Meguro, Shu

写真a

Affiliation

School of Medicine, Department of Internal Medicine (Nephrology, Endocrinology and Metabolism) （Shinanomachi）

Position

Assistant Professor/Senior Assistant Professor
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Career 【 Display / hide 】

  • 1993.04
    -
    1995.03

    慶應義塾大学病院　内科研修医

  • 1995.04
    -
    1997.03

    慶應義塾大学医学部内科学教室　助手

  • 1997.04
    -
    2001.06

    慶應義塾大学医学部　腎臓内分泌代謝内科　助手

  • 2001.07
    -
    2010.06

    東京都済生会中央病院

  • 2010.07
    -
    2012.03

    慶應義塾大学医学部　腎臓内分泌代謝内科　助教

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Academic Background 【 Display / hide 】

  • 1993.03

    Hokkaido University, Faculty of Medicine

    University, Graduated

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Academic Degrees 【 Display / hide 】

  • 医学博士, Keio University, Dissertation, 2003

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Licenses and Qualifications 【 Display / hide 】

  • fellow of the Japanese Society of Internal Medicine, 2006.12

  • 日本糖尿病学会　専門医, 2009.04

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Research Areas 【 Display / hide 】

  • Life Science / Metabolism and endocrinology (Metabolism Studies)

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Papers 【 Display / hide 】

  • Transient Dexamethasone Loading Induces Prolonged Hyperglycemia in Male Mice with Histone Acetylation in Dpp-4 Promoter

    Uto A., Miyashita K., Endo S., Sato M., Ryuzaki M., Kinouchi K., Mitsuishi M., Meguro S., Itoh H.

    Endocrinology (United States) （Endocrinology (United States))  162 （ 12 ）  2021.12

    ISSN  00137227

    　View Summary

    Glucocorticoid causes hyperglycemia, which is common in patients with or without diabetes. Prolonged hyperglycemia can be experienced even after the discontinuation of glucocorticoid use. In the present study, we examined the time course of blood glucose level in hospital patients who received transient glucocorticoid treatment. In addition, the mechanism of prolonged hyperglycemia was investigated by using dexamethasone (Dexa)-treated mice and cultured cells. The blood glucose level in glucose tolerance tests, level of insulin and glucagon-like peptide 1 (GLP-1), and the activity of dipeptidyl peptidase 4 (DPP-4) were examined during and after Dexa loading in mice, with histone acetylation level of the promoter region. Mice showed prolonged hyperglycemia during and after transient Dexa loading accompanied by persistently lower blood GLP-1 level and higher activity of DPP-4. The expression level of Dpp-4 was increased in the mononuclear cells and the promoter region of Dpp-4 was hyperacetylated during and after the transient Dexa treatment. In vitro experiments also indicated development of histone hyperacetylation in the Dpp-4 promoter region during and after Dexa treatment. The upregulation of Dpp-4 in cultured cells was significantly inhibited by a histone acetyltransferase inhibitor. Moreover, the histone hyperacetylation induced by Dexa was reversible by treatment with a sirtuin histone deacetylase activator, nicotinamide mononucleotide. We identified persistent reduction in blood GLP-1 level with hyperglycemia during and after Dexa treatment in mice, associated with histone hyperacetylation of promoter region of Dpp-4. The results unveil a novel mechanism of glucocorticoid-induced hyperglycemia, and suggest therapeutic intervention through epigenetic modification of Dpp-4.

  • One-year estimated glomerular filtration rate decline as a risk factor of cardiovascular and renal end-points in high-risk Japanese patients

    Meguro S., Inaishi J., Sato Y., Komuro I., Itoh H.

    Journal of Diabetes Investigation （Journal of Diabetes Investigation)  12 （ 7 ） 1212 - 1219 2021.07

