{"title":"Elucidation of the clinical traits of diabetic chorea through a questionnaire survey of people with diabetic chorea from 59 Japanese hospitals.","authors":"Naoko Arakawa, Tomohisa Aoyama, Hirotsugu Suwanai, Gotaro Toda, Iseki Takamoto, Yukiko Okazaki, Takashi Kadowaki, Toshimasa Yamauchi","doi":"10.1111/jdi.14392","DOIUrl":"https://doi.org/10.1111/jdi.14392","url":null,"abstract":"<p><strong>Aims: </strong>Diabetic chorea refers to sudden involuntary movements developing in people with diabetes mellitus and is known to occur mainly in those with severe hyperglycemia. We conducted a questionnaire survey of case-reporting facilities in Japan to elucidate their clinical characteristics.</p><p><strong>Methods: </strong>We searched the PubMed and Ichushi databases for case reports published from January 1, 2012, to December 31, 2017, using \"diabetes\" and \"chorea\" as keywords, and sent a questionnaire to the reporting institutions.</p><p><strong>Results: </strong>Data from a total of 64 cases were included in this study. While most cases had severe hyperglycemia at the onset of diabetic chorea, hypoglycemia/improvement of the plasma glucose served as the trigger for the symptom in 14 cases (21.9%). The Early Remission Group (≤6 months) consisted of 39 cases (60.9%), while the Prolonged Partial Remission Group (>6 months) included 25 cases (39.1%). In the Prolonged Partial Remission Group (>6 months), there were more cases with widespread involuntary movement symptoms, a higher number of cases exhibiting typical imaging findings, and a greater incidence of chorea onset after the initiation of antidiabetic treatment, including hypoglycemia.</p><p><strong>Conclusions: </strong>Most reported cases of diabetic chorea in Japan were elderly persons with type 2 diabetes mellitus and severe hyperglycemia, although there were also some cases in which the symptom developed in the setting of hypoglycemia. It has been suggested that rapid plasma glucose correction and hypoglycemia might be associated with the risk of development and prognosis of diabetic chorea.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875828","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}
Qiaoli Cui, Zhenming Zhang, Lang Qin, Zhaolin Teng, Zhihong Wang, Wei Wu, Linling Fan, Jing Su, Yexuan Hao, Ji Qin, Li Zhang, Qi Wang, Yuan Zhuang, Hangping Zheng, Shuo Zhang, Xiang Geng, Lei Zhu, Yijian Chen, Bin Lu, Yiming Li, Xiaoming Zhu
{"title":"Interleukin-37 promotes wound healing in diabetic mice by inhibiting the MAPK/NLRP3 pathway.","authors":"Qiaoli Cui, Zhenming Zhang, Lang Qin, Zhaolin Teng, Zhihong Wang, Wei Wu, Linling Fan, Jing Su, Yexuan Hao, Ji Qin, Li Zhang, Qi Wang, Yuan Zhuang, Hangping Zheng, Shuo Zhang, Xiang Geng, Lei Zhu, Yijian Chen, Bin Lu, Yiming Li, Xiaoming Zhu","doi":"10.1111/jdi.14389","DOIUrl":"https://doi.org/10.1111/jdi.14389","url":null,"abstract":"<p><strong>Aims/introduction: </strong>Diabetic foot ulcer (DFU) is a prevalent complication of diabetes characterized by heightened inflammation and impaired wound-healing processes. Interleukin-37 (IL-37) is a natural suppressor of innate inflammation. Here, we aim to investigate the potential of IL-37 in enhancing the healing process of diabetic wounds.</p><p><strong>Materials and methods: </strong>The skin samples of DFU and non-diabetic patients during foot and ankle orthopedic surgery were collected. The IL-37 transgenic mice (IL-37Tg) were created using CRISPR/Cas-mediated genome engineering. Mice were administered streptozotocin (STZ, 150 mg/kg) to induce a diabetic model. After 4 weeks, an equidistant full-thickness excisional wound measuring 8 mm was created on the central back of each mouse and allowed to heal naturally. Body weight and blood glucose levels were measured weekly. The wound area was measured, and skin samples were collected on Day 10 for further Quantitative polymerase chain reaction (qPCR) and WB detection and RNA sequencing analysis.