Journal of Diabetes Research最新文献

{"title":"First-Time Usage of SGLT2 Inhibitors in Patients With Type 2 Diabetes Who Are Fasting Ramadan: Efficacy and Safety.","authors":"Hany Ahmed Muhammed Khalil, Sara Kasem Abdelal, Ahmed Faysal El-Rawy, Alshimaa Lotfy Hamed Abodahab","doi":"10.1155/jdr/4321423","DOIUrl":"https://doi.org/10.1155/jdr/4321423","url":null,"abstract":"<p><p><b>Introduction:</b> Ramadan fasting claims a necessary role in the management of diabetes. Many people with Type 2 diabetes insist on fasting during the holy month of Ramadan, which represents a challenge to their physicians to provide balance between preventing hypoglycemia or diabetic ketoacidosis (DKA) and good control of hyperglycemia with its short- and long-term complications. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are a glucose-lowering therapy for Type 2 diabetes, which are generally well tolerable but may carry the risk of dehydration and hypoglycemia particularly during the long fasting hours. The study aimed to assess the efficacy and safety of the use of SGLT2i for the first time during Ramadan fasting. <b>Methods:</b> This prospective cohort study was carried out on 61 Egyptian Muslim patients, aged ≥ 18 years old, both sexes, with Type 2 diabetes mellitus (T2DM), prepared to fast during Ramadan, and treated with SGLT2i for the first time as a supplementary to metformin or another oral hypoglycemic drug. The dose of SGLT2i started after Iftar time. During and 6 weeks after Ramadan, evaluations were conducted. <b>Results:</b> Glycated hemoglobin (HbA1c), blood pressure (systolic and diastolic), and creatinine were significantly lower after Ramadan than at the beginning of Ramadan. The estimated glomerular filtration rate (eGFR) was significantly higher after Ramadan than at the beginning of Ramadan. Hypoglycemia, dehydration, and DKA did not occur in any patient. There was a significant negative correlation between age and HbA1c (<i>r</i> = -0.267, 95% CI: -0.48 to -0.05; <i>p</i> = 0.037) and eGFR (<i>r</i> = -0.684, 95% CI: -0.79 to -0.54; <i>p</i> < 0.001) after Ramadan, while there was no correlation between the duration of DM and HbA1c before and after Ramadan. HbA1c was significantly lower after Ramadan than during Ramadan in patients with ischemic heart disease (IHD), hypertension (HTN), peripheral neuropathy (PN), and chronic kidney disease (CKD) (<i>p</i> < 0.05). <b>Conclusions:</b> SGLT2i is effective and safe during Ramadan fasting with a significant reduction in HBA1c, blood pressure, and creatinine and a significant elevation of eGFR. <b>Trial Registration:</b> ClinicalTrials.gov identifier: NCT06370247.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2025 ","pages":"4321423"},"PeriodicalIF":3.6,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trial and Participant Characteristics of a Home-Visiting Diabetes Intervention: The <i>Together Overcoming Diabetes</i> Study.","authors":"Melissa L Walls, Kelley J Sittner, Gabby J Gomez, Reagan E Cole, Sylvie R Perkins, Rachel I Steinberg, Angie K Forsberg, Emily E Haroz, Allison Barlow","doi":"10.1155/jdr/6591307","DOIUrl":"https://doi.org/10.1155/jdr/6591307","url":null,"abstract":"<p><p><b>Background:</b> American Indians (AIs) endure the most severe health inequities in the nation, including disproportionately high rates of Type 2 diabetes (T2D). We describe baseline characteristics for AI participants enrolled in a culturally grounded, intergenerational, home-based T2D preventive intervention called <i>Together Overcoming Diabetes</i> (TOD). <b>Methods:</b> This community-based participatory research collaboration between five tribal nations and university-based researchers launched recruitment for a waitlist randomized control trial (RCT) design in 2021. Eligible participants were adults diagnosed with T2D who self-identified as AI, lived on or near participating reservations, and were caregivers to youth aged 10-16 years. Participants completed baseline assessments upon enrollment before being randomized to the intervention or waitlist group. <b>Results:</b> A total of <i>N</i> = 162 individuals (81 adults and 81 