Diabetes, Obesity & Metabolism最新文献

{"title":"Diabetic Charcot neuroarthropathy: A threat to both limb and life.","authors":"David S H Bell, Terri Jerkins","doi":"10.1111/dom.15994","DOIUrl":"https://doi.org/10.1111/dom.15994","url":null,"abstract":"<p><p>Diabetic Charcot neuroarthropathy (DCN), first described in 1936, occurs in less than 1% of diabetic patients, but in those diabetic subjects with distal symmetrical polyneuropathy, the overall incidence increases to 30% and the risk is even greater in those with type 1 diabetes. Factors that precipitate DCN are trauma, ischaemia due to arterio-venous shunting, increased osteoclastic activity and inflammation. DCN usually presents with a painless swollen foot and/or ankle which is 'hot to the touch'. These clinical findings are soon followed by characteristic magnetic resonance imaging (MRI) abnormalities and later X-ray changes. The joints that are most typically involved in chronological order are the tarsometatarsals followed by the naviculocuniform, sub-tarsal, talonavicular and metatarsal and tarsophalangeal. The cornerstone of therapy is prolonged (3-12 months) offloading with immobilization. Bisphosphonates may possibly accelerate recovery, whereas other unproven possible therapies include rhPTH, 1-34, calcitonin and methylprednisolone, which are not only ineffective but in some cases may also prolong the time to healing. Denosumab is potentially an efficacious, if unproven, therapy to accelerate healing. The risk of amputation is high and increases in the presence of a foot ulcer. DCN is associated with manifestations of autonomic neuropathy, including cardiac denervation, so that the risks of a cardiac event and heart failure are increased with DCN. Mortality is also increased with DCN, especially in the presence of a foot ulcer. To avoid the recurrence of DCN and especially to lower the risk of the recurrence of a foot ulcer recurrence reconstructive, surgery may be needed.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-effectiveness of finerenone added to standard of care for patients with type 2 diabetes-related chronic kidney disease in the United States.","authors":"Cailin Zheng, Jinneng Wu, Na Li, Xiaoxia Wei, Zhixiong Huang, Lingbin Chen, Zhou Chen","doi":"10.1111/dom.15997","DOIUrl":"https://doi.org/10.1111/dom.15997","url":null,"abstract":"<p><strong>Aim: </strong>To examine the cost-effectiveness of adding finerenone to standard of care (SoC) for treating type 2 diabetes mellitus (T2DM)-related chronic kidney disease (CKD) in the United States.</p><p><strong>Materials and methods: </strong>Based on the clinical data analysed by FIDELITY, we referenced the validated FINE-CKD model (Markov model) to evaluate the cost-effectiveness of SoC versus SoC + finerenone from the perspective of US payers. The model was cycled for 35 years in 4-month cycles, with cost and utility values derived from the published literature. The primary outcomes were incremental cost-effectiveness ratio (ICER) and quality-adjusted life years (QALYs). Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of the base-case results.</p><p><strong>Results: </strong>The treatment strategy of finerenone plus SoC led to gains of 6.95 QALYs and had a lifetime cost of $491 745.31. Compared to SoC, that strategy yielded 0.48 more QALYs at an added cost of $65 305.72. The ICER for finerenone was $135 257.06 per QALY, which is below the willingness-to-pay threshold of United States ($150 000/QALY). The results were sensitive to the hazard ratios associated with the efficacy of finerenone and its cost. Probabilistic sensitivity analyses showed that the probability that finerenone plus SoC would be cost-effective was 57.6%.</p><p><strong>Conclusions: </strong>For patients with T2DM-related CKD, adding finerenone to SoC may be a cost-effective option in the United States. Reasonable price reductions for finerenone could potentially benefit more patients.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship of high-density lipoprotein subfractions and apolipoprotein A-I with fat in the pancreas.","authors":"Yutong Liu, Xiatiguli Shamaitijiang, Loren Skudder-Hill, Wandia Kimita, Ivana R Sequeira-Bisson, Maxim S Petrov","doi":"10.1111/dom.15990","DOIUrl":"https://doi.org/10.1111/dom.15990","url":null,"abstract":"<p><strong>Aim: </strong>To investigate the associations of high-density lipoprotein (HDL) subfractions and apolipoprotein A-I (apo A-I) with fat in the pancreas.