</p><p><strong>Results: </strong>The proinflammation cytokines such as TNF-α and IL-1β and the MAPK signaling pathway were significantly increased in the wound margin of DFU patients. Compared with diabetic mice, diabetic IL-37Tg mice showed a significantly accelerated healing process. The enriched signaling pathways in RNA sequencing included cytokine-cytokine receptor interaction, TNF signaling pathway, and NOD-like receptor signaling pathway. Through QPCR and WB detection, we found that IL-37 could inhibit the activated MAPK and NOD-like signaling pathway, reducing TNF-α, IL-1β, and NLRP3 expression in the diabetic wound.</p><p><strong>Conclusions: </strong>IL-37 promotes skin wound healing in diabetic mice, providing a new possible target for treating diabetic wounds.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875834","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}
Junko Oya, Mika Shimizu, Ryo Kubota, Rika Suda, Tomoko Nagkagami
{"title":"Effectiveness for adding or switching from other incretin-related drugs to oral semaglutide in type 2 diabetes.","authors":"Junko Oya, Mika Shimizu, Ryo Kubota, Rika Suda, Tomoko Nagkagami","doi":"10.1111/jdi.14391","DOIUrl":"https://doi.org/10.1111/jdi.14391","url":null,"abstract":"<p><strong>Aims/introduction: </strong>This study aimed to evaluate and compare the effectiveness of oral semaglutide after adding to or switching from incretin-related drugs by assessing the changes in HbA1c and body weight (BW) in participants with type 2 diabetes in clinical settings.</p><p><strong>Materials and methods: </strong>A total of 368 participants were divided into groups according to antidiabetic medications before oral semaglutide treatment; incretin-related drug-naïve (naïve), switching from dipeptidyl peptide-4 inhibitors (DPP-4i) or glucagon-like peptide-1 receptor agonist (GLP-1 RA) groups. Adjusted mean changes in HbA1c and BW at 6 months after oral semaglutide administration were compared among the three groups. Similar analyses were performed in the GLP-1 RAs group between GLP-1RAs before switching.</p><p><strong>Results: </strong>Mean change of HbA1c in DPP-4i and GLP-1 RA groups was -0.67% (95% confidence interval [CI]: -0.79 to -0.54) and -0.13% (95% CI: -0.40 to 0.15), respectively, which were significantly smaller than incretin-related drug-naïve group; -0.85% (95% CI: -1.08 to -0.62). Mean change in BW between the naïve and DPP-4i groups had no differences; however, these changes were lower in the GLP-1 RA group than in the naïve group. Mean change in HbA1c between pretreatment with GLP-1 RAs had no differences; however, the mean change in BW in the dulaglutide group was significantly higher than that in the injectable semaglutide group.</p><p><strong>Conclusion: </strong>Oral semaglutide reduced HbA1c levels and BW after adding or switching from other incretin-related drugs in Japanese participants with type 2 diabetes.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870565","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":"Association between obstructive sleep apnea syndrome and type1/type2 diabetes mellitus: A systematic review and meta-analysis.","authors":"Huiling Huang, Zhang Chen","doi":"10.1111/jdi.14354","DOIUrl":"https://doi.org/10.1111/jdi.14354","url":null,"abstract":"<p><strong>Introduction: </strong>Obstructive sleep apnea (OSA) is characterized by a complete or partial obstruction of the upper airway, along with hypoxemia, microarousals, and sleep fragmentation. Compelling evidence has clarified a bidirectional correlation between OSA and diabetes mellitus (DM). This paper was to assess the link between OSA and DM via meta-analysis, consisting of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM).