Diabetes & Metabolic Syndrome-Clinical Research & Reviews最新文献

{"title":"A systematic review on the impact of type 2 diabetes on Leydig and Sertoli cells: Molecular mechanisms and functional consequences","authors":"Ali Akbar Oroojan ,&nbsp;Hooman Etedali ,&nbsp;Homa Shirani Lapari","doi":"10.1016/j.dsx.2026.103423","DOIUrl":"10.1016/j.dsx.2026.103423","url":null,"abstract":"<div><h3>Background and aims</h3><div>Type 2 diabetes (T2D) disrupts male reproductive function by impairing Leydig and Sertoli cell activity, leading to hormonal imbalances and defective spermatogenesis. This systematic review explores the molecular mechanisms underlying T2D-induced dysfunction in these testicular cells, emphasizing alterations in steroidogenesis, cell signaling, and metabolic regulation.</div></div><div><h3>Methods</h3><div>A systematic review of peer-reviewed studies was conducted using databases such as PubMed. to identify relevant studies published between January 1, 2010, and December 30, 2024. Studies investigating the effects of type 2 diabetes mellitus on Leydig and Sertoli cells. Key molecular markers, androgen receptors, insulin-like growth factor-binding proteins (Igfbp5), and cell junction proteins (Cx43, TJP1, GJA1), were analyzed. Additionally, pathways such as PI3K/Akt, MEK5-ERK5-MEF2C, and inflammatory markers (PERK, IKKβ) were reviewed to understand their roles in diabetic testicular dysfunction. The risk of bias was assessed using the SYRCLE tool.</div></div><div><h3>Results</h3><div>T2D reduces Leydig cell function by downregulating insulin receptors (IR-β, IR-α) and disrupting steroidogenic pathways, leading to lower testosterone levels. Increased miR-504 and miR-935 expression suppresses the MEK5-ERK5-MEF2C survival pathway, promoting apoptosis in Leydig cells. Sertoli cell dysfunction is characterized by decreased VEGF expression, impaired BTB integrity, and metabolic shifts favoring glycogen accumulation instead of lactate production. Insulin resistance further exacerbates these effects, leading to defective spermatogenesis.</div></div><div><h3>Conclusions</h3><div>Diabetes-induced dysfunction in Leydig and Sertoli cells is a key contributor to male infertility. Targeting VEGF restoration, insulin signaling pathways, and miRNA regulation may offer potential therapeutic strategies. Further studies are needed to develop interventions that preserve testicular function in diabetic individuals.</div></div>","PeriodicalId":48252,"journal":{"name":"Diabetes & Metabolic Syndrome-Clinical Research & Reviews","volume":"20 5","pages":"Article 103423"},"PeriodicalIF":3.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147849051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoplasmic reticulum stress in diabetes mellitus: A comprehensive review of emerging insights and recent progress","authors":"Harsh Kumar ,&nbsp;Reena Kumari ,&nbsp;Vineet Kumar Maurya ,&nbsp;Saroj Kumar Amar ,&nbsp;Prawej Ansari ,&nbsp;Veronique Seidel ,&nbsp;James Harper ,&nbsp;Ashish Kothari ,&nbsp;Anoop Misra ,&nbsp;Sandeep Kumar","doi":"10.1016/j.dsx.2026.103420","DOIUrl":"10.1016/j.dsx.2026.103420","url":null,"abstract":"<div><h3>Background/ aim</h3><div>Endoplasmic reticulum stress (ERS), caused by excessive buildup of misfolded proteins in the ER lumen, has emerged as a major contributor to diabetes mellitus (type-1 and type-2; T1DM and T2DM), leading to β-cell dysfunction, insulin resistance, and related comorbidities. In this review, we aim to characterize the signal transduction pathways in normal versus diseased conditions and their impact on the development of insulin-dependent and insulin-independent diabetes.</div></div><div><h3>Methods</h3><div>Evidence on ERS and diabetes were searched in MEDLINE and Google scholar databases using search strings that incorporated synonyms of ERS, diabetes, β-cell dysfunction and insulin resistance and their impact in disease progression. Our search was guided by the pertinent keywords as mentioned in the “keywords” section, that encompassed past twenty-five years of body of literature in this field as evident from <em>Urano</em> et al. <em>2000</em> till <em>Sue</em> et al. <em>2025</em>.