Makoto Tominaga

Mitsui Memorial Hospital, Edo, Tōkyō, Japan

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Publications (130)292.59 Total impact

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    ABSTRACT: The beta3-adrenergic receptor (ADRB3), primarily expressed in adipose tissue, is involved in the regulation of energy metabolism. This study hypothesized that ADRB3 (Trp64Arg, rs4994) polymorphisms modulate the effects of lifestyle intervention on weight and metabolic parameters in subjects with impaired glucose tolerance. Data were analyzed from 112 subjects with impaired glucose tolerance in the Japan Diabetes Prevention Program (JDPP), a lifestyle intervention trial, randomized to either an intensive lifestyle intervention group (ILG) or usual care group (UCG). Changes in weight and metabolic parameters were measured after the 6-month intervention. The ADRB3 polymorphisms were determined using PCR-RFLP method. Non-carriers showed a greater weight reduction compared with the carriers in both ILG and UCG, and a greater increase of high-density lipoprotein cholesterol levels than the carries only in ILG. ADRB3 polymorphisms could influence the effects of lifestyle interventions on weight and lipid parameters in impaired glucose tolerance subjects.This article is protected by copyright. All rights reserved.
    09/2015; DOI:10.1111/jdi.12426
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    ABSTRACT: Glycated albumin (GA) is an intermediate glycemic control marker for which there are several measurement procedures with entirely different reference intervals. We have developed a reference measurement procedure for the purpose of standardizing GA measurements. The isotope dilution liquid chromatography / tandem mass spectrometry (ID-LC/MS) method was developed as a reference measurement procedure for GA. The stable isotopes of Lys and fructosyl-lysine, which serve as an internal standard, were added to albumin isolated from serum, followed by hydrogenation. After hydrolysis of albumin with hot hydrochloric acid, the liberated lysine and fructosyl-lysine were measured by LC/MS, and their concentrations were determined from each isotope ratio. The reference materials (JCCRM611) for determining of GA were prepared from pooled patient blood samples. The ID-MS calibration curve of fructosyl-lysine and lysine showed good linearity (r = 0.999). The interassay and intraassay CV (coefficient of variation) values of GA measurement were 1.2% and 1.4%, respectively. The GA values of serum in patients with diabetes assessed through the use of this method showed a good relationship with routine measurement procedures (r = 0.997). The relationship of GA values of the reference material (JCCRM611) between these two methods was the same as the relationship with the patient serum samples. The Committee on Diabetes Mellitus Indices of the Japan Society of Clinical Chemistry recommends the ID-LC/MS method as a reference measurement procedure, and JCCRM611 as a certified reference material for GA measurement. In addition, we recommend the traceability system for GA measurement. © 2015 SAGE Publications.
    Annals of Clinical Biochemistry 07/2015; DOI:10.1177/0004563215599178 · 2.34 Impact Factor
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    ABSTRACT: To determine the effects of a lifestyle intervention on the development of type 2 diabetes mellitus (T2DM) among participants with impaired glucose tolerance (IGT), in particular in the subgroup with baseline glycated hemoglobin (HbA1c) levels ≥5.7%, in primary healthcare settings. Randomized controlled trial. 32 healthcare centers in Japan. Participants with IGT, aged 30-60 years, were randomly assigned to either an intensive lifestyle intervention group (ILG) or a usual care group (UCG). During the initial 6 months, participants in the ILG received four group sessions on healthy lifestyles by public health providers. An individual session was further conducted biannually during the 3 years. Participants in the UCG received usual care such as one group session on healthy lifestyles. The primary endpoint was the development of T2DM based on an oral glucose tolerance test. The mean follow-up period was 2.3 years. The annual incidence of T2DM were 2.7 and 5.1/100 person-years of follow-up in the ILG (n=145) and UCG (n=149), respectively. The cumulative incidence of T2DM was significantly lower in the ILG than in the UCG among participants with HbA1c levels ≥5.7% (log-rank=3.52, p=0.06; Breslow=4.05, p=0.04; Tarone-Ware=3.79, p=0.05), while this was not found among participants with HbA1c levels <5.7%. Intensive lifestyle intervention in primary healthcare setting is effective in preventing the development of T2DM in IGT participants with HbA1c levels ≥5.7%, relative to those with HbA1c levels <5.7%. UMIN000003136.