</p><p><strong>Materials and methods: </strong>Four databases (PubMed, Cochrane Library, Embase, and CNKI) were screened from inception to March 2024 for observational studies of OSA and DM, including case-control studies and cohort studies. Bidirectional associations between OSA and DM were analyzed, consisting of T1DM and T2DM. Random-effect models were employed to determine the pooled odds ratio (OR) and 95% confidence intervals (CIs) to compare prevalence. Traditional subgroup analyses were implemented. Review Manager 5.3 and Stata 16.0 were utilized for data analyses.</p><p><strong>Results: </strong>Thirty-five studies were enrolled, including 12 prospective cohort studies, 4 retrospective cohort studies, and 19 case-control studies. DM prevalence was notably higher in OSA patients than in non-OSA patients (OR: 2.29, 95% CI: 1.93-2.72), and OSA prevalence was notably higher in DM patients than in non-DM patients (OR: 2.12, 95% CI: 1.73-2.60). Subgroup analysis uncovered that DM prevalence in the OSA population was more significant in the group <50 years (OR: 3.28, 95% CI: 2.20-4.89) and slightly decreased in the group >50 years (OR: 1.82, 95% CI: 1.38-2.40).</p><p><strong>Conclusions: </strong>The meta-analysis reveals a bidirectional link between OSA and DM.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869278","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}
Ye Feng, Xi Jin, Jing Zhu, Meng Yuan, Liang Zhu, Dan Ye, Yuqing Shen
{"title":"Association between endogenous estradiol, testosterone, and long-term mortality in adults with prediabetes and diabetes: Evidence from NHANES database.","authors":"Ye Feng, Xi Jin, Jing Zhu, Meng Yuan, Liang Zhu, Dan Ye, Yuqing Shen","doi":"10.1111/jdi.14367","DOIUrl":"https://doi.org/10.1111/jdi.14367","url":null,"abstract":"<p><strong>Aim and introduction: </strong>Diabetes and prediabetes pose significant global public health challenges. Sex steroids, particularly testosterone and estradiol, play crucial roles in various metabolic processes. This study investigates the relationship between sex hormone levels and long-term mortality in adults with prediabetes and diabetes, as well as those without glucose intolerance.</p><p><strong>Material and methods: </strong>This retrospective cohort study utilized data from the NHANES 2013-2016, including adults aged 50-79 across prediabetic, diabetic, and non-diabetic groups. Serum testosterone, estradiol, and their ratios (T/E) were analyzed. The primary outcomes were all-cause mortality and CVD mortality tracked until December 2019. Cox regression models estimated the associations between hormone levels and mortality risks.</p><p><strong>Results: </strong>The study included 3,665 participants (male: 2,140; female: 1,775). In males with prediabetes, higher estradiol (adjusted hazard ratio [aHR] = 0.17, 95% confidence interval [CI]: 0.07-0.43) or testosterone (aHR = 0.39, 95% CI: 0.31-0.50) was significantly associated with lower risk of all-cause mortality. Higher estradiol (aHR = 0.12, 95% CI: 0.04-0.32) or testosterone (aHR = 0.36, 95% CI: 0.27-0.48) was significantly associated with lower CVD mortality risk. In females with diabetes, there was a significant association between higher estradiol levels (aHR = 0.22, 95% CI: 0.06-0.83) or T/E ratio (aHR = 0.18, 95% CI: 0.04-0.73) with a reduced all-cause mortality risk.</p><p><strong>Conclusions: </strong>This study identifies some novel associations between estradiol, testosterone, and their ratios with long-term mortality in men and women across different glycemic statuses. These findings suggest a potential protective role of sex hormones in individuals with altered glucose metabolism, with gender difference, warranting further investigation.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869277","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}
Jae-Heon Kang, Soo Lim, Jee-Hyun Kang, Yang-Hyun Kim, Hae-Jin Ko, Yoshihiro Ogawa, Iichiro Shimomura, YouSun Ha, Shogo Wada, Toshimasa Yamauchi, Masato Iwabu
