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Article: A New Modality in Dyslipidemia Treatment: Antisense Oligonucleotide Therapy.

Kim, Kyuho / Choi, Sung Hee

2022 Volume 11, Issue 3, Page(s) 250–261

Abstract: There are unmet needs for pharmacologic agents beyond current medications, such as statins, to effectively lower low-density lipoprotein cholesterol levels to target goals, especially in patients with very high or extremely high risk. Pharmacological ... ...

Abstract	There are unmet needs for pharmacologic agents beyond current medications, such as statins, to effectively lower low-density lipoprotein cholesterol levels to target goals, especially in patients with very high or extremely high risk. Pharmacological targeting of mRNA represents an emerging, innovative approach with the potential to expand upon current therapies. In RNA-targeted therapeutics, a novel approach is the use of chemically modified oligonucleotides to inhibit the production of target proteins at their sites of gene coding. There are two main classes of RNA-targeted therapeutics: single-stranded antisense oligonucleotides (ASOs) and double-stranded small inhibiting RNAs. ASOs are synthetic molecules with a length of 15-30 nucleotides that are designed specifically to bind to a target mRNA in a sequence-specific manner. Using these agents to inhibit the translation of key regulatory proteins, such as apolipoprotein CIII, apolipoprotein(a), and angiopoietin-like protein 3, has demonstrated treatment efficacy for dyslipidemia. Many cardiovascular outcome trials with ASOs are ongoing. As clinicians, we must carefully monitor the long-term safety and efficacy of this new modality through large clinical trials in the future.
Language	English
Publishing date	2022-08-29
Publishing country	Korea (South)
Document type	Journal Article ; Review
ZDB-ID	3016001-7
ISSN	2288-2561 ; 2287-2892
ISSN (online)	2288-2561
ISSN	2287-2892
DOI	10.12997/jla.2022.11.3.250
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Article ; Online: Cardiovascular Safety of SGLT2 Inhibitors Compared to DPP4 Inhibitors and Sulfonylureas as the Second-Line of Therapy in T2DM Using Large, Real-World Clinical Data in Korea.

Kim, Kyuho / Choi, Sung Hee

Diabetes & metabolism journal

2021 Volume 45, Issue 4, Page(s) 502–504

MeSH term(s)	Diabetes Mellitus, Type 2/drug therapy ; Dipeptidyl Peptidase 4 ; Dipeptidyl-Peptidase IV Inhibitors/adverse effects ; Humans ; Republic of Korea ; Sodium-Glucose Transporter 2 Inhibitors/adverse effects ; Sulfonylurea Compounds/adverse effects
Chemical Substances	Dipeptidyl-Peptidase IV Inhibitors ; Sodium-Glucose Transporter 2 Inhibitors ; Sulfonylurea Compounds ; DPP4 protein, human (EC 3.4.14.5) ; Dipeptidyl Peptidase 4 (EC 3.4.14.5)
Language	English
Publishing date	2021-07-30
Publishing country	Korea (South)
Document type	Editorial ; Comment
ZDB-ID	2602402-0
ISSN	2233-6087 ; 2233-6087
ISSN (online)	2233-6087
ISSN	2233-6087
DOI	10.4093/dmj.2021.0158
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Article: Effect of olmesartan and amlodipine on serum angiotensin-(1-7) levels and kidney and vascular function in patients with type 2 diabetes and hypertension.

Kim, Kyuho / Moon, Ji Hye / Ahn, Chang Ho / Lim, Soo

Diabetology & metabolic syndrome

2023 Volume 15, Issue 1, Page(s) 43

Abstract: Background: Recent studies suggest that angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1-7) [Ang-(1-7)] might have beneficial effects on the cardiovascular system. We investigated the effects of olmesartan on the changes in serum ACE2 and Ang-( ... ...

