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  1. Article ; Online: A new era of diabetic kidney disease treatment with sodium-glucose cotransporter-2 inhibitors.

    Kume, Shinji / Maegawa, Hiroshi

    Journal of diabetes investigation

    2022  Volume 13, Issue 5, Page(s) 765–767

    Abstract: SGLT2 inhibitors may have a potential to stop the decline of renal function independent of the stage of albuminuria in diabetic kidney disease, and can be a new light in the post-RAS inhibitor era. ...

    Abstract SGLT2 inhibitors may have a potential to stop the decline of renal function independent of the stage of albuminuria in diabetic kidney disease, and can be a new light in the post-RAS inhibitor era.
    MeSH term(s) Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Diabetic Nephropathies/drug therapy ; Female ; Glucose ; Humans ; Kidney ; Male ; Sodium ; Sodium-Glucose Transporter 2 ; Sodium-Glucose Transporter 2 Inhibitors/pharmacology ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
    Chemical Substances Sodium-Glucose Transporter 2 ; Sodium-Glucose Transporter 2 Inhibitors ; Sodium (9NEZ333N27) ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2022-02-03
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 2625840-7
    ISSN 2040-1124 ; 2040-1116
    ISSN (online) 2040-1124
    ISSN 2040-1116
    DOI 10.1111/jdi.13747
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  2. Article: [Management for diabetes mellitus to prevent its complications].

    Maegawa, Hiroshi

    Nihon rinsho. Japanese journal of clinical medicine

    2016  Volume 74 Suppl 2, Page(s) 40–45

    MeSH term(s) Blood Glucose/analysis ; Blood Glucose/metabolism ; Combined Modality Therapy ; Diabetes Complications/prevention & control ; Diabetes Mellitus/therapy ; Disease Progression ; Humans
    Chemical Substances Blood Glucose
    Language Japanese
    Publishing date 2016-04
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 390903-7
    ISSN 0047-1852
    ISSN 0047-1852
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  3. Article ; Online: Lipotoxicity, Nutrient-Sensing Signals, and Autophagy in Diabetic Nephropathy.

    Kume, Shinji / Maegawa, Hiroshi

    JMA journal

    2020  Volume 3, Issue 2, Page(s) 87–94

    Abstract: Diabetic nephropathy is a leading cause of proteinuria, kidney fibrosis, and subsequent end-stage renal disease. The renal prognosis of diabetic patients with refractory proteinuria is extremely poor. Therefore, identification of novel therapeutic ... ...

    Abstract Diabetic nephropathy is a leading cause of proteinuria, kidney fibrosis, and subsequent end-stage renal disease. The renal prognosis of diabetic patients with refractory proteinuria is extremely poor. Therefore, identification of novel therapeutic targets to combat this serious condition and improve renal prognosis is urgently necessary. In diabetic patients, in addition to blood glucose levels, serum levels of free fatty acids (FFAs) are chronically elevated, even during postprandial periods. Of the various types of FFAs, saturated FFAs are highly cytotoxic and their levels are elevated in the serum of patients with diabetes. Thus, an increase in saturated FFAs is currently thought to contribute to proximal tubular cell damage and podocyte injury in diabetic nephropathy. Therefore, protecting both types of kidney cells from saturated FFA-related lipotoxicity may become a novel therapeutic approach for diabetic patients with refractory proteinuria. Interestingly, accumulating evidence suggests that controlling intracellular nutrient signals and autophagy can ameliorate the FFA-related kidney damage. Here, we review the evidence indicating possible mechanisms underlying cell injury caused by saturated FFAs and cell protective roles of intracellular nutrient signals and autophagy in diabetic nephropathy.
    Language English
    Publishing date 2020-04-07
    Publishing country Japan
    Document type Journal Article ; Review
    ISSN 2433-3298
    ISSN (online) 2433-3298
    DOI 10.31662/jmaj.2020-0005
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  4. Article ; Online: Role of O-linked N-acetylglucosamine in the homeostasis of metabolic organs, and its potential links with diabetes and its complications.

