المؤلفون: Nomoto, Hiroshi, Kito, Kenichi, Iesaka, Hiroshi, Handa, Takahisa, Yanagiya, Shingo, Miya, Aika, Kameda, Hiraku, Cho, Kyu Yong, Takeuchi, Jun, Nagai, So, Sakuma, Ichiro, Nakamura, Akinobu, Atsumi, Tatsuya

المصدر: Diabetology & Metabolic Syndrome ; volume 15, issue 1 ; ISSN 1758-5996

مصطلحات موضوعية: Endocrinology, Diabetes and Metabolism, Internal Medicine

الوصف: Background Pemafibrate has been reported to ameliorate lipid profiles and liver dysfunction. However, which patients derive benefit from the hepatoprotective effects of pemafibrate is unclear. Methods We conducted a sub-analysis of the PARM-T2D study where subjects with type 2 diabetes complicated by hypertriglyceridemia were prospectively treated with pemafibrate or conventional therapies for 52 weeks. From the original cohort, subjects who had metabolic-associated fatty liver disease without changing their treatment regimens for comorbidities were analyzed. Eligible subjects (n = 293) (average age 61.2 ± 11.7 years, 37.5% female) treated with pemafibrate (pemafibrate, n = 152) or controls who did not change their treatment regimens (controls, n = 141) were divided into three groups based on their alanine aminotransferase (ALT) levels: ALT ≤ upper normal limit (UNL) (pemafibrate, n = 65; controls, n = 50), UNL < ALT ≤ 2×UNL (pemafibrate, n = 58; controls, n = 54), and 2×UNL < ALT (pemafibrate, n = 29; controls, n = 27). Results Pemafibrate treatment significantly ameliorated ALT levels (from 29 to 22 U/L, p < 0.001 by Wilcoxon’s signed-rank test) in the total cohort and subjects with high ALT levels (2×ULN < ALT), and improved liver fibrosis as assessed by the Fibrosis-4 index (mean change − 0.05 (95% confidence interval: −0.22 to − 0.02), p < 0.05 versus baseline by the Mann-Whitney U -test and p < 0.05 versus the ALT ≤ UNL group by the Kruskal–Wallis test followed by Dunn’s post-hoc analysis). Conclusions The hepatoprotective effects of pemafibrate were dominant in subjects with type 2 diabetes complicated with liver dysfunction. Trial registration This study was registered with the University Hospital Medical Information Network Center Clinical Trials Registry (UMIN000037385).

الإتاحة: https://doi.org/10.1186/s13098-023-01187-7Test

المؤلفون: Iesaka, Hiroshi, Kameda, Hiraku, Miya, Aika, Nomoto, Hiroshi, Cho, Kyu Yong, Nakamura, Akinobu, Abe, Takashige, Shinohara, Nobuo, Atsumi, Tatsuya

المصدر: Medicine ; volume 102, issue 51, page e36664 ; ISSN 0025-7974 1536-5964

الوصف: Rationale: The increasing use of immune checkpoint inhibitors (ICIs) for treating malignant tumors result in the concomitant rise of immune-related adverse events (irAEs). This case report may provide useful insight to understanding the etiology of ICI-induced hypophysitis, a severe irAE leading to potentially fatal secondary adrenal insufficiency. Patient concerns: An 81-year-old Japanese man was hospitalized for diabetic ketoacidosis following 4 courses of ICI combination therapy with nivolumab and ipilimumab for metastatic renal cell carcinoma. Diagnosis: Insulin secretion was depleted, leading to diagnosis of fulminant type 1 diabetes. Adrenocorticotropic hormone (ACTH) and cortisol levels were very high (60.8 pmol/L and 1575 nmol/L, respectively) upon admission. ACTH and cortisol returned to normal ranges on the 2nd day. On the 8th day, an ACTH loading test showed intact cortisol response (peak value 519 nmol/L). However, on the 14th day, there was a sharp decrease in ACTH and cortisol levels (10.5 pmol/L and 47 nmol/L, respectively) accompanied by fatigue and a drop in blood pressure to 97/63 mm Hg. As secondary adrenal insufficiency was suspected, hydrocortisone replacement was initiated. An ACTH loading test on the 17th day revealed low cortisol peak (peak value 232 nmol/L), indicating sudden disruption of adrenal function. Magnetic resonance imaging showed no abnormal findings and there was no other pituitary hormone deficiency. These findings, along with the patient clinical course, suggest that secondary adrenal insufficiency was caused by acute ACTH producing cell destruction as an irAE associated with ICI therapy. Interventions: The patient hyperglycemia and ketoacidosis were treated using extracellular fluid and insulin therapy. After development of adrenal insufficiency, hydrocortisone 20 mg was started, and the patient symptoms improved. Outcomes: He was continued on insulin therapy, hydrocortisone, and reinitiated nivolumab. Lessons: This case provides a detailed course of the fulminant onset of ...

