Nisha Krishnan, Nancy A. Crimmins, Debi Swertfeger, Lisa Schaaf, Amy S. Shah
{"title":"Early Versus Late Diagnosis of Youth-Onset Type 2 Diabetes","authors":"Nisha Krishnan, Nancy A. Crimmins, Debi Swertfeger, Lisa Schaaf, Amy S. Shah","doi":"10.1002/edm2.70116","DOIUrl":"10.1002/edm2.70116","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To determine if earlier age of diabetes onset (< 15 years of age) is associated with a worse metabolic phenotype compared to diabetes diagnosed at a later age (≥ 15 years of age).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Retrospective cross-sectional study of our clinical cohort was performed at a tertiary clinic between 2018 and 2023. Diabetes presentation (diabetic ketoacidosis, C-peptide levels, ketonuria), metabolic phenotype (body mass index (BMI) <i>z</i>-score, hypertension, dyslipidemia, elevated liver enzymes, and haemoglobin A1c) were compared between youth diagnosed with type 2 diabetes who were < 15 years of age and those ≥ 15 years of age. A <i>p</i> value of < 0.05 was considered significant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We studied <i>n</i> = 336 youth. Mean age was 14.5 years at type 2 diabetes diagnosis, <i>n</i> = 198 were < 15 years and <i>n</i> = 138 were ≥ 15 years old. Youth diagnosed at < 15 years versus ≥ 15 years old had a lower systolic and diastolic blood pressure (121.0 ± 12.0 vs. 125.0 ± 12.3 mmHg, <i>p</i> = 0.004 and 72.0 ± 9.8 vs. 74.9 ± 11.1 mmHg, <i>p</i> = 0.013 respectively), and higher HDL cholesterol (38.3 ± 11.7 vs. 35.7 ± 8.7 mg/dL, <i>p</i> = 0.049). There were no differences in the frequency of diabetic ketoacidosis, urine ketones at presentation, C-peptide concentrations, haemoglobin A1c, liver enzymes, total or LDL cholesterol, or BMI <i>z</i>-scores by age group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>A worse metabolic profile was not observed in youth diagnosed at a younger age. In fact, youth who were at an older age at diabetes diagnosis tended to have higher blood pressure and lower HDL-C. Establishing the risk factors for why some youth develop type 2 diabetes at earlier ages is needed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"8 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shima Tavalaie, Saeed Darroudi, Niloofar Shabani, Artemis AzadAra, Ali Mottaghi-Moghaddam, Mohammad Kalate Rahmani, Maryam Mohammadi-Bajgiran, Gordon A. Ferns, Maryam Saberi-Karimian, Majid Ghayour-Mobarhan
{"title":"Association Between Serum Syndecan 1 Levels and Metabolic Syndrome Parameters: A Comparative Cross-Sectional Study","authors":"Shima Tavalaie, Saeed Darroudi, Niloofar Shabani, Artemis AzadAra, Ali Mottaghi-Moghaddam, Mohammad Kalate Rahmani, Maryam Mohammadi-Bajgiran, Gordon A. Ferns, Maryam Saberi-Karimian, Majid Ghayour-Mobarhan","doi":"10.1002/edm2.70108","DOIUrl":"https://doi.org/10.1002/edm2.70108","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Previous studies have linked Syndecans (SDCs) to hypertension (HTN), BMI and the prevalence of coronary artery disease (CAD). The relationship between SDCs and metabolic syndrome (MetS) has not been explored. This study aimed to investigate the association between serum SDC1 level and MetS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a comparative cross-sectional study conducted on the subjects from phase II of the MASHAD study. A total of 81 subjects were divided into three groups: (1) healthy controls (<i>N</i> = 26), (2) subjects with MetS and hypertension with serum ALT < 43 U/L (MetS+ HTN+ ALT–), (<i>N</i> = 29), and (3) subjects with MetS and hypertension with serum ALT ≥ 43 U/L (MetS+ HTN+ ALT+), (<i>N</i> = 26). Serum SDC1 levels were measured using a commercial ELISA kit. Data were analysed using SPSS version 26 and R version 4.0.5 software.