    Morino, Katsutaro / Maegawa, Hiroshi

    Journal of diabetes investigation

    2020  Volume 12, Issue 2, Page(s) 130–136

    Abstract: Recent studies using genetically manipulated mouse models have shown the pivotal role of O-linked N-acetylglucosamine modification (O-GlcNAcylation) in the metabolism of multiple organs. The molecular mechanism involves the sensing of glucose flux by the ...

    Abstract Recent studies using genetically manipulated mouse models have shown the pivotal role of O-linked N-acetylglucosamine modification (O-GlcNAcylation) in the metabolism of multiple organs. The molecular mechanism involves the sensing of glucose flux by the hexosamine biosynthesis pathway, which leads to the adjustment of cellular metabolism to protect against changes in the environment of each organ through O-GlcNAcylation. More recently, not only glucose, but also fluxes of amino acids and fatty acids have been reported to induce O-GlcNAcylation, affecting multiple cellular processes. In this review, we discuss how O-GlcNAcylation maintains homeostasis in organs that are affected by diabetes mellitus: skeletal muscle, adipose tissue, liver and pancreatic β-cells. Furthermore, we discuss the importance of O-GlcNAcylation in the pathogenesis of diabetic complications. By elucidating the molecular mechanisms whereby cellular homeostasis is maintained, despite changes in metabolic flux, these studies might provide new targets for the treatment and prevention of diabetes and its complications.
    MeSH term(s) Acetylglucosamine/chemistry ; Animals ; Diabetes Complications/etiology ; Diabetes Complications/metabolism ; Diabetes Complications/pathology ; Diabetes Mellitus/metabolism ; Diabetes Mellitus/physiopathology ; Glucose/metabolism ; Homeostasis ; Humans ; Multiple Organ Failure/etiology ; Multiple Organ Failure/metabolism ; Multiple Organ Failure/pathology ; Protein Processing, Post-Translational
    Chemical Substances Glucose (IY9XDZ35W2) ; Acetylglucosamine (V956696549)
    Language English
    Publishing date 2020-08-25
    Publishing country Japan
    Document type Journal Article ; Review
    ZDB-ID 2625840-7
    ISSN 2040-1124 ; 2040-1116
    ISSN (online) 2040-1124
    ISSN 2040-1116
    DOI 10.1111/jdi.13359
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  5. Article ; Online: Clinical course of different long-acting insulin therapies-glargine U100, U300, degludec, and insulin degludec/insulin aspart-among Japanese patients with type 2 diabetes: a multicenter retrospective observational study (JDDM65 study).

    Iwamoto, Masahiro / Nakanishi, Shuhei / Iwamoto, Hideyuki / Kaneto, Hideaki / Maegawa, Hiroshi

    Endocrine journal

    2022  Volume 69, Issue 7, Page(s) 763–771

    Abstract: This study aimed to retrospectively compare the clinical efficacy of different types of long-acting insulin therapies-glargine U100, glargine U300, degludec, and insulin degludec/insulin aspart-among Japanese patients with type 2 diabetes after insulin ... ...

