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Antoniou S, Naka KK, Papadakis M, Bechlioulis A, Tsatsoulis A, Michalis LK, Tigas S. Effect of glycemic control on markers of subclinical atherosclerosis in patients with type 2 diabetes mellitus: A review. World J Diabetes 2021; 12:1856-1874. [PMID: 34888012 PMCID: PMC8613661 DOI: 10.4239/wjd.v12.i11.1856] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 07/29/2021] [Accepted: 10/09/2021] [Indexed: 02/06/2023] Open
Abstract
Cardiovascular disease is the predominant cause of death in type 2 diabetes mellitus (T2DM). Evidence suggests a strong association between duration and degree of hyperglycemia and vascular disease. However, large trials failed to show cardiovascular benefit after intensive glycemic control, especially in patients with longer diabetes duration. Atherosclerosis is a chronic and progressive disease, with a long asymptomatic phase. Subclinical atherosclerosis, which is impaired in T2DM, includes impaired vasodilation, increased coronary artery calcification (CAC), carotid intima media thickness, arterial stiffness, and reduced arterial elasticity. Each of these alterations is represented by a marker of subclinical atherosclerosis, offering a cost-effective alternative compared to classic cardiac imaging. Their additional use on top of traditional risk assessment strengthens the predictive risk for developing coronary artery disease (CAD). We, herein, review the existing literature on the effect of glycemic control on each of these markers separately. Effective glycemic control, especially in earlier stages of the disease, attenuates progression of structural markers like intima-media thickness and CAC. Functional markers are improved after use of newer anti-diabetic agents, such as incretin-based treatments or sodium-glucose co-transporter-2 inhibitors, especially in T2DM patients with shorter disease duration. Larger prospective trials are needed to enhance causal inferences of glycemic control on clinical endpoints of CAD.
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Affiliation(s)
- Sofia Antoniou
- Department of Endocrinology, University of Ioannina, Ioannina 45110, Greece
| | - Katerina K Naka
- 2nd Department of Cardiology and Michaelidion Cardiac Center, University of Ioannina, Ioannina 45110, Greece
| | - Marios Papadakis
- Department of Surgery II, University of Witten-Herdecke, Wuppertal 42283, Germany
| | - Aris Bechlioulis
- 2nd Department of Cardiology and Michaelidion Cardiac Center, University of Ioannina, Ioannina 45110, Greece
| | | | - Lampros K Michalis
- 2nd Department of Cardiology and Michaelidion Cardiac Center, University of Ioannina, Ioannina 45110, Greece
| | - Stelios Tigas
- Department of Endocrinology, University of Ioannina, Ioannina 45110, Greece
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Saad MAEL, Fahmy MIM, Al-Shorbagy M, Assaf N, Hegazy AAEA, El-Yamany MF. Nateglinide Exerts Neuroprotective Effects via Downregulation of HIF-1α/TIM-3 Inflammatory Pathway and Promotion of Caveolin-1 Expression in the Rat's Hippocampus Subjected to Focal Cerebral Ischemia/Reperfusion Injury. Inflammation 2021; 43:401-416. [PMID: 31863220 DOI: 10.1007/s10753-019-01154-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Ischemic stroke is a major cause of death and motor disabilities all over the world. It is a muti-factorial disorder associated with inflammatory, apoptotic, and oxidative responses. Nateglinide (NAT), an insulinotropic agent used for the treatment of type 2 diabetes mellitus, recently showed potential anti-inflammatory and anti-apoptotic effects. The aim of our study was to elucidate the unique neuroprotective role of NAT in the middle cerebral artery occlusion (MCAO)-induced stroke in rats. Fifty-six male rats were divided to 4 groups (n = 14 in each group): the sham-operated group, sham receiving NAT (50 mg/kg/day, p.o) group, ischemia/reperfusion (IR) group, and IR receiving NAT group (50 mg/kg/day, p.o). MCAO caused potent deficits in motor and behavioral functions of the rats. Significant increase in inflammatory and apoptotic biomarkers has been observed in rats' hippocampi. Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway was significantly stimulated causing activation of series inflammatory biomarkers ending up neuro-inflammatory milieu. Pretreatment with NAT preserved rats' normal behavioral and motor functions. Moreover, NAT opposed the expression of hypoxia-inducible factor-1α (HIF-1α) resulting in downregulation of more inflammatory mediators namely, NF-κB, tumor necrosis factor-β (TNF-β), and the anti-survival gene PMAIP-1. NAT stimulated caveolin-1 (Cav-1) which prevented expression of oxidative biomarkers, nitric oxide (NO), and myeloperoxidase (MPO) and hamper the activation of apoptotic biomarker caspase-3. In conclusion, our work postulated that NAT exhibited its neuroprotective effects in rats with ischemic stroke via attenuation of different unique oxidative, apoptotic, and inflammatory pathways.
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Affiliation(s)
- Muhammad Abd El-Latif Saad
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Giza, Egypt.,School of Pharmacy, NewGiza University, Giza, Egypt
| | - Mohamed Ibrahim Mohamed Fahmy
- Department of Pharmacology and Toxicology, Faculty of Pharmacy and Drug Technology, Heliopolis University for Sustainable Development, Cairo, Egypt.