{"title":"Perceptions, attitudes, and management of obesity in East Asians vs global: A pooled analysis of the ACTION IO survey.","authors":"Jae-Heon Kang, Soo Lim, Jee-Hyun Kang, Yang-Hyun Kim, Hae-Jin Ko, Yoshihiro Ogawa, Iichiro Shimomura, YouSun Ha, Shogo Wada, Toshimasa Yamauchi, Masato Iwabu","doi":"10.1111/jdi.14387","DOIUrl":"https://doi.org/10.1111/jdi.14387","url":null,"abstract":"<p><strong>Objective: </strong>This ACTION-IO sub-analysis compared attitudes of people with obesity (PwO) and healthcare professionals (HCPs) between South Korea/Japan and global.</p><p><strong>Methods: </strong>Responses from overall (body mass index [BMI] ≥ 25 kg/m<sup>2</sup>) and higher BMI (30.0-34.9 kg/m<sup>2</sup>) groups were compared descriptively; t-and z-tests were used to test for statistical significant difference.</p><p><strong>Results: </strong>Total responses from South Korea/Japan vs global were as follows: overall (PwO: 3,501 vs 14,502; HCPs: 502 vs 2,785); higher BMI (PwO: 530 vs 7,460) groups. Compared to global, more South Korea/Japan-PwO considered improving existing health condition as top weight loss (WL) goal (overall: 37% vs 28%, higher BMI: 35% vs 26%; P < 0.05) and fear of weight regain as top WL barrier (overall: 52% vs 45%, higher BMI: 65% vs 42%; P < 0.05). Fewer South Korea/Japan-PwO reported discussing weight (overall: 25% vs 51%, higher BMI: 31% vs 54%; P < 0.05). More South Korea/Japan-HCPs felt PwO as themselves responsible for WL (74% vs 55%; P < 0.05). More than two-of-three South Korea/Japan-HCPs (vs four-of-five global) were motivated to help PwO in WL.</p><p><strong>Conclusions: </strong>South Korea/Japan PwO had differences in their attitudes and behaviors toward obesity care. These findings support the need for increased public awareness of obesity as a disease and for HCPs to play active role initiating weight management dialogue.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870656","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}
Mushood Ahmed, Abdullah Nofal, Aimen Shafiq, Hira Javaid, Areeba Ahsan, Zain Ali Nadeem, Raheel Ahmed, Mahboob Alam, Mamas A Mamas, Marat Fudim, Gregg C Fonarow
{"title":"Rising mortality rates linked to type-2 diabetes and obesity in the United States: An observational analysis from 1999 to 2022.","authors":"Mushood Ahmed, Abdullah Nofal, Aimen Shafiq, Hira Javaid, Areeba Ahsan, Zain Ali Nadeem, Raheel Ahmed, Mahboob Alam, Mamas A Mamas, Marat Fudim, Gregg C Fonarow","doi":"10.1111/jdi.14386","DOIUrl":"https://doi.org/10.1111/jdi.14386","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of type 2 diabetes (T2D) and obesity are increasing in the United States. However, population-level data for mortality trends due to T2D and obesity are limited. This study aims to assess these death trends among adults in the United States categorized by sex, race, and geographical location.</p><p><strong>Methods: </strong>We queried the CDC-WONDER database for multiple cause of death data of adults aged ≥25 years. The crude mortality rates (CMR), age-adjusted mortality rates (AAMRs), annual percent change (APC), and the average APC (AAPC) along with a 95% confidence interval (CI) were analyzed.</p><p><strong>Results: </strong>From 1999 to 2022, a total of 88,597 T2DM and obesity-related deaths were recorded in the United States. The AAMR consistently increased from 1999 to 2017 (APC: 7.64; 95% CI: 1.91-9.96), followed by a marked rise from 2017 to 2022 (APC: 20.13; 95% CI: 12.88-38.57). The AAMR was approximately 3.58 times higher during the COVID-19 pandemic compared to the period from 1999 to 2019. The AAMR for males was consistently greater than that for females. The highest AAMR was observed in non-Hispanic (NH) Blacks or African Americans, followed by NH White, Hispanic or Latino, and other NH populations. Rural areas (AAMR: 1.86, 95% CI: 1.83-1.89) exhibited a greater AAMR than urban regions 1.26 (95% CI: 1.25-1.27).</p><p><strong>Conclusions: </strong>Our results indicate a substantial increasing trend of T2D and obesity-related deaths in the United States especially during the COVID-19 pandemic.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851809","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}