    04/2014; 2(1):e000003. DOI:10.1136/bmjdrc-2013-000003
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    ABSTRACT: The aim of this investigation is to examine the correlation between the HbA1c numbers used by the National Glycohemoglobin Standardization Program (NGSP) and the Japan Diabetes Society (JDS) and to validate the HbA1c cutoff values of 6.5 and 6.1 % set for the diagnosis of diabetes mellitus by the American Diabetes Association (ADA) and the JDS, respectively. NGSP HbA1c values obtained from the monthly monitoring program of the performance of the NGSP Secondary Reference Laboratories (SRLs) were provided by the NGSP. The samples used in the NGSP monitoring program were also assayed to obtain the JDS values at the Laboratory of Reference Material Institute for Clinical Chemistry Standards (ReCCS) using the KO 500 designated comparison method (DCM) calibrated with a reference material, JDS Lot 4, issued by ReCCS. The results were compared, and the correlation between the two data sets was examined by linear regression. The relationship between the NGSP SRLs values and JDS values for the monitoring program samples was as follows: NGSP = 1.029 × JDS + 0.216. For another sample, JDS Lot 4, the correlation was: NGSP = 1.029 × JDS + 0.187. The two equations are consistent with the cutoff points 6.5 and 6.1 %, used by the ADA and the JDS, respectively.
    Diabetology International 03/2014; 6(1). DOI:10.1007/s13340-014-0173-z
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    Diabetology International 02/2012; 3(1). DOI:10.1007/s13340-012-0069-8
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    ABSTRACT: A randomized control trial was performed to test whether a lifestyle intervention program, carried out in a primary healthcare setting using existing resources, can reduce the incidence of type 2 diabetes in Japanese with impaired glucose tolerance (IGT). The results of 3 years' intervention are summarized. Through health checkups in communities and workplaces, 304 middle-aged IGT subjects with a mean body mass index (BMI) of 24.5 kg/m2 were recruited and randomized to the intervention group or control group. The lifestyle intervention was carried out for 3 years by public health nurses using the curriculum and educational materials provided by the study group. After 1 year, the intervention had significantly improved body weight (-1.5 ± 0.7 vs. -0.7 ± 2.5 kg in the control; p = 0.023) and daily non-exercise leisure time energy expenditure (25 ± 113 vs. -3 ± 98 kcal; p = 0.045). Insulin sensitivity assessed by the Matsuda index was improved by the intervention during the 3 years. The 3-year cumulative incidence tended to be lower in the intervention group (14.8% vs.8.2%, log-rank test: p = 0.097). In a sub-analysis for the subjects with a BMI > 22.5 kg/m2, a significant reduction in the cumulative incidence was found (p = 0.027). The present lifestyle intervention program using existing healthcare resources is beneficial in preventing diabetes in Japanese with IGT. This has important implications for primary healthcare-based diabetes prevention. UMIN000003136.