| | - Muhammad Al-Shorbagy
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Giza, Egypt.,School of Pharmacy, NewGiza University, Giza, Egypt
| | - Naglaa Assaf
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr University for Science and Technology (MUST), Giza, Egypt
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Li H, Kim HW, Shin SE, Seo MS, An JR, Jung WK, Ha KS, Han ET, Hong SH, Bang H, Choi IW, Na SH, Park WS. The vasorelaxant effect of antidiabetic drug nateglinide via activation of voltage-dependent K + channels in aortic smooth muscle. Cardiovasc Ther 2017; 36. [PMID: 28834298 DOI: 10.1111/1755-5922.12299] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Revised: 07/25/2017] [Accepted: 08/13/2017] [Indexed: 01/16/2023] Open
Abstract
AIMS We investigated the vasorelaxant effect of nateglinide and its related mechanisms using phenylephrine (Phe)-induced precontracted aortic rings. METHODS Arterial tone measurement was performed in aortic smooth muscle. RESULTS The application of nateglinide induced vasorelaxation in a concentration-dependent manner. Pretreatment with the large-conductance Ca2+ -activated K+ (BKCa ) channel inhibitor paxilline, the inwardly rectifying K+ (Kir) channel inhibitor Ba2+ , and ATP-sensitive K+ (KATP ) channel inhibitor glibenclamide did not affect the vasorelaxant effect of nateglinide. However, pretreatment with the voltage-dependent K+ (Kv) channel inhibitor 4-aminopyridine (4-AP) effectively reduced the vasorelaxant effect of nateglinide. Pretreatment with the Ca2+ inhibitor nifedipine and the sarcoplasmic/endoplasmic reticulum Ca2+ -ATPase inhibitor thapsigargin did not change the vasorelaxant effect of nateglinide. Additionally, the vasorelaxant effect of nateglinide was not altered in the presence of an adenylyl cyclase, a protein kinase A, a guanylyl cyclase, or a protein kinase G inhibitor. The vasorelaxant effect of nateglinide was not affected by the elimination of the endothelium. In addition, pretreatment with a nitric oxide synthase inhibitor, L-NAME, and a small-conductance Ca2+ -activated K+ (SKCa ) channel inhibitor, apamin, did not change the vasorelaxant effect of nateglinide. CONCLUSION Nateglinide induced vasorelaxation via the activation of the Kv channel independent of other K+ channels, Ca2+ channels, intracellular Ca2+ ([Ca2+ ]i ), and the endothelium.
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Affiliation(s)
- Hongliang Li
- Department of Physiology, Kangwon National University School of Medicine, Chuncheon, South Korea
| | - Hye Won Kim
- Department of Physiology, Kangwon National University School of Medicine, Chuncheon, South Korea
| | - Sung Eun Shin
- Department of Physiology, Kangwon National University School of Medicine, Chuncheon, South Korea
| | - Mi Seon Seo
- Department of Physiology, Kangwon National University School of Medicine, Chuncheon, South Korea
| | - Jin Ryeol An
- Department of Physiology, Kangwon National University School of Medicine, Chuncheon, South Korea
| | - Won-Kyo Jung
- Department of Biomedical Engineering, and Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan, South Korea
| | - Kwon-Soo Ha
- Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chuncheon, South Korea
| | - Eun-Taek Han
- Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine, Chuncheon, South Korea
| | - Seok-Ho Hong
- Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, South Korea
| | - Hyoweon Bang
- Department of Physiology, College of Medicine, Chung-Ang University, Seoul, South Korea
| | - Il-Whan Choi
- Department of Microbiology, Inje University College of Medicine, Busan, South Korea
| | - Sung Hun Na
- Department of Obstetrics and Gynecology, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, South Korea
| | - Won Sun Park
- Department of Physiology, Kangwon National University School of Medicine, Chuncheon, South Korea
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Bethel MA, Xu W, Theodorakis MJ. Pharmacological interventions for preventing or delaying onset of type 2 diabetes mellitus. Diabetes Obes Metab 2015; 17:231-44. [PMID: 25312701 DOI: 10.1111/dom.12401] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2013] [Revised: 10/07/2014] [Accepted: 10/09/2014] [Indexed: 01/11/2023]
Abstract
Prevention or delay of onset of type 2 diabetes in individuals at varying risk across the dysglycaemia continuum before overt diabetes becomes clinically manifest constitutes a leading objective of global disease prevention schemes. Pharmacological intervention has been suggested as a means to help prevent diabetes and reduce the global burden of this chronic condition. However, there is no credible evidence that early pharmacological intervention leads to long-term benefit in reducing diabetes-related complications or preventing early mortality, compared to treating people with diagnosed diabetes who have crossed the glycaemic threshold. In this review, we examine published evidence from trials using pharmacological agents to delay or prevent progression to diabetes. We also explore the benefit/risk impact of such therapies, safety issues and relevant off-target effects. Current evidence suggests none of the drugs currently available sustainably lower cumulative diabetes incidence, none provides a durable delay in diabetes diagnosis and none provides a convincing concomitant excess benefit for microvascular or macrovascular risk.
