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Biomedical subjects

M Takeuchi

Publications and source records attributed to M Takeuchi.

At least 19 recordsLinked to original sources
PubMed2006

High peak reflux velocity in the proximal deep veins is a strong predictor of advanced post-thrombotic sequelae.

BACKGROUND: The presence of reflux in the femoral vein (FV) and popliteal vein (POPV) after acute deep vein thrombosis (DVT) is considered to contribute to the development of advanced post-thrombotic syndrome (PTS). However, a quantification of reflux has yet to be determined. The purpose of study was to determine the indicative parameters reflecting the progression of PTS. METHODS: Venous abnormalities were evaluated in 131 limbs out of 130 patients who completed a six-year follow-up after an acute DVT. Clinical manifestations were categorized according to the clinical, etiologic, anatomic, and pathophysiologic (CEAP) classification, and the patients were divided into two groups at a six-year follow-up point: group I, C(0-3)E(s),A(s,d,p),P(r,o), early chronic venous insufficiency (CVI); group II, C(4-6)E(s),A(s,d,p),P(r,o), advanced CVI. Venous segments were examined whether they were occluded or recanalized. The reflux parameters assessed were the diameter (cm), the reflux time (RT; s), the peak reflux velocity (PRV; cm s(-1)), and total refluxed volume, and these parameters were assessed especially in the FV and POPV at the two-year (early phase) and subsequent six-year (late phase) follow-up points after DVT. RESULTS: There were 98 limbs in group I and 33 in group II. The frequency of venous reflux was significantly higher in group II (<0.0001). In contrast, the proportion of occlusion did not differ between the groups (P = 0.138). The proportions of FV and POPV incompetence were significantly higher in group II (P < 0.0001 and P < 0.0001, respectively). In these veins, the RT did not improve the discrimination power between the two groups. In contrast, the PRV had significant discrimination power in these veins at both the two- and six-year follow-up points. In the superficial venous system, there were no significant differences in any of the determined parameters between the groups. In group II, 19 patients (58%), who had early symptoms of CVI at the two-year follow-up point, subsequently developed advanced symptoms of PTS. After calculating a suitable cutoff point using receiver operating characteristic curves analysis at the two-year follow-up point, multivariable analysis showed that a PRV of >25.4 cm s(-1) in the POPV was the strongest independent predictor of advanced CVI [odds ratio (OR) 60.32; 95% confidence interval (95CI) 43.1-1238.97, P < 0.0001]. Similarly, in the FV, a PRV of >24.5 cm s(-1) was found to be a strong predictor of advanced CVI (OR 25.77, 95CI 10.56-331.12, P < 0.0001). CONCLUSIONS: These findings suggest that the presence of a high PRV in the proximal deep veins is an independent predictor of advanced symptoms of PTS.

Aged↗
PubMed2006

Telmisartan inhibits AGE-induced C-reactive protein production through downregulation of the receptor for AGE via peroxisome proliferator-activated receptor-gamma activation.

AIMS/HYPOTHESIS: C-reactive protein (CRP), an acute-phase reactant produced mainly by the liver, is elevated in diabetes, thus contributing to the development and progression of atherosclerosis. However, the molecular mechanism underlying the elevation of CRP in diabetes is not fully understood. Since a crosstalk between AGE and angiotensin II (Ang II) has been proposed in the pathogenesis of accelerated atherosclerosis in diabetes, we examined here whether and how telmisartan, a unique Ang II type 1 receptor blocker (ARB) with peroxisome proliferator-activated receptor-gamma (PPAR-gamma)-modulating activity, could inhibit AGE-induced CRP expression in a human hepatoma cell line, Hep3B cells. METHODS: Protein levels of the receptor for AGE (RAGE) were analysed by western blots. Gene expression was analysed by quantitative real-time RT-PCR. CRP released into the medium was measured with ELISA. Intracellular formation of reactive oxygen species (ROS) was measured using the fluorescent probe CM-H(2)DCFDA. RESULTS: Telmisartan, but not candesartan, another ARB, downregulated RAGE mRNA levels in a dose-dependent manner. Telmisartan decreased basal as well as AGE-induced RAGE protein expression in Hep3B cells. Furthermore, telmisartan dose-dependently inhibited AGE-induced ROS generation and subsequent CRP gene and protein induction in Hep3B cells. GW9662, an inhibitor of PPAR-gamma, blocked the inhibitory effects of telmisartan on RAGE expression and its downstream signalling in Hep3B cells. CONCLUSIONS/INTERPRETATION: Our present study indicates a unique beneficial aspect of telmisartan: it may work as an anti-inflammatory agent against AGE by suppressing RAGE expression via PPAR-gamma activation in the liver and may play a protective role in vascular injury in diabetes.