</p><p><strong>Methods: </strong>A total of 170 individuals were studied. All participants underwent magnetic resonance imaging on a single 3.0-Tesla scanner to determine the presence/absence of fatty pancreas. HDL subfractions were measured using a commercially available lipoprotein subfractions testing system and classed as large, intermediate and small HDL. Both unadjusted and adjusted (accounting for demographics, anthropometrics, insulin resistance and other covariates) logistic regression models were built.</p><p><strong>Results: </strong>Individuals with fatty pancreas had significantly lower circulating levels of the large HDL class and apo A-I. Every unit decrease in the large HDL class was associated with a 93% increase in the likelihood of fatty pancreas in the most adjusted model (P < .001). Every unit decrease in apo A-I was associated with a 45% increase in the likelihood of fatty pancreas in the most adjusted model (P = .012). The intermediate and small HDL classes were not significantly associated with fatty pancreas.</p><p><strong>Conclusions: </strong>Fat in the pancreas is inversely associated with the circulating levels of large HDL particles and apo A-I. Purposely designed studies are warranted to investigate the potential of fatty pancreas as an indicator of the risk of cardiovascular diseases.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of individuals with diabetes and chronic kidney disease indicated for finerenone treatment in the United States: A National Health and Nutrition Examination Survey-based estimation.","authors":"Xiufang Kong, Wei Wang","doi":"10.1111/dom.16006","DOIUrl":"https://doi.org/10.1111/dom.16006","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Somatic and mental symptoms associated with dysglycaemia, diabetes-related complications and mental conditions in people with diabetes: Assessments in daily life using continuous glucose monitoring and ecological momentary assessment.","authors":"Norbert Hermanns, Dominic Ehrmann, Bernhard Kulzer, Laura Klinker, Thomas Haak, Andreas Schmitt","doi":"10.1111/dom.15983","DOIUrl":"https://doi.org/10.1111/dom.15983","url":null,"abstract":"<p><strong>Aim: </strong>To analyse the potential drivers (glucose level, complications, diabetes type, gender, age and mental health) of diabetes symptoms using continuous glucose monitoring (CGM) and ecological momentary assessment.</p><p><strong>Materials and methods: </strong>Participants used a smartphone application to rate 25 diabetes symptoms in their daily lives over 8 days. These symptoms were grouped into four blocks so that each symptom was rated six times on 2 days (noon, afternoon and evening). The symptom ratings were associated with the glucose levels for the previous 2 hours, measured with CGM. Linear mixed-effects models were used, allowing for nested random effects and the conduct of N = 1 analysis of individual associations.</p><p><strong>Results: </strong>In total, 192 individuals with type 1 diabetes and 179 with type 2 diabetes completed 6380 app check-ins. Four symptoms showed a significant negative association with glucose values, indicating higher ratings at lower glucose (speech difficulties, P = .003; coordination problems, P = .00005; confusion, P = .049; and food cravings, P = .0003). Four symptoms showed a significant positive association with glucose values, indicating higher scores at higher glucose (thirst, P = .0001; urination, P = .0003; taste disturbances, P = .021; and itching, P = .0120). There were also significant positive associations between microangiopathy and eight symptoms. Elevated depression and diabetes distress were associated with higher symptom scores. N = 1 analysis showed highly idiosyncratic associations between symptom reports and glucose levels.</p><p><strong>Conclusions: </strong>The N = 1 analysis facilitated the creation of personalized symptom profiles related to glucose levels with consideration of factors such as complications, gender, body mass index, depression and diabetes distress. This approach can enhance precision monitoring for diabetes symptoms in precision medicine.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A randomized phase I study of BI 1820237, a novel neuropeptide Y receptor type 2 agonist, alone or in combination with low-dose liraglutide in otherwise healthy men with overweight or obesity.","authors":"Nadine Beetz, Brigitte Kalsch, Thomas Forst, Bernhard Schmid, Armin Schultz, Anita M Hennige","doi":"10.1111/dom.15984","DOIUrl":"https://doi.org/10.1111/dom.15984","url":null,"abstract":"<p><strong>Aims: </strong>Pharmacotherapeutic options for obesity treatment include glucagon-like peptide-1 receptor (GLP-1R) agonists, for example, liraglutide. However, an unmet need remains, particularly in patients with a high body mass index (BMI), as GLP-1R agonists are associated with gastrointestinal adverse events (AEs) and some patients do not respond to treatment. Neuropeptide Y (NPY) and peptide YY bind G-protein-coupled Y receptors and represent attractive targets for modulating bodyweight.