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Affiliation(s)
- M A Bethel
- Diabetes Trials Unit, University of Oxford, Churchill Hospital, Oxford, UK; Division of Endocrinology, Department of Medicine, Duke University Medical Center, Durham, NC, USA
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Kato T, Node K. Therapeutic Potential of α-Glucosidase Inhibitors to Prevent Postprandial Endothelial Dysfunction. Int Heart J 2014; 55:386-90. [DOI: 10.1536/ihj.14-194] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Affiliation(s)
- Toru Kato
- Department of Clinical Research, Tochigi Medical Center
| | - Koichi Node
- Department of Cardiovascular and Renal Medicine, Saga University Faculty of Medicine
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Shimabukuro M, Higa M, Yamakawa K, Masuzaki H, Sata M. Miglitol, α-glycosidase inhibitor, reduces visceral fat accumulation and cardiovascular risk factors in subjects with the metabolic syndrome: A randomized comparable study. Int J Cardiol 2013; 167:2108-13. [DOI: 10.1016/j.ijcard.2012.05.109] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2011] [Revised: 03/16/2012] [Accepted: 05/27/2012] [Indexed: 01/01/2023]
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Wang L, Guo L, Zhang L, Zhou Y, He Q, Zhang Z, Wang M. Effects of glucose load and nateglinide intervention on endothelial function and oxidative stress. J Diabetes Res 2013; 2013:849295. [PMID: 23691521 PMCID: PMC3647564 DOI: 10.1155/2013/849295] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2012] [Revised: 02/17/2013] [Accepted: 02/18/2013] [Indexed: 11/18/2022] Open
Abstract
We analysed endothelial function and oxidative stress in patients with abnormal glucose metabolism, the effect of glucose load, and the impact of nateglinide. 109 participants were grouped into newly diagnosed diabetes, prediabetes, and control. Fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycosylated haemoglobin (HbA1c), and glycated albumin (GA) varied significantly among the study groups (P < 0.01). Nitric oxide (NO) and insulin resistance index (HOMA-IRI) levels were markedly different between the newly diagnosed diabetes and the control (P < 0.01). Glucose loading lowered flow-mediated endothelium-dependent dilation (FMEDD), NO, and superoxide dismutase (SOD) (P < 0.01). Fasting and glucose loading FMEDD, FPG, PPG, HbA1c, and GA were negatively correlated (r = -0.4573, -0.4602, -0.3895, -0.3897, and r = -0.4594, -0.4803, -0.4494, -0.3885; P < 0.01), whereas NO, SOD, and HOMA- β were positively correlated (r = 0.2983, 0.3211, 0.311, and r = 0.1954, 0.361, 0.2569; P < 0.05). After the treatment with nateglinide, significant decreases in FPG, PPG, GA, HbA1C, endothelin-1(ET-1), malondialdehyde (MDA), and HOMA-IRI were observed, whereas FMEDD, NO, and SOD increased (P < 0.01). Thus, the study demonstrated the adverse effect of glucose load on endothelial function and oxidative stress. Nateglinide lowers blood glucose, reduces insulin resistance and oxidative stress, and improves endothelial function in newly diagnosed diabetes.
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Affiliation(s)
- Leilei Wang
- VIP Department, Beijing Hospital of the Ministry of Health, Dongdan Dahua, Road Number One, Beijing 100730, China
| | - Lixin Guo
- Endocrinology and Metabolism Department, Beijing Hospital of the Ministry of Health, Dongdan Dahua, Road Number One, Beijing 100730, China
- *Lixin Guo:
| | - Lina Zhang
- Endocrinology and Metabolism Department, Beijing Hospital of the Ministry of Health, Dongdan Dahua, Road Number One, Beijing 100730, China
| | - Yan Zhou
- Endocrinology and Metabolism Department, Beijing Hospital of the Ministry of Health, Dongdan Dahua, Road Number One, Beijing 100730, China
| | - Qinghua He
- Endocrinology and Metabolism Department, Beijing Hospital of the Ministry of Health, Dongdan Dahua, Road Number One, Beijing 100730, China
| | - Zheng Zhang
- Ultrasound Division, Beijing Hospital of the Ministry of Health, Dongdan Dahua, Road Number One, Beijing 100730, China
| | - Meng Wang
- Laboratory Division, Beijing Hospital of the Ministry of Health, Dongdan Dahua, Road Number One, Beijing 100730, China
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Kato T, Inoue T, Node K. Postprandial endothelial dysfunction in subjects with new-onset type 2 diabetes: an acarbose and nateglinide comparative study. Cardiovasc Diabetol 2010; 9:12. [PMID: 20334663 PMCID: PMC2861640 DOI: 10.1186/1475-2840-9-12] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2009] [Accepted: 03/24/2010] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Postprandial hyperglycemia is believed to affect vascular endothelial function. The aim of our study was to compare the effects of acarbose and nateglinide on postprandial endothelial dysfunction. METHODS We recruited a total of 30 patients with newly diagnosed type 2 diabetes (19 men and 11 women, age 67.8 +/- 7.3 years). Patients were randomly assigned to 3 groups receiving either 300 mg/day acarbose, 270 mg/day nateglinide, or no medication. A cookie test (consisting of 75 g carbohydrate, 25 g butter fat, and 7 g protein for a total of 553 kcal) was performed as dietary tolerance testing. During the cookie test, glucose and insulin levels were determined at 0, 30, 60, and 120 min after load. In addition, endothelial function was assessed by % flow-mediated dilation (FMD) of the brachial artery at 0 and 120 min after cookie load. RESULTS Postprandial glucose and insulin levels were similar in the 3 groups. Postprandial endothelial dysfunction was similar in the 3 groups before treatment. After 12 weeks of intervention, postprandial FMD was significantly improved in the acarbose group compared with the control group (6.8 +/- 1.3% vs 5.2 +/- 1.1%, p = 0.0022). Area under the curve (AUC) for insulin response was significantly increased in the nateglinide and control groups; however, no significant change was observed in the acarbose group. CONCLUSIONS Our results suggest that acarbose improves postprandial endothelial function by improvement of postprandial hyperglycemia, independent of postprandial hyperinsulinemia. Acarbose may thus have more beneficial effects on postprandial endothelial function in patients with type 2 diabetes than nateglinide.
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Affiliation(s)
- Toru Kato
- Department of Cardiovascular Medicine, Dokkyo Medical University, Mibu, Tochigi, Japan.