Benzimidazoles↗
PubMed2006

Supplementation of CD4+CD25+ regulatory T cells suppresses experimental autoimmune uveoretinitis.

AIMS: To investigate whether supplementation of natural CD4+CD25+ regulatory T cells ameliorates mouse experimental autoimmune uveoretinitis (EAU) induced by CD4+ T cell-dependent interphotoreceptor retinoid-binding protein (IRBP). METHODS: C57BL/6 mice were immunised with human interphotoreceptor retinoid-binding protein peptide 1-20 (IRBP(1-20)), and IRBP(1-20)-sensitised T cells were obtained. CD4+CD25+ T cells derived from naive mice were cocultured with IRBP(1-20)-sensitised T cells, and their proliferation responses and cytokine production were measured. In addition, CD4+CD25+ T cells were transferred intravenously into mice 7 or 15 days after immunisation with IRBP(1-20), and the severity of EAU and T cell proliferation responses were evaluated. RESULTS: CD4+CD25+ regulatory T cells effectively inhibited both the proliferation of, and interleukin (IL)2, IL5 and interferon (IFN)gamma production by, IRBP(1-20)-sensitised T cells. Adoptive transfer of CD4+CD25+ regulatory T cells to IRBP(1-20)-immunised mice conferred considerable protection from EAU development and inhibition of T cell proliferation responses to IRBP(1-20). CONCLUSION: These findings show that natural CD4+CD25+ regulatory T cells possess the ability to inhibit activation of IRBP-reactive T cells that have been already sensitised in vivo, and adoptive transfer of these cells ameliorates EAU even in the effector phase. Supplementation of natural CD4+CD25+ regulatory T cells may have therapeutic potential for effective treatment of uveitis.

Adoptive Transfer↗
PubMed2006

Comparison of manual compression release with distal pneumatic cuff maneuver in the ultrasonic evaluation of superficial venous insufficiency.

BACKGROUND: Venous reflux can be elicited either manually or by pneumatic tourniquet, and previous studies did not indicate any significant difference between these manoeuvres in patients with superficial venous insufficiency (SVI). PURPOSE: To investigate if two methods correlate in patients with CVI. MATERIALS AND METHODS: Venous reflux was studied in 94 venous segments of 57 limbs in 52 consecutive patients with SVI. Limbs were divided into two groups: group I (CEAP C2-C3) and group II (CEAP C4-C6). A colour duplex scanner was used to determine quantitative venous reflux at the sapheno-femoral junction (SFJ), at the sapheno-popliteal junction (SPJ), and in the greater saphenous vein in the thigh (GSV). Patients received both manual compression and cuff deflation method in eliciting venous reflux. The parameters assessed were the duration of reflux (second) and the peak reflux velocity (cm/s). STATISTICS: Paired t-test was used to evaluate differences between the two methods. Statistical significance was recorded when the p-value was <0.05. Bland and Altman plot was also used to assess the agreement of the same measurement. RESULTS: There were 58 venous segments in group I and 36 in group II. In group I, there were no significant differences in the duration of reflux at the SFJ, SPJ, and in the GSV. On the contrary, peak reflux velocity was found to be significantly higher at the SFJ and in the GSV (p=0.022 and 0.006, respectively). In group II, there was no significant difference in the duration of reflux at the SFJ and SPJ between the two methods. On the contrary, manual compression maneuver produced significantly higher peak reflux velocity than at the SFJ and in the GSV (p=0.023 and 0.002, respectively). Bland and Altman plot analysis, manual compression method displayed a relatively good agreement with cuff deflation manoeuvre both in group I and group II. In contrast, concerning the peak reflux velocity, relative wide limits of agreement were found between the two methods. CONCLUSIONS: Unlike previously published reports, our results lead to apparent discrepancies in the quantitative evaluation of venous reflux using different methodology.