youth) enrolled in the study. Most of the adult (Indigenous) sample reported being female (77.8%) and were on average 49.5 years old. Average age of youth participants was 13.2 years, with similar representation of girls and boys. Mean adult HbA1c (primary outcome for the trial) was 7.93 (SD = 1.99) at baseline. Around 19% of youth participants reported a T2D or prediabetes diagnosis. Additional demographic and holistic health results are presented. <b>Conclusion:</b> This study provides comprehensive information about physiological, psychological, behavioral, and sociodemographic characteristics for a sample of AI families enrolled in a T2D intervention study. Findings suggest that intervention goals to improve behaviors like diet and physical activity are warranted and highlight the need for policy changes to address the social determinants of health. <b>Trial Registration:</b> ClinicalTrials.gov identifier: NCT04734015.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2025 ","pages":"6591307"},"PeriodicalIF":3.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gender Bias in Clinical Trials of Sodium-Glucose Cotransporter 2 Inhibitors for the Treatment of Type 2 Diabetes Mellitus: A Systematic Review.","authors":"Santiago José Lora-Escobar, Lupe Rodríguez-de Francisco, Manuel López-Feijoo, Bernardo Santos-Ramos, Virginia Bellido, Rosa Casado-Mejía, Héctor Acosta-García","doi":"10.1155/jdr/3733178","DOIUrl":"https://doi.org/10.1155/jdr/3733178","url":null,"abstract":"<p><p><b>Aims:</b> The study is aimed at assessing gender bias in Phase III clinical trials (CTs) of sodium-glucose cotransporter type 2 (iSGLT2) inhibitors in adults with Type 2 diabetes mellitus (T2DM). <b>Methods:</b> We searched PubMed and EMBASE databases until June 2023. To estimate sex bias in recruitment, the difference between F-Particip (fraction of women recruited) and F-Prev (prevalence fraction of women with T2DM) was calculated. A significant sex bias in recruitment was considered to exist when the difference between F-Particip and F-Prev was greater than 0.05, 0.1, and 0.2. The analysis was considered to have a sex bias when the efficacy variables were not analyzed by sex. Gender of the first, last, and corresponding author was also assessed. <b>Results:</b> In total, 70 articles met all inclusion criteria. Sex bias in recruitment showed variable results depending on the reference value. No significant sex bias in recruitment was found in the total number of included patients. Examining each CT individually, using values of significant sex bias in recruitment of ±0.05, ±0.1, or ±0.2, we found that 41.4%, 20%, and 5.7% of the trials, respectively, showed this bias. In 34.3% of the articles, women were the first, last, or corresponding authors. Sex-based analysis of the results was performed in five studies. <b>Conclusions:</b> Although the proportion of women included in iSGLT2 CTs seems acceptable, gender bias persists in the analysis of variables and in the study authors. However, the lack of gender focus may be explained by the characteristics of the patients included in the CTs.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2025 ","pages":"3733178"},"PeriodicalIF":3.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence of Prediabetes and Diabetes in a European Longitudinal General Population Cohort and Its Associated Factors-Results From the Austrian LEAD Study.","authors":"Amiria Dal Grande, Maarten Van Herck, Robab Breyer-Kohansal, Tobias Mraz, Ahmad Karimi, Mohammad Azizzadeh, Sylvia Hartl, Otto C Burghuber, Emiel F M Wouters, Alexandra Kautzky-Willer, Caspar Schiffers, Marie K Breyer","doi":"10.1155/jdr/5540276","DOIUrl":"https://doi.org/10.1155/jdr/5540276","url":null,"abstract":"<p><p><b>Aims:</b> This study evaluates the incidence of (pre)diabetes in an Austrian population over a broad age span and addresses whether alterations in lifestyle, blood markers, and body composition are associated with the development of (pre)diabetes. <b>Material and Methods:</b> Data from the first and second phases of the Austrian LEAD study, a longitudinal population-based cohort study, were