Dai Yamagami, Takahisa Deguchi, Aiko Arimura, Yoshihiko Nishio
{"title":"Relationship between the progression of diabetic polyneuropathy and impaired circadian blood pressure variability.","authors":"Dai Yamagami, Takahisa Deguchi, Aiko Arimura, Yoshihiko Nishio","doi":"10.1111/jdi.14282","DOIUrl":"https://doi.org/10.1111/jdi.14282","url":null,"abstract":"<p><strong>Aims/introduction: </strong>We evaluated the 24-h ambulatory blood pressure monitoring data of patients to investigate the relationship between the progression of diabetic polyneuropathy and impaired circadian blood pressure variability.</p><p><strong>Materials and methods: </strong>This study included 154 patients with diabetes who were hospitalized for hyperglycemic control. Routine biochemical and hematological tests, ambulatory blood pressure monitoring, screening for diabetic complications, nerve conduction studies, and Holter electrocardiography were carried out on all patients. They were classified according to the Baba classification and the clinical staging for diabetic polyneuropathy, and their ambulatory blood pressure monitoring data were compared.</p><p><strong>Results: </strong>The patients were classified into stages 0 (n = 64), I (n = 42), II (n = 24), III (n = 11) and IV (n = 13) according to the Baba classification. As the severity of diabetic polyneuropathy progressed, the degree of nocturnal blood pressure reduction decreased and the percentage of patients with riser-type impaired circadian blood pressure variability increased. Similar results were observed in patients classified according to the clinical staging for diabetic polyneuropathy. In the multivariate logistic regression analysis, the severity of diabetic neuropathy and urinary albumin excretion were independently associated with the percentage of patients with riser-type. However, the adjusted odds ratio was the highest for Baba class I and decreased with increasing severity.</p><p><strong>Conclusions: </strong>Patients with progressive diabetic polyneuropathy and renal impairment often show impaired circadian blood pressure variability. The progression of electrophysiological and clinical neuropathy is associated with riser-type circadian blood pressure variability independent of urinary albumin excretion, insulin therapy, renin-angiotensin-aldosterone system inhibitor medication and body mass index.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851808","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}
Xiaoting Xi, Xuewei Wang, Jia Ma, Qianbo Chen, Yuxin Zhang, Yaxian Song, Yan Li
{"title":"miR-130a-3p enhances autophagy through the YY1/PI3K/AKT/mTOR signaling pathway to regulate macrophage polarization and alleviate diabetic retinopathy.","authors":"Xiaoting Xi, Xuewei Wang, Jia Ma, Qianbo Chen, Yuxin Zhang, Yaxian Song, Yan Li","doi":"10.1111/jdi.14381","DOIUrl":"https://doi.org/10.1111/jdi.14381","url":null,"abstract":"<p><strong>Aims/introduction: </strong>Diabetic retinopathy (DR) is a common complication of diabetes that can lead to poor vision and blindness. This study aimed to explore the mechanism of action of miR-130a-3p in DR progression.</p><p><strong>Materials and methods: </strong>In this study, we administered a single intraperitoneal injection of 100 mg/kg streptozotocin (STZ) to construct a DR mouse model, and induced a human monocyte cell line (THP-1) to differentiate into M0 macrophages, after which the M0 macrophages were cultured with 30 mM high glucose (HG) as a model of inflammation. The relative gene and protein levels were validated by RT-qPCR and western blotting. Macrophage polarization and retinal damage in the mice were tested using ELISA, MDC staining, immunofluorescence staining, and HE staining.