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Affiliation(s)
- Antonio Ceriello
- Warwick Medical School. Clinical Science Research Institute. University of Warwick. UK
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Voulgari C, Tentolouris N. Combination of nateglinide with thiazolidinediones in Type 2 diabetes. Expert Rev Endocrinol Metab 2009; 4:537-552. [PMID: 30780794 DOI: 10.1586/eem.09.40] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Insulin sensitivity and insulin secretion are reciprocally related such that insulin resistance is adapted by increased insulin secretion to maintain normal glucose and lipid homeostasis. Treatment of Type 2 diabetes should aim to restore and sustain the normal relationship between insulin sensitivity and secretion. Nateglinide is a rapid-onset, short-acting insulin-secretion enhancer that restores early-phase insulin secretion, reduces postprandial glucose excursions and prevents long-term hyperinsulinemia. Given its mechanism of action, it is evident that nateglinide would be more effective when used in combination with an insulin sensitizer, such as the thiazolidinediones. Thiazolidinediones do not stimulate insulin release and, therefore, are potentially suitable candidates for combination therapy with an insulin-secretion enhancer, such as nateglinide. Combination therapy of thiazolidinediones with nateglinide is effective, carries low risk of hypoglycemia and is suitable for patients with moderate renal impairment, although weight gain and edema are common side effects. Further studies are needed to determine whether nateglinide in combination with thiazolidinediones will help clinicians better achieve their treatment goals in targeting Type 2 diabetes. Moreover, comparative studies between nateglinide and medications targeting postprandial glycemia, such as dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 analogues, are necessary. This article summarizes data concerning the mechanism of action, efficacy and safety of therapy with nateglinide and thiazolidinediones as monotherapy and in combination treatment, and aims at a better understanding of the substrate defects their synergy hopes to defy.
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Affiliation(s)
- Christina Voulgari
- a First Department of Propaedeutic Medicine, Athens University Medical School, Laiko General Hospital, 17 Agiou Thoma Street, 11527, Athens, Greece.
| | - Nicholas Tentolouris
- b First Department of Propaedeutic Medicine, Athens University Medical School, Laiko General Hospital, 17 Agiou Thoma Street, 11527, Athens, Greece.
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Node K, Inoue T. Postprandial hyperglycemia as an etiological factor in vascular failure. Cardiovasc Diabetol 2009; 8:23. [PMID: 19402896 PMCID: PMC2688503 DOI: 10.1186/1475-2840-8-23] [Citation(s) in RCA: 115] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2009] [Accepted: 04/29/2009] [Indexed: 01/04/2023] Open
Abstract
Postprandial hyperglycemia is characterized by hyperglycemic spikes that induce endothelial dysfunction, inflammatory reactions and oxidative stress, which may lead to progression of atherosclerosis and occurrence of cardiovascular events. Emerging data indicate that postprandial hyperglycemia or even impaired glucose tolerance may predispose to progression of atherosclerosis and cardiovascular events. There is evidence that postprandial hyperglycemia, but not fasting hyperglycemia, independently predicts the occurrence of cardiovascular events. We proposed a concept of 'vascular failure' as a comprehensive syndrome of vascular dysfunction extending from risk factors to advanced atherosclerotic disease. Postprandial hyperglycemia is therefore one of the very important pathophysiological states contributing to vascular failure. Accordingly, controlling postprandial hyperglycemia should be the focus of future clinical investigation as a potential target for preventing vascular failure.
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Affiliation(s)
- Koichi Node
- Department of Cardiovascular and Renal Medicine, Saga University Faculty of Medicine, Saga, Japan.
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Effects of oral glucose load on endothelial function and on insulin and glucose fluctuations in healthy individuals. EXPERIMENTAL DIABETES RESEARCH 2008; 2008:672021. [PMID: 18350125 PMCID: PMC2266989 DOI: 10.1155/2008/672021] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/22/2007] [Accepted: 12/31/2007] [Indexed: 01/04/2023]
Abstract
Background/aims. Postprandial hyperglycemia, an independent risk factor for cardiovascular disease, is accompanied by endothelial dysfunction. We studied the effect of oral glucose load on insulin and glucose fluctuations, and on postprandial endothelial function in healthy individuals in order to better understand and cope with the postprandial state in insulin resistant individuals. Methods. We assessed post-oral glucose load endothelial function (flow mediated dilation), plasma insulin, and blood glucose in 9 healthy subjects. Results. The largest increases in delta FMD values (fasting FMD value subtracted from postprandial FMD value) occurred at 3 hours after both glucose or placebo load, respectively: 4.80 ± 1.41 (P = .009) and 2.34 ± 1.47 (P = .15). Glucose and insulin
concentrations achieved maximum peaks at one hour post-glucose load. Conclusion. Oral glucose load does not induce endothelial dysfunction in healthy individuals with mean insulin and glucose values of 5.6 mmol/L and 27.2 mmol/L, respectively, 2 hours after glucose load.
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Maenaka T, Oshima M, Itokawa Y, Masubuchi T, Takagi Y, Choi JS, Ishida T, Gu Y. Effects of Fuscoporia obliqua on Postprandial Glucose Excursion and Endothelial Dysfunction in Type 2 Diabetic Patients. J TRADIT CHIN MED 2008; 28:49-57. [DOI: 10.1016/s0254-6272(08)60014-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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González-Clemente JM. Improvement of glycaemic control by nateglinide decreases systolic blood pressure in drug-naive patients with type 2 diabetes. Eur J Clin Invest 2008; 38:174-9. [PMID: 18257780 DOI: 10.1111/j.1365-2362.2007.01918.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
BACKGROUND It has been speculated that oral hypoglycaemic agents that block K-ATP channels could potentially increase blood pressure by blocking such channels in vascular myocytes. No information about this issue exists regarding nateglinide. DESIGN A multicentre, double-blind, placebo-controlled, randomized trial was conducted in 109 drug-naive 30- to 75-year-old patients with type 2 diabetes and < 5 years of diabetes diagnosis, who are not taking antihypertensive drugs. These patients were assigned to receive placebo or fixed doses of nateglinide (120 mg before each main meal: breakfast, lunch and dinner) and evaluated at weeks 0 and 12 for (i) body mass index and blood pressure; (ii) standard laboratory tests, including haemoglobin A1c (HbA1c) and fasting plasma glucose; and (iii) incremental area under the curve for glucose and C-peptide after a standardized liquid breakfast challenge, homeostasis model assessment (HOMA)-B% (as surrogate of beta-cell activity) and HOMA-S% (as surrogate of insulin sensitivity). RESULTS At the end of the follow-up period, patients in the nateglinide group (n = 55), compared to patients in the placebo group (n = 54), showed lower values of HbA1c (6.7 +/- 0.6 vs. 7.2 +/- 0.7%, respectively; P < 0.001), fasting plasma glucose (7.9 +/- 2.1 vs. 8.5 +/- 2.0 mmol L(-1); P = 0.023) and systolic blood pressure (125.3 +/- 15.4 vs. 129.3 +/- 18.7 mmHg; P = 0.015), and higher values of HOMA-B%[75.7 (51.8-99.4) vs. 57.7 (42.2-83.4); P = 0.033]. A positive correlation was found between changes in HbA1c and systolic blood pressure in the nateglinide group (r = 0.355, P = 0.011). CONCLUSIONS In drug-naive patients with type 2 diabetes, the improvement in glycaemic control with nateglinide is associated with a decrease in systolic blood pressure.