used. Inclusion criteria were a valid glycaemic status (i.e., normoglycaemia, prediabetes, and diabetes) at both phases using American Diabetes Association criteria. Besides blood samples, body composition parameters and an interviewer-administered questionnaire were assessed. A binary logistic regression was performed to answer the research question. <b>Results:</b> In total, 7822 individuals (51% females, 46 ± 19 years with 9.6% aged < 18 years, median follow-up time 4.1 [3.9-4.5] years) were included. The overall incidence rate was estimated at 63.0 (95% CI [59.7; 66.3]) and 8.4 (95% CI [7.4; 9.5]) per 1000 person-years for prediabetes and diabetes, respectively. In the 6-<10-, 10-<20-, and 20-<30-year age bins, an incidence rate of, respectively, 30.2, 16.3, and 13.4 per 1000 person-years (prediabetes) and 2.0, 3.5, and 1.3 (diabetes) was observed. Further, 38.3% of diabetic individuals at Visit 2 were undiagnosed and thus untreated. Factors identified as being significantly associated with progression towards (pre)diabetes included changes in triglycerides, high-density lipoprotein cholesterol, total cholesterol, and visceral adipose tissue mass, besides male sex, older age, low education level, and urban residence. <b>Conclusions:</b> The overall incidence of (pre)diabetes in the Austrian population is high and highlights the need for screening from a young age and on a regular basis so that preventive and treatment strategies can be implemented at an early stage. <b>Trial Registration:</b> ClinicalTrials.gov identifier: NCT01727518.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2025 ","pages":"5540276"},"PeriodicalIF":3.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spontaneously Diabetic Torii Fatty Rat Shows Early Stage of Diabetic Retinopathy Characterized by Capillary Changes and Inflammation.","authors":"Kasumi Kikuchi, Miyuki Murata, Yasushi Kageyama, Masami Shinohara, Tomohiko Sasase, Kousuke Noda, Susumu Ishida","doi":"10.1155/jdr/3800292","DOIUrl":"https://doi.org/10.1155/jdr/3800292","url":null,"abstract":"<p><p><b>Purpose:</b> The Spontaneously Diabetic Torii (SDT) fatty rat is an animal model of obese Type 2 diabetes. We previously reported that the SDT fatty rats develop diabetic cataracts. This study aimed to elucidate early diabetic changes in the retina of the SDT fatty rats. <b>Materials and Methods:</b> The retinal thickness, capillary diameter, and pericyte/endothelial cell (P/E) ratio were assessed in the male SDT fatty rats and Sprague-Dawley (SD) rats at 24 weeks of age. Immunostaining was performed to assess the intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels in the retinal capillaries. DNA microarray analysis was performed to detect inflammation-associated molecules in the retina of the SDT fatty rats. Real-time PCR and Magnetic Luminex Assay were performed to validate the results. <b>Results:</b> The retinal thickness in the SDT fatty rats was significantly greater than that in SD rats. The capillary diameter in the retina of the SDT fatty rats was significantly higher than that of SD rats. The P/E ratio in the SDT fatty rats was significantly lower than that in SD rats. ICAM-1 and VCAM-1 were observed in the retinal vessels of the SDT fatty rats. The levels of mRNA and protein of <i>Mcp1</i>, <i>Il1b</i>, <i>Icam1</i>, and <i>Tnf</i> were upregulated in the retinal tissues of the 24-week-old SDT fatty rats. <b>Conclusions:</b> Our study demonstrated that the SDT fatty rats exhibited early diabetic retinal changes, suggesting that the SDT fatty rats may be useful in research on the pathogenesis of early human diabetic retinopathy.