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The analysis showed that mean serum SDC1 levels did not significantly differ between healthy and MetS+ groups overall. Among MetS+ subjects, males had significantly higher SDC1 levels than females (17.57 ± 8.48 vs. 12.85 ± 5.59 ng/mL, <i>p</i> = 0.018). In the MetS+ HTN+ ALT+ group, males also had higher SDC1 levels compared to females (20.19 ± 10.56 vs. 11.82 ± 5.09 ng/mL, <i>p</i> = 0.020), while no significant differences were observed across the MetS groups overall (<i>p</i> = 0.474). Additionally, in both the total study sample and the MetS+ HTN+ ALT+ group, SDC1 levels were positively correlated with diastolic blood pressure (DBP) (<i>r</i> = 0.256, <i>p</i> = 0.021; <i>r</i> = 0.463, <i>p</i> = 0.017, respectively), with no significant associations found with other metabolic parameters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings suggest that SDC1 levels are higher in males with MetS, particularly those with hypertension and elevated ALT, and are positively associated with DBP in both the total study sample and the MetS+ HTN+ ALT+ group. There were no significant associations with other metabolic parameters. This indicates that SDC1 may serve as a gender-specific biomarker for vascular risk in MetS, potentially aiding clinicians in identifying high-risk MetS subjects.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"8 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Concha F. García-Prieto, Fernando Gómez-Peralta, Rocío Villar-Taibo, Sergio Cinza-Sanjurjo, Jennifer Redondo-Antón, Silvia Díaz-Cerezo, Miriam Rubio-de Santos
{"title":"Insights Into the Management of Type 2 Diabetes at Diagnosis in Spain: The NEW2TYPE2 Study","authors":"Concha F. García-Prieto, Fernando Gómez-Peralta, Rocío Villar-Taibo, Sergio Cinza-Sanjurjo, Jennifer Redondo-Antón, Silvia Díaz-Cerezo, Miriam Rubio-de Santos","doi":"10.1002/edm2.70095","DOIUrl":"https://doi.org/10.1002/edm2.70095","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>This study analysed the opinions and perceptions of Spanish physicians towards the management of people newly diagnosed with type 2 diabetes (T2D) aged ≤ 65 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Online survey targeting primary care physicians (PCPs) and endocrinologists (members of three national scientific societies) treating people with T2D. Management practices and factors determining prescribed therapies and treatment goals were captured in general and by patient profile. The respondents' perception of the limitations in setting strict glycaemic control objectives and weight loss targets, and the feasibility and impact of possible solutions, were examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 105 physicians (60% PCPs, 40% endocrinologists) responded to the survey; 98% of respondents reported following clinical practice guidelines; 53.3% and 27.6% considered stringent glycaemic control to be HbA1c levels of 6.0%–6.5% and 6.5%–7.0%, respectively. In patient profiles with overweight/obesity, > 90% reported setting weight loss goals, with 5%–10% weight loss being the most common target. The most limiting factors for the establishment of stringent glycaemic and weight loss targets were the lack of awareness of self-care of the disease (74.3%) and the cost to the healthcare system of the most effective drugs (72.4%). Training and the implementation of simple protocols and algorithms were the solutions perceived as having the greatest impact and feasibility. Redefining visa criteria was considered the solution with the highest impact.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The results are consistent with clinical practice guidelines' recommendations in Spain, but early and intensive interventions focused on reducing the risk of long-term complications in people with T2D who have longer life expectancy could be promoted at diagnosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"8 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145146655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Muhammad Saad, Dua Ali, Taimor Mohammed Khan, Ruqiat Masooma Batool, Muhammad Sameer Arshad, Peter Collins, Raheel Ahmed