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Affiliation(s)
- J-M González-Clemente
- Department of Diabetes, Endocrinology and Nutrition, Hospital de Sabadell, Sabadell, Spain.
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Abstract
Islet dysfunction and peripheral insulin resistance are both present in type 2 diabetes and are both necessary for the development of hyperglycemia. In both type 1 and type 2 diabetes, large, prospective clinical studies have shown a strong relation between time-averaged mean values of glycemia, measured as glycated hemoglobin (HbA1c), and vascular diabetic complications. These studies are the basis for the American Diabetes Association's current recommended treatment goal that HbA1c should be <7%. The measurement of the HbA1c concentration is considered the gold standard for assessing long-term glycemia; however, it does not reveal any information on the extent or frequency of blood glucose excursions, but provides an overall mean value only. Postprandial hyperglycemia occurs frequently in patients with diabetes receiving active treatment and can occur even when metabolic control is apparently good. Interventional studies indicate that reducing postmeal glucose excursions is as important as controlling fasting plasma glucose in persons with diabetes and impaired glucose tolerance. Evidence exists for a causal relation between postmeal glucose increases and microvascular and macrovascular outcomes; therefore, it is not surprising that treatment with different compounds that have specific effects on postprandial glucose regulation is accompanied by a significant improvement of many pathways supposed to be involved in diabetic complications, including oxidative stress, endothelial dysfunction, inflammation, and nuclear factor-kappaB activation. The goal of therapy should be to achieve glycemic status as near to normal as safely possible in all 3 components of glycemic control: HbA1c, fasting glucose, and postmeal glucose peak.
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Affiliation(s)
- Dario Giugliano
- Department of Geriatrics and Metabolic Diseases, University of Naples SUN, Italy.
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Shimabukuro M, Chinen I, Higa N, Takasu N, Yamakawa K, Ueda S. Effects of dietary composition on postprandial endothelial function and adiponectin concentrations in healthy humans: a crossover controlled study. Am J Clin Nutr 2007; 86:923-8. [PMID: 17921366 DOI: 10.1093/ajcn/86.4.923] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Abnormalities during the postprandial state contribute to the development of atherosclerosis. Reportedly, postprandial hyperglycemia, hypertriglyceridemia, and hyperlipacidemia independently cause postprandial cytokine activation. However, it is not clear which dietary composition preferentially affects postprandial endothelial function in healthy subjects. OBJECTIVE We aimed to examine the associations of dietary composition and postprandial endothelial function in healthy subjects. DESIGN The effects of a single ingestion of a high-carbohydrate meal (300 kcal, 100% carbohydrate), a high-fat meal (30 g fat/m(2), 35% fat), or a standard test meal (478 kcal; 16.4% protein, 32.7% fat, 50.4% carbohydrate) on postprandial plasma concentrations of adiponectin and forearm blood flow (FBF) during reactive hyperemia were studied in healthy subjects. RESULTS The peak FBF response and the total reactive hyperemic flow (flow debt repayment; FDR), indexes of resistance artery endothelial function, were unchanged after ingestion of a high-carbohydrate and standard test meal but decreased 120 and 240 min after a high-fat meal. After a high-fat meal, decreases in peak FBF and FDR were well correlated with an increase in plasma free fatty acid (FFA) concentrations but not with the other biochemical variables, including triacylglycerol, insulin, glucose, total cholesterol, HDL cholesterol, and adiponectin. CONCLUSIONS Postprandial endothelial function was impaired only after the high-fat diet and not after the high-carbohydrate or standard test meal in healthy subjects. Because such endothelial dysfunction after a high-fat meal was closely correlated with FFA concentrations, postprandial state could be hazardous, mostly through acute hyperlipacidemia in healthy subjects.