    Abstract This study aimed to retrospectively compare the clinical efficacy of different types of long-acting insulin therapies-glargine U100, glargine U300, degludec, and insulin degludec/insulin aspart-among Japanese patients with type 2 diabetes after insulin use was initiated in an outpatient setting. The study consisted of 822 insulin-naïve patients in Japan who started using long-acting insulin for treatment of type 2 diabetes and continued for over 12 months. In addition, the impact of insulin type on insulin withdrawal was investigated by dividing the participants into two groups: those who achieved insulin withdrawal and those who did not, during the 12-month observation period based on a Cox proportional hazards model. As a result, HbA1c was decreased, and BMI was increased in all participants regardless of the insulin type used. A total of 185 participants succeeded in insulin withdrawal. After adjustment was made for several confounders, the positive determinant factors for withdrawal were short duration of diabetes and the choice of IDegAsp when compared with Gla100; the negative determinant factor was use of insulin secretagogues at the start of the study. In conclusion, all long-acting insulins were a powerful tool for treatment of type 2 diabetes, and patients with short duration of diabetes and/or no usage of insulin secretagogues resulted in favorable outcomes in terms of insulin withdrawal within a year in an outpatient setting. In addition, insulin degludec/insulin aspart was found to possibly be a better choice for treatment when it was compared with glargine U100 among the four types of insulin.
    MeSH term(s) Blood Glucose ; Diabetes Mellitus, Type 2/drug therapy ; Glycated Hemoglobin A/analysis ; Humans ; Hypoglycemia/chemically induced ; Hypoglycemic Agents/therapeutic use ; Insulin/therapeutic use ; Insulin Aspart/therapeutic use ; Insulin Glargine/therapeutic use ; Insulin, Long-Acting/therapeutic use ; Japan ; Retrospective Studies ; Secretagogues/therapeutic use
    Chemical Substances Blood Glucose ; Glycated Hemoglobin A ; Hypoglycemic Agents ; Insulin ; Insulin, Long-Acting ; Secretagogues ; Insulin Glargine (2ZM8CX04RZ) ; insulin degludec (54Q18076QB) ; Insulin Aspart (D933668QVX)
    Language English
    Publishing date 2022-01-26
    Publishing country Japan
    Document type Journal Article ; Multicenter Study ; Observational Study
    ZDB-ID 1151918-6
    ISSN 1348-4540 ; 0918-8959
    ISSN (online) 1348-4540
    ISSN 0918-8959
    DOI 10.1507/endocrj.EJ21-0647
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  6. Article: Roles of mTOR in Diabetic Kidney Disease.

    Yasuda-Yamahara, Mako / Kume, Shinji / Maegawa, Hiroshi

    Antioxidants (Basel, Switzerland)

    2021  Volume 10, Issue 2

    Abstract: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease and the number of patients affected is increasing worldwide. Thus, there is a need to establish a new treatment for DKD to improve the renal prognosis of diabetic patients. ... ...

    Abstract Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease and the number of patients affected is increasing worldwide. Thus, there is a need to establish a new treatment for DKD to improve the renal prognosis of diabetic patients. Recently, it has shown that intracellular metabolic abnormalities are involved in the pathogenesis of DKD. In particular, the activity of mechanistic target of rapamycin complex 1 (mTORC1), a nutrient-sensing signaling molecule, is hyperactivated in various organs of diabetic patients, which suggests the involvement of excessive mTORC1 activation in the pathogenesis of diabetes. In DKD, hyperactivated mTORC1 may be involved in the pathogenesis of podocyte damage, which causes proteinuria, and tubular cell injury that decreases renal function. Therefore, elucidating the role of mTORC1 in DKD and developing new therapeutic agents that suppress mTORC1 hyperactivity may shed new light on DKD treatments in the future.
    Language English
    Publishing date 2021-02-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox10020321
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  7. Article: Safety and Effectiveness of Ipragliflozin in Elderly Versus Non-elderly Japanese Patients with Type 2 Diabetes: Subgroup Analysis of STELLA-LONG TERM.

    Nakamura, Ichiro / Maegawa, Hiroshi / Tobe, Kazuyuki / Uno, Satoshi

    Diabetes therapy : research, treatment and education of diabetes and related disorders

    2021  Volume 12, Issue 5, Page(s) 1359–1378

    Abstract: Introduction: STELLA-LONG TERM is a post-marketing surveillance study evaluating the safety and effectiveness of ipragliflozin in Japanese patients with type 2 diabetes mellitus.: Methods: Patients were classified by age at ipragliflozin initiation (< ...