    BMC Public Health 01/2011; 11(1):40. DOI:10.1186/1471-2458-11-40 · 2.26 Impact Factor
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    ABSTRACT: We have reported in this journal in vitro susceptibilities of clinical isolates to antibiotics every year since 1992. In this paper, we report the results of an analysis of in vitro susceptibilities of 12,919 clinical isolates from 72 centers in Japan to selected antibiotics in 2007 compared with the results from previous years. The common respiratory pathogens, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae maintained a high susceptibility to fluoroquinolones (FQs). The resistance of S. pyogenes to macrolides has been increasing every year and this was especially clear this year. Most strains of Enterobacteriaceae except for Escherichia coli showed a high susceptibility to FQs. Almost 30% of E. coli strains were resistant to FQs and the resistance increased further this year. FQs resistance of methicillin-resistant Staphylococcus aureus (MRSA) was approximately 95% with the exception of 45% for sitafloxacin (STFX). FQs resistance of methicillin-susceptible S. aureus (MSSA) was low at about 10%. FQs resistance of methicillin-resistant coagulase negative Staphylococci (MRCNS) was higher than that of methicillin-susceptible coagulase negative Staphylococci (MSCNS), but it was lower than that of MRSA. However, FQs resistance of MSCNS was higher than that of MSSA. FQs resistance of Enterococcus faecalis was 22.5% to 29.6%, while that of Enterococcusfaecium was more than 85% except for STFX (58.3%). In clinical isolates of Pseudomonas aeruginosa derived from urinary tract infections, FQs resistance was 21-27%, which was higher than that of P. aeruginosa from respiratory tract infections at 13-21%, which was the same trend as in past years. Multidrug resistant strains accounted for 5.6% in the urinary tract and 1.8% in the respiratory tract. Acinetobacter spp. showed high susceptibility to FQs. The carbapenem resistant strains, which present a problem at present, accounted for 2.7%. Neisseria gonorrhoeae showed high resistance of 86-88% to FQs. The results of the present survey indicated that although methicillin-resistant Staphylococci, Enterococci, E. coli, P. aeruginosa, and N. gonorrhoeae showed resistance tendencies, and other species maintained high susceptibility rates more than 90% against FQs, which have been used clinically for over 15 years.
    The Japanese journal of antibiotics 08/2009; 62(4):346-70.
  • A Hirata · M Igarashi · H Iwai · M Tominaga ·
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    ABSTRACT: This study investigates the effects of miglitol, an alpha-glucosidase inhibitor, on the development of balloon-injured neointimal thickening in left common carotid artery, and the changes of glucose metabolism and inflammatory responses in Wistar fatty rats, an obese-hyperglycemic animal model, and their littermates, Wistar lean rats. Miglitol was orally administered at 40 mg/100 g of high-fat diet containing 45% kcal as fat to 12-week-old rats for 29 days, and age-matched rats without the agent were used as the respective controls. Balloon catheterization in the left common carotid artery was performed on day 15, and the artery was removed on day 29. Compared with the area ratio of the neointima/media in fatty rats without treatment, those in fatty rats with miglitol and lean rats without treatment were significantly decreased to 80%. The administration of miglitol significantly decreased the levels of plasma glucose, glycoalbumin and high-sensitivity C-reactive protein, and elevated the high-density lipoprotein-cholesterol level in fatty rats. These findings suggest that miglitol could be effective for the suppression of atherogenic outcomes in diabetic Wistar fatty rat, suggesting that the agent may have clinical benefits and contribute to prevent diabetic macroangiopathy.
    Hormone and Metabolic Research 03/2009; 41(3):213-20. DOI:10.1055/s-0028-1105919 · 2.12 Impact Factor
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    ABSTRACT: This study was performed to examine the changes in rapid turnover proteins (RTPs), such as retinol-binding protein, transthyretin and transferrin, which are known nutritional parameters, during the perioperative period for digestive system operations. The study was performed with 62 subjects who underwent elective surgery of the digestive system. The RTP measurements were performed approx. seven times for each subject (approx. 20 times in total) from the preoperative period to the 14th postoperative day. For 20 subjects who exhibited no recurrence of a malignant tumor, additional measurements were performed 6 to 12 months after the operation. RTPs were measured more than 1,400 times in total for all subjects. The three types of RTPs all exhibited similar changes, but the largest change was observed for retinol-binding protein. The changes in RTPs were significantly larger than those for albumin. RTP levels were lowest on the 3rd postoperative day and gradually increased thereafter. The RTP levels recovered to approx. 80% of the preoperative values on the 14th postoperative day. In the measurements performed 6 to 12 months after the operation, the levels recovered to 90% or higher of the preoperative values. No significant differences were observed between the cases utilizing different operation methods. The administration of fresh frozen plasma had no impact on the postoperative changes. No correlation was observed between the calories obtained by oral intake during the period from the 5th to 10th postoperative days and the changes in RTPs. The study results suggested that changes in RTPs would not affected by the calories obtained by oral intake during the early postoperative days. In patients who returned to their daily life after an invasive surgery or reconstruction of the digestive tract, RTP levels were restored to the preoperative values 6 to 12 months after the operation.
