Journal of Diabetes Investigation最新文献

{"title":"Epidemiological characteristics and risk factors for heart failure in Japanese patients with type 2 diabetes: A retrospective analysis of the J-DREAMS database.","authors":"Mitsuru Ohsugi, Daisuke Nitta, Yusuke Naito, Kohjiro Ueki","doi":"10.1111/jdi.14378","DOIUrl":"https://doi.org/10.1111/jdi.14378","url":null,"abstract":"<p><strong>Aim: </strong>To determine the epidemiological characteristics and risk factors for heart failure (HF) among Japanese patients with type 2 diabetes.</p><p><strong>Methods: </strong>A retrospective cohort analysis, using J-DREAMS database, was conducted from December 2015 to January 2020 with type 2 diabetes. The primary objectives were to describe patient characteristics stratified by HF history at baseline and new HF events during follow-up. The secondary objectives were to clarify the association between HF history or new HF events and clinical characteristics. The association between renal disease stage and HF was also studied.</p><p><strong>Results: </strong>Among 18,250 adult patients with type 2 diabetes, 3,613 (19.8%) patients had HF history and the mean age was 68.46 years, predominantly male (66.4%) with 13.32 years of mean duration of type 2 diabetes. Patients with HF history had a higher proportion of patients with nephropathy (51.2%) and coronary heart disease (55.6%) than those without HF history. Coronary heart disease (CHD) and deteriorating renal function were strongly associated with both HF history (CHD adjusted odds ratio [OR]: 7.41, 95% confidence interval [CI]: 6.05-9.08; eGFR G5 stage adjusted OR: 6.56, 95% CI: 2.97-14.49) and new HF events (CHD adjusted OR: 1.63, 95% CI: 1.17-2.29; eGFR G4 stage adjusted OR: 3.42, 95% CI: 1.81-6.47).</p><p><strong>Conclusions: </strong>Comorbidities, especially CHD and deteriorating renal function, were strongly associated with HF history and new HF events among Japanese patients with type 2 diabetes. The study results suggested the importance of early intervention to treat comorbidities and maintain renal function.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to Editor in response to the article \"Rising mortality rates linked to type-2 diabetes and obesity in the United States: An observational analysis from 1999 to 2022\".","authors":"Muheem Khan","doi":"10.1111/jdi.14412","DOIUrl":"https://doi.org/10.1111/jdi.14412","url":null,"abstract":"","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The PKM2 activator TEPP-46 suppresses cellular senescence in hydrogen peroxide-induced proximal tubular cells and kidney fibrosis in CD-1^db/db mice.","authors":"Shin-Ichiro Ishihara, Md Imrul Kayes, Hirofumi Makino, Hiroaki Matsuda, Asako Kumagai, Yoshihiro Hayashi, Sara Amelia Ferdaus, Emi Kawakita, Daisuke Koya, Keizo Kanasaki","doi":"10.1111/jdi.14397","DOIUrl":"https://doi.org/10.1111/jdi.14397","url":null,"abstract":"<p><strong>Aim/introduction: </strong>Senescence is a key driver of age-related kidney dysfunction, including diabetic kidney disease. Oxidative stress activates cellular senescence, induces abnormal glycolysis, and is associated with pyruvate kinase muscle isoform 2 (PKM2) dysfunction; however, the mechanisms linking PK activation to cellular senescence have not been elucidated. We hypothesized that PKM2 activation by TEPP-46 could suppress oxidative stress-induced renal tubular cell injury and cellular senescence.</p><p><strong>Materials and methods: </strong>To investigate the effects of PKM2 activation on oxidative stress-induced cellular senescence, we conducted β-galactosidase staining and western blot analysis on human primary renal tubular cells (pRPTECs) treated with hydrogen peroxide with or without TEPP-46. IL-6 levels and glycolytic flux were measured. Cell viability and apoptosis were assessed via the MTS assay and caspase 3 cleavage. For in vivo experiments, we utilized CD-1^db/db mice, a fibrotic type 2 diabetes model, which exhibit kidney fibrosis. After 4 weeks of TEPP-46 intervention, kidney fibrosis and the expression of senescence markers were analyzed.