الإتاحة: https://doi.org/10.1097/md.0000000000036664Test

المؤلفون: Takahashi, Akihiro, Nomoto, Hiroshi, Onishi, Kinnosuke, Manda, Satoru, Miya, Aika, Kameda, Hiraku, Nakamura, Akinobu, Atsumi, Tatsuya

المصدر: Diabetes, Obesity & Metabolism; Aug2024, Vol. 26 Issue 8, p3471-3474, 4p

مصطلحات موضوعية: TYPE 2 diabetes, METFORMIN, ENDOPLASMIC reticulum, CONTINUOUS glucose monitoring

مستخلص: This article discusses a comparative study that examines the effects of imeglimin add-on therapy and metformin dose escalation on glycaemic variability in individuals with type 2 diabetes. The study found that while both treatments resulted in a decrease in mean blood glucose levels, only imeglimin add-on therapy significantly reduced measures of glycaemic variability, such as mean amplitude of glycaemic excursions (MAGE), coefficient of variation (CV), and standard deviation (SD). The study suggests that imeglimin may be effective in suppressing glucose spikes and improving glycaemic control in individuals with type 2 diabetes. [Extracted from the article]

: Copyright of Diabetes, Obesity & Metabolism is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Furusawa, Sho, Nomoto, Hiroshi, Yokoyama, Hiroki, Suzuki, Yuka, Tsuzuki, Atsushi, Takahashi, Kiyohiko, Miya, Aika, Kameda, Hiraku, Cho, Kyu Yong, Takeuchi, Jun, Nagai, So, Taneda, Shinji, Kurihara, Yoshio, Nakamura, Akinobu, Atsumi, Tatsuya

المصدر: Diabetes, Obesity & Metabolism; Mar2024, Vol. 26 Issue 3, p961-970, 10p

مصطلحات موضوعية: GLYCEMIC control, CD26 antigen, TYPE 2 diabetes, SODIUM-glucose cotransporters, SEMAGLUTIDE, INSULIN aspart, MULTIPLE regression analysis

مستخلص: Aim: To assess whether oral semaglutide provides better glycaemic control, compared with dipeptidyl peptidase‐4 inhibitor (DPP‐4i) continuation, in people with type 2 diabetes. Materials and Methods: In this multicentre, open‐label, prospective, randomized, parallel‐group comparison study, participants receiving DPP‐4is were either switched to oral semaglutide (3‐14 mg/day) or continued on DPP‐4is. The primary endpoint was the change in glycated haemoglobin (HbA1c) over 24 weeks. Secondary endpoints included changes in metabolic parameters and biomarkers, along with the occurrence of adverse events. Factors associated with HbA1c improvement were also explored. Results: In total, 174 eligible participants were enrolled; 17 dropped out of the study. Consequently, 82 participants in the DPP‐4i group and 75 participants in the semaglutide group completed the study and were included in the analysis. Improvement in HbA1c at week 24 was significantly greater when switching to semaglutide compared with DPP‐4i continuation [−0.65 (95% confidence interval: −0.79, −0.51) vs. +0.05 (95% confidence interval: −0.07, 0.16) (p <.001)]. Body weight, lipid profiles and liver enzymes were significantly improved in the semaglutide group than in the DPP‐4i continuation group. Multiple linear regression analysis revealed that baseline HbA1c and homeostasis model assessment 2‐R were independently associated with HbA1c improvement after switching to semaglutide. Seven participants in the semaglutide group discontinued medication because of gastrointestinal symptoms. Conclusions: Although the potential for gastrointestinal symptoms should be carefully considered, switching from DPP‐4is to oral semaglutide may be beneficial for glycaemic control and metabolic abnormalities in people with higher HbA1c and insulin resistance. [ABSTRACT FROM AUTHOR]