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2025 ","pages":"3800292"},"PeriodicalIF":3.6,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12037240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Neuropathy on Well-Being and Health-Related Quality of Life in Adolescents With Type 1 Diabetes.","authors":"Vinni Faber Rasmussen, Mathilde Thrysøe, Páll Karlsson, Jens Randel Nyengaard, Kurt Kristensen, Esben Thyssen Vestergaard","doi":"10.1155/jdr/6620727","DOIUrl":"https://doi.org/10.1155/jdr/6620727","url":null,"abstract":"<p><p><b>Aim:</b> This study is aimed at assesing the impact of neuropathy on well-being and health-related quality of life (HRQoL) in adolescents with Type 1 diabetes (T1D). <b>Methods:</b> In a cross-sectional study, 60 adolescents with T1D (15-18 years, diabetes duration > 5 years) were enrolled. Clinical and biochemical data were collected, and well-being and HRQoL were assessed using the WHO-5 well-being index and DISABKIDS questionnaires, including diabetes-specific modules. Diagnostic tests for large fiber neuropathy (LFN), small fiber neuropathy (SFN), and autonomic neuropathy were performed as part of the T1DANES study. The participants were divided into groups depending on the presence or absence of specific forms of neuropathy. Those with autonomic neuropathy were further divided depending on reported autonomic symptoms (Composite Autonomic Symptom Scale 31 (COMPASS-31) score ≥ 24 or < 24). Additionally, the data was compared to 23 healthy control subjects. <b>Results:</b> The median diabetes duration was 8.5 years (range 5-17), and the HbA1c was 60 mmol/mol (7.6%) (range 41-93 [5.9%-10.6%]). Adolescents who had abnormal autonomic function test(s) and a COMPASS-31 score ≥ 24 exhibited lower WHO-5 well-being index compared to the following groups: those with abnormal autonomic test(s) and fewer autonomic symptoms (COMPASS-31 < 24), the remaining adolescents with T1D, and the control subjects (<i>p</i> values < 0.05). There was no significant difference in the total score of DISABKIDS between the groups; however, the subdomain <i>social inclusion</i> was lowest in the group with COMPASS-31 ≥ 24. Gastric motility index (<i>p</i> = 0.04) and uroflow acceleration (<i>p</i> = 0.02) were positively associated with the total score of DISABKIDS. Females reported lower well-being and HRQoL than males (<i>p</i> values < 0.05); in total, 28% had a WHO-5 well-being index < 50. <b>Conclusion:</b> In conclusion, adolescents with diabetic autonomic neuropathy who also reported autonomic symptoms had lower well-being and impaired social inclusion. Adolescents with symptoms of neuropathy and females appear to be at higher risk of lower well-being, and using standardized screening tools helps to identify the subjects at risk.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2025 ","pages":"6620727"},"PeriodicalIF":3.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12021488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Diabetic Cognitive Impairment Score for Early Screening of Cognitive Impairment in Type 2 Diabetes Patients.","authors":"Shujun Zhang, Xiaoli Shi, Shaolin Zheng, Xiaoli Liang, Fen Wang, Weijie Xu, Xuefeng Yu, Yan Yang","doi":"10.1155/jdr/8029913","DOIUrl":"https://doi.org/10.1155/jdr/8029913","url":null,"abstract":"<p><p><b>Purpose:</b> Diabetes has been associated with an excess risk of cognitive impairment. The hyperphosphorylation of tau protein leads to neurodegeneration and is closely related to Type 2 diabetes (T2D). This study aimed to characterize the association between P-tau181 and diabetic cognitive impairment and to develop a nomogram-based score to screen cognitive impairment in T2D patients. <b>Methods:</b> We used a cohort of 379 patients diagnosed with T2D as a training dataset to develop a predictive model. Risk factors associated with cognitive impairment were identified using stepwise multivariate logistic regressive analysis. A nomogram was established by incorporating these risk factors, and the diabetic cognitive impairment score (DCIS) was built and externally validated in another cohort. <b>Results:</b> In the training cohort, patients with cognitive impairment had higher levels of P-tau181 (13.3 [10.5-18.7] vs. 10.0 [8.0-13.0], <i>p</i> < 0.001). P-tau181 was negatively correlated with MOCA (<i>r</i> = -0.308, <i>p</i> < 0.001) and MMSE (<i>r</i> = -0.289, <i>p</i> < 0.001), and it was independently associated with cognitive impairment in T2D patients (OR, 1.137 [95% CI, 1.080-1.198]; <i>p</i> < 0.001). Other independent risk factors of diabetic cognitive impairment included age, education level, and diabetic