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Affiliation(s)
- Michio Shimabukuro
- Second Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
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Mita T, Watada H, Shimizu T, Tamura Y, Sato F, Watanabe T, Choi JB, Hirose T, Tanaka Y, Kawamori R. Nateglinide reduces carotid intima-media thickening in type 2 diabetic patients under good glycemic control. Arterioscler Thromb Vasc Biol 2007; 27:2456-62. [PMID: 17872451 DOI: 10.1161/atvbaha.107.152835] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVE Postprandial hyperglycemia observed in type 2 diabetes mellitus is a risk factor for atherosclerosis. The aim of this study was to investigate the effect of strict glycemic control by nateglinide on common carotid far wall intima-media thickness in type 2 diabetic patients who were already under good glycemic control. METHODS AND RESULTS We performed an open labeled randomized prospective trial on 78 drug-naive type 2 diabetic patients whose HbA1c was less than 6.5%. Thirty-eight patients were randomly assigned to receive nateglinide (270 mg/dL) and 40 to control group (no treatment). After 12 months, a significant reduction in HbA1c was observed in the nateglinide group, whereas a significant increase of HbA1c was observed in the untreated group. The carotid intima-media thickness at the end of 1-year follow-up was significantly reduced in the nateglinide group compared with the untreated group (-0.017+/-0.054 mm/year versus 0.024+/-0.066 mm/year, P=0.0064). Whereas nateglinide treatment also reduced triglyceride, highly-sensitive C-reactive protein, and E-selectin, multiple regression analysis identified HbA1c as the only significant independent determinant of the change in carotid intima-media thickness. CONCLUSION In type 2 diabetic patients with good glycemic control, further strict glycemic control by nateglinide results in regression of carotid intima-media thickness.
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Affiliation(s)
- Tomoya Mita
- Department of Medicine, Metabolism, and Endocrinology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
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O'Keefe JH, Bell DSH. Postprandial hyperglycemia/hyperlipidemia (postprandial dysmetabolism) is a cardiovascular risk factor. Am J Cardiol 2007; 100:899-904. [PMID: 17719342 DOI: 10.1016/j.amjcard.2007.03.107] [Citation(s) in RCA: 399] [Impact Index Per Article: 22.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2007] [Revised: 03/28/2007] [Accepted: 03/28/2007] [Indexed: 01/12/2023]
Abstract
Epidemiologic data indicate that a postprandial state characterized by abnormally increased levels of glucose and lipids (also referred to as postprandial dysmetabolism) is an independent predictor of future cardiovascular events, even in nondiabetic subjects. The cardiovascular toxicity of postprandial dysmetabolism is mediated by oxidant stress, which is directly proportional to the increase in glucose after a meal. This transient increase in free radicals acutely triggers inflammation, endothelial dysfunction, hypercoagulability, sympathetic hyperactivity, and a cascade of other atherogenic changes. The postprandial dysmetabolism hypothesis has been bolstered by interventional studies that have demonstrated that blunting the postprandial spikes in glucose and lipids improves inflammation and endothelial function immediately. Early randomized controlled trials indicate that reducing postprandial dysmetabolism appears to significantly slow atherosclerotic progression and may improve cardiovascular prognosis. In conclusion, postprandial dysmetabolism appears to be an important proximate cause of adverse cardiovascular events. Addressing this fundamental and largely unrecognized condition will require specific screening and treatment strategies. Diet, exercise, and various pharmacologic agents can improve postprandial dysmetabolism. Using these strategies may help improve the prognosis for patients with diabetes mellitus and/or coronary heart disease.
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Affiliation(s)
- James H O'Keefe
- University of Missouri-Kansas City, Kansas City, Missouri, USA.
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Gao HW, Xie C, Wang HN, Lin YJ, Hong TP. Beneficial metabolic effects of nateglinide versus acarbose in patients with newly-diagnosed type 2 diabetes. Acta Pharmacol Sin 2007; 28:534-9. [PMID: 17376293 DOI: 10.1111/j.1745-7254.2007.00534.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
AIM To investigate the acute and chronic effects of nateglinide versus acarbose on plasma asymmetric dimethylarginine (ADMA) levels and lipid profiles in patients with newly-diagnosed type 2 diabetes. METHODS A crossover trial of nateglinide and acarbose was conducted on 16 drug-naïve patients with newly-diagnosed type 2 diabetes during a total period of 9 weeks. Plasma glucose, serum insulin, free fatty acids (FFA), lipids and lipoproteins, and plasma ADMA were measured. RESULTS The efficiencies of a single dose of nateglinide (120 mg) and acarbose (50 mg) for lowering postprandial hyperglycemia were similar. Compared to acarbose, nateglinide significantly increased postprandial insulin release after a standard meal test in patients with type 2 diabetes. Nateglinide acutely decreased postprandial 120 min FFA concentrations and 240 min ADMA levels more significantly than acarbose. The fasting high-density lipoprotein cholesterol level increased and the low-density lipoprotein cholesterol level decreased significantly, but the fasting levels of triglycerides, total cholesterol, and ADMA were unchanged after 4 weeks of treatment with nateglinide. Acarbose did not affect fasting lipid profiles or the ADMA levels after 4 weeks of treatment. CONCLUSION These results suggest that the reduction of postprandial FFA and ADMA concentrations induced by nateglinide may be associated with the partial restoration of early-phase insulin secretion and may impart a cardiovascular advantage in comparison with acarbose.
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Affiliation(s)
- Hong-wei Gao
- Department of Endocrinology, Peking University Third Hospital, Beijing 100083, China
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Abstract
Atherosclerosis is characterized by the response of the vessel wall to chronic multifactorial injury leading to the formation of atheromatous or fibrous plaques. Endothelial dysfunction represents an initial stage of atherosclerosis. In addition to endothelial dysfunction, smooth muscle dysfunction, metabolic abnormalities of the vessel wall including inflammation, oxidative stress and alterations of neurohormonal balance occur in various stages of atherosclerosis. We now propose a new clinical entity 'vascular failure', defined as the integration of all of these vascular abnormalities. Vascular failure is not an anatomical disease, but rather a comprehensive syndrome of abnormal vascular function. Vascular failure extends from risk factors to established atherosclerotic disease with arterial stenosis, and further to calcification of the vessel wall or serious vascular events that may be caused by plaque rupture and thromboembolic occlusion. We propose aggressive intervention to modify various risk factors, applying to this integrated new entity, vascular failure.