    ISSN  20401116

    　View Summary

    Aims/Introduction: As estimated glomerular filtration rate (eGFR) progression might correlate with cardiovascular prognosis, the correlation between 1-year decline in eGFR and cardiovascular incidences and renal outcome was investigated. Materials and Methods: The 1-year percentage decline in eGFR at the first observation year was calculated in a cohort of the standard versus intEnsive statin therapy for hypercholesteroleMic Patients with diAbetic retinopaTHY (EMPATHY) trial participants. The primary end-point was the composite cardiovascular end-point including the renal end-point. The associations between the incidence of each end-point and clinical markers were analyzed using the Cox proportional hazards regression model. Results: A total of 4,461 patients were analyzed. The mean observation period was 765.3 ± 363.1 days. The best cut-off value of 1-year eGFR decline was 0.099 in the first year for renal end-point prediction by receiver operating characteristic curve analysis. The area under the curve of the model including the 1-year eGFR decline of the first year was significantly larger than the model without it (0.943, 95% confidence interval 0.915–0.971 to 0.967, 95% confidence interval 0.950–0.983, P = 0.019). Primary end-point incidences and the renal end-point were much higher in rapid eGFR decliners compared with non-decliners (P < 0.0001). The cardiovascular end-point incidence, except for the renal end-point, was not different between the groups. According to Cox regression analysis, 1-year eGFR decline during the first year was a significant risk factor for the end-points, including the renal end-point, independent of albuminuria and eGFR at baseline. Conclusions: The 1-year eGFR decline rate provided useful information for cardiovascular end-point predictions, including the renal end-point, in addition to the conventional risk factors.

  • Efficacy and safety of once-weekly exenatide after switching from twice-daily exenatide in patients with type 2 diabetes

    Watanabe Y., Saisho Y., Inaishi J., Kou K., Yamauchi A., Kanazawa Y., Okubo Y., Tokui M., Imai T., Murakami R., Tsuchiya T., Sasaki H., Masaoka T., Irie J., Meguro S., Itoh H.

    Journal of Diabetes Investigation （Journal of Diabetes Investigation)  11 （ 2 ） 382 - 388 2020.03

    ISSN  20401116

    　View Summary

    Aims/Introduction: To evaluate the efficacy and safety of once-weekly (q.w.) extended-release exenatide after switching from twice-daily (b.i.d.) exenatide in patients with type 2 diabetes. Materials and Methods: This was an investigator-initiated, prospective, single-arm, multicenter study. Individuals with type 2 diabetes who had been treated with exenatide b.i.d. for at least 3 months were enrolled and switched to exenatide q.w. for 24 weeks. The primary end-point was change in HbA1c at week 24 to test the glucose-lowering effect of exenatide q.w. versus exenatide b.i.d. Results: A total of 58 Japanese individuals with type 2 diabetes completed the study. Glycated hemoglobin was reduced by 0.2% at week 24 (7.2 ± 1.2% vs 7.0 ± 1.2% [56 ± 13 vs 53 ± 13 mmol/mol], 95% confidence interval −0.4 to −0.03%, P < 0.005 for non-inferiority, P = 0.01 for superiority). Fasting plasma glucose was reduced by 12 mg/dL at week 24 (154 ± 46 vs 142 ± 46 mg/dL, P = 0.02). β-Cell function assessed by homeostasis model assessment of β-cell function and C-peptide index was significantly improved at week 24. The incidence of self-reported hypoglycemia was reduced, and treatment satisfaction assessed by the Diabetes Treatment Satisfaction Questionnaire and Diabetes Medication Satisfaction Questionnaire was improved at week 24, with no change in body weight. There was no serious adverse event related to the study drug. Conclusions: Switching from exenatide b.i.d. to exenatide q.w. resulted in a reduction in glycated hemoglobin, fasting plasma glucose and the incidence of hypoglycemia, and improvement in β-cell function and treatment satisfaction in patients with type 2 diabetes. These findings will be useful for selecting optimal treatment in individuals with type 2 diabetes.

  • Treatment preference for weekly versus daily DPP-4 inhibitors in patients with type 2 diabetes mellitus: outcomes from the TRINITY trial

    Meguro S., Matsui S., Itoh H.

    Current Medical Research and Opinion （Current Medical Research and Opinion)  35 （ 12 ） 2071 - 2078 2019.12