    Hepato-gastroenterology 01/2009; 56(89):167-73. · 0.93 Impact Factor
  • Masahiko Igarashi · Akihiko Hirata · Makoto Tominaga ·
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    ABSTRACT: In September, 2007, the Japanese Ministry of Health, Labor and Welfare legislated that clinical laboratory doctors can advocate the clinical laboratory in hospitals and clinical offices. The decision was monumentous, and we, clinical laboratory physicians, can see patients from April, 2008. Although our roles and/or details have not officially been determined, we must definite the contribution of clinical laboratory doctors. One of our plans is to set up a conference room in the Division of Clinical Laboratory to explain their medical tests to patients. Laboratory data are not always explained in detail by doctors, since they are busy and do not have enough time to see patients. Subsequently, clinical laboratory physicians will be able to comply with patients' wishes for medical testing. In addition, to prevent the development of lifestyle-related diseases and their related metabolic syndrome in Japanese people, a new specified health checkup system has recently been established by the Japanese Ministry of Health, Labor and Welfare, and the system will start from April, 2008. Since more than 20 million people from 40 to 74 years old are estimated to undergo this health checkup, total quality assurance in the clinical laboratory is required to provide accurate and precise test values by the government. Therefore, our clinical laboratory physicians should play a central role to guarantee the specified health checkup system.
    Rinsho byori. The Japanese journal of clinical pathology 09/2008; 56(8):689-95.
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    ABSTRACT: Impaired glucose tolerance (IGT) is a known risk factor for cardiovascular disease, which includes stroke as well as coronary heart disease (CHD). We investigated whether IGT is a risk factor for stroke. The incidence of stroke and CHD in a cohort population (n = 2938) consisting of participants of the 1990-1997 Funagata study was assessed through interviews with the participants and their family members and reviews of death certificates and residence transfer documents through 2002. Glucose tolerance at the baseline was classified according to the criteria of the 1998 World Health Organization (normal glucose tolerance, n = 2189; IGT, n = 320; and diabetes, n = 286). The cumulative incidences among the groups were compared using the Kaplan-Meier product-limit method, and the risks of these conditions were evaluated by person-year and Cox proportional hazard methods. During the 147-month (mean, 116.5 months) follow-up, 158 (normal glucose tolerance, IGT, and diabetes: 94, 35, and 29, respectively) participants experienced a stroke and 94 (54, 16, and 24, respectively) experienced CHD. By the person-year method, IGT and diabetes were shown to be significant risk factors for stroke and CHD (odds ratio, 1.87 [95% confidence interval, 1.73-2.03] and 3.57 [3.21-3.98] for stroke; 1.53 [1.31-1.78] and 3.47 [2.91-4.14] for CHD, respectively). Cox proportional hazard analysis showed that IGT was a risk factor for stroke (age-, sex-, and hypertension-adjusted hazard ratio: 1.51 [95% confidence interval, 1.02-2.24], P = .039) but not for CHD (1.21 [0.69-2.313], .509). Impaired glucose tolerance is a risk factor for future stroke in a Japanese population.