</div></div><div><h3>Results/ conclusion</h3><div>Our results and conclusion are the distillation of past two and half decades of scientific research dedicated towards understanding the biology of ERS dependent diabetes. The ERS-induced Unfolded Protein Response (UPR), comprising of three signaling cascades, is pivotal in either protecting against or contributing to the pathophysiology of T1DM and T2DM. Clinically, ERS manifests as insulin resistance, heightened inflammation, and β-cell destruction. Consequently, ERS effectors and proteins involved in the UPR pathways have become attractive targets for pharmacological investigation. We also review some of the protein biomarkers of ERS dependent diabetes and relevant <em>in vivo/ex vivo</em> models used in clinical versus preclinical settings, as well as the latest state-of-the-art targeted molecular and cellular therapies that are currently being tried for the diabetic patients.</div></div>","PeriodicalId":48252,"journal":{"name":"Diabetes & Metabolic Syndrome-Clinical Research & Reviews","volume":"20 5","pages":"Article 103420"},"PeriodicalIF":3.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147807517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Letter to the Editor regarding “Prediction of retinopathy risk: A prospective cohort study in China”","authors":"Xiaohan Xu ,&nbsp;Duolao Wang ,&nbsp;Uazman Alam ,&nbsp;Shanhu Qiu ,&nbsp;Yuzhi Ding ,&nbsp;Zilin Sun ,&nbsp;Anupam Garrib","doi":"10.1016/j.dsx.2026.103414","DOIUrl":"10.1016/j.dsx.2026.103414","url":null,"abstract":"","PeriodicalId":48252,"journal":{"name":"Diabetes & Metabolic Syndrome-Clinical Research & Reviews","volume":"20 4","pages":"Article 103414"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147660309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of the American diabetes association risk test, BMI, and estimated cardiorespiratory fitness with incident prediabetes and type 2 diabetes: A cohort study","authors":"Robert A. Sloan ,&nbsp;Jaca Maison Lailo ,&nbsp;Sang-Ah Lee ,&nbsp;Jiae Shin ,&nbsp;Soyoung Yu ,&nbsp;Marco Visentini-Scarzanella ,&nbsp;Duck-Chul Lee ,&nbsp;Xuemei Sui","doi":"10.1016/j.dsx.2026.103421","DOIUrl":"10.1016/j.dsx.2026.103421","url":null,"abstract":"<div><h3>Aim(s)</h3><div>To compare associations of nonexercise estimated cardiorespiratory fitness (eCRF), the American Diabetes Association Risk Test (ADART), and body mass index (BMI) with incident prediabetes and type 2 diabetes in adults with normoglycemia.</div></div><div><h3>Methods</h3><div>Participants were 10,715 healthy men and women aged 20–81 years from the Aerobics Center Longitudinal Study. eCRF was calculated in metabolic equivalents using sex-specific equations including age, BMI, resting heart rate, blood pressure, and smoking status. Incident prediabetes and type 2 diabetes were identified by fasting glucose or diagnosis. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for risk factors.</div></div><div><h3>Results</h3><div>Over a median follow-up of 5.1 years for prediabetes and 6.7 years for type 2 diabetes, 3912 and 320 cases occurred, respectively. Compared with unfit participants, fit individuals had a lower risk of prediabetes (HR: 0.83; 95% CI: 0.77–0.90) and type 2 diabetes (HR: 0.72; 95% CI: 0.55–0.95). Associations were significant in men for both outcomes and in women for prediabetes only. ADART and BMI predicted prediabetes but not type 2 diabetes after adjustment.</div></div><div><h3>Conclusions</h3><div>eCRF demonstrated reliability as a noninvasive risk assessment tool for determining prediabetes and type 2 diabetes risk, particularly in men, highlighting its potential value for early risk assessment in lower-risk populations. All tools effectively assessed prediabetes risk.