Adult↗
PubMed2006

Frequent immune response to a melanocyte specific protein KU-MEL-1 in patients with Vogt-Koyanagi-Harada disease.

AIM: To isolate autoantigens possibly involved in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease. METHODS: Autoantigens recognised by immunoglobulin G antibodies (IgG Ab) in sera from VKH patients were isolated by screening the lambda phage cDNA libraries made from melanocytes and a highly pigmented melanoma cell line with the patients' sera. Presence of IgG specific for the autoantigens in sera from patients with various panuveitis and healthy individuals was evaluated. Relation between the specific IgG and various clinicopathological features was examined. RESULTS: KU-MEL-1 was found to be one of the 81 isolated positive clones representing 35 distinct genes, which is a previously isolated melanoma antigen preferentially expressed in melanocytes. The IgG Ab specific for KU-MEL-1 was detected in sera from patients with VKH in significantly higher amounts than in sera from patients with Behçet's disease, sarcoidosis, and from healthy individuals. Positive serum KU-MEL-1 Ab was significantly associated with HLA-DRB1*0405 and male VKH patients. CONCLUSION: KU-MEL-1 was identified as a new autoantigen for VKH. The highly frequent induction of IgG Ab for KU-MEL-1 in HLA-DRB1*0405 positive VKH patients may suggest the possible involvement of KU-MEL-1 specific CD4(+) T cells in the pathogenesis of VKH, suggesting the possible use in the development of diagnostic and therapeutic treatments for VKH patients.

Adult↗
PubMed2006

Embolization for asymptomatic aneurysms of the first jejunal artery.

In a 71-year-old man with a history of coronary artery bypassing using the left internal thoracic and gastroepiploic arteries, the first jejunal artery aneurysms were found by chance at 3D-CT performed to evaluate conditions of the grafts. He was successfully treated by transcatheter embolization using interlocking detachable coils. During a follow-up period of 5 months, the patient did well and had no sign of intestinal ischemia.

Aged↗
PubMed2006

Chylothorax as a complication of innominate vein thrombosis induced by a peripherally inserted central catheter.

A 5-month-old boy with hypoplastic left heart syndrome developed chylothorax and oedema of the left upper arm more than 2 months after recovering from a Norwood stage II operation. Venography showed occlusion of the innominate vein with abundant collaterals crossing the midline to join the right internal jugular vein. The occlusion was caused by a peripherally inserted central catheter under systemic heparinisation. This case highlights the importance of a patent venous pathway, especially in patients with a cavopulmonary connection in the upper extremities.

Brachiocephalic Veins↗
PubMed2006

The utility of quantitative calf muscle near-infrared spectroscopy in the follow-up of acute deep vein thrombosis.