</p><p><strong>Materials and methods: </strong>This first-in-human, three-part, partially blinded phase I study (NCT04903509) investigated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending doses of the peptidic NPY2R agonist BI 1820237, with/without low-dose liraglutide: part 1 (participants randomized to receive BI 1820237: 0.075-2.4 mg or placebo), part 2 (BI 1820237: 1.2 mg or placebo) and part 3 (BI 1820237: 0.025-1.2 mg + liraglutide 0.6 mg or placebo + liraglutide 0.6 mg). Primary endpoint is the proportion of participants with drug-related AEs. Secondary endpoints are tolerability, PK and PD.</p><p><strong>Results: </strong>In total, 95 otherwise healthy men with increased BMI (25.0-34.9 kg/m²) were randomized. Drug-related AEs, mainly gastrointestinal events, were reported by 39.0% of participants (n = 23) in parts 1 + 2 and 30.6% of participants (n = 11) in part 3; one drug-related AE (11.1%, part 3) was reported in a participant receiving placebo with liraglutide. Post-dose paracetamol PK suggested that BI 1820237 and low-dose liraglutide exhibited additive effects on gastric emptying.</p><p><strong>Conclusions: </strong>BI 1820237 treatment was associated with transient nausea and vomiting at higher doses. No differences in tolerability were observed when combined with liraglutide; effects on gastric emptying appeared additive.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term glycaemic improvement with the initiation of an automated insulin delivery system in insulin pump-naïve older adults with type 1 diabetes.","authors":"Kagan E Karakus, Emma Mason, Halis K Akturk","doi":"10.1111/dom.15996","DOIUrl":"https://doi.org/10.1111/dom.15996","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of a fixed-dose combination of dapagliflozin and linagliptin (AJU-A51) in patients with type 2 diabetes mellitus: A multicentre, randomized, double-blind, parallel-group, placebo-controlled phase III study.","authors":"Jun Hwa Hong, Myung Jin Kim, Kyung Wan Min, Jong Chul Won, Tae Nyun Kim, Byung-Wan Lee, Jun Goo Kang, Jae Hyeon Kim, Jung Hwan Park, Bon Jeong Ku, Chang Beom Lee, Sang Yong Kim, Ho Sang Shon, Woo Je Lee, Joong-Yeol Park","doi":"10.1111/dom.15985","DOIUrl":"https://doi.org/10.1111/dom.15985","url":null,"abstract":"<p><strong>Aims: </strong>To evaluate the efficacy and safety of add-on dapagliflozin in patients with type 2 diabetes mellitus (T2D) who had inadequate glycaemic control with metformin and linagliptin.</p><p><strong>Materials and methods: </strong>A total of 235 patients with inadequate response to metformin (≥1000 mg/day) plus linagliptin (5 mg/day) were randomized to receive either dapagliflozin/linagliptin fixed-dose combination (FDC [AJU-A51]) 10/5 mg/day (n = 117) or linagliptin 5 mg plus placebo (n = 118) for 24 weeks. After the main treatment period, patients who received linagliptin plus placebo were treated with AJU-A51 for an additional 28 weeks. Change in glycated haemoglobin (HbA1c) from baseline to Week 24 was the primary endpoint.</p><p><strong>Results: </strong>AJU-A51 significantly reduced HbA1c levels (from 7.93% ± 0.82% to 7.11% ± 0.61%) compared with linagliptin plus placebo (from 7.80% ± 0.71% to 7.87% ± 0.94%), with a least squares mean difference of -0.88% (95% confidence interval -1.07 to -0.68; p < 0.0001) at 24 weeks. The AJU-A51 group had a significantly higher proportion of patients who achieved HbA1c <7.0% at Week 24 than the control group (44.8% vs. 18.6%; p < 0.001). The AJU-A51 group maintained glycaemic efficacy up to 52 weeks, whereas the control group showed a substantial reduction in HbA1c after switching to AJU-A51 in the extension study period. Both groups had similar incidence of treatment-emergent and serious adverse events, and no cases of symptomatic hypoglycaemia were reported.</p><p><strong>Conclusions: </strong>Dapagliflozin and linagliptin FDC (AJU-A51) showed potent glucose-lowering effects, with good tolerability, in patients with T2D who had poor glycaemic control on metformin and linagliptin (ClinicalTrials.gov [NCT06329674]).