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Affiliation(s)
- Teruo Inoue
- Department of Cardiovascular and Renal Medicine, Saga University Faculty of Medicine, Saga, Japan.
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Ceriello A, Davidson J, Hanefeld M, Leiter L, Monnier L, Owens D, Tajima N, Tuomilehto J. Postprandial hyperglycaemia and cardiovascular complications of diabetes: an update. Nutr Metab Cardiovasc Dis 2006; 16:453-456. [PMID: 16934443 DOI: 10.1016/j.numecd.2006.05.006] [Citation(s) in RCA: 117] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2006] [Revised: 05/07/2006] [Accepted: 05/25/2006] [Indexed: 11/16/2022]
Abstract
Type 2 diabetes is characterised by a gradual decline in insulin secretion in response to nutrient loads; hence, it is primarily a disorder of postprandial glucose (PPG) regulation. However, physicians continue to rely on fasting plasma glucose (FPG) and glycosylated haemoglobin (HbA1c) levels as indicators for disease management. There is a linear relationship between the risk of cardiovascular disease (CVD) and the two-hour oral glucose tolerance test (OGTT), while a recent study confirms postprandial hyperglycaemia as an independent risk factor for CVD in type 2 diabetes. At the same time, several intervention studies have shown that treating postprandial hyperglycaemia may reduce the incidence of new cardiovascular events. Evidence supports the hypothesis that postprandial hyperglycaemia may be linked to CVD through the generation of oxidative stress. Furthermore, clinical data suggest that postprandial hyperglycaemia is a common phenomenon, even in patients who may be considered in 'good metabolic control'. Therefore, in addition to HbA1c and FPG, physicians should consider monitoring and targeting PPG in patients with type 2 diabetes.
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Affiliation(s)
- Antonio Ceriello
- Clinical Science Research Institute, Clinical Science Building, Warwick Medical School, University of Warwick, Coventry, UK.
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Nakamura T, Sugaya T, Kawagoe Y, Ueda Y, Koide H. Effect of pioglitazone on urinary liver-type fatty acid-binding protein concentrations in diabetes patients with microalbuminuria. Diabetes Metab Res Rev 2006; 22:385-9. [PMID: 16506273 DOI: 10.1002/dmrr.633] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
BACKGROUND Urinary liver-type fatty acid-binding protein (L-FABP) is a useful marker for renal tubulointerstitial injury. Pioglitazone is reported to be effective in early diabetic nephropathy. The aim of the present study was to determine whether pioglitazone affects urinary L-FABP levels in diabetic nephropathy patients with microalbuminuria. METHODS Sixty-eight patients with type 2 diabetes and microalbuminuria were randomized to a 12-month treatment with pioglitazone (30 mg/d, n = 17), glibenclamide (5 mg/d, n = 18), voglibose (0.6 mg/d, n = 17), or nateglinide (270 mg/d, n = 16). Pre- and posttreatment urinary albumin excretion (UAE) and urinary L-FABP concentrations were compared between the four treatment groups and 40 age-matched healthy subjects. RESULTS Pretreatment UAE and urinary L-FABP levels differed little between the four groups. UAE and urinary L-FABP levels were significantly greater in the diabetes patients than in the healthy subjects (UAE: p < 0.001; L-FABP: p < 0.01). After 6 and 12 months, UAE and urinary L-FABP were significantly lower in the pioglitazone treatment group than in the other treatment groups (UAE: 6 months, p < 0.01 and 12 months, p < 0.001; L-FABP: 6 months, p < 0.05 and 12 months, p < 0.01). CONCLUSIONS Pioglitazone, but not glibenclamide, voglibose, or nateglinide, appears to be effective in reducing UAE and the urinary L-FABP level, suggesting that pioglitazone has a specific role in ameliorating both glomerular and tubulointerstitial lesions associated with early diabetic nephropathy.
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Affiliation(s)
- Tsukasa Nakamura
- Department of Medicine, Shinmatsudo Central General Hospital, Chiba, Japan
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Shimabukuro M, Higa N, Takasu N. Comparison of the antioxidant and vascular effects of gliclazide and glibenclamide in Type 2 diabetic patients: a randomized crossover study. J Diabetes Complications 2006; 20:179-83. [PMID: 16632238 DOI: 10.1016/j.jdiacomp.2005.06.012] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2004] [Revised: 06/23/2005] [Accepted: 06/24/2005] [Indexed: 12/15/2022]
Abstract
The aim of the present study is to compare the short-term effects of gliclazide and glibenclamide on the oxidative state and vascular endothelium function of Type 2 diabetic patients in an observer-blinded, randomized crossover study. Thirteen Type 2 diabetic patients were enrolled: one group of seven patients took daily 160 mg of gliclazide for the first 4 weeks and then daily 5 mg of glibenclamide for the next 4 weeks; another group of six patients took daily 5 mg of glibenclamide for the first 4 weeks and 160 mg of gliclazide for the next 4 weeks. Forearm blood flow (FBF) measurement for endothelial function and biochemical analyses were conducted before and after each crossover treatment. Four weeks of treatment with either sulfonylurea showed the similar antihyperglycemic effects and enhancement of the peak FBF and total reactive hyperemic flow (flow debt repayment: FDR) during reactive hyperemia. Treatment with gliclazide resulted in the significant reduction to about 60% of baseline in urinary 8-iso-prostaglandin F2alpha (8iPGF2alpha) excretion while no such change was detected in the glibenclamide period. The increases in peak FBF and FDR were in parallel with its anti-hyperglycemic effect, but not with antioxidant state. Results suggest that gliclazide and glibenclamide can protect vascular endothelium from hyperglycemia-induced injury in Type 2 diabetic patients.