{"title":"Trends and Disparities in Cancer-Related Mortality Among Adults With Diabetes in the United States: 1999–2019","authors":"Muhammad Saad, Dua Ali, Taimor Mohammed Khan, Ruqiat Masooma Batool, Muhammad Sameer Arshad, Peter Collins, Raheel Ahmed","doi":"10.1002/edm2.70092","DOIUrl":"https://doi.org/10.1002/edm2.70092","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Cancer and diabetes are major public health concerns, with diabetes linked to increased cancer-related mortality. However, national trends and disparities remain underexplored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using CDC WONDER data, we analysed deaths where both diabetes and cancer were listed as causes. Age-adjusted mortality rates (AAMRs) were calculated for diabetic cancer patients aged ≥ 25 years and stratified by demographics and geography. Joinpoint regression estimated annual percent changes (APCs) and average annual percent changes (AAPCs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>From 1999 to 2019, 699,007 cancer-related deaths occurred among individuals with diabetes. The overall AAMR increased from 15.06 to 15.23 per 100,000 (AAPC: +0.07%; <i>p</i> = 0.20), with a rise from 1999 to 2003, a decline from 2003 to 2015, and a resurgence from 2015 to 2019. Men (AAMR: 20.83) had higher mortality than women (AAMR: 11.80). Non-Hispanic Black individuals had the highest AAMRs (23.72), but NH American Indian/Alaska Natives had the largest increase (AAPC: 0.60). The Midwest (AAMR: 17.03) and rural areas (AAMR: 18.70) had the highest mortality, with rural rates rising significantly (AAPC: 0.92). Gastrointestinal cancers were the leading cause (AAMR: 4.31), followed by haematological (AAMR: 1.80), prostate (AAMR: 1.59), and breast cancer (AAMR: 1.38).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Cancer-related mortality in individuals with diabetes has increased, with notable disparities. Targeted interventions, screening, and better diabetes management are essential to reducing risks in high-risk populations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"8 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145146654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluating the Rates of Pancreatitis and Pancreatic Cancer Among GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis of Randomised Controlled Trials","authors":"Jimmy Wen, Denise Nadora, Ethan Bernstein, Christiane How-Volkman, Alina Truong, Bethany Joy, Megan Kou, Zohaer Muttalib, Arsh Alam, Eldo Frezza","doi":"10.1002/edm2.70113","DOIUrl":"10.1002/edm2.70113","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This meta-analysis evaluates the rates of pancreatitis/pancreatic cancer among glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in randomised controlled trials (RCTs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a systematic search was performed in PubMed, Embase, and Cochrane Library for GLP-1 RA RCTs that evaluated pancreatitis/pancreatic cancer. A meta-analysis was conducted to evaluate this risk; subgroup analysis was performed with and without background medications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>62 studies utilising dulaglutide, exenatide, liraglutide, semaglutide, beinaglutide, retatrutide, or tirzepatide, with 66,232 patients, mean age of 58.3 years (14.4 to 68), and mean follow-up of 43.5 weeks (1 to 198) were included in this study. Meta-analysis showed a significantly increased risk of pancreatitis (RR: 1.44, 95% CI 1.09–1.89, <i>p</i> = 0.009), but not when stratified by background medications (RR: 1.28, 95% CI 0.87–1.87) and without background medications (RR: 1.37, 95% CI 0.91–2.05). Pancreatic cancer and GLP-1 RA use showed no significant association (RR: 1.30, 95% CI 0.86–1.97). However, a significant increase was found with background medications (RR: 1.85, 95% CI 1.05–3.26, <i>p</i> = 0.03), but not without (RR: 0.81, 95% CI 0.43–1.55).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>GLP-1 RAs carry a slightly increased risk of pancreatitis, which is not significant when stratified by background medication use. Overall risk for pancreatic cancer was not observed, but a slight association was found when stratified with background medications. However, this difference is likely minimal, given the numerous studies excluded from the meta-analysis where both treatment arms had zero events.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"8 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Roshvin Kailashnath Pillai, Rishvini Kailashnath Pillai, Vinibha Rajakumari Illankovan, Vinod Balasubramaniam, A. M. Alabsi, Anupam Biswas, Hari Kumar Darnal, Saminathan Kayarohanam, Madhan Kumar Soutallu Janakiram, Vetriselvan Subramaniyan