BACKGROUND: To investigate patterns of venous insufficiency and changes in calf muscle deoxygenated hemoglobin (HHb) levels after an acute deep vein thrombosis (DVT). METHODS: A total of 78 limbs with an acute DVT involving 156 anatomic segments were evaluated with duplex scanning and near-infrared spectroscopy (NIRS) at 1, 3, 6 and 12 months. Venous segments were examined whether they were occluded, partially recanalized, and totally recanalized, and the development of venous reflux was noted. The NIRS was used to measure calf muscle HHb levels. Calf venous blood filling index (HHbFI) was calculated on standing, then the calf venous ejection index (HHbEI), and the venous retention index (HHbRI) were obtained after exercise. RESULTS: The segments investigated were the common femoral vein (CFV; 38 segments), femoral vein (FV; 37), popliteal vein (POPV; 44), and calf veins (CV; 37). At 1 year, thrombi had fully resolved in 67% of the segments, 27% remained partially recanalized, 6% were occluded. The venous occlusion was predominant in the FV (24%) at 1 year. On the contrary, rapid recanalization was obtained in CV than proximal veins at each examination (P < 0.01). Venous reflux was predominant in POPV (55%), followed by FV (19%), and no reflux was found in CV. At 1 year, the HHbFI in POPV reflux patients was significantly higher than those with resolution (0.19 +/- 0.14, 0.11 +/- 0.05 microm s, P = 0.009, respectively). Similarly, there was a significant difference in the HHbRI between the two groups (3.08 +/- 1.91, 1.42 +/- 1.56, P = 0.002, respectively). In patients with FV occlusion, the value of HHbRI was significantly higher than those with complete resolution (2.59 +/- 1.50, 1.42 +/- 1.56, P = 0.011, respectively). CONCLUSIONS: The lower extremity venous segments show different proportions of occlusion, partial recanalization, and total recanalization. The CV shows more rapid recanalization than proximal veins. The NIRS-derived HHbFI and HHbRI could be promising parameters as the overall venous function in the follow-up of acute DVT. These findings might be very helpful for physician in detecting patients who require much longer follow-up studies.

Acute Disease↗
PubMed2006

Resource recovery from excess sludge by subcritical water combined with magnesium ammonium phosphate process.

The amount of excess sludge produced in municipal wastewater treatment plants in Japan is increasing every year as the urban population increases. Phosphorus in excess sludge could be a potential phosphorus resource since at present, phosphate rock is being exhausted all over the world. Every year, Japan imports large quantities of phosphorus from abroad but much is discharged as excess sludge. Therefore, the solubilization process, one method of recovering phosphorus from sludge, could be a promising solution. In this study, a subcritical water process, a new technology that solubilizes sludge under subcritical conditions, was applied before the phosphorus in sludge was recovered with the magnesium ammonium phosphate (MAP) process. As a result, the solubilization rate of excess sludge achieved approximately 80% and about 94-97% of the phosphorus could be recovered.

Cities↗
PubMed2006

Heme arginate pretreatment attenuates pulmonary NF-kappaB and AP-1 activation induced by hemorrhagic shock via heme oxygenase-1 induction.

Hemorrhagic shock followed by resuscitation (HSR) induces oxidative stress that leads to acute lung injury. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme catabolism, is induced by oxidative stress and is thought to play an important role in the protection from oxidative tissue injuries. We previously demonstrated that HO-1 induction by heme arginate (HA), a strong inducer of HO-1, ameliorated HSR-induced lung injury and inflammation. Cellular redox state is known to modulate the DNA biding activity of the transcription factors; nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). In the present study, we treated rats with HA (30 mg/kg of hemin) 18 h prior to HSR and examined its effect on the DNA binding activity of NF-kappaB and AP-1 at 1.5 h after HSR. HSR significantly increased the DNA binding activity of NF-kappaB as well as AP-1, while HA pretreatment markedly attenuated the activities of these transcription factors. In contrast, administration of tin mesoporphyrin, a specific competitive inhibitor of HO activity, to HA-pretreated animals abolished the suppressive effect of HA on the activities of NF-kappaB and AP-1, and increased these activities to almost the same level as those in HSR animals. Our findings indicate that HA pretreatment can significantly suppress the increased activity of NF-kappaB and AP-1 induced by HSR by virtue of its ability to induce HO-1. Our findings also suggest that HO-1 induced by HA pretreatment ameliorates HSR-induced lung injury at least in part mediated through the suppression of the activities of these transcription factors.