</p><p><strong>Results: </strong>In pRPTECs, hydrogen peroxide increased the number of β-galactosidase-positive cells, the expression of senescence markers (p16, p21, p53), and p38 phosphorylation; co-incubation with TEPP-46 suppressed these alterations. Hydrogen peroxide reduced cell viability, induced apoptosis, mesenchymal alterations, and increased lactate production and IL-6 secretion; co-incubation with TEPP-46 or a p38 inhibitor mitigated these effects. In CD-1^db/db mice, TEPP-46 intervention suppressed apoptosis, fibrosis, and tended to reduce the levels of senescence-associated molecules in the kidney.</p><p><strong>Conclusions: </strong>PKM2 activation could be a molecular target for protection against senescence-associated organ damage, including diabetic kidney disease.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary on \"Prognostic value of longitudinal HbA1c variability in predicting the development of diabetic sensorimotor polyneuropathy among patients with type 2 diabetes mellitus: A prospective cohort observational study\".","authors":"Fatemeh Rasulpur, Mohammad Barary, Mostafa Javanian, Soheil Ebrahimpour","doi":"10.1111/jdi.14408","DOIUrl":"https://doi.org/10.1111/jdi.14408","url":null,"abstract":"","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imeglimin, unlike metformin, does not perturb differentiation of human induced pluripotent stem cells towards pancreatic β-like cells and rather enhances gain in β cell identity gene sets.","authors":"Tasuku Imada, Shugo Sasaki, Hiroki Yamaguchi, Ayaka Ueda, Dan Kawamori, Naoto Katakami, Iichiro Shimomura","doi":"10.1111/jdi.14410","DOIUrl":"https://doi.org/10.1111/jdi.14410","url":null,"abstract":"<p><strong>Aims/introduction: </strong>Metformin treatment for hyperglycemia in pregnancy (HIP) beneficially improves maternal glucose metabolism and reduces perinatal complications. However, metformin could impede pancreatic β cell development via impaired mitochondrial function. A new anti-diabetes drug imeglimin, developed based on metformin, improves mitochondrial function. Here we examine the effect of imeglimin on β cell differentiation using human induced pluripotent stem cell (iPSC)-derived pancreatic islet-like spheroid (SC-islet) models.</p><p><strong>Materials and methods: </strong>Human iPSCs are differentiated into SC-islets by three-dimensional culture with and without imeglimin or metformin. Differentiation efficiencies of SC-islets were analyzed by flow cytometry, immunostaining, quantitative PCR, and insulin secretion assay. RNA sequencing and oxygen consumption rate were obtained for further characterization of SC-islets. SC-islets were cultured with proinflammatory cytokines, in part mimicking the uterus environment in HIP.</p><p><strong>Results: </strong>Metformin perturbed SC-islet differentiation while imeglimin did not alter it. Furthermore, imeglimin enhanced the gene expressions of β cell lineage markers. Maintenance of mitochondrial function and optimization of TGF-β and Wnt signaling were considered potential mechanisms for augmented β cell maturation by imeglimin. In the presence of proinflammatory cytokines, imeglimin ameliorated β cell differentiation impaired by cytokines and metformin.</p><p><strong>Conclusions: </strong>Imeglimin does not perturb differentiation of SC-islet cells and rather enhances gain in β cell identity gene sets in contrast to metformin. This may lead to the improvement of in vitro β cell differentiation protocols.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An interventional study of digital therapy on blood glucose and weight management in Chinese patients with type 2 diabetes.","authors":"Difei Lu, Wenfeng Jiang, Dongyan Ai, Chaoping Cen, Qianying Ou, Kaining Chen, Junqing Zhang","doi":"10.1111/jdi.14376","DOIUrl":"https://doi.org/10.1111/jdi.14376","url":null,"abstract":"<p><strong>Objective: </strong>Our study aimed to evaluate the effectiveness of a 3-months digital therapy (DTx) intervention in the real world for the management of blood glucose in 3,902 Chinese patients with type 2 diabetes (T2D) in Lingshui, Hainan.