    Metabolism 04/2008; 57(3):333-8. DOI:10.1016/j.metabol.2007.10.007 · 3.89 Impact Factor
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    ABSTRACT: To determine the relationship of metabolic syndrome and its components with retinopathy and other retinal microvascular signs in a Japanese population. The Funagata study recruited 1961 (53.3% of eligible) Japanese aged 35 or older. The metabolic syndrome was diagnosed primarily using definitions of the International Diabetes Federation. Retinopathy and retinal microvascular signs were assessed from fundus photographs. Retinal arteriolar and venular diameters were measured using a computer-assisted programme. Data were available for analysis in 1638 persons for retinopathy and retinal microvascular signs and 921 persons for retinal vessel diameters. Various components of the metabolic syndrome were associated with retinal microvascular signs: a larger waist circumference was associated with wider venular diameter and retinopathy lesions; a higher blood pressure level was associated with focal arteriolar narrowing, arteriovenous nicking, enhanced arteriolar wall reflex and narrower arteriolar diameter; and a higher triglyceride level was associated with enhanced arteriolar wall reflex. Overall, persons with the metabolic syndrome were more likely to have retinopathy (odds ratio 1.64, 95% CI: 1.02 to 2.64) and wider venular diameter 4.69 microm (95% CI: 1.20 to 8.19 microm) than persons without the metabolic syndrome. We report associations of metabolic syndrome components with retinopathy and wider venular diameter in Japanese adults. These data suggest that metabolic abnormalities, indicated by metabolic syndrome components, are associated with microvascular changes in the retina. There was no synergistic effect of the metabolic syndrome on retinal microvascular changes beyond its individual components.
    The British journal of ophthalmology 03/2008; 92(2):161-6. DOI:10.1136/bjo.2007.127449 · 2.98 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the anti-atherogenic outcomes of pioglitazone, a thiazolidinedione derivative, in type 2 diabetic patients. Eight patients with poor diabetic control were treated with 15 mg of pioglitazone for 4 months. Blood samples were collected monthly, and the levels of fasting plasma glucose (FPG), HbA1c, and lipids, such as triglycerides, total cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol, were measured. Other parameters, including immunorecative insulin (IRI), remnant-like particle-cholesterol (RLP-C), adiponectin, plasminogen activator inhibitor type 1 (PAI-1), tumor necrosis factor (TNF)- alpha , leptin, brain natriuretic peptide (BNP), and high-sensitivity (hs)-C-reactive protein (CRP), were examined at the beginning and end of the study. In addition, clinically adverse side-effects were evaluated. Treatment with pioglitazone significantly decreased the levels of HbA1c, FPG, the homeostasis model assessment of insulin resistance (HOMA-IR) index, RLP-C, PAI-1, TNF- alpha , and hs-CRP, but not the level, IRI, lipids, or leptin. In contrast, adverse side-effects, including body weight gain, liver dysfunction and edema, were not observed during this study. These results strongly suggested that treatment with pioglitazone has a greater clinical benefit for the prevention of atherosclerosis, including coronary heart diseases, without any adverse side-effects.
    Journal of atherosclerosis and thrombosis 03/2008; 15(1):34-40. DOI:10.5551/jat.E528 · 2.73 Impact Factor
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    ABSTRACT: Measurement of glycated albumin (GA) has been introduced into clinical laboratory medicine as a new marker for diabetes, and it is now widely used as a routine test in Japan. However, due to absence of a reference measurement method, it was necessary to promptly establish a standardized procedure. Since 2002, the following activities have been conducted as part of the GA standardization project: 1) a survey of the actual conditions to understand the current status of GA measurement; 2) a basic study to define GA; 3) preparation of reference materials and establishment of a reference method; and 4) determination of reference intervals. The basic study to define GA involved peptide mapping, since albumin has multiple glycation sites and it was necessary to determine suitable glycation sites exist in GA. Based on these results, in the present study, GA was defined as "albumin containing lysine residues bound to glucose (Nε-D-fructos-1-yl) -L-lysine: DOF-Lys). "A method based on isotope dilution mass spectrometry (ID-MS) is proposed as the reference measurement procedure to be used as a traceable tool of GA standardization. Herein, we present the ID-MS procedure and its performance results. Methods: After isolating albumin from serum, stable isotopes of DOF-Lys and lysine (Lys) were added to albumin fractions as internal standards and glycation sites were subject to hydrogenation followed by hydrolysis. All freed DOF-Lys and Lys residues were recovered by reduced pressure drying, and their isotopic ratios were determined using liquid chromatography-mass spectrometry. GA levels were expressed in terms of molar ratios (unit: mmol/mol) of all liberated DOF-Lys residues and albumin calculated from all liberated Lys residues. Results: The measurement precision of the present method was CV 1.2% for within-run reproducibility (n = 10) and CV 1.4% for day-to-day reproducibility (n = 15); favorable compatibility with routine tests (r = 0.996) was demonstrated. Conclusion: The present ID-MS method of GA measurement is a valid reference measurement procedure for GA.