Animals↗
PubMed2006

[Intermediate results of aortic valve replacement using 19 mm bioprosthetic valve].

Pre- and postoperative hemodynamic parameters and activity of daily life were reviewed to estimate the effectiveness of the valve in 12 cases of single aortic valve replacement (AVR) using 19 mm bioprosthesis. All implanted prostheses were stented-valves. Carpentier-Edwards pericardial valve was used in 7 cases and Mosaic valve in 5. Left ventricular mass index (LVMI) significantly decreased from 167 +/- 36 to 133 +/- 27 g/m2 in the early postoperative period, and to 115 +/- 24 g/m2 in the intermediate phase. However, postoperative LVMI remained higher in patients with body surface area (BSA) over 1.5 m2 than in those under 1.5 m2. Postoperative activity indicated by New York Heart Association (NYHA) grade significantly improved from 2.3 +/- 1.1 to 1.4 +/- 0.5. These results indicates usefulness of 19 mm bioprosthetic valve for reducing left ventricular hypertrophy and improving activity, especially in patients with BSA smaller than 1.5 m2.

Aged↗
PubMed2005

Monocyte chemoattractant protein-4 (MCP-4)/CCL13 is highly expressed in cartilage from patients with rheumatoid arthritis.

OBJECTIVES: To study the role of monocyte chemoattractant protein-4 (MCP-4)/CCL13 in the pathogenesis of rheumatoid arthritis (RA), we analysed the expression of MCP-4/CCL13 in chondrocytes, synovial fluid and serum from patients with RA and investigated the effect of MCP-4/CCL13 on the proliferation of synovial cells. METHODS: Human articular cartilage specimens were obtained from joints from RA and osteoarthritis (OA) patients and normal joints (controls). Transcript levels of MCP-4 in cartilage were determined by real-time polymerase chain reaction. Protein levels were measured by enzyme-linked immunoassay. Cultured fibroblast-like synoviocytes (FLS) were treated with various concentrations of recombinant MCP-4/CCL13 protein, and cell proliferation was evaluated with a viability assay. RESULTS: The gene expression of MCP-4 was significantly higher in cartilage from RA patients than in that from OA patients (P = 0.00902) and in normal cartilage (P = 0.00902). The concentration of MCP-4/CCL13 protein in serum from RA patients (mean 94.7 +/- 37.6 pg/ml) was significantly higher than in serum from OA patients (mean 49.2 +/- 31.2 pg/ml, P = 0.0051) and controls (mean 32.6 +/- 23.9 pg/ml, P = 0.0001). The concentration of MCP-4/CCL13 protein in synovial fluid from RA patients (mean 247.2 +/- 161.2 pg/ml) was also significantly higher than in that from OA patients (mean 29.6 +/- 50.5 pg/ml, P = 0.000019). Moreover, MCP-4/CCL13 enhanced the proliferation of FLS in a dose-dependent manner. CONCLUSIONS: MCP-4/CCL13 is highly expressed in RA joints at the mRNA and protein levels. Our results suggest that MCP-4/CCL13 is secreted from chondrocytes and activates the proliferation of rheumatoid synovial cells, thereby leading to joint destruction in RA.

Arthritis, Rheumatoid↗
PubMed2005

Inhibition of intestinal cholesterol absorption by ezetimibe is a novel therapeutic target for fatty liver.