: Copyright of Diabetes, Obesity & Metabolism is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Nomoto, Hiroshi, Furusawa, Sho, Nakamura, Akinobu, Takeuchi, Jun, Nagai, So, Yokoyama, Hiroki, Sakuma, Ichiro, Taneda, Shinji, Kurihara, Yoshio, Aoki, Shin, Miya, Aika, Kameda, Hiraku, Cho, Kyu Yong, Atsumi, Tatsuya, Miyoshi, Hideaki

المصدر: BMJ Open ; volume 12, issue 5, page e056885 ; ISSN 2044-6055 2044-6055

الوصف: Introduction Incretin-based therapies exert antihyperglycaemic effects in patients with type 2 diabetes (T2D) in a blood glucose concentration-dependent fashion. The first-in-class oral glucagon-like peptide-1 receptor agonist semaglutide has potent effects on glycaemic and weight control, but little evidence has been published for the superiority of semaglutide for glycaemic control in patients after switching from a dipeptidyl peptidase-4 (DPP-4) inhibitor. Therefore, we aim to verify the efficacy of oral semaglutide in patients with T2D being treated with a DPP-4 inhibitor. Methods and analysis This study is a multicentre, prospective, randomised, open-label, parallel-group trial. In total, 172 participants with T2D who have been treated with a DPP-4 inhibitor for more than 12 weeks and who have a glycated haemoglobin (HbA1c) level of 7.0%–9.9% will be randomised to continue using their existing DPP-4 inhibitor or switch to oral semaglutide for 24 weeks. Biochemical analyses and physical assessment will be performed, and adverse events will be recorded at baseline and at the end of the study. The primary endpoint will be the effect of oral semaglutide on the change in HbA1c. The secondary endpoints will be the mean changes in body weight, abdominal circumference, systolic and diastolic blood pressure (BP), pulse rate, the relationship between improvement of metabolic parameters including HbA1c and patient background characteristics, side effects and other laboratory parameters. Ethics and dissemination This will be the first study to compare the effects of switching from a DPP-4 inhibitor to oral semaglutide on glycaemic control in patients with T2D. The results will be disseminated in peer-reviewed journals and at scientific conferences. Hokkaido University Certified Review Board (CRB no.1180001) has approved the protocol (no. 020–013). Trial registration number UMIN000045270 in the University Hospital Medical Information Network; jRCT1011210032 in the Japan Registry of Clinical Trials.

الإتاحة: https://doi.org/10.1136/bmjopen-2021-056885Test

المؤلفون: Nomoto, Hiroshi, Takahashi, Akihiro, Nakamura, Akinobu, Kurihara, Hiroyoshi, Takeuchi, Jun, Nagai, So, Taneda, Shinji, Miya, Aika, Kameda, Hiraku, Cho, Kyu Yong, Miyoshi, Hideaki, Atsumi, Tatsuya

المصدر: BMJ Open Diabetes Research & Care ; volume 10, issue 6, page e002988 ; ISSN 2052-4897