    Japanese Journal of Clinical Chemistry 01/2008; 37(2):178-191.
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    ABSTRACT: The present study examined the prevalence of metabolic syndrome (MetS) when the Japanese diagnostic criteria was used, the prevalence of each component in the criteria, and also the validity of the waist circumference cut-off value measured at the navel level, using the results obtained from the Japanese National Health and Nutrition Survey (NHNS) in 2003. The prevalence of MetS in 2113 subjects according to the Japanese diagnostic criteria was 22.8% (95% CI: 20.2-25.5) for males and 8.7% (7.1-10.4) for females. The prevalence for high blood pressure (HBP), dyslipidemia (DLP), high fasting blood glucose (HFG) and central obesity for males/females were 59.1% (56.0-62.2)/47.2% (44.3-50.1), 40.5% (37.3-43.6)/27.9% (25.4-30.5), 19.1% (16.6-21.6)/16.2% (14.0-18.3) and 45.9% (42.7-49.0)/17.4% (15.3-19.5), respectively. The low prevalence of MetS for females was attributed to a larger waist circumference cut-off value for females (90 cm) than for males (85 cm). Optimal waist circumference cut-off values of subjects, who fulfil at least two of HBP, DLP or HFG, estimated from the receiver operating characteristic curve were subsequently found to be 85 cm for males and 80 cm for females. Based on the new values, the prevalence of MetS was found to be 22.8% for males and 19.2% for females. The present study revealed that optimal waist circumference cut-off value was much shorter than that previously proposed in females.
    Diabetes Research and Clinical Practice 11/2007; 78(1):77-84. DOI:10.1016/j.diabres.2007.02.015 · 2.54 Impact Factor
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    ABSTRACT: This study was investigated to characterize the activation mechanism of a mitogen-activated protein (MAP) kinase superfamily in diabetes in aortae and cultured vascular smooth muscle cells (VSMCs) from rats. Male Sprague-Dawley rats were used for this procedure, and diabetes was induced by streptozotocin injection at 50 mg/kg. After 6 weeks, the thoracic aortae from normal and diabetic rats were removed for detection of the MAP kinase superfamily by immunoblot analysis. In aortae, the protein levels of extracellular signal-regulated protein kinase (ERK)-1, c-jun NH2-terminal protein kinase (JNK)-1 and -2, and p38 increased significantly more in diabetic rats than in normal rats. In contrast, phosphorylated protein levels of ERK-1 and -2, JNK-1, and p38 were significantly more elevated in diabetic rats than in normal rats. In VSMCs from normal rats, a high concentration of glucose cultured for three days significantly increased the phosphorylated protein levels of ERKs and p38, but not JNKs, without any change of these protein levels. Serum interleukin (IL)-1beta was significantly higher in diabetic rats than in normal rats. Several types of proinflammatory cytokine dose-dependently phosphorylated the levels of ERKs, JNK-1, and p38, but not JNK-2, in VSMCs from normal rats. In cells from diabetic rats, phosphorylated protein levels of ERKs and p38 were significantly elevated by IL-1beta. In addition, interferon-gamma phosphorylated the levels of ERKs in diabetic cells more than in normal cells. Our results suggest that, under diabetic conditions, the MAP kinase superfamily was activated by different pathways in the vasculature; i.e., ERKs and p38 might be mainly phosphorylated by a complex of high concentrations of glucose and of several types of proinflammatory cytokines, but the phosphorylation of JNK-1 might depend on the concentration of proinflammatory cytokines such as IL-1beta, and/or additional unknown factors, except glucose.
