Updates on dyslipidemia in patients with diabetes

IF 3.2 3区 医学
Shintaro Ide, Yoshiro Maezawa, Koutaro Yokote
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Patients with diabetes mellitus show atherogenic lipid profiles exhibiting elevated low-density lipoprotein cholesterol (LDL-C) levels with small dense LDL particles; decreased high-density lipoprotein cholesterol (HDL-C) levels; and hypertriglyceridemia (TG) due to insufficient insulin action. Furthermore, a retrospective cohort study identified an elevated LDL-C/HDL-C ratio as a potential independent risk factor for new-onset diabetes<span><sup>4</sup></span>. Therefore, abnormal lipid profiles must be managed to reduce the risk of cardiovascular (CV) events and microvascular complications.</p><p>A high LDL-C level is a strong risk factor for ASCVD in patients with and without diabetes mellitus. Numerous outcome trials have shown that cholesterol-lowering therapy using 3-hydroxy 3-methylglutaryl-coenzyme A reductase inhibitors (statins) reduces the relative risk of primary and secondary ASCVD events<span><sup>5</sup></span>. Furthermore, a recent randomized controlled trial showed that LDL-C control using statins reduced the risk of kidney events in patients with diabetic kidney disease<span><sup>6</sup></span>. In addition to statin therapy, proprotein convertase subtilisin/kexin type 9 inhibitors and ezetimibe therapies reduced CV event risk<span><sup>7-9</sup></span>.</p><p>Although these LDL-C-lowering therapies can decrease the risk of ASCVD, the risk rate reduction is only 30–40%, suggesting the presence of residual risk factors, such as hypertriglyceridemia, low HDL-C levels and highly oxidized or small dense LDL particles. Interestingly, a recent prospective study showed the TG/HDL-C ratio to be correlated with an increased risk of major ASCVD events, suggesting that the TG/HDL-C ratio can be a parameter for assessing atherogenic dyslipidemia<span><sup>10</sup></span>. Furthermore, in addition to fasting hypertriglyceridemia, postprandial hypertriglyceridemia is a risk factor for CV events<span><sup>11</sup></span>.</p><p>Several epidemiological, genetic and clinical studies have shown that a high TG level is a residual risk factor; however, neither the Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial nor the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study reported reduced CV events in patients with type 2 diabetes<span><sup>12</sup></span>. A meta-analysis of fibrate users in 11,590 patients with type 2 diabetes mellitus showed that fibrate use significantly reduced the risk of non-fatal myocardial infarction, but had no effect on the risk of overall or coronary mortality<span><sup>13</sup></span>. As evidenced in the Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT) trial, the use of pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, to reduce TG also did not significantly mitigate CV events as an add-on statin in patients with diabetes<span><sup>14</sup></span>. In addition, the effects of TG-lowering therapy using N-3 unsaturated fatty acids are unclear. Although the Japan Eicosapentaenoic Acid Lipid Intervention Study (JELIS) and Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention (REDUCE-IT) showed that combination therapy with eicosapentaenoic acid and statins reduced residual CV risk, the Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia (STRENGTH) trial was not able to confirm these results using a combination of eicosapentaenoic acid, docosahexaenoic acid and statins<span><sup>15</sup></span>. Nevertheless, a meta-analysis of 49 randomized controlled trials including 374,358 participants showed that TG-lowering therapy reduced major vascular events by 16% per 1-mmol/L TG, which is comparable with an LDL-C reduction of 20% per 1-mmol/L<span><sup>16</sup></span>. Furthermore, Mendelian randomization studies have shown that TG is a causal risk factor of CVD<span><sup>17</sup></span>, suggesting that the effect of TG-lowering therapy on CV risk is controversial. Currently, one report showed that the TG-lowering effect on small dense LDL particles is limited when LDL-C levels are tightly controlled, which might explain why TG-lowering therapy as an add-on to statins did not reduce ASCVD events<span><sup>18</sup></span>. Considering this finding, a subsequent analysis of the PROMINENT trial would show why CVD risk was not reduced by pemafibrate administration.