to treatment with 40 mg of olmesartan medoxomil once daily or placebo. Goal blood pressure will be 130/80 mmHg. The primary endpoint of the study is the occurrence of microalbuminuria. In ROADMAP, we will also assess as secondary endpoints the effects of olmesartan on fatal and non-fatal cardiovascular events in patients with diabetes. In addition, within subgroups of the ROADMAP patients, the effects of olmesartan on retinopathy and other microvascular circulations will be analysed. The study is expected to last a median of 5 years. The ROADMAP study will answer the question whether an ARB can prevent or delay the onset of microalbuminuria and whether this translates into protection against cardiovascular events and renal disease.