</p><p><strong>Methods: </strong>Adults with T2D who were capable of using DTx application (app) were enrolled. Fasting blood glucose (FBG), 2-h postprandial blood glucose (2hPBG), and body weight before and after the intervention were collected. Participants recorded blood glucose and body weight at least once weekly, and attended diabetes education program with the app during online follow-up once weekly.</p><p><strong>Results: </strong>A total of, 3,902 patients with T2D were enrolled, including 46.3% of men, with an average age of 64.3 years. After 3-months of DTx, FBG decreased by 0.52 mmol/L (8.05-7.53, P < 0.001) from baseline, 2hPBG decreased by 1.18 mmol/L (11.95-10.77, P < 0.001), and body weight decreased by 1.50 kg (61.18-59.68, P < 0.001). The median number of glucose self-reports for each patient was three (0, 273) times. Defining participants who finished glucose or weight self-report for once within 7 days as the motivated group (n = 1,013), the motivated group showed significant weight loss after DTx intervention (motivated group vs inactive group, -3.01 kg vs -0.36 kg, P < 0.01). No significant difference was found in FBG and 2hPBG between the two groups.</p><p><strong>Conclusions: </strong>DTx reveals significant efficacy on glucose and weight control in patients with T2D, which can reduce FBG, PBG, and body weight. Better compliance and motivation with DTx and frequent weight monitoring help achieve better weight control.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High HOMA2-B: A novel risk factor for diabetic peripheral neuropathy beyond metabolic syndrome components in type 2 diabetes.","authors":"Koichi Kato","doi":"10.1111/jdi.14403","DOIUrl":"https://doi.org/10.1111/jdi.14403","url":null,"abstract":"","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-hoc analysis of the tofogliflozin post-marketing surveillance study (J-STEP/LT): Tofogliflozin improves liver function in type 2 diabetes patients regardless of BMI.","authors":"Hiroyuki Uchinuma, Mitsunori Matsushita, Masaya Tanahashi, Hideki Suganami, Kazunori Utsunomiya, Kohei Kaku, Kyoichiro Tsuchiya","doi":"10.1111/jdi.14402","DOIUrl":"https://doi.org/10.1111/jdi.14402","url":null,"abstract":"<p><strong>Aims/introduction: </strong>Patients with type 2 diabetes are at high risk of developing steatotic liver disease (SLD). Weight loss has proven effective in treating metabolic dysfunction-associated steatotic liver disease (MASLD) in obese patients with type 2 diabetes, with sodium-glucose cotransporter 2 (SGLT2) inhibitors showing promising results. However, lean MASLD is more prevalent in Japan, necessitating alternative approaches to body weight reduction.</p><p><strong>Materials and methods: </strong>We used the J-STEP/LT dataset including up to 3-year treatment data to analyze the effects of the SGLT2 inhibitor tofogliflozin on liver function and treatment safety and conducted a subgroup analysis based on body mass index (BMI; kg/m², <20, 20-<23, 23-<25, 25-<30, and ≥30).</p><p><strong>Results: </strong>This study included 4,208 participants. Tofogliflozin significantly reduced alanine aminotransferase (ALT) levels in participants with baseline ALT levels >30 U/L across all BMI groups, with median changes of -12, -16, -13, -15, and -15 U/L, respectively (P = 0.9291 for trends). However, median changes in body weight with tofogliflozin were -2.00, -2.75, -2.00, -3.00, and -3.80 kg, respectively (P < 0.0001 for trends), with no significant weight loss observed in the BMI <20 group. ALT levels were also significantly decreased in participants who did not lose weight. Safety assessments according to BMI and age categories revealed no clear differences in the frequency of adverse events.</p><p><strong>Conclusions: </strong>Tofogliflozin reduced ALT levels without substantial body weight reduction among lean participants. These findings suggest that SGLT2 inhibitors may be a viable treatment option for non-obese patients with type 2 diabetes and SLD.