</div></div>","PeriodicalId":48252,"journal":{"name":"Diabetes & Metabolic Syndrome-Clinical Research & Reviews","volume":"20 4","pages":"Article 103421"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147795114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the editor: “Prediction of retinopathy risk: A prospective cohort study in China”","authors":"Rachana Mehta ,&nbsp;Ranjana Sah","doi":"10.1016/j.dsx.2026.103415","DOIUrl":"10.1016/j.dsx.2026.103415","url":null,"abstract":"","PeriodicalId":48252,"journal":{"name":"Diabetes & Metabolic Syndrome-Clinical Research & Reviews","volume":"20 4","pages":"Article 103415"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147635614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the editor-The predictive value of estimated glucose disposal rate for all-cause and cardiovascular mortality in the US non-diabetic population aged ≥60 years: A population-based cohort study","authors":"Longqian Li ,&nbsp;ZhuoLin Qin ,&nbsp;Cheng Wang","doi":"10.1016/j.dsx.2026.103419","DOIUrl":"10.1016/j.dsx.2026.103419","url":null,"abstract":"","PeriodicalId":48252,"journal":{"name":"Diabetes & Metabolic Syndrome-Clinical Research & Reviews","volume":"20 4","pages":"Article 103419"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147795096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thyroid function influences insulin requirements in patients with type 1 diabetes mellitus and chronic autoimmune thyroiditis: A cross-sectional study","authors":"Rossella Cannarella ,&nbsp;Marta Marino ,&nbsp;Rosita A. Condorelli ,&nbsp;Aversa Antonio ,&nbsp;Aldo E. Calogero ,&nbsp;Sandro La Vignera","doi":"10.1016/j.dsx.2026.103416","DOIUrl":"10.1016/j.dsx.2026.103416","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the association between serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels and basal and bolus fast-acting insulin doses in patients with type 1 diabetes mellitus (T1DM) and chronic autoimmune thyroiditis (CAT).</div></div><div><h3>Patients and methods</h3><div>This retrospective study included 30 patients with T1DM, CAT, and hypothyroidism treated with levothyroxine (LT4), using the Omnipod DASH insulin pump system and flash glucose monitoring (FGM) (FreeStyle Libre 2). Insulin delivery parameters were analyzed in relation to thyroid function.</div></div><div><h3>Results</h3><div>Basal and bolus insulin doses were positively correlated with TSH (r = 0.77, p &lt; 0.001 and r = 0.74 p &lt; 0.001, respectively) and negatively correlated with FT4 (r = −0.75, p &lt; 0.001 and r = −0.82, p &lt; 0.001) and FT3 (r = −0.71, p &lt; 0.001 and r = −0.82, p &lt; 0.001), independently of HbA1c, T1DM duration, and body mass index. Patients with higher TSH and lower FT4 and/or FT3 levels required higher insulin doses.</div></div><div><h3>Conclusion</h3><div>Reduced thyroid function in patients with T1DM and CAT is associated with increased insulin requirements, underscoring the importance of considering thyroid status in individualized insulin therapy. However, these findings should be interpreted with caution given the cross-sectional design and limited sample size, and should be regarded as hypothesis-generating.</div></div>","PeriodicalId":48252,"journal":{"name":"Diabetes & Metabolic Syndrome-Clinical Research & Reviews","volume":"20 4","pages":"Article 103416"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147660226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of baseline prediabetes on the relation between lipoprotein (a) and incident type 2 diabetes mellitus and cardiovascular outcomes: observations from the UK-Biobank","authors":"Sudipta Chattopadhyay ,&nbsp;Jason Sangha ,&nbsp;Thozhukat Sathyapalan","doi":"10.1016/j.dsx.2026.103422","DOIUrl":"10.1016/j.dsx.2026.103422","url":null,"abstract":"<div><h3>Aims</h3><div>To explore the effect of prevalent prediabetes (preDM) on relation between lipoprotein (a) Lp(a) and incident diabetes mellitus (T2DM) and cardiovascular outcomes.</div></div><div><h3>Method</h3><div>Subjects without diabetes with available Lp(a) in UK-Biobank database, were divided into Group 1 (HbA1c &lt;5.7%, (39 mmol/mol)), Group 2 (HbA1c 5.7-&lt;6.0% (39-&lt;42 mmol/mol)) and Group 3 (HbA1c ≥ 6.0% (42 mmol/mol)). Incident T2DM and major adverse cardiovascular event (MACE) (death, non-fatal myocardial infarction, ischaemic stroke, or coronary revascularisation) during follow up was identified. The unadjusted and adjusted risk of T2DM and MACE between Lp(a) quartiles was estimated in the 3 groups.