retinopathy. The DCIS was built by nomogram based on the four risk factors, which had an area under the receiver operating characteristic curve (AUC) of 0.795 (95% CI, 0.751-0.840). The optimal cut-off of DCIS for the diagnosis of cognitive impairment in T2D patients was 139.5, with a sensitivity of 72.9% and a specificity of 75.3%. In the validation cohort, the AUC of DCIS for screening diabetic cognitive impairment was 0.770 (95% CI, 0.716-0.824). <b>Conclusions:</b> P-tau181 was independently associated with diabetic cognitive impairment. The DCIS, based on P-tau181, age, education level, and diabetic retinopathy, is effective to identify cognitive impairment in T2D patients.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2025 ","pages":"8029913"},"PeriodicalIF":3.6,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12017955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Simplifying Complex Insulin Regimen on Glycometabolic Parameters and Target Organ Damage in Type 2 Diabetes: A Retrospective Cohort Study.","authors":"Roland Fejes, Csilla Kádár, Róbert Kovács-Huber, Zoltán Taybani, László Juhász, Attila Rutai, Szabolcs Péter Tallósy","doi":"10.1155/jdr/9141564","DOIUrl":"https://doi.org/10.1155/jdr/9141564","url":null,"abstract":"<p><p><b>Background:</b> Fixed-ratio combinations (FRCs) provide an alternative to intensified conservative insulin treatments (ICTs); however, therapy simplification in patients with high total daily insulin dose (TDD) or high HbA_1c is a debated issue; additionally, its influence on target organ damage (TOD) is less known. <b>Methods:</b> Data were retrospectively collected from patients with Type 2 diabetes, including 58 patients who continued ICT and 104 patients who underwent therapy simplification between January 1, 2017, and January 1, 2023. Patient characteristics and therapy details are at baseline and 3, 6, 12, and 24 months after FRC initiation. <b>Results:</b> HbA_1c significantly decreased in both groups (-0.9% [-1.6%, -0.5%] with ICT vs. -1.3% [-2.1%, -0.3%] with FRC), whereas body weight significantly decreased only after simplification (-1 kg [-4, 1] vs. -5 kg [-7, -2]). Diabetes duration was not associated with therapy efficacy. Significant HbA_1c reduction and FRC dose elevation occurred earlier in patients with an initial HbA_1c > 8.0% than in those with an initial HbA_1c < 8.0%. FRC dose was significantly higher at 3 months in patients with a TDD of > 60 U/day than in those with lower TDD. Relative risk reduction with therapy simplification was 72.1%, 50.6%, 32.3%, and 59.7% for hypoglycemia, renal function decline, microalbuminuria, and macrovascular complications, respectively. Risk of retinopathy, neuropathy, and chronic kidney disease did not significantly change with FRCs. <b>Discussion:</b> FRCs are safe and as effective as ICT even in patients with high initial HbA_1c, high TDD, or long diabetes duration. A protective role of FRCs in diabetic ASCVD has been proven, but their protective role in CKD was not observed. <b>Conclusions:</b> The significant improvements in glycemic and weight control, as well as in TODs, suggest that therapy simplification may represent a more favorable approach compared to the continuation of previous ICT even in patients characterized by high baseline TDD and HbA_1c levels.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2025 ","pages":"9141564"},"PeriodicalIF":3.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12014261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimized Effects of Fisetin and Hydroxychloroquine on ER Stress and Autophagy in Nonalcoholic Fatty Pancreas Disease in Mice.","authors":"Mahboobe Sattari, Amin Karimpour, Maryam Akhavan Taheri, Bagher Larijani, Reza Meshkani, Ozra Tabatabaei-Malazy, Ghodratollah Panahi","doi":"10.1155/jdr/2795127","DOIUrl":"https://doi.org/10.1155/jdr/2795127","url":null,"abstract":"<p><p><b>Background:</b> Fat accumulation in the pancreas, known as nonalcoholic fatty pancreatic disease (NAFPD), is associated with obesity and may lead to prediabetes and Type 2 diabetes. Reducing endoplasmic reticulum stress and enhancing