الوصف: Introduction Imeglimin is a novel anti-hyperglycemic drug that improves both insulin resistance and insulin secretion. The effects of imeglimin on glycemic control were confirmed in phase III clinical trials, but little is known about its effectiveness in daily clinical practice settings, especially compared with metformin. Therefore, we aim to clarify the efficacy of imeglimin in patients with type 2 diabetes (T2D) being treated with a dipeptidyl peptidase-4 (DPP-4) inhibitor plus low-dose metformin. Research design and methods This is a multicenter, randomized, prospective, open-label, parallel-group trial. Seventy participants with T2D treated with a DPP-4 inhibitor plus metformin (500–1000 mg/day) for more than 12 weeks and a glycated hemoglobin (HbA1c) level of 52–85 mmol/mol (7.0%–9.9%) will be randomized to receive add-on imeglimin 1000 mg two times per day or metformin dose escalation for 24 weeks. Biochemical analyses and physical assessments will be performed at baseline and at the end of the study, and adverse events will be recorded. The primary endpoint is the change in HbA1c after 24 weeks. The secondary endpoints comprise the changes in blood pressure, pulse rate, body weight, abdominal circumference, and other laboratory parameters; the relationship between improvements of biological parameters including glycemic control and patient background characteristics; and side effects. Results This study will reveal new insights into the incorporation of imeglimin into the diabetes treatment strategy. Conclusions This will be the first randomized controlled trial to compare the efficacy of adding imeglimin versus metformin dose escalation on glycemic control in patients with T2D. Trial registration number jRCT1011220005.

الإتاحة: https://doi.org/10.1136/bmjdrc-2022-002988Test

المؤلفون: Kito, Kenichi, Nomoto, Hiroshi, Sakuma, Ichiro, Nakamura, Akinobu, Cho, Kyu Yong, Kameda, Hiraku, Miya, Aika, Omori, Kazuno, Yanagiya, Shingo, Handa, Takahisa, Taneda, Shinji, Takeuchi, Jun, Nagai, So, Yamashita, Kumiko, Kurihara, Yoshio, Atsumi, Tatsuya, Miyoshi, Hideaki

المصدر: Diabetes Research and Clinical Practice ; volume 192, page 110091 ; ISSN 0168-8227

مصطلحات موضوعية: Endocrinology, General Medicine, Endocrinology, Diabetes and Metabolism, Internal Medicine

الإتاحة: https://doi.org/10.1016/j.diabres.2022.110091Test
https://api.elsevier.com/content/article/PII:S0168822722009056?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0168822722009056?httpAccept=text/plainTest

المؤلفون: Cho, Kyu Yong, Nomoto, Hiroshi, Nakamura, Akinobu, Kawata, Shinichiro, Sugawara, Hajime, Takeuchi, Jun, Nagai, So, Omori, Kazuno, Tsuchida, Kazuhisa, Miya, Aika, Shigesawa, Ikumi, Tsuchida, Kenichi, Yanagiya, Shingo, Kameda, Hiraku, Yokoyama, Hiroki, Taneda, Shinji, Kurihara, Yoshio, Aoki, Shin, Nishimoto, Naoki, Atsumi, Tatsuya, Miyoshi, Hideaki

المساهمون: Mitsubishi Tanabe Pharma Corporation

المصدر: Journal of Diabetes Investigation ; volume 12, issue 8, page 1417-1424 ; ISSN 2040-1116 2040-1124

الوصف: Aims/Introduction We recently reported the beneficial effect of the combination of sodium–glucose cotransporter 2 inhibitor and dipeptidyl peptidase‐4 inhibitor on daily glycemic variability in patients with type 2 diabetes mellitus. Additional favorable effects of combination therapy were explored in this secondary analysis. Materials and Methods The CALMER study was a multicenter, open‐label, prospective, randomized, parallel‐group comparison trial for type 2 diabetes mellitus involving continuous glucose monitoring under meal tolerance tests. Patients were randomly assigned to switch from teneligliptin to canagliflozin (SWITCH group) or to add canagliflozin to teneligliptin (COMB group). The continuous glucose monitoring metrics, including time in target range, were investigated. Results All 99 participants (mean age 62.3 years; mean glycated hemoglobin 7.4%) completed the trial. The time in target range was increased in the COMB group (71.2–82.7%, P < 0.001). The extent of the reduction in time above target range was significantly larger in the COMB group compared with the SWITCH group (−14.8% vs −7.5%, P < 0.01). Area under the curve values for glucose at 120 min after all meal tolerance tests were significantly decreased in the COMB group compared with the SWITCH group ( P < 0.05). Conclusions Sodium–glucose cotransporter 2 inhibitor combined with dipeptidyl peptidase‐4 inhibitor improved the quality of glycemic variability and reduced postprandial hyperglycemia compared with each monotherapy.