{"title":"Unveiling Molecular Mechanisms Underlying Obesity-Associated Systemic Lupus Erythematosus","authors":"Roshvin Kailashnath Pillai, Rishvini Kailashnath Pillai, Vinibha Rajakumari Illankovan, Vinod Balasubramaniam, A. M. Alabsi, Anupam Biswas, Hari Kumar Darnal, Saminathan Kayarohanam, Madhan Kumar Soutallu Janakiram, Vetriselvan Subramaniyan","doi":"10.1002/edm2.70077","DOIUrl":"https://doi.org/10.1002/edm2.70077","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Systemic lupus erythematosus (SLE) is a chronic autoimmune disease primarily affecting women of childbearing age, characterised by relapsing inflammation across multiple organ systems. Its aetiology involves genetic and environmental factors that trigger immune dysregulation, leading to the excessive release of autoantibodies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study discusses the pathogenesis, diagnosis, management and emerging therapeutic targets in SLE, with a focus on metabolic reprogramming and the role of obesity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Diagnosis is based on clinical and laboratory findings, with the EULAR and ACR criteria being the most advanced. SLE management requires individualised treatment, addressing the severity and organs affected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SLE presents with symptoms ranging from mild skin rashes to severe conditions like pulmonary hypertension and kidney failure. Advances in care have improved outcomes, with 80%–90% of patients achieving normal life expectancy with proper treatment. Metabolic reprogramming in immune cells is crucial to SLE pathogenesis, as altered glycolysis and fatty acid oxidation contribute to inflammation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Obesity is recognised to aggravate SLE by fostering chronic inflammation, immunological dysregulation and dysbiosis of the gut microbiota. These situations may exacerbate autoimmunity, especially in genetically predisposed individuals. It is suggested that obesity significantly contributes to the pathogenesis of SLE, and additional study should investigate metabolic therapy aimed at obesity and microbiota to re-establish immunological equilibrium and mitigate disease development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Targeting metabolic pathways may offer new therapeutic options for improved disease management. Particular abnormalities in gut microbiota, characterised by reduced diversity and an increase in pro-inflammatory species, influence obesity-related immunological dysregulation in systemic lupus erythematosus and may present new therapeutic targets.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"8 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70077","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Livio Tarchi, Lorenzo Bonacchi, Andrea Di Santo, Paolo Rovero, Chiara Sassoli, Rachele Garella, Roberta Squecco, Gianluca Villa, Romina Nassini, Francesco De Logu, Valdo Ricca, Giovanni Castellini
{"title":"CAMKK1 in Obesity and Type 2 Diabetes Mellitus: Evidence of Interaction With Appetite-Regulating, Metabolic and Inflammatory Factors","authors":"Livio Tarchi, Lorenzo Bonacchi, Andrea Di Santo, Paolo Rovero, Chiara Sassoli, Rachele Garella, Roberta Squecco, Gianluca Villa, Romina Nassini, Francesco De Logu, Valdo Ricca, Giovanni Castellini","doi":"10.1002/edm2.70109","DOIUrl":"10.1002/edm2.70109","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Calcium/calmodulin-dependent protein kinase kinase 1 (CAMKK1) regulates energy homeostasis through AMP-activated protein kinase (AMPK). CAMKK1 has been implicated in appetite and satiety regulation; however, its role in obesity or type 2 diabetes mellitus (T2DM) remains unexplored. In this cross-sectional study, the primary aim was to confirm whether CAMKK1 is elevated in individuals with diabetes. The secondary aim was to investigate CAMKK1's molecular correlates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>CAMKK1 serum levels in individuals with obesity (<i>n</i> = 3,061), patients with T2DM (<i>n</i> = 4,910) and controls (<i>n</i> = 44,257) were retrieved and compared (age, body mass index—BMI and sex-adjusted ANCOVA). Pearson correlation coefficients and linear regression coefficients (age and BMI-adjusted) were computed. The moderation effect of diagnostic groups was also assessed. The interaction between factors was explored by mixed graphical models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CAMKK1 was elevated in patients with