    Abstract Introduction: STELLA-LONG TERM is a post-marketing surveillance study evaluating the safety and effectiveness of ipragliflozin in Japanese patients with type 2 diabetes mellitus.
    Methods: Patients were classified by age at ipragliflozin initiation (< 65 and ≥ 65 years), and elderly patients were subclassified by baseline body mass index (BMI) < 25.0 or ≥ 25.0 kg/m
    Results: Among 11,051 patients, 7894 (71.4%) were aged < 65 years and 3157 (28.6%) ≥ 65 years. The 3-year ADR incidence was similar in patients aged ≥ 65 (19.04%) and < 65 years (19.36%; P = 0.701). Serious ADRs were more frequent in the subgroup ≥ 65 years (2.79% vs 1.55%; P < 0.001). In terms of ADRs of special interest, a significantly greater proportion of elderly patients had skin complications (2.22% vs 1.62%, P = 0.033), renal disorders (2.28% vs 1.51%, P = 0.005), hypoglycemia (0.73% vs 0.43%, P = 0.048), or malignant tumors (1.01% vs 0.24%, P < 0.001), while the incidence of polyuria/pollakiuria (5.97% vs 4.47%, P = 0.002) and hepatic disorders (1.39% vs 0.73%, P = 0.004) was significantly higher in non-elderly than elderly patients. In patients aged ≥ 65 years, the incidence of ADRs was higher when baseline BMI was ≥ 25 kg/m
    Conclusions: Ipragliflozin was well tolerated and effective for 3 years in routine clinical use in elderly and non-elderly patients, although elderly patients had a higher rate of serious ADRs. No new safety concerns were identified.
    Clinical trial registration: ClinicalTrials.gov identifier NCT02479399.
    Language English
    Publishing date 2021-03-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2566702-6
    ISSN 1869-6961 ; 1869-6953
    ISSN (online) 1869-6961
    ISSN 1869-6953
    DOI 10.1007/s13300-021-01042-w
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  8. Article: Correction to: Safety and Effectiveness of Ipragliflozin in Elderly Versus Non-elderly Japanese Patients with Type 2 Diabetes: Subgroup Analysis of STELLA-LONG TERM.

    Nakamura, Ichiro / Maegawa, Hiroshi / Tobe, Kazuyuki / Uno, Satoshi

    Diabetes therapy : research, treatment and education of diabetes and related disorders

    2021  Volume 12, Issue 6, Page(s) 1765–1768

    Language English
    Publishing date 2021-05-20
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2566702-6
    ISSN 1869-6961 ; 1869-6953
    ISSN (online) 1869-6961
    ISSN 1869-6953
    DOI 10.1007/s13300-021-01073-3
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  9. Article: [Recent advance in treatment of diabetes mellitus, impact of incretin-based therapy].

    Maegawa, Hiroshi

    Nihon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology

    2013  Volume 110, Issue 11, Page(s) 1922–1926

    MeSH term(s) Diabetes Mellitus, Type 2/physiopathology ; Diabetes Mellitus, Type 2/therapy ; Fatty Liver/drug therapy ; Fatty Liver/etiology ; Humans ; Incretins/therapeutic use ; Liver/physiopathology ; Non-alcoholic Fatty Liver Disease
    Chemical Substances Incretins
    Language Japanese
    Publishing date 2013-10-17
    Publishing country Japan
    Document type Journal Article ; Review
    ZDB-ID 708695-7
    ISSN 1349-7693 ; 0446-6586
    ISSN (online) 1349-7693
    ISSN 0446-6586
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  10. Article: Correction to: Safety and Effectiveness of Ipragliflozin in Elderly Versus Non-elderly Japanese Patients with Type 2 Diabetes: Subgroup Analysis of STELLA-LONG TERM.

    Nakamura, Ichiro / Maegawa, Hiroshi / Tobe, Kazuyuki / Uno, Satoshi

    Diabetes therapy : research, treatment and education of diabetes and related disorders

    2021  Volume 12, Issue 10, Page(s) 2801–2805

    Language English
    Publishing date 2021-08-31
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2566702-6
    ISSN 1869-6961 ; 1869-6953
    ISSN (online) 1869-6961
    ISSN 1869-6953
    DOI 10.1007/s13300-021-01134-7
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