</p><p><strong>Results: </strong>The results revealed that the expression of miR-130a-3p was low in M1 macrophages, whereas the expression of miR-130a-3p was high in M2 macrophages, and the level of miR-130a-3p was reduced after HG treatment of macrophages. The overexpression of miR-130a-3p attenuated HG- or STZ-induced inflammation, promoted macrophage autophagy, inhibited M1 polarization of macrophages, and attenuated the progression of DR. In addition, YY1 was the downstream target gene of miR-130a-3p, and overexpression of miR-130a-3p inhibited YY1 expression. However, overexpression of YY1 weakened the effect of miR-130a-3p mimic. After further treatment with the PI3K/Akt/mTOR pathway activator 740 Y-P, the effect of YY1 knockdown was weakened, macrophage autophagy was inhibited, and M1 polarization and inflammation were promoted.</p><p><strong>Conclusion: </strong>miR-130a-3p inhibited the activation of the PI3K/Akt/mTOR pathway by downregulating YY1 expression, thus facilitating macrophage autophagy, inhibiting M1 polarization and the inflammatory response of macrophages, and finally attenuating the progression of DR. The results of this study provide theoretical support for the use of miR-130a-3p as a new target for the treatment of DR.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816683","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":"Pharmacological characteristics of once-weekly insulin icodec in Japanese individuals with type 1 diabetes.","authors":"Takashi Eto, Miwa Haranaka, Niels Rode Kristensen, Andrea Navarria, Tomoyuki Nishida, Rasmus Ribel-Madsen, Stinne Byrholdt Søgaard, Inge Birk Halberg","doi":"10.1111/jdi.14384","DOIUrl":"https://doi.org/10.1111/jdi.14384","url":null,"abstract":"<p><strong>Introduction: </strong>Insulin icodec is a basal insulin designed for once-weekly administration. This study assessed the pharmacological properties of icodec in Japanese individuals with type 1 diabetes (T1D).</p><p><strong>Materials and methods: </strong>In a randomized, open-label, crossover study, 24 Japanese individuals with T1D (20-64 years; glycated hemoglobin ≤9.0%) received once-weekly icodec for 8 weeks and once-daily insulin glargine U100 for 14 days at individual constant equimolar doses per week together with bolus insulin aspart. Individual doses were determined during run-in with glargine U100 titrated to prebreakfast self-measured plasma glucose (SMPG) of 4.4-7.2 mmol/L. Blood samples for icodec pharmacokinetics were taken from the first icodec dose until 35 days after last dose. The steady-state glucose-lowering effect was measured in glucose clamps (target 6.7 mmol/L) during 24-48 h and 150-168 h after last icodec dose and 0-24 h after last glargine U100 dose. One-week glucose-lowering effect of icodec was simulated using a pharmacokinetic/pharmacodynamic model. Hypoglycemia was identified from SMPG during the treatment periods.</p><p><strong>Results: </strong>Icodec pharmacokinetic steady state was achieved on average after 2-3 weeks of treatment. Model-derived daily glucose-lowering effect during the weekly dosing interval averaged 14.6%, 18.0%, 16.6%, 14.9%, 13.3%, 11.9%, and 10.7%, respectively. Rates of level 2 hypoglycemia (PG <3.0 mmol/L) were 37.3 vs 30.6 episodes per patient-year of exposure for icodec vs glargine U100.</p><p><strong>Discussion: </strong>Icodec pharmacological properties in Japanese individuals with T1D in this study support the potential of icodec to provide basal insulin coverage with once-weekly dosing in Japanese individuals with diabetes.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811705","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}