</p><p>Several glucose-lowering medications have been reported to exert a beneficial effect on lipid metabolism. A meta-analysis of 48 randomized controlled trials showed that the use of sodium–glucose cotransporter 2 (SGLT2) inhibitors decreased serum TG, and increased total cholesterol, HDL-C and LDL-C levels<span><sup>19</sup></span>. However, this slight increase in LDL-C levels on using an SGLT2 inhibitor was due to the decreased level of small dense LDL particles and the increased level of large buoyant LDL particles, contributing to the beneficial effect on ASCVD<span><sup>20</sup></span>. Furthermore, TG reduction by empagliflozin administration is strongly associated with endothelial function recovery<span><sup>21</sup></span>. Glucagon-like peptide-1 receptor agonist (GLP-1 RAs) therapy also improved lipid profiles by decreasing the LDL-C (−0.08 to −0.16 mmol/L) and TG (−0.17 to −0.3 mmol/L) levels<span><sup>22</sup></span>. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide, and GLP-1 RAs significantly reduced the TG (−19% to −24.8%) levels and increased the HDL-C levels (6.8% to 7.9%)<span><sup>23</sup></span>. In addition, these medications have favorable effects on non-alcoholic fatty liver disease (NAFLD). NAFLD is a complication in &gt;70% of patients with diabetes; type 2 diabetes promotes the progression to non-alcoholic steatohepatitis and severe fibrosis<span><sup>24</sup></span>. A randomized study showed that dapagliflozin and pioglitazone had beneficial effects on NAFLD; they decreased the visceral fat area and increased the adiponectin levels in patients with diabetes<span><sup>25</sup></span>. Furthermore, SGLT-2 inhibitors and GLP-1 RAs might decrease the incidence of NAFLD<span><sup>26</sup></span>. Meanwhile, tirzepatide significantly reduced the liver fat content by 8.09%<span><sup>27</sup></span>. These pleiotropic effects might be associated with the protective effects of SGLT-2 inhibitors and GLP-1 RAs against ASCVD.</p><p>Dyslipidemia in managed in daily clinical settings according to guidelines established in the USA, Europe and Japan<span><sup>28, 29</sup></span>. Although all guidelines are based on similar concepts, the lipid management goals and therapeutic recommendations differ by area (Table 1). The American Diabetes Association standards of care in diabetes 2023 and the 2019 European Society of Cardiology/European Atherosclerosis Society guidelines recommend statin therapy, and have set more intensive LDL-C target levels than the Japan Atherosclerosis Society guidelines. The Japan Atherosclerosis Society guidelines do not mention the selection of medications, because there is little evidence in Asian populations. After achieving the target LDL-C levels, other lipid parameters, such as TG and HDL-C levels, must be considered. In the 2022 Japan Atherosclerosis Society guidelines, both fasting and postprandial TG goals were set. Similarly, the American Diabetes Association guidelines recommend intensive lifestyle therapy and optimization of glycemic control in patients with high TG and low HDL-C levels.</p><p>The present article briefly reviews the update on dyslipidemia in patients with diabetes regarding treatment evidence and lipid management goals based on major guidelines. Although LDL-C-lowering therapy provides robust evidence for ASCVD risk reduction, further evidence for achieving residual risk reduction is required.</p><p>KY has participated on advisory panels for AstraZeneca, Kowa Company and Novo Nordisk Pharma; and has received research grants from Abbott Diabetes care, Astellas Pharma, Bayer Yakuhin, Daiichi Sankyo Company, Eli Lily Japan, Kowa Company, Merck Sharp and Dohme, Mitsubishi Tanabe Pharma, Nippon Boehringer Ingelheim, Novo Nordisk Pharma, Ono Pharmaceutical, Pfizer, Shionogi, Sumitomo Dainippon Pharma, Taisho Toyama Pharmaceutical Company, and Takeda Pharmaceutical Company. The other authors declare no conflict of interest.</p><p>Approval of the research protocol: N/A.</p><p>Informed consent: N/A.</p><p>Registry and the registration no. of the study/trial: N/A.</p><p>Animal studies: N/A.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":"14 9","pages":"1041-1044"},"PeriodicalIF":3.2000,"publicationDate":"2023-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.14042","citationCount":"2","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Diabetes Investigation","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/jdi.14042","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 2