</div></div><div><h3>Results</h3><div>11.9 years follow up; 3.3% subjects developed T2DM. Lp(a) Q2-4 had 7-11% lower risk of T2DM compared to Q1. Adjusted risk of T2DM was lower in Q3 (HR 0.88, 0.80-0.98, p = 0.017) and Q4 (HR 0.82, 0.74-0.91, p &lt; 0.001) only in Group 3. MACE was higher in Q3 and Q4 in whole cohort and Group 1(Q3: HR 1.04, 1.01-1.08, p = 0.025; Q4: HR 1.16, 1.11-1.20, p &lt; 0.0001) but only in Q4 (HR 1.14, 1.07-1.23, p = 0.0002) in Group 2. MACE was similar between quartiles in Group 3.</div></div><div><h3>Conclusion</h3><div>Lp(a) is inversely related to T2DM risk only in subjects with severe prediabetes. Direct association between Lp(a) and cardiovascular outcomes is seen only in subjects without prediabetes.</div></div>","PeriodicalId":48252,"journal":{"name":"Diabetes & Metabolic Syndrome-Clinical Research & Reviews","volume":"20 4","pages":"Article 103422"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147795136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of retinal biomarkers in diabetes detection and risk prediction: A systematic scoping review","authors":"Soujanya Kaup ,&nbsp;Sowrabha Bhat ,&nbsp;Erin E. Reardon ,&nbsp;Vijayaraghavan Prathiba ,&nbsp;Ramachandran Rajalakshmi ,&nbsp;Rodrigo M. Carrillo-Larco ,&nbsp;Ram Jagannathan ,&nbsp;Ranjit Mohan Anjana ,&nbsp;Mohammed K. Ali ,&nbsp;Viswanathan Mohan ,&nbsp;Sudeshna Sil Kar ,&nbsp;Anant Madabhushi ,&nbsp;Mary Beth Weber ,&nbsp;K.M. Venkat Narayan","doi":"10.1016/j.dsx.2026.103405","DOIUrl":"10.1016/j.dsx.2026.103405","url":null,"abstract":"<div><h3>Aims</h3><div>This systematic scoping review was conducted to map and synthesize literature on retinal biomarkers associated with type 2 diabetes (T2D), including conventional and Artificial Intelligence(AI)-derived features, while considering ethnic/geographic diversity.</div></div><div><h3>Methods</h3><div>Following PRISMA-ScR statement, seven databases were searched up to January 28, 2026 for cross-sectional and longitudinal studies in adults (≥18 years) with or without T2D. Included studies required a normoglycemic comparator and quantitative retinal assessment, with or without AI. Two reviewers independently performed title/abstract screening, full-text review and quality appraisal (using Newcastle Ottawa scale(NOS)/modified NOS); disagreements were resolved by a third reviewer. Data extraction focused on biomarker type, methodology, and population characteristics.</div></div><div><h3>Result</h3><div>Thirty-four studies (27 cross-sectional; 7 longitudinal) were included, mostly evaluating Caucasian/White [n = 18], Asian [n = 15] and Mixed/Latin American [n = 1] populations. Consistent vascular diabetes biomarkers included wider arteriolar and venular calibers. Arteriolar narrowing predicted incident diabetes in longitudinal analyses. Increased vessel tortuosity and altered fractal dimension were frequently observed. Ethnic variation was more pronounced in longitudinal studies; AI-based research was largely confined to China.</div></div><div><h3>Conclusions</h3><div>Retinal biomarkers show promise for early diabetes detection, but research remains geographically skewed and requires multiethnic validation to ensure clinical impact. These findings provide the biological ground truth necessary for handcrafted feature extraction in the development of interpretative artificial intelligence.</div></div>","PeriodicalId":48252,"journal":{"name":"Diabetes & Metabolic Syndrome-Clinical Research & Reviews","volume":"20 4","pages":"Article 103405"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147588073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on “Effects of GLP-1 agonists on 10-year cardiovascular risk reduction in primary prevention: A 44-week open label prospective study”","authors":"S. Dhanya Dedeepya ,&nbsp;Vaishali Goel ,&nbsp;Nivedita Nikhil Desai","doi":"10.1016/j.dsx.2026.103418","DOIUrl":"10.1016/j.dsx.2026.103418","url":null,"abstract":"","PeriodicalId":48252,"journal":{"name":"Diabetes & Metabolic Syndrome-Clinical Research & Reviews","volume":"20 4","pages":"Article 103418"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147660227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}