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ERK1/2 gene expression and hypomethylation of Alu and LINE1 elements in patients with type 2 diabetes with and without cataract: Impact of hyperglycemia-induced oxidative stress.","authors":"Elham Zeinali Nia, Ruhollah Najjar Sadeghi, Mostafa Ebadi, Mohammad Faghihi","doi":"10.1111/jdi.14405","DOIUrl":"https://doi.org/10.1111/jdi.14405","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to delineate the effect of hyperglycemia on the Alu/LINE-1 hypomethylation and in ERK1/2 genes expression in type 2 diabetes with and without cataract.</p><p><strong>Methods: </strong>This study included 58 diabetic patients without cataracts, 50 diabetic patients with cataracts, and 36 healthy controls. After DNA extraction and bisulfite treatment, LINE-1 and Alu methylation levels were assessed using Real-time MSP. ERK1/2 gene expression was analyzed through real-time PCR. Total antioxidant capacity (TAC), and fasting plasma glucose (FPG) were measured using colorimetric methods. Statistical analysis was performed with SPSS23, setting the significance level at P < 0.05.</p><p><strong>Results: </strong>The TAC levels were significantly lower for cataract and diabetic groups than controls (259.31 ± 122.99, 312.43 ± 145.46, 372.58 ± 132.95 nanomole of Trolox equivalent) with a significant correlation between FPG and TAC levels in both the cataract and diabetic groups (P < 0.05). Alu and LINE-1 sequences were found to be statistically hypomethylated in diabetic and cataract patients compared to controls. In these groups, TAC levels were directly correlated with Alu methylation (P < 0.05) but not LINE-1. ERK1/2 gene expression was significantly higher in diabetic and cataract patients, showing increases of 2.41-fold and 1.43-fold for ERK1, and 1.27-fold and 1.5 for ERK2, respectively. ERK1 expression correlated significantly with FPG levels. A reverse correlation was observed between TAC levels and ERK1/2 expression.</p><p><strong>Conclusions: </strong>Our findings indicate that hyperglycemia-induced oxidative stress may alter ERK1/2 gene expression patterns and induce aberrant hypomethylation in Alu and LINE-1 sequences. These aberrant changes may play a contributing role in diabetic complications such as cataracts.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced maternal age is a risk factor for both early and late gestational diabetes mellitus: The Japan Environment and Children's Study.","authors":"Kazuma Tagami, Noriyuki Iwama, Hirotaka Hamada, Hasumi Tomita, Rie Kudo, Natsumi Kumagai, Hongxin Wang, Seiya Izumi, Zen Watanabe, Mami Ishikuro, Taku Obara, Hirohito Metoki, Yuichiro Miura, Chiharu Ota, Takashi Sugiyama, Shinichi Kuriyama, Takahiro Arima, Nobuo Yaegashi, Masatoshi Saito","doi":"10.1111/jdi.14400","DOIUrl":"https://doi.org/10.1111/jdi.14400","url":null,"abstract":"<p><strong>Aims: </strong>This study investigated the association between maternal age and early and late gestational diabetes mellitus (GDM).</p><p><strong>Methods: </strong>In total, 72,270 pregnant women were included in this prospective birth cohort study. Associations between maternal age and early GDM (diagnosed at <24 gestational weeks) and late GDM (diagnosed at ≥24 gestational weeks) were evaluated using a multinomial logistic regression model with possible confounding factors. The reference category was maternal age of 30-34.9 years.</p><p><strong>Results: </strong>Higher maternal age was associated with higher odds of early and late GDM (P-value for trend <0.0001 and <0.0001, respectively). The adjusted odds ratios (aORs) for early GDM with maternal age of 35-39.9 years and ≥40 were 1.399 (95% confidence interval [CI]: 1.134-1.725) and 2.494 (95% CI: 1.828-3.402), respectively. The aORs for late GDM with maternal age of 35-39 years and ≥40 were 1.603 (95% CI: 1.384-1.857) and 2.276 (95% CI: 1.798-2.881), respectively.</p><p><strong>Conclusions: </strong>Higher maternal age was associated with an increased risk of GDM regardless of when GDM was diagnosed. The association between maternal age and early GDM was similar to that between maternal age and late GDM.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}