    ISSN  03007995

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    Objective: To examine patient preference for treatment with the oral once-weekly dipeptidyl peptidase-4 inhibitor (DPP-4i), trelagliptin, and oral once-daily DPP-4i, alogliptin, administered for 8 weeks each in patients with type 2 diabetes mellitus prescribed a daily DPP-4i. Methods: In this randomized, open-label, two-way crossover study, patients received trelagliptin followed by alogliptin (T-A group) or alogliptin followed by trelagliptin (A-T group), for 8 weeks each (NCT03231709, JapicCTI-173662). Treatment preference was assessed using a standardized questionnaire in the overall population and by baseline characteristics. Other outcomes included patient satisfaction with diabetes treatment (assessed using the Diabetes Treatment Satisfaction Questionnaire [DTSQ]), hemoglobin A1c (HbA1c) levels after 8 weeks of treatment with each agent, and safety. Results: Sixty patients from two clinical sites were randomized 1:1 to T-A and A-T groups (each n = 30); baseline characteristics were similar between groups. After 16 weeks of treatment, 51.7% of patients preferred treatment with alogliptin compared with 30.0% selecting trelagliptin (p =.014); preference for alogliptin was consistently greater than for trelagliptin in the secondary analyses by baseline characteristics. DTSQ score and HbA1c levels were similar between treatments after 8 weeks of therapy. Both treatments demonstrated favorable safety and tolerability profiles. Conclusions: Patients expressed a significantly greater treatment preference for once-daily alogliptin than once-weekly trelagliptin, although patient satisfaction and HbA1c levels were similar across treatments. The decision to administer a once-weekly or once-daily DPP-4i is likely to depend on patient preference, patient-physician discussions, and treatment practices of the prescribing physician.

  • Efficacy and safety of switching to insulin glargine 300 U/mL from 100 U/mL in Japanese patients with type 2 diabetes: A 12-month retrospective analysis

    Sugiyama K., Meguro S., Saisho Y., Irie J., Tanaka M., Itoh H.

    Heliyon （Heliyon)  5 （ 2 ）  2019.02

    ISSN  24058440

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    © 2019 The Authors Aims: To evaluate the efficacy and safety of switching to insulin glargine 300 U/mL (Gla-300) from insulin glargine 100 U/mL (Gla-100) in Japanese patients with type 2 diabetes (T2DM). Methods: This was a 12-month retrospective study comprising 109 patients. Primary endpoint was glycated hemoglobin (HbA1c) level at month 12. Secondary endpoints were hypoglycemia for the overall study period as well as body weight and insulin dose at month 12. Results: Similar glycemic control was achieved with mean (standard deviation) HbA1c level of 7.7 (1.1)% (61 [12] mmol/mol) at baseline and 7.7 (1.3)% (61 [14] mmol/mol) at month 12. Fewer confirmed (<3.0 mmol/L [< 54 mg/dL]) or severe hypoglycemic events were observed (0.52 vs. 0.85 events per patient-year; rate ratio 0.61; 95% confidence interval 0.38–0.97; p = 0.037), but the percent of patients experiencing ≥1 hypoglycemic event did not differ. There was no difference in confirmed (≤3.9 mmol/L [≤ 70 mg/dL]) or severe hypoglycemia and nocturnal hypoglycemia. Conclusions: In Japanese patients with T2DM who switched to Gla-300 from Gla-100, similar glycemic control was achieved with fewer confirmed (<3.0 mmol/L [< 54 mg/dL]) or severe hypoglycemic events over a 12-month period, although the absolute benefit was marginal.

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Reviews, Commentaries, etc. 【 Display / hide 】

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Courses Taught 【 Display / hide 】

  • PATHOPHYSIOLOGICAL ISSUES IN CHRONIC CARE

    2023

  • LECTURE SERIES, INTERNAL MEDICINE (NEPHROLOGY, ENDOCRINOLOGY, AND METABOLISM)

    2023

  • LECTURE SERIES, INTERNAL MEDICINE

    2023

  • CASE STUDIES OF INTERNAL MEDICINE

    2023

  • LECTURE SERIES, INTERNAL MEDICINE (NEPHROLOGY, ENDOCRINOLOGY, AND METABOLISM)

    2022

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Courses Previously Taught 【 Display / hide 】

  • Internal medicine

    Keio University

    2017.04
    -
    2018.03
    , 

    Full academic year, Lecture

  • 内科学「腎臓・内分泌・代謝」　糖尿病（薬物療法（インクレチン、インスリン含む）

    Keio University

    2015.04
    -
    2016.03
    , 

    Spring Semester, Lecture, Within own ｆaculty

  • 内科学臨床実習アドバンスト　腎臓内分泌代謝

    Keio University

    2015.04
    -
    2016.03
    , 

    Spring Semester, Laboratory work/practical work/exercise

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Memberships in Academic Societies 【 Display / hide 】

  • Japanese Society of Internal Medicine

    　

  • Japan Diabetes Society

    　

  • Japan Endocrine Society

    　
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