Abstract	Background: Recent studies suggest that angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1-7) [Ang-(1-7)] might have beneficial effects on the cardiovascular system. We investigated the effects of olmesartan on the changes in serum ACE2 and Ang-(1-7) levels as well as kidney and vascular function in patients with type 2 diabetes and hypertension. Methods: This was a prospective, randomized, active comparator-controlled trial. Eighty participants with type 2 diabetes and hypertension were randomized to receive 20 mg of olmesartan (N = 40) or 5 mg of amlodipine (N = 40) once daily. The primary endpoint was changes of serum Ang-(1-7) from baseline to week 24. Results: Both olmesartan and amlodipine treatment for 24 weeks decreased systolic and diastolic blood pressures significantly by > 18 mmHg and > 8 mmHg, respectively. Serum Ang-(1-7) levels were more significantly increased by olmesartan treatment (25.8 ± 34.5 pg/mL → 46.2 ± 59.4 pg/mL) than by amlodipine treatment (29.2 ± 38.9 pg/mL → 31.7 ± 26.0 pg/mL), resulting in significant between-group differences (P = 0.01). Serum ACE2 levels showed a similar pattern (6.31 ± 0.42 ng/mL → 6.74 ± 0.39 ng/mL by olmesartan treatment vs. 6.43 ± 0.23 ng/mL → 6.61 ± 0.42 ng/mL by amlodipine treatment; P < 0.05). The reduction in albuminuria was significantly associated with the increases in ACE2 and Ang-(1-7) levels (r = - 0.252 and r = - 0.299, respectively). The change in Ang-(1-7) levels was positively associated with improved microvascular function (r = 0.241, P < 0.05). Multivariate regression analyses showed that increases in serum Ang-(1-7) levels were an independent predictor of a reduction in albuminuria. Conclusions: These findings suggest that the beneficial effects of olmesartan on albuminuria may be mediated by increased ACE2 and Ang-(1-7) levels. These novel biomarkers may be therapeutic targets for the prevention and treatment of diabetic kidney disease. Trial registration: ClinicalTrials.gov NCT05189015.
Language	English
Publishing date	2023-03-11
Publishing country	England
Document type	Journal Article
ZDB-ID	2518786-7
ISSN	1758-5996
ISSN	1758-5996
DOI	10.1186/s13098-023-00987-1
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Article ; Online: Lipoprotein Lipase: Is It a Magic Target for the Treatment of Hypertriglyceridemia.

Moon, Joon Ho / Kim, Kyuho / Choi, Sung Hee

Endocrinology and metabolism (Seoul, Korea)

2022 Volume 37, Issue 4, Page(s) 575–586

Abstract: High levels of triglycerides (TG) and triglyceride-rich lipoproteins (TGRLs) confer a residual risk of cardiovascular disease after optimal low-density lipoprotein cholesterol (LDL-C)-lowering therapy. Consensus has been made that LDL-C is a non-arguable ...

Abstract	High levels of triglycerides (TG) and triglyceride-rich lipoproteins (TGRLs) confer a residual risk of cardiovascular disease after optimal low-density lipoprotein cholesterol (LDL-C)-lowering therapy. Consensus has been made that LDL-C is a non-arguable primary target for lipid lowering treatment, but the optimization of TGRL for reducing the remnant risk of cardiovascular diseases is urged. Omega-3 fatty acids and fibrates are used to reduce TG levels, but many patients still have high TG and TGRL levels combined with low high-density lipoprotein concentration that need to be ideally treated. Lipoprotein lipase (LPL) is a key regulator for TGs that hydrolyzes TGs to glycerol and free fatty acids in lipoprotein particles for lipid storage and consumption in peripheral organs. A deeper understanding of human genetics has enabled the identification of proteins regulating the LPL activity, which include the apolipoproteins and angiopoietin-like families. Novel therapeutic approach such as antisense oligonucleotides and monoclonal antibodies that regulate TGs have been developed in recent decades. In this article, we focus on the biology of LPL and its modulators and review recent clinical application, including genetic studies and clinical trials of novel therapeutics. Optimization of LPL activity to lower TG levels could eventually reduce incident atherosclerotic cardiovascular disease in conjunction with successful LDL-C reduction.
MeSH term(s)	Atherosclerosis/genetics ; Atherosclerosis/metabolism ; Cardiovascular Diseases/genetics ; Cardiovascular Diseases/metabolism ; Cholesterol, LDL/blood ; Humans ; Hypertriglyceridemia/blood ; Hypertriglyceridemia/drug therapy ; Hypertriglyceridemia/metabolism ; Lipoprotein Lipase/genetics ; Lipoprotein Lipase/metabolism
Chemical Substances	Cholesterol, LDL ; Lipoprotein Lipase (EC 3.1.1.34)
Language	English
Publishing date	2022-08-29
Publishing country	Korea (South)
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2802452-7
ISSN	2093-5978 ; 2093-5978
ISSN (online)	2093-5978
ISSN	2093-5978
DOI	10.3803/EnM.2022.402
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Article ; Online: New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond Statins.