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Affiliation(s)
- Michio Shimabukuro
- Second Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
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Hazama Y, Matsuhisa M, Ohtoshi K, Gorogawa SI, Kato K, Kawamori D, Yoshiuchi K, Nakamura Y, Shiraiwa T, Kaneto H, Yamasaki Y, Hori M. Beneficial effects of nateglinide on insulin resistance in type 2 diabetes. Diabetes Res Clin Pract 2006; 71:251-5. [PMID: 16214255 DOI: 10.1016/j.diabres.2005.08.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2005] [Revised: 07/28/2005] [Accepted: 08/10/2005] [Indexed: 12/23/2022]
Abstract
Nateglinide, a rapid insulin secretagogue, is known to facilitate the early phase of insulin secretion and has been used for the treatment of type 2 diabetic patients with postprandial hyperglycemia. The aim of this study is to evaluate the effect of nateglinide on insulin resistance as well as insulin secretory defects in type 2 diabetic patients. Insulin secretion ability was evaluated by the hyperglycemic clamp test, and insulin sensitivity was evaluated by the euglycemic hyperinsulinemic clamp test, using an artificial pancreas. The hyperglycemic clamp test showed that a 7-day treatment with nateglinide significantly increased insulin secretion in response to high glucose. Interestingly, although nateglinide is known to facilitate insulin secretion, daily urinary C-peptide excretion was decreased after nateglinide treatment. Moreover, in the euglycemic hyperinsulinemic clamp test, glucose infusion rate was significantly increased by nateglinide treatment, indicating that nateglinide functions to decrease insulin resistance. Nateglinide ameliorates insulin resistance as well as insulin secretory defects in type 2 diabetic patients.
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Affiliation(s)
- Yoji Hazama
- Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
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Ishibashi Y, Takahashi N, Shimada T, Sugamori T, Sakane T, Umeno T, Hirano Y, Oyake N, Murakami Y. Short duration of reactive hyperemia in the forearm of subjects with multiple cardiovascular risk factors. Circ J 2006; 70:115-23. [PMID: 16377935 DOI: 10.1253/circj.70.115] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Peripheral vascular endothelial dysfunction is an independent predictor of cardiovascular events, and can be assessed noninvasively by measuring reactive hyperemia, either by vascular ultrasound measurement of flow-mediated vasodilatation or, less commonly, by measurement of blood flow using plethysmography. In the present study reactive hyperemia was measured using plethysmography in healthy subjects with multiple cardiovascular risk factors. METHODS AND RESULTS Reactive hyperemia was measured following 5-min occlusion of the upper arm in 449 healthy subjects (302 men, 147 women, age range 20-70 years) with (n=352) and without (n=97) risk factors such as smoking, hypertension, diabetes mellitus, hypercholesterolemia, obesity, family history of cardiovascular disease, and menopause. Maximum blood flow and minimum vascular resistance in reactive hyperemia did not differ between subjects with and without risk factors regardless of gender. Duration of reactive hyperemia, however, was significantly shorter in subjects with risk factors. Age-adjusted mean value of duration of reactive hyperemia was significantly smaller in men with a smoking habit, diabetes mellitus, hypercholesterolemia or obesity, and in women with smoking habit, hypertension, diabetes mellitus or obesity. The number of risk factors significantly correlated with the duration of reactive hyperemia in both men (r=-0.56, p<0.001) and women (r=-0.62, p<0.001), suggesting that endothelial dysfunction increases with the number of risk conditions clustering in a single individual. CONCLUSIONS Duration of reactive hyperemia reflects cardiovascular risk factors and decreases with the number of risk conditions. These findings suggest that the duration of reactive hyperemia measured with plethysmography is potentially useful for assessing endothelial dysfunction.
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Affiliation(s)
- Yutaka Ishibashi
- Division of Cardiovascular Medicine, Department of Internal Medicine, Shimane University Faculty of Medicine, Izumo, Japan.
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Abstract
Therapy for type 2 diabetes mellitus should aim to control not only fasting, but also postprandial glucose levels. Nateglinide, a d-phenylalanine derivative, restores postprandial early phase insulin secretion in a transient and glucose-sensitive manner without affecting basal insulin levels. As nateglinide is administered immediately before meals it provides greater lifestyle flexibility than agents that require patients to eat to avoid hypoglycemic events (e.g. long-acting sulfonylureas). In randomised, double-blind trials in patients with type 2 diabetes, nateglinide monotherapy (mealtime treatment of 120 mg three times daily) significantly improved long-term glycaemic control by significantly reducing glyated haemoglobin (HbA 1c) and preventing mealtime glucose spikes. The combination of nateglinide with insulin-sensitising agents, for example, metformin and thiazolidinediones, addresses the dual defects of loss of insulin secretion and insulin resistance to provide optimal management of type 2 diabetes, and more patients achieve HbA 1c goal with nateglinide combination therapy rather than with monotherapy with other oral agents. Nateglinide also restores early insulin secretion and reduces postprandial hyperglycaemia in prediabetic subjects with impaired glucose tolerance (IGT) and appears similarly effective in elderly and non-elderly populations with type 2 diabetes. It has an excellent safety and tolerability profile, with a low propensity to cause hypoglycaemia due to its transient, selective effect on early phase insulin secretion. Nateglinide as monotherapy or combination therapy is an effective option to reduce mealtime glucose in patients with type 2 diabetes. The results of ongoing research into its potential role in delaying progression to overt diabetes, and protecting against cardiovascular events, in prediabetic patients with IGT are awaited.
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Affiliation(s)
- I W Campbell
- Victoria Hospital, Kirkcaldy and Bute Medical School, University of St Andrews, Fife, Scotland.
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Current literature in diabetes. Diabetes Metab Res Rev 2005; 21:297-308. [PMID: 15858786 DOI: 10.1002/dmrr.565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
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