T2DM, in comparison to both individuals with obesity and controls (post hoc comparison, Tukey-adjusted <i>p</i> = 0.010 and <i>p</i> = 0.044, respectively). Across diagnostic groups, positive associations were observed between CAMKK1 and AMPK (min <i>β</i> > 0.400, max <i>p</i> < 0.001) or TNFα (min <i>> β</i> 0.070, max <i>p</i> < 0.001). A positive association with leptin (<i>β</i> = 0.010, <i>p =</i> 0.002) and ghrelin (<i>β =</i> 0.005, <i>p =</i> 0.048) was observed only within controls. Multivariate multivariable models confirmed that specific interactions between factors were disrupted in patients with T2DM (<i>p</i> < 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings provide new insights into the role of CAMKK1 in obesity and T2DM. Future research may further explore CAMKK1's interplay with inflammatory pathways.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"8 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pooya Eini, Peyman Eini, Homa Serpoush, Mohammad Rezayee
{"title":"Diagnostic Performance of Machine Learning Algorithms for Predicting Heart Failure in Diabetic Patients: A Systematic Review and Meta-Analysis","authors":"Pooya Eini, Peyman Eini, Homa Serpoush, Mohammad Rezayee","doi":"10.1002/edm2.70111","DOIUrl":"10.1002/edm2.70111","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Heart failure is a significant complication in diabetic patients, and machine learning algorithms offer potential for early prediction. This systematic review and meta-analysis evaluated the diagnostic performance of ML models in predicting HF among diabetic patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We searched PubMed, Web of Science, Embase, ProQuest, and Scopus, identifying 2830 articles. After deduplication and screening, 16 studies were included, with 7 providing data for meta-analysis. Study quality was assessed using PROBAST+AI. A bivariate random-effects model (Stata, midas, metadta) pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratio (DOR) for best-performing algorithms, with subgroup analyses. Heterogeneity (<i>I</i><sup>2</sup>) and publication bias were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This meta-analysis of seven studies evaluating machine learning models for heart failure detection demonstrated a pooled sensitivity of 84% (95% CI: 0.75–0.90), specificity of 86% (95% CI: 0.56–0.97), and an area under the ROC curve of 0.90 (95% CI: 0.87–0.93). The pooled positive likelihood ratio was 6.6 (95% CI: 1.2–35.9), and the negative likelihood ratio was 0.17 (95% CI: 0.08–0.36), with a diagnostic odds ratio of 39 (95% CI: 4–423). Significant heterogeneity was observed, primarily related to differences in study populations, machine learning algorithms, dataset sizes, and validation methods. No significant publication bias was detected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Machine learning models demonstrate promising diagnostic accuracy for heart failure detection and have the potential to support early diagnosis and risk assessment in clinical practice. However, considerable heterogeneity across studies and limited external validation highlight the need for standardised development, prospective validation, and improved interpretability of ML models to ensure their effective integration into healthcare systems.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"8 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Revisiting the Obesity–Anaemia Paradox: Inflammation and Iron Homeostasis in the BMI–Haemoglobin Relationship","authors":"Ali Hemade, Pascale Salameh","doi":"10.1002/edm2.70110","DOIUrl":"10.1002/edm2.70110","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Obesity and anaemia are global epidemics with complex, overlapping pathophysiology. While excess adiposity is known to induce chronic inflammation that disrupts iron homeostasis, multiple population studies paradoxically report higher haemoglobin levels and lower anaemia prevalence among obese individuals. The nonlinear and potentially suppressive role of inflammation in this relationship remains understudied.