Ezetimibe is a novel lipid-lowering agent that inhibits intestinal absorption of dietary and biliary cholesterol. The effects of ezetimibe on low-density lipoprotein (LDL)-cholesterol were found to generally consistent across all subgroups analyzed, including baseline lipid profile, hypertension, diabetes mellitus, and body mass index. Furthermore, recent clinical studies also revealed that co-administration of ezetimibe with on-going statins offered a well-tolerated and efficacious treatment to lower LDL-cholesterol levels in hypercholesterolemic patients with diabetes mellitus or the metabolic syndrome. Niemann-Pick C1 like 1 (NPC1L1) protein is recently found to be critical for intestinal cholesterol absorption, and is a target protein for ezetimibe. Human NPC1L1 protein is predominantly expressed in liver, whereas small intestine expression is only about 2-4% of that found in the liver. Thus, NPC1L1 does not function solely in the intestinal cholesterol absorption. Furthermore, loss of NPC1L1 expression has been shown to protect against diet-induced fatty liver. These observations let us to speculate that ezetimibe will become a new therapeutic approach for the treatment of non-alcoholic fatty liver, the hepatic manifestation of insulin resistant patients with the metabolic syndrome. In this paper, we would like to propose the possible ways of testing our hypothesis as follows. (1) Does ezetimibe treatment improve fatty liver in patients with hypercholesterolemia or the metabolic syndrome? If the answers are yes, are these beneficial effects of ezetimibe superior to those of other anti-hyperlipidemic resins with equihypolipidemic properties? (2) Does ezetimibe treatment improve insulin sensitivity in fatty liver patients with the metabolic syndrome? (3) How about the effects of ezetimibe treatment on serum levels of adiponectin, a key adipokine with insulin-sensitizing property? Large clinical trials will provide us with more definite information whether ezetimibe treatment can improve fatty liver and resultantly reduce the risk of progression of liver diseases in patients with the metabolic syndrome.

Adiponectin↗
PubMed2005

Potential utility of statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in diabetic retinopathy.

Diabetic retinopathy is a common and potentially devastating microvascular complication in diabetes and is a leading cause of acquired blindness among the people of occupational age. However, therapeutic options for the treatment of proliferative diabetic retinopathy, photocoagulation and vitrectomy, are limited by considerable side effects. Therefore, to develop novel therapeutic strategies that specifically target diabetic retinopathy is desired for patients with diabetes. In diabetes mellitus, the formation and accumulation of advanced glycation end products (AGEs) progress. There is a growing body of evidence to show that AGEs-their receptor (RAGE) interactions are involved in the development and progression of diabetic retinopathy. Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, have been recently shown to reduce the risk for cardiovascular events in diabetic patients with or without coronary artery disease. However, the efficacy of statin therapy for diabetic retinopathy is not fully investigated. We have recently found that protein prenylation is crucial for the AGE-RAGE signaling in microvascular endothelial cells. By blocking the protein prenylation, cerivastatin completely prevented the AGE-RAGE-elicited angiogenesis via suppression of vascular endothelial growth factor (VEGF). These observations let us to speculate that statins might be a promising remedy for treating patients with diabetic retinopathy by acting as a potential inhibitor of the AGE-RAGE signaling pathway in microvascular endothelial cells. In this paper, we would like to propose the possible ways of testing our hypotheses. (1) Does treatment with statins decrease the risk for the development and progression of diabetic retinopathy in patients with normocholesterolemia? (2) If the answer is yes, is this beneficial effect of statins superior to that of other cholesterol-lowering agents with equihypolipidemic properties? (3) Does statin treatment suppress retinal VEGF expression in diabetic patients? (4) Does treatment with pyridoxamine, a post-Amadori inhibitor of AGE formation, attenuate the beneficial effects of statins on diabetic retinopathy? These clinical studies could clarify whether the use of statins is of benefit in patients with AGE-RAGE-related disorders such as diabetic retinopathy, even in the absence of hypercholesterolemia.

Acyl Coenzyme A↗
PubMed2005

Protective role of pravastatin in the pathogenesis of the metabolic syndrome.