Kim, Kyuho / Ginsberg, Henry N / Choi, Sung Hee

Diabetes & metabolism journal

2022 Volume 46, Issue 4, Page(s) 517–532

Abstract: Statins are the cornerstone of the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). However, even under optimal statin therapy, a significant residual ASCVD risk remains. Therefore, there has been an unmet clinical need for ... ...

Abstract	Statins are the cornerstone of the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). However, even under optimal statin therapy, a significant residual ASCVD risk remains. Therefore, there has been an unmet clinical need for novel lipid-lowering agents that can target low-density lipoprotein cholesterol (LDL-C) and other atherogenic particles. During the past decade, several drugs have been developed for the treatment of dyslipidemia. Inclisiran, a small interfering RNA that targets proprotein convertase subtilisin/kexin type 9 (PCSK9), shows comparable effects to that of PCSK9 monoclonal antibodies. Bempedoic acid, an ATP citrate lyase inhibitor, is a valuable treatment option for the patients with statin intolerance. Pemafibrate, the first selective peroxisome proliferator-activated receptor alpha modulator, showed a favorable benefit-risk balance in phase 2 trial, but the large clinical phase 3 trial (PROMINENT) was recently stopped for futility based on a late interim analysis. High dose icosapent ethyl, a modified eicosapentaenoic acid preparation, shows cardiovascular benefits. Evinacumab, an angiopoietin-like 3 (ANGPTL3) monoclonal antibody, reduces plasma LDL-C levels in patients with refractory hypercholesterolemia. Novel antisense oligonucleotides targeting apolipoprotein C3 (apoC3), ANGPTL3, and lipoprotein(a) have significantly attenuated the levels of their target molecules with beneficial effects on associated dyslipidemias. Apolipoprotein A1 (apoA1) is considered as a potential treatment to exploit the athero-protective effects of high-density lipoprotein cholesterol (HDL-C), but solid clinical evidence is necessary. In this review, we discuss the mode of action and clinical outcomes of these novel lipid-lowering agents beyond statins.
MeSH term(s)	Angiopoietin-Like Protein 3 ; Angiopoietin-like Proteins ; Atherosclerosis/drug therapy ; Atherosclerosis/prevention & control ; Cardiovascular Diseases/complications ; Cholesterol, LDL ; Dyslipidemias/complications ; Dyslipidemias/drug therapy ; Heart Disease Risk Factors ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Hypolipidemic Agents/therapeutic use ; Proprotein Convertase 9/therapeutic use ; Risk Factors
Chemical Substances	ANGPTL3 protein, human ; Angiopoietin-Like Protein 3 ; Angiopoietin-like Proteins ; Cholesterol, LDL ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hypolipidemic Agents ; PCSK9 protein, human (EC 3.4.21.-) ; Proprotein Convertase 9 (EC 3.4.21.-)
Language	English
Publishing date	2022-07-27
Publishing country	Korea (South)
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2602402-0
ISSN	2233-6087 ; 2233-6087
ISSN (online)	2233-6087
ISSN	2233-6087
DOI	10.4093/dmj.2022.0198
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Article ; Online: New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond Statins.

Kim, Kyuho / Ginsberg, Henry N / Choi, Sung Hee

Diabetes & metabolism journal

2022 Volume 46, Issue 5, Page(s) 817–818

Language	English
Publishing date	2022-09-19
Publishing country	Korea (South)
Document type	Journal Article ; Published Erratum
ZDB-ID	2602402-0
ISSN	2233-6087 ; 2233-6087
ISSN (online)	2233-6087
ISSN	2233-6087
DOI	10.4093/dmj.2022.0295
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Article ; Online: Independent Impact of Diabetes on the Severity of Coronavirus Disease 2019 in 5,307 Patients in South Korea: A Nationwide-Cohort Study (Diabetes Metab J 2020;44:737-46).