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed adults aged 18–64 from the 2015–2023 National Health and Nutrition Examination Survey (NHANES). Haemoglobin was modelled as a function of body-mass index (BMI) using survey-weighted linear regression with restricted cubic splines. Interactions with log-transformed CRP were assessed, and ferritin was corrected for inflammation using BRINDA regression-residual methods. Causal mediation analysis decomposed the total effect of BMI on haemoglobin into indirect (mediated by CRP) and direct effects. Secondary models examined anaemia (Hb < 13.0 g/dL in men, < 12.0 g/dL in women) using logistic regression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Haemoglobin increased steeply across lower BMI ranges but plateaued above 30 kg/m<sup>2</sup> (p-nonlinearity < 0.001). The haemoglobin–BMI curve flattened significantly at higher CRP levels, with strong evidence of interaction (p-interaction < 0.001). Mediation analysis showed that CRP significantly suppressed the BMI–haemoglobin relationship (ACME = −0.044 g/dL, <i>p</i> < 0.001; ADE = 0.216 g/dL, <i>p</i> < 0.001). In contrast, BRINDA-adjusted ferritin mediated < 2% of the association. Logistic models showed that anaemia risk declined sharply with increasing BMI but rose consistently with CRP. Anaemia mediation analysis revealed suppression as well (ACME > 0; ADE < 0), precluding interpretation of proportion mediated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>BMI is positively associated with haemoglobin in a non-linear, CRP-dependent fashion. Inflammation significantly suppresses the haematologic benefit of excess adiposity, while inflammation-adjusted ferritin plays a minimal mediating role. These findings underscore the importance of modelling non-linearity and correcting iron biomarkers for inflammation when studying obesity-related anaemia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"8 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Plasma Fatty Acid Profiles Modulate PPARγ Expression in Adipose Tissue: A Lipidomic Insight Into Obesity-Related Metabolic Dysregulation","authors":"Maryam Sanoie, Farshad Teymoori, Raziyeh Abooshahab, Mahdi Akbarzadeh, Golaleh Asghari, Emad Yuzbashian, Mehdi Hedayati, Alireza Khalaj, Maryam Zarkesh","doi":"10.1002/edm2.70080","DOIUrl":"10.1002/edm2.70080","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This study aimed to investigate the relationship between plasma fatty acids (FAs), FA-derived factors and PPARγ expression in visceral and subcutaneous adipose tissues (VAT and SAT) of obese and nonobese adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cross-sectional study involved 167 adults aged 19 to 65. Samples of VAT and SAT were obtained during elective abdominal surgeries. Participants were divided into two groups: nonobese (BMI < 30 kg/m<sup>2</sup>) and obese (BMI ≥ 30 kg/m<sup>2</sup>). Anthropometric and biochemical measurements were taken, and plasma fatty acids (FAs) were analysed using gas chromatography flame ionisation detection (GC/FID). PPARγ mRNA levels were measured through real-time RT-qPCR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Obese individuals had higher PPARγ gene expression in both VAT and SAT compared to nonobese participants (<i>p</i> < 0.001). Eighteen FFAs and three new FA-derived factors were identified in both groups, accounting for 69% of the variance in nonobese individuals and 71% in obese individuals. After adjusting for confounding factors, saturated FA (SFA) was associated with PPARγ expression in the SAT of the nonobese group (<i>β</i> = −0.12, <i>p</i> = 0.019). Additionally, total FAs (<i>β</i> = −0.02, <i>p</i> = 0.017), SFA (<i>β</i> = −0.06, <i>p</i> = 0.048), monounsaturated FA (MUFA) (<i>β</i> = −0.08, <i>p</i> = 0.020), polyunsaturated FA (PUFA) (<i>β</i> = −0.03, <i>p</i> = 0.039) and omega-6 FA (<i>β</i> = −0.03, <i>p</i> = 0.040) were associated with VAT PPARγ expression among obese individuals. Conversely, an inverse correlation was observed between factor I of FAs and SAT PPARγ expression in nonobese individuals (<i>β</i> = −0.15; <i>p</i> = 0.027).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that alterations in plasma FA profiles are associated with PPARγ gene expression, particularly in obese individuals. This fact highlights the potential role of dietary FAs in metabolic regulation and health issues related to obesity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"8 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}