The metabolic syndrome is strongly associated with insulin resistance and consists of a constellation of factors such as hypertension and hyperlipidemia that raise the risk for cardiovascular diseases and diabetes mellitus. There is a growing body of evidence to show that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, statins, reduce cardiovascular-related morbidity and mortality in patients with or without coronary artery disease. Recent clinical observations argue for a simple strategy of considering routine statin therapy for patients with type 2 diabetes. Furthermore, statin therapy is also found to be effective in allowing LDL-cholesterol goal achievement in hypercholesterolemic high-risk patients with the metabolic syndrome. However, the effects of statins on the pathogenesis of the metabolic syndrome remain to be elucidated. Several types of statins are commercially available now. Among them, pravastatin is unique because it is the only statin that has been shown to have protective role against the development of diabetes in a large clinical trial. Moreover, a recent clinical study revealed that pravastatin treatment improved insulin sensitivity in 25 women with the metabolic syndrome with impaired glucose intolerance. These observations let us to speculate that pravastatin is a promising strategy for the treatment of hypercholesterolemic patients with the metabolic syndrome. It may improve the insulin sensitivity in these patients and subsequently prevent the development of type 2 diabetes. In this paper, we would like to propose the possible ways of testing our hypothesis as follows. (1) Does pravastatin treatment improve insulin resistance in patients of the metabolic syndrome or in insulin resistant hypertensive or obese patients? If the answers are yes, are these beneficial effects of pravastatin superior to those of other anti-hyperlipidemic statins with equihypolipidemic properties? (2) Does pravastatin treatment actually reduce the development of diabetes in these insulin resistant patients? At that time, does pravastatin treatment increase serum levels of adiponectin, a key adipokine with insulin-sensitizing property? How about the effects of pravastatin treatment on adipokines that could elicit insulin resistance such as tumor necrosis factor-alpha? These clinical studies will provide further information whether pravastatin treatment can improve insulin resistance and subsequently reduce the development of diabetes in insulin resistant patients with the metabolic syndrome.

Clinical Trials as Topic↗
PubMed2005

Inhibition of postprandial hyperglycemia by acarbose is a promising therapeutic strategy for the treatment of patients with the metabolic syndrome.

The metabolic syndrome is strongly associated with insulin resistance and has been recognized as a cluster of risk factors for cardiovascular diseases such as visceral obesity, hypertension, diabetes, and atherogenic dyslipidemia. Recently, insulin resistance in the absence of overt diabetes or the metabolic syndrome itself has been associated with endothelial dysfunction, one of the initial steps in the process of atherosclerosis. Postprandial hyperglycemia, one of the characteristic features of insulin resistance, induces oxidative stress generation and elicits vascular inflammation and platelet activation, thus being involved in the pathogenesis of atherosclerosis. A recent multicenter, placebo-controlled randomized trial, STOP-NIDDM trial, revealed that acarbose (Glucobay R), an alpha-glucosidase inhibitor, improved postprandial hyperglycemia and subsequently reduced the risk of development of type 2 diabetes in patients with impaired glucose tolerance (IGT). In this study, acarbose treatment was also found to slow the progression of intima-media thickness of the carotid arteries, a surrogate marker for atherosclerosis, and to reduce the incidence of cardiovascular diseases and newly diagnosed hypertension in subjects with IGT. Acarbose significantly reduced body mass index and waist circumference in these patients over 3 years. Furthermore, a meta-analysis of seven long-term studies has also shown that intervention with acarbose prevents myocardial infarction and cardiovascular diseases in type 2 diabetic patients. In this analysis, glycemic control, triglyceride levels, body weight and systolic blood pressure was also significantly improved during acarbose treatment. These observations suggest that prevention of postprandial hyperglycemia by acarbose may be a promising therapeutic strategy for reducing the increased risk for diabetes, hypertension, dyslipidemia, obesity, and cardiovascular diseases in patients with the metabolic syndrome. Acarbose improves postprandial hyperglycemia by delaying the release of glucose from complex carbohydrates in the absence of an increase in insulin secretion. Therefore, we would like to hypothesize here that this improvement in glucose metabolism could be associated with amelioration in insulin sensitivity, thus explaining the above-mentioned beneficial cardiometabolic actions of acarbose. Large clinical trials will provide us with more definite information whether acarbose treatment can improve insulin sensitivity and resultantly reduce the risk of diabetes, hypertension and cardiovascular diseases in patients with the metabolic syndrome.

Acarbose↗