الإتاحة: https://doi.org/10.1111/jdi.13498Test

المؤلفون: Miya, Aika, Nakamura, Akinobu, Cho, Kyu Yong, Kawata, Shinichiro, Nomoto, Hiroshi, Nagai, So, Sugawara, Hajime, Taneda, Shinji, Tsuchida, Kazuhisa, Omori, Kazuno, Yokoyama, Hiroki, Takeuchi, Jun, Aoki, Shin, Kurihara, Yoshio, Atsumi, Tatsuya, Miyoshi, Hideaki

المساهمون: Mitsubishi Tanabe Pharma Corporation

المصدر: Journal of Diabetes Investigation ; volume 12, issue 8, page 1395-1399 ; ISSN 2040-1116 2040-1124

الوصف: Aims/Introduction To identify the effect of combination therapy with a dipeptidyl peptidase‐4 inhibitor and a sodium–glucose cotransporter 2 inhibitor compared with switching from a dipeptidyl peptidase‐4 inhibitor to a sodium–glucose cotransporter 2 inhibitor on improving the glucose variability in patients with or without impaired endogenous insulin secretion. Materials and Methods A secondary analysis regarding the relationship between endogenous insulin secretion and the change in mean amplitude of glycemic excursions (ΔMAGE) was carried out in a multicenter, prospective, randomized, parallel‐group comparison trial that enrolled patients with type 2 diabetes who had been taking teneligliptin and were treated by switching to canagliflozin (SWITCH) or adding canagliflozin (COMB). Participants were categorized into the following four subgroups: SWITCH or COMB and high or low fasting C‐peptide (CPR) divided at baseline by the median. Results ΔMAGE in the COMB group was greatly improved independent of a high or low CPR (−29.2 ± 28.3 vs −20.0 ± 24.6, respectively; P = 0.60). However, ΔMAGE was not ameliorated in the low CPR SWITCH group, and the ΔMAGE was significantly smaller than that in the high CPR COMB group ( P < 0.01). Conclusions COMB would be a better protocol rather than switching teneligliptin to canagliflozin to improve daily glucose variability in patients with impaired endogenous insulin secretion.

الإتاحة: https://doi.org/10.1111/jdi.13479Test

المؤلفون: Miya, Aika, Nakamura, Akinobu, Handa, Takahisa, Nomoto, Hiroshi, Kameda, Hiraku, Cho, Kyu Yong, Nagai, So, Ito, Yoichi M., Miyoshi, Hideaki, Atsumi, Tatsuya

المصدر: Scientific Reports ; volume 11, issue 1 ; ISSN 2045-2322

مصطلحات موضوعية: Multidisciplinary

الوصف: The contribution of endogenous insulin secretion to glycemic variability (GV) may differ between patients with impaired insulin secretion and those with preserved secretion. Our objective was to determine the linearity of the relationship between fasting C-peptide (CPR) as a marker of endogenous insulin secretion and GV in type 2 diabetes (T2DM), regardless of the type of antidiabetic treatment. We conducted a prospective observational study using continuous glucose monitoring obtained from 284 Japanese outpatients with T2DM with various HbA1c values and antidiabetic treatment. We constructed a prediction curve of base-line CPR versus coefficient of variation (CV) and identified the clinical factors associated with CV using multiple regression analysis. Fasting CPR showed a significant negative log-linear relationship with CV ( P < 0.0001), and the latter being strikingly high in the low-CPR group. The multiple regression analysis showed that low CPR was an independent predictor of high CV ( P < 0.0001). The significant correlations were sustained in both patients with/without insulin treatment. The contribution of endogenous insulin secretion to GV depends on the extent of insulin secretion impairment. Fasting CPR may represent a useful indicator of GV instability in T2DM.

الإتاحة: https://doi.org/10.1038/s41598-021-88749-9Test
https://www.nature.com/articles/s41598-021-88749-9.pdfTest
https://www.nature.com/articles/s41598-021-88749-9Test