</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Semaglutide in patients with kidney failure and obesity undergoing dialysis and wishing to be transplanted: A prospective, observational, open-label study","authors":"Lenka Vanek MD,&nbsp;Amelie Kurnikowski MD,&nbsp;Simon Krenn MD,&nbsp;Sebastian Mussnig MD,&nbsp;Manfred Hecking PhD","doi":"10.1111/dom.15967","DOIUrl":"10.1111/dom.15967","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Chronic kidney disease (CKD) and obesity are major global health challenges, eventually leading to kidney replacement therapy (KRT), but body mass index (BMI) thresholds hinder kidney transplantation. Glucagon-like peptide-1 receptor agonists induce weight loss, thereby offering attractive treatment options; however, their safety and efficacy have not been systematically investigated in patients undergoing dialysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We conducted a prospective 12-week, open-label trial with 13 patients who had a BMI ≥ 30.00 kg/m², were undergoing dialysis (12 haemodialysis and 1 peritoneal dialysis) and had not been listed for transplantation due to their weight. Semaglutide was administered once weekly subcutaneously, and the dose was increased from 0.25 mg to 0.5 mg and then to 1 mg. Study endpoints included change in body weight and BMI (primary – statistically evaluated by repeated measures analysis of variance [ANOVA]), side effects, adverse events, blood parameters and patient-reported outcomes (secondary).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At baseline, the mean age ± standard deviation of patients was 64.0 ± 6.4 years, the mean weight was 113.9 ± 16.6 kg, and the mean BMI was 37.3 ± 3.9 kg/m². At week 12, average weight reduction under semaglutide treatment was 4.6 ± 2.4 kg and ranged from 2.0 to 9.7 kg (<i>p</i> &lt; 0.001 for weight and BMI reduction across the study period). One patient discontinued treatment due to nausea/vomiting, two patients died of unrelated causes and six patients reported side effects. Approximately 9 months after the treatment started, three patients were able to seriously reconsider being listed for transplantation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Semaglutide treatment resulted in significant reduction in weight and BMI in patients with obesity undergoing dialysis, while maintaining an acceptable side effect profile comparable to that of the non-dialysis population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"26 12","pages":"5931-5941"},"PeriodicalIF":5.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/dom.15967","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated approach of machine learning, Mendelian randomization and experimental validation for biomarker discovery in diabetic nephropathy","authors":"Yidong Zhu MD,&nbsp;Jun Liu MD,&nbsp;Bo Wang MD","doi":"10.1111/dom.15933","DOIUrl":"10.1111/dom.15933","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Aim&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;To identify potential biomarkers and explore the mechanisms underlying diabetic nephropathy (DN) by integrating machine learning, Mendelian randomization (MR) and experimental validation.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Microarray and RNA-sequencing datasets (GSE47184, GSE96804, GSE104948, GSE104954, GSE142025 and GSE175759) were obtained from the Gene Expression Omnibus database. Differential expression analysis identified the differentially expressed genes (DEGs) between patients with DN and controls. Diverse machine learning algorithms, including least absolute shrinkage and selection operator, support vector machine-recursive feature elimination, and random forest, were used to enhance gene selection accuracy and predictive power. We integrated summary-level data from genome-wide association studies on DN with expression quantitative trait loci data to identify genes with potential causal relationships to DN. The predictive performance of the biomarker gene was validated using receiver operating characteristic (ROC) curves. Gene set enrichment and correlation analyses were conducted to investigate potential mechanisms. Finally, the biomarker gene was validated using quantitative real-time polymerase chain reaction in clinical samples from patients with DN and controls.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Based on identified 314 DEGs, seven characteristic genes with high predictive performance were identified using three integrated machine learning algorithms. MR analysis revealed 219 genes with significant causal effects on DN, ultimately identifying one co-expressed gene, carbonic anhydrase II (&lt;i&gt;CA2&lt;/i&gt;), as a key biomarker for DN. The ROC curves demonstrated the excellent predictive performance of &lt;i&gt;CA2&lt;/i&gt;, with area under the curve values consistently above 0.878 across all datasets. Additionally, our analysis indicated a significant association between &lt;i&gt;CA2&lt;/i&gt; and infiltrating immune cells in DN, providing potential mechanistic insights. This biomarker was