    Journal of atherosclerosis and thrombosis 11/2007; 14(5):235-44. DOI:10.5551/jat.E514 · 2.73 Impact Factor
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    ABSTRACT: Type 2 diabetes mellitus (DM) is a common and serious condition related with considerable morbidity. Screening for DM is one strategy for reducing this burden. In Japan National Diabetes Screening Program (JNDSP) guideline, the combined use of fasting plasma glucose (FPG) and glycated hemoglobin A1c (HbA1c) in a stepwise fashion has been recommended to identify the group of people needing life-style counseling or medical care. However, the efficacy of this program has not been fully evaluated, as an oral glucose tolerance test (OGTT) is not mandatory in the guideline. The aim of this study was to assess the validity of the screening test scenario, in which an OGTT would be applied to people needing life-style counseling or medical care on this guideline: FPG 110-125 mg/dl and HbA1c over 5.5%. Subjects were 1,726 inhabitants without a previous history of DM in the Funagata study, which is a population-based survey conducted in Yamagata prefecture to clarify the risk factors, related conditions, and consequences of DM. DM was diagnosed according to the 1999 World Health Organization criteria. The prevalence of undiagnosed DM was 6.6%. The tested screening scenario gave a sensitivity of 55.3%, a specificity of 98.4%, a positive predictive value of 70.8%, and a negative predictive value of 96.9% for undiagnosed DM. In conclusion, the screening test scenario, in which an OGTT would be followed by the combined use of FPG and HbA1c in a stepwise fashion according to the JNDSP guideline, was not effective in identifying people with undiagnosed DM.
    The Tohoku Journal of Experimental Medicine 10/2007; 213(1):25-32. DOI:10.1620/tjem.213.25 · 1.35 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the anti-atherogenic efficacy of pioglitazone, a thiazolidinedione derivative, on the change in atherogenic outcomes by comparing responder and non-responder groups in type 2 diabetic patients. Twenty-three patients with poor diabetic control were treated with 15 mg of pioglitazone for 12 months. The levels of fasting plasma glucose (FPG), HbA1c, triglycerides (TG), total cholesterol (T-Cho), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C) were measured monthly, and those of remnant-like particle-cholesterol (RLP-C) and lipoprotein (a) [Lp (a)] were measured every 3 months. In Month 6, the patients were divided into two groups according to the decrease in HbA1c level: the responder group showed a decrease of > or =1%; the non-responder group, a decrease of <1%. In the responder group, the levels of FPG and HbA1c decreased significantly after Month 3. The values of the body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR) index, LDL-C, and RLP-C were significantly higher in the responder group than in the non-responder group. Although the levels of T-Cho and HDL-C were unchanged in both groups, those of TG and RLP-C were drastically reduced in the responder group. Interestingly, the relative change in Lp (a) was significantly decreased in both groups. These results strongly suggest that pioglitazone is beneficial for type 2 diabetic patients with high levels of BMI, HOMA-IR, LDL-C, and RLP-C, as it helps to prevent the progression of atherosclerosis, including coronary heart diseases.
