Circadian blood pressure rhythm as a possible key target of SGLT2 inhibitors used for the treatment of Type 2 diabetes.
Circadian blood pressure rhythm as a possible key target of SGLT2 inhibitors used for the treatment of Type 2 diabetes.
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昼夜血压节律是 SGLT2 抑制剂治疗 2 型糖尿病的可能关键目标。
DOI：
10.1038/hr.2016.1
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Umemura S.
中科院分区：
文献类型：
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作者：
Tamura K;Wakui H;Azushima K;Uneda K;Umemura S.
越来越多的证据表明，2型糖尿病(T2 DM)的患病率正在迅速上升，肾脏和心血管并发症往往会导致糖尿病患者的严重病情。1尤其是心血管并发症是糖尿病肾病患者死亡的主要原因。2型糖尿病患者心血管疾病的主要危险因素包括高血压、血脂异常、蛋白尿(蛋白尿)和肾小球滤过率(GFR)降低。2-4在治疗2型糖尿病时，重要的是适当地控制糖脂代谢、体重和血压，并抑制糖尿病并发症的发生和进展，以使生活质量恢复到与健康人相当的水平。T2 DM的一线治疗包括改变饮食和运动疗法，如果这些措施不够，就开抗糖尿病药物。2型糖尿病的药物治疗包括口服治疗和注射治疗。越来越多的报道称，在疾病进展的早期阶段进行治疗干预对于有效管理T2 DM和糖尿病肾病非常重要；因此，对蛋白尿的具体诊断是这一方法的关键组成部分。因此，日本糖尿病学会和日本肾脏病学会糖尿病肾病联合委员会最近修订了其糖尿病肾病分类(糖尿病肾病分类2014)，5在这个新版本中突出了蛋白尿在T2 DM治疗中的临床意义。在蛋白尿对心血管风险的重要性的一个例子中，血管紧张素II拮抗剂氯沙坦(RENAAL)研究和厄贝沙坦糖尿病肾病试验(IDNT)对NIDDM终点降低的子分析表明，心血管风险的降低不仅依赖于充分的血压控制，还取决于蛋白尿的充分降低，与达到的血压水平无关。6因此，无论糖尿病肾病处于哪个阶段，有效改善蛋白尿的治疗干预对于降低T2 DM患者心血管风险是至关重要的。为此，除了降低血压外，适当的血糖控制对于减少糖尿病肾病患者的蛋白尿至关重要。达到O7的目标HbA1c。日本肾脏病学会2013年的循证临床实践指南推荐使用0%(国家糖化血红蛋白标准化计划(NGSP))对伴有微量白蛋白尿的T2 DM患者进行血糖控制。7在最近对Advance试验的一项特别后分析中，一种强化降糖方案(目标HbA1C为o6。5%)降低了终末期肾病的风险，并导致蛋白尿的改善。8此外，先前的一项随机对照试验的荟萃分析表明，强化降糖治疗与T2 DM患者微量白蛋白尿的风险显著降低有关。9目前，在CKD患者中管理T2 DM是一项临床挑战，因为治疗选择有限，因为大多数口服降糖药在GFR为每1.73平方米每分钟O60ml的T2 DM患者中表现出疗效降低和/或清除延迟，以及更多的不良事件。10尽管如此，先前的几项研究已经证明，加强多因素干预，如严格的血糖调节和肾素-血管紧张素系统阻滞剂、阿司匹林和降脂治疗…
Accumulating evidence has demonstrated that the prevalence of Type 2 diabetes mellitus (T2DM) is rapidly increasing and that renal and cardiovascular complications often provoke serious conditions in diabetic patients. 1 Particularly, cardiovascular complications are the primary cause of death in diabetic patients with nephropathy. Major risk factors for cardiovascular disease (CVD) in patients with T2DM include hypertension, dyslipidemia, albuminuria (proteinuria) and decreased glomerular filtration rate (GFR). 2–4 In treating T2DM, it is important to appropriately manage glucose and lipid metabolism, body weight and blood pressure (BP) and to suppress the development and progression of diabetic complications to restore the quality of life to a level comparable with healthy subjects. First-line therapy for T2DM includes diet modifications and exercise therapy, and if these measures are insufficient anti-diabetic medications are prescribed. Pharmacotherapy for T2DM consists of oral and injectable treatments. It is increasingly being reported that therapeutic intervention in the early stages of disease progression is important for the effective management of T2DM and diabetic nephropathy; thus, the specific diagnosis of albuminuria is a key component of this approach. Therefore, the Joint Committee on Diabetic Nephropathy of the Japan Diabetes Society and the Japanese Society of Nephrology has recently revised its Classification of Diabetic Nephropathy (Classification of Diabetic Nephropathy2014), 5 and the clinical significance of albuminuria in the management of T2DM has been highlighted in this new version. In one example of the significance of albuminuria to cardiovascular risk, a subanalysis of the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study and Irbesartan Diabetic Nephropathy Trial (IDNT), which included diabetic patients with overt albuminuria, demonstrated that the reduction of CVD risk was dependent not only on the achievement of adequate BP control but also on the sufficient decrease in albuminuria, independent of the achieved BP levels. 6 Therefore, therapeutic intervention to effectively improve albuminuria is essential for reducing CVD risk in patients with T2DM, regardless of the stage of diabetic nephropathy. To that end, appropriate glycemic control, in addition to BP reduction, is critical for reducing albuminuria in patients with diabetic nephropathy. Achieving the target HbA1c of o7. 0%(National Glycohemoglobin Standardization Program (NGSP)) for glycemic control in T2DM patients with microalbuminuria is recommended in the Evidence-based Clinical Practice Guidelines for Chronic Kidney Disease (CKD) by the Japanese Society of Nephrology 2013. 7 In a recent post hoc subanalysis of the ADVANCE trial, an intensive glucose-lowering regimen (with a target HbA1C of o6. 5%) reduced the risk of end-stage renal disease and led to improvements in albuminuria. 8 In addition, a previous meta-analysis of randomized controlled trials demonstrated that intensive glucose-lowering treatment was associated with a significant reduction in the risk of microalbuminuria in patients with T2DM. 9Currently, managing T2DM in patients with CKD represents a clinical challenge because of limited treatment options, as most oral anti-hyperglycemic agents exhibit decreased efficacy and/or delayed clearance and more adverse events in T2DM patients with a GFR of o60ml per min per 1.73 m2. 10 Nevertheless, several previous studies have demonstrated that intensified multi-factorial intervention with tight glucose regulation and renin–angiotensin system blockers, aspirin and lipid-lowering …