Abstract

The main aim of diabetes management is to prevent atherosclerotic cardiovascular diseases (ASCVD) and microvascular complications. ASCVD, the major cause of diabetes-related mobility and mortality, greatly increases healthcare costs in patients with type 2 diabetes1. Dyslipidemia often coexists with diabetes mellitus and is a significant risk factor for ASCVD, along with smoking, hypertension and chronic kidney disease. Dyslipidemia is involved in the progression of diabetic kidney disease2 and diabetic retinopathy3. Patients with diabetes mellitus show atherogenic lipid profiles exhibiting elevated low-density lipoprotein cholesterol (LDL-C) levels with small dense LDL particles; decreased high-density lipoprotein cholesterol (HDL-C) levels; and hypertriglyceridemia (TG) due to insufficient insulin action. Furthermore, a retrospective cohort study identified an elevated LDL-C/HDL-C ratio as a potential independent risk factor for new-onset diabetes4. Therefore, abnormal lipid profiles must be managed to reduce the risk of cardiovascular (CV) events and microvascular complications.

A high LDL-C level is a strong risk factor for ASCVD in patients with and without diabetes mellitus. Numerous outcome trials have shown that cholesterol-lowering therapy using 3-hydroxy 3-methylglutaryl-coenzyme A reductase inhibitors (statins) reduces the relative risk of primary and secondary ASCVD events5. Furthermore, a recent randomized controlled trial showed that LDL-C control using statins reduced the risk of kidney events in patients with diabetic kidney disease6. In addition to statin therapy, proprotein convertase subtilisin/kexin type 9 inhibitors and ezetimibe therapies reduced CV event risk7-9.

Although these LDL-C-lowering therapies can decrease the risk of ASCVD, the risk rate reduction is only 30–40%, suggesting the presence of residual risk factors, such as hypertriglyceridemia, low HDL-C levels and highly oxidized or small dense LDL particles. Interestingly, a recent prospective study showed the TG/HDL-C ratio to be correlated with an increased risk of major ASCVD events, suggesting that the TG/HDL-C ratio can be a parameter for assessing atherogenic dyslipidemia10. Furthermore, in addition to fasting hypertriglyceridemia, postprandial hypertriglyceridemia is a risk factor for CV events11.

Several epidemiological, genetic and clinical studies have shown that a high TG level is a residual risk factor; however, neither the Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial nor the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study reported reduced CV events in patients with type 2 diabetes12. A meta-analysis of fibrate users in 11,590 patients with type 2 diabetes mellitus showed that fibrate use significantly reduced the risk of non-fatal myocardial infarction, but had no effect on the risk of overall or coronary mortality13. As evidenced in the Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT) trial, the use of pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, to reduce TG also did not significantly mitigate CV events as an add-on statin in patients with diabetes14. In addition, the effects of TG-lowering therapy using N-3 unsaturated fatty acids are unclear. Although the Japan Eicosapentaenoic Acid Lipid Intervention Study (JELIS) and Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention (REDUCE-IT) showed that combination therapy with eicosapentaenoic acid and statins reduced residual CV risk, the Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia (STRENGTH) trial was not able to confirm these results using a combination of eicosapentaenoic acid, docosahexaenoic acid and statins15. Nevertheless, a meta-analysis of 49 randomized controlled trials including 374,358 participants showed that TG-lowering therapy reduced major vascular events by 16% per 1-mmol/L TG, which is comparable with an LDL-C reduction of 20% per 1-mmol/L16. Furthermore, Mendelian randomization studies have shown that TG is a causal risk factor of CVD17, suggesting that the effect of TG-lowering therapy on CV risk is controversial. Currently, one report showed that the TG-lowering effect on small dense LDL particles is limited when LDL-C levels are tightly controlled, which might explain why TG-lowering therapy as an add-on to statins did not reduce ASCVD events18. Considering this finding, a subsequent analysis of the PROMINENT trial would show why CVD risk was not reduced by pemafibrate administration.

Several glucose-lowering medications have been reported to exert a beneficial effect on lipid metabolism. A meta-analysis of 48 randomized controlled trials showed that the use of sodium–glucose cotransporter 2 (SGLT2) inhibitors decreased serum TG, and increased total cholesterol, HDL-C and LDL-C levels19. However, this slight increase in LDL-C levels on using an SGLT2 inhibitor was due to the decreased level of small dense LDL particles and the increased level of large buoyant LDL particles, contributing to the beneficial effect on ASCVD20. Furthermore, TG reduction by empagliflozin administration is strongly associated with endothelial function recovery21. Glucagon-like peptide-1 receptor agonist (GLP-1 RAs) therapy also improved lipid profiles by decreasing the LDL-C (−0.08 to −0.16 mmol/L) and TG (−0.17 to −0.3 mmol/L) levels22. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide, and GLP-1 RAs significantly reduced the TG (−19% to −24.8%) levels and increased the HDL-C levels (6.8% to 7.9%)23. In addition, these medications have favorable effects on non-alcoholic fatty liver disease (NAFLD). NAFLD is a complication in >70% of patients with diabetes; type 2 diabetes promotes the progression to non-alcoholic steatohepatitis and severe fibrosis24. A randomized study showed that dapagliflozin and pioglitazone had beneficial effects on NAFLD; they decreased the visceral fat area and increased the adiponectin levels in patients with diabetes25. Furthermore, SGLT-2 inhibitors and GLP-1 RAs might decrease the incidence of NAFLD26. Meanwhile, tirzepatide significantly reduced the liver fat content by 8.09%27. These pleiotropic effects might be associated with the protective effects of SGLT-2 inhibitors and GLP-1 RAs against ASCVD.

Dyslipidemia in managed in daily clinical settings according to guidelines established in the USA, Europe and Japan28, 29. Although all guidelines are based on similar concepts, the lipid management goals and therapeutic recommendations differ by area (Table 1). The American Diabetes Association standards of care in diabetes 2023 and the 2019 European Society of Cardiology/European Atherosclerosis Society guidelines recommend statin therapy, and have set more intensive LDL-C target levels than the Japan Atherosclerosis Society guidelines. The Japan Atherosclerosis Society guidelines do not mention the selection of medications, because there is little evidence in Asian populations. After achieving the target LDL-C levels, other lipid parameters, such as TG and HDL-C levels, must be considered. In the 2022 Japan Atherosclerosis Society guidelines, both fasting and postprandial TG goals were set. Similarly, the American Diabetes Association guidelines recommend intensive lifestyle therapy and optimization of glycemic control in patients with high TG and low HDL-C levels.

The present article briefly reviews the update on dyslipidemia in patients with diabetes regarding treatment evidence and lipid management goals based on major guidelines. Although LDL-C-lowering therapy provides robust evidence for ASCVD risk reduction, further evidence for achieving residual risk reduction is required.

KY has participated on advisory panels for AstraZeneca, Kowa Company and Novo Nordisk Pharma; and has received research grants from Abbott Diabetes care, Astellas Pharma, Bayer Yakuhin, Daiichi Sankyo Company, Eli Lily Japan, Kowa Company, Merck Sharp and Dohme, Mitsubishi Tanabe Pharma, Nippon Boehringer Ingelheim, Novo Nordisk Pharma, Ono Pharmaceutical, Pfizer, Shionogi, Sumitomo Dainippon Pharma, Taisho Toyama Pharmaceutical Company, and Takeda Pharmaceutical Company. The other authors declare no conflict of interest.

Approval of the research protocol: N/A.

Informed consent: N/A.

Registry and the registration no. of the study/trial: N/A.

Animal studies: N/A.

糖尿病患者血脂异常的最新进展
糖尿病管理的主要目的是预防动脉粥样硬化性心血管疾病(ASCVD)和微血管并发症。ASCVD是糖尿病相关流动性和死亡率的主要原因,极大地增加了2型糖尿病患者的医疗费用1。血脂异常常与糖尿病共存,与吸烟、高血压和慢性肾脏疾病一样,是ASCVD的重要危险因素。血脂异常参与糖尿病肾病2和糖尿病视网膜病变3的进展。糖尿病患者表现为致动脉粥样硬化的脂质谱,表现为低密度脂蛋白胆固醇(LDL- c)水平升高,伴小密度LDL颗粒;降低高密度脂蛋白胆固醇(HDL-C)水平;和高甘油三酯血症(TG)由于胰岛素作用不足。此外,一项回顾性队列研究发现,LDL-C/HDL-C比值升高是新发糖尿病的潜在独立危险因素。因此,必须控制血脂异常以降低心血管(CV)事件和微血管并发症的风险。无论是否患有糖尿病,高LDL-C水平都是ASCVD的一个重要危险因素。大量结果试验表明,使用3-羟基3-甲基戊二酰辅酶A还原酶抑制剂(他汀类药物)进行降胆固醇治疗可降低原发性和继发性ASCVD事件的相对风险5。此外,最近的一项随机对照试验表明,使用他汀类药物控制LDL-C可降低糖尿病肾病患者发生肾脏事件的风险6。除他汀类药物治疗外,蛋白转化酶枯草素/kexin 9型抑制剂和依折替米贝治疗可降低CV事件风险7-9。虽然这些降LDL- c疗法可以降低ASCVD的风险,但风险降低率仅为30-40%,提示存在残留的危险因素,如高甘油三酯血症、低HDL-C水平和高度氧化或小密度LDL颗粒。有趣的是,最近的一项前瞻性研究显示TG/HDL-C比值与主要ASCVD事件的风险增加相关,这表明TG/HDL-C比值可以作为评估动脉粥样硬化性血脂异常的一个参数10。此外,除了空腹高甘油三酯血症外,餐后高甘油三酯血症也是心血管事件的危险因素11。一些流行病学、遗传学和临床研究表明,高TG水平是一个残留的危险因素;然而,控制糖尿病心血管风险的行动(ACCORD)脂质试验和非诺贝特干预和降低糖尿病事件(FIELD)研究均未报告2型糖尿病患者的心血管事件减少12。一项对11590例2型糖尿病患者使用贝特的荟萃分析显示,贝特可显著降低非致死性心肌梗死的风险,但对总死亡率或冠状动脉死亡率没有影响13。在通过降低糖尿病患者甘油三酯来降低心血管结局(PROMINENT)试验中,作为他汀类药物的补充,使用Pemafibrate(一种选择性过氧化物酶体增殖激活受体α调节剂)来降低TG也没有显著减轻心血管事件。此外,使用N-3不饱和脂肪酸降低tg治疗的效果尚不清楚。尽管日本二十碳五烯酸脂质干预研究(JELIS)和二十碳六烯酸乙基干预减少心血管事件(REDUCE-IT)显示,二十碳五烯酸和他汀类药物联合治疗可降低剩余CV风险,但高甘油三酯血症高危心血管患者中他汀类药物与Epanova的残留风险(STRENGTH)试验无法证实这些结果。然而,一项包含374,358名参与者的49项随机对照试验的荟萃分析显示,每1 mmol/L TG降低TG治疗可减少16%的主要血管事件,与每1 mmol/L TG降低20%的LDL-C相当16。此外,孟德尔随机化研究表明,TG是CVD17的一个因果危险因素,这表明降TG治疗对CV风险的影响存在争议。目前,一份报告显示,当LDL- c水平受到严格控制时,降低tg对小密度LDL颗粒的作用有限,这可能解释了为什么降低tg治疗作为他汀类药物的补充并不能减少ASCVD事件18。考虑到这一发现,对PROMINENT试验的后续分析将表明为什么使用压脉颤药不能降低心血管疾病的风险。据报道,几种降糖药物对脂质代谢有有益作用。48项随机对照试验的荟萃分析显示,使用钠-葡萄糖共转运蛋白2 (SGLT2)抑制剂可降低血清TG,增加总胆固醇、HDL-C和LDL-C水平19。 然而,使用SGLT2抑制剂时LDL- c水平的轻微增加是由于小密度LDL颗粒水平的降低和大浮力LDL颗粒水平的增加,这有助于对ASCVD20的有益作用。此外,恩格列净降低TG与内皮功能恢复密切相关。胰高血糖素样肽-1受体激动剂(GLP-1 RAs)治疗也通过降低LDL-C(- 0.08至- 0.16 mmol/L)和TG(- 0.17至- 0.3 mmol/L)水平改善脂质谱22。tizepatide,一种双葡萄糖依赖的胰岛素依赖性多肽,和GLP-1 RAs显著降低TG(- 19%至- 24.8%)水平,升高HDL-C水平(6.8%至7.9%)23。此外,这些药物对非酒精性脂肪性肝病(NAFLD)有良好的作用。NAFLD是70%糖尿病患者的并发症。2型糖尿病可促进发展为非酒精性脂肪性肝炎和严重纤维化24。一项随机研究表明,达格列净和吡格列酮对NAFLD有有益作用;他们减少了糖尿病患者的内脏脂肪面积,增加了脂联素水平25。此外,SGLT-2抑制剂和GLP-1 RAs可能降低NAFLD26的发生率。同时,替西肽显著降低肝脏脂肪含量8.09%27。这些多效性作用可能与SGLT-2抑制剂和GLP-1 RAs对ASCVD的保护作用有关。根据美国、欧洲和日本制定的指南,在日常临床环境中管理血脂异常28,29。尽管所有指南都基于类似的概念,但脂质管理目标和治疗建议因地区而异(表1)。美国糖尿病协会2023年糖尿病护理标准和2019年欧洲心脏病学会/欧洲动脉粥样硬化学会指南推荐他汀类药物治疗,并设定了比日本动脉粥样硬化学会指南更严格的LDL-C目标水平。日本动脉粥样硬化协会的指南没有提到药物的选择,因为在亚洲人群中几乎没有证据。在达到目标LDL-C水平后,必须考虑其他脂质参数,如TG和HDL-C水平。在2022年日本动脉粥样硬化协会指南中,设定了禁食和餐后TG目标。同样,美国糖尿病协会的指南建议对高TG和低HDL-C患者进行强化生活方式治疗和优化血糖控制。本文简要回顾了糖尿病患者血脂异常的最新进展,包括治疗证据和基于主要指南的脂质管理目标。尽管降ldl - c治疗为ASCVD风险降低提供了强有力的证据,但需要进一步的证据来实现剩余风险降低。KY参与了阿斯利康、科和公司和诺和诺德制药公司的顾问小组;并获得了雅培糖尿病护理、安斯泰来制药、拜耳Yakuhin、Daiichi Sankyo公司、Eli Lily日本、koa公司、默克夏普和Dohme、三菱田边制药、日本勃林格殷格翰、诺和诺德制药、小野制药、辉瑞、盐野义、住友Dainippon制药、大正富山制药公司和武田制药公司的研究资助。其他作者声明没有利益冲突。研究方案的批准:无。知情同意:无。注册表及注册编号研究/试验:无。动物研究:无。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Diabetes Investigation
Journal of Diabetes Investigation Medicine-Internal Medicine
自引率
9.40%
发文量
218
期刊介绍: Journal of Diabetes Investigation is your core diabetes journal from Asia; the official journal of the Asian Association for the Study of Diabetes (AASD). The journal publishes original research, country reports, commentaries, reviews, mini-reviews, case reports, letters, as well as editorials and news. Embracing clinical and experimental research in diabetes and related areas, the Journal of Diabetes Investigation includes aspects of prevention, treatment, as well as molecular aspects and pathophysiology. Translational research focused on the exchange of ideas between clinicians and researchers is also welcome. Journal of Diabetes Investigation is indexed by Science Citation Index Expanded (SCIE).
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