    Diabetes Research and Clinical Practice 09/2007; 77(3):389-98. DOI:10.1016/j.diabres.2006.12.022 · 2.54 Impact Factor
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    ABSTRACT: The aim of the study was to assess the screening test properties of HbA1c for undiagnosed diabetes (DM) according to the 1999-WHO criteria and its relevance of the Japan National Diabetes Survey Cut-off points for possible and probable DM: HbA1c >or=5.6 and 6.1%. Screening properties of HbA1c predicting undiagnosed DM was examined and compared with that of fasting plasma glucose (FPG) in 1904 Funagata-town inhabitants aged 35-89 years old. The prevalence of previous DM, undiagnosed DM, and impaired glucose regulation (IGR) were 5.5, 6.0, and 18.6%, while the prevalence of probable and possible DM were 7.7 and 5.4%. The area under the receiver operating characteristic curve for undiagnosed DM was similar between HbA1c (0.856 [95% CI: 0.812-0.899]) and FPG (0.902 [0.869-0.936]). HbA1c of 5.6% gave a sensitivity of 56.5%, a specificity of 95.1%, positive and negative predictive values of 44.2 and 97.0%, and a proportion of people above the cut-off point of 8.2%. True positive tests were significantly higher with mean levels of BMI, fasting, and 2-h plasma glucose, and HbA1c, but lower with mean levels of high-density-lipoprotein cholesterol than in false negative tests. The measurement of HbA1c alone may be efficient to screen undiagnosed DM and the cut-off point of 5.6% might be proper with respect to screening tests properties for undiagnosed DM, and prediction of vascular complications in Japan.
    Diabetes Research and Clinical Practice 06/2007; 76(2):251-6. DOI:10.1016/j.diabres.2006.09.015 · 2.54 Impact Factor
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    ABSTRACT: This study investigates the mechanisms whereby angiotensin II (Ang II) signaling contributes to cell growth and glucose metabolism in cultured vascular smooth muscle cells (VSMCs) from male Wistar fatty rats (WF) and their littermates (Wistar lean rats, WL). The levels of the medial outgrowth rate of VSMCs and Ang II type-1 receptors (AT1R) in aortae from WF were more enhanced than those in aortae from WL, but the level of Ang II type-2 receptors (AT2R) was not different. A mixture of insulin and Ang II additively increased the values of [(3)H]-thymidine incorporation in WF and WL, which was inhibited by olmesartan, an AT1 receptor blockade (ARB), but not by PD123,319, an AT2 receptor blockade. Similarly, insulin and Ang II phosphorylated extracellular-regulated protein kinase 1/2, retinoblastoma tumor suppressor protein, and cyclic AMP response element binding protein, and these levels were higher in WF than in WL. In contrast, the phosphorylation was suppressed by olmesartan but not PD123,319. Insulin-stimulated Akt phosphorylation and 2-deoxy-d-glucose uptake in WF were significantly reduced by Ang II, and the reduction was ameliorated by olmesartan but not PD123,319. Differently from the result of Akt, the phosphorylation of the insulin-stimulated insulin receptor beta-subunit was not affected by Ang II, olmesartan, or PD123,319. However, the phosphorylation of insulin-stimulated insulin-related substrate (IRS)-1 was suppressed by Ang II, and the suppression was ameliorated by olmesartan, but not PD123,319, in both WF and WL. In contrast, the phosphorylation of IRS-1 on Ser(307) was elevated by the Ang II, and the elevation was suppressed by olmesartan, but not by PD123,319, in both WF and WL. These findings demonstrated that Ang II signaling contributes to cell proliferation and inhibition of the insulin signaling pathways through AT1R, but not trough AT2R, in both non-diabetic and diabetic VSMCs.
    Diabetes Research and Clinical Practice 04/2007; 75(3):267-77. DOI:10.1016/j.diabres.2006.06.032 · 2.54 Impact Factor

Publication Stats

3k Citations
292.59 Total Impact Points


  • 2012
    • Mitsui Memorial Hospital
      Edo, Tōkyō, Japan
  • 1981-2009
    • Yamagata University
      • • Department of Laboratory Medicine
      • • Department of Clinical Laboratory
      • • Third Department of Internal Medicine
      • • School of Medicine
      Ямагата, Yamagata, Japan
  • 1992
    • Shinshu University
      • Division of Endocrinology and Metabolism
      Shonai, Nagano, Japan
  • 1991
    • Yamaguchi University
      • Division of Internal Medicine III
      Yamaguti, Yamaguchi, Japan