autophagy could offer therapeutic benefits. This study examines the effects of fisetin (FSN) and hydroxychloroquine (HCQ) on NAFPD. <b>Method:</b> Forty-eight Male C57BL/6 J mice were assigned to a standard chow diet (SCD) or a high-fat diet (HFD) for 16 weeks. The HFD group was divided into five subgroups; each group contains eight mice: HFD, HFD + V (vehicle), HFD + FSN, HFD + HCQ, and HFD + FSN + HCQ. FSN was given daily at 80 mg/kg, and HCQ was injected IP at 50 mg/kg twice weekly for more 8 weeks. Insulin resistance was assessed through OGTT and HOMA-IR. Histological analysis of pancreatic tissue was conducted, and the protein and mRNA levels of molecules associated with ER stress and autophagy were assessed using PCR and immunoblotting techniques. <b>Result:</b> FSN and HCQ significantly reduced weight gain, pancreatic adipocyte accumulation, and insulin resistance caused by HFD in obese mice, with the combination of the two compounds producing even more pronounced effects. Additionally, the HFD increased the expression of UPR markers ATF4 and CHOP, a response that was further intensified by HCQ. In contrast, FSN attenuated the UPR by regulating GRP78 levels. Furthermore, the HFD resulted in a significant decrease in the LC3II/LC3I ratio and an accumulation of p62 protein due to reduced p-AMPK levels. Following treatment with FSN, these alterations were reversed, leading to decreased mTOR expression and increased levels of autophagy markers such as ATG5 and Beclin1. <b>Conclusion:</b> Our study reveals that FSN and HCQ effectively combat HFD-induced NAFPD, improving insulin sensitivity and addressing pancreatic fat deposition linked to metabolic syndrome. While HCQ may cause endoplasmic reticulum stress, FSN offers protective effects, supporting their combined use for better treatment outcomes.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2025 ","pages":"2795127"},"PeriodicalIF":3.6,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations in Corneal Nerve Structure and Function in Prediabetes.","authors":"Jun Ma, Junfang Zhang, Mengjia Tan, Min Ji, Jianfeng Yu, Huaijin Guan","doi":"10.1155/jdr/4586856","DOIUrl":"https://doi.org/10.1155/jdr/4586856","url":null,"abstract":"<p><p><b>Background:</b> Although prediabetes increases the risk of developing diabetes, its role in neuropathy remains unclear. We aim to assess alterations in the corneal nerve structure and function in prediabetes and risk factors for corneal nerve loss. <b>Methods:</b> An examination of IVCM and corneal sensitivity was conducted on a cohort of 75 participants, comprising 23 controls, 32 prediabetes, and 20 Type 2 diabetes. Semiautomatic analysis was employed to quantify the corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), and dendritic cell (DC) density. <b>Results:</b> CNFL and CNFD were lower in prediabetes and Type 2 diabetes than in the controls, and they were associated with DC density. CNFL and CNFD were lower in Type 2 diabetes than in prediabetes. DC density was higher in prediabetes and Type 2 diabetes than in controls. However, there were no differences in corneal sensitivity between controls and prediabetes. Multivariable regression analysis demonstrated an association between reduced CNFL and age, BMI, fasting plasma glucose (FPG), and uric acid (UA) levels in prediabetes. In Type 2 diabetes, age, HbA1c, blood urea nitrogen (BUN), creatinine (Cr), and triglyceride levels exhibited associations with reduced CNFL. <b>Conclusions:</b> Corneal nerve damage was detected in prediabetes using IVCM. The patients with prediabetes showed signs of nerve structure damage, and the corneal nerve structure damage occurred before the nerve function changes. Immune cells also participate in the occurrence and development of DCN and are related to the corneal neuropathy. Understanding the corneal nerve fiber condition through IVCM may prove crucial in monitoring prediabetic neuropathy.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2025 ","pages":"4586856"},"PeriodicalIF":3.6,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12009175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}