Kim, Kyuho / Oh, Tae Jung

Diabetes & metabolism journal

2020 Volume 44, Issue 6, Page(s) 938–939

MeSH term(s)	COVID-19 ; Cohort Studies ; Diabetes Mellitus ; Humans ; Republic of Korea/epidemiology ; SARS-CoV-2
Language	English
Publishing date	2020-12-23
Publishing country	Korea (South)
Document type	Letter ; Comment
ZDB-ID	2602402-0
ISSN	2233-6087 ; 2233-6087
ISSN (online)	2233-6087
ISSN	2233-6087
DOI	10.4093/dmj.2020.0236
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Article ; Online: Glucose Regulation after Partial Pancreatectomy: A Comparison of Pancreaticoduodenectomy and Distal Pancreatectomy in the Short and Long Term.

Lee, Jun Suh / Sohn, Minji / Kim, Kyuho / Yoon, Yoo-Seok / Lim, Soo

Diabetes & metabolism journal

2023 Volume 47, Issue 5, Page(s) 703–714

Abstract: Backgruound: Long term quality of life is becoming increasingly crucial as survival following partial pancreatectomy rises. The purpose of this study was to investigate the difference in glucose dysregulation after pancreaticoduodenectomy (PD) or distal ...

Abstract	Backgruound: Long term quality of life is becoming increasingly crucial as survival following partial pancreatectomy rises. The purpose of this study was to investigate the difference in glucose dysregulation after pancreaticoduodenectomy (PD) or distal pancreatectomy (DP). Methods: In this prospective observational study from 2015 to 2018, 224 patients who underwent partial pancreatectomy were selected: 152 (67.9%) received PD and 72 (32.1%) received DP. Comprehensive assessment for glucose regulation, including a 75 g oral glucose tolerance test was conducted preoperatively, and 1, 12, and 52 weeks after surgery. Patients were further monitored up to 3 years to investigate development of new-onset diabetes mellitus (NODM) in patients without diabetes mellitus (DM) at baseline or worsening of glucose regulation (≥1% increase in glycosylated hemoglobin [HbA1c]) in those with preexisting DM. Results: The disposition index, an integrated measure of β-cell function, decreased 1 week after surgery in both groups, but it increased more than baseline level in the PD group while its decreased level was maintained in the DP group, resulting in a between-group difference at the 1-year examination (P<0.001). During follow-up, the DP group showed higher incidence of NODM and worsening of glucose regulation than the PD group with hazard ratio (HR) 4.29 (95% confidence interval [CI], 1.49 to 12.3) and HR 2.15 (95% CI, 1.09 to 4.24), respectively, in the multivariate analysis including dynamic glycemic excursion profile. In the DP procedure, distal DP and spleen preservation were associated with better glucose regulation. DP had a stronger association with glucose dysregulation than PD. Conclusion: Proactive surveillance of glucose dysregulation is advised, particularly for patients who receive DP.
MeSH term(s)	Humans ; Pancreatectomy/adverse effects ; Pancreatectomy/methods ; Pancreaticoduodenectomy/adverse effects ; Glucose ; Quality of Life ; Diabetes Mellitus/epidemiology
Chemical Substances	Glucose (IY9XDZ35W2)
Language	English
Publishing date	2023-06-22
Publishing country	Korea (South)
Document type	Observational Study ; Journal Article
ZDB-ID	2602402-0
ISSN	2233-6087 ; 2233-6087
ISSN (online)	2233-6087
ISSN	2233-6087
DOI	10.4093/dmj.2022.0205
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Article ; Online: Associations of polyneuropathy with risk of all-cause and cardiovascular mortality, cardiovascular disease events stratified by diabetes status.

Kim, Kyuho / Lee, Su-Nam / Ahn, Yu-Bae / Ko, Seung-Hyun / Yun, Jae-Seung

Journal of diabetes investigation

2023 Volume 14, Issue 11, Page(s) 1279–1288

Abstract: Aims/introduction: We investigated the association of polyneuropathy (PN) with all-cause and cardiovascular (CV) mortality and with cardiovascular disease (CVD) events stratified by diabetes status.: Materials and methods: This prospective cohort ... ...

Abstract	Aims/introduction: We investigated the association of polyneuropathy (PN) with all-cause and cardiovascular (CV) mortality and with cardiovascular disease (CVD) events stratified by diabetes status. Materials and methods: This prospective cohort study used the UK Biobank. Polyneuropathy was defined based on nurse-led interviews or ICD codes for polyneuropathy. Cox proportional hazards models were used to investigate the association of polyneuropathy with clinical outcomes. Results: A total of 459,127 participants were included in the analysis. Polyneuropathy was significantly associated with all-cause and cardiovascular mortality, and with CVD events even after adjusting for CVD risk factors across all diabetes statuses. Metabolic parameters HbA Conclusions: Polyneuropathy was associated with all-cause and cardiovascular mortality, and with CVD events in subjects with diabetes or prediabetes, even those having normal glucose tolerance. This study suggests the importance of polyneuropathy as a risk factor for death and highlights the necessity of early diagnosis and lifestyle intervention for those with type 2 diabetes and polyneuropathy.
MeSH term(s)	Humans ; Diabetes Mellitus, Type 2/complications ; Cardiovascular Diseases/complications ; Cardiovascular Diseases/epidemiology ; Prospective Studies ; Risk Factors ; Polyneuropathies
Language	English
Publishing date	2023-07-30
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2625840-7
ISSN	2040-1124 ; 2040-1116
ISSN (online)	2040-1124
ISSN	2040-1116
DOI	10.1111/jdi.14063
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Article ; Online: Glucose Profiles Assessed by Intermittently Scanned Continuous Glucose Monitoring System during the Perioperative Period of Metabolic Surgery.

Kim, Kyuho / Choi, Sung Hee / Jang, Hak Chul / Park, Young Suk / Oh, Tae Jung

Diabetes & metabolism journal

2022 Volume 46, Issue 5, Page(s) 713–721

Abstract: Background: Continuous glucose monitoring (CGM) has been widely used in the management of diabetes. However, the usefulness and detailed data during perioperative status were not well studied. In this study, we described the immediate changes of glucose ...

Abstract	Background: Continuous glucose monitoring (CGM) has been widely used in the management of diabetes. However, the usefulness and detailed data during perioperative status were not well studied. In this study, we described the immediate changes of glucose profiles after metabolic surgery using intermittently scanned CGM (isCGM) in individuals with type 2 diabetes mellitus (T2DM). Methods: This was a prospective, single-center, single-arm study including 20 participants with T2DM. The isCGM (FreeStyle Libre CGM) implantation was performed within 2 weeks before surgery. We compared CGM metrics of 3 days before surgery and 3 days after surgery, and performed the correlation analyses with clinical variables. Results: The mean glucose significantly decreased after surgery (147.0±40.4 to 95.5±17.1 mg/dL, P<0.001). Time in range (TIR; 70 to 180 mg/dL) did not significantly change after surgery in total. However, it was significantly increased in a subgroup of individuals with glycosylated hemoglobin (HbA1c) ≥8.0%. Time above range (>250 or 180 mg/dL) was significantly decreased in total. In contrast, time below range (<70 or 54 mg/dL) was significantly increased in total and especially in a subgroup of individuals with HbA1c <8.0% after surgery. The coefficient of variation significantly decreased after surgery. Higher baseline HbA1c was correlated with greater improvement in TIR (rho=0.607, P=0.005). Conclusion: The isCGM identified improvement of mean glucose and glycemic variability, and increase of hypoglycemia after metabolic surgery, but TIR was not significantly changed after surgery. We detected an increase of TIR only in individuals with HbA1c ≥8.0%.
MeSH term(s)	Bariatric Surgery ; Blood Glucose/metabolism ; Blood Glucose Self-Monitoring ; Diabetes Mellitus, Type 1 ; Diabetes Mellitus, Type 2/surgery ; Glucose ; Glycated Hemoglobin A ; Humans ; Hypoglycemic Agents ; Perioperative Period ; Prospective Studies
Chemical Substances	Blood Glucose ; Glycated Hemoglobin A ; Hypoglycemic Agents ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2022-01-24
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	2602402-0
ISSN	2233-6087 ; 2233-6087
ISSN (online)	2233-6087
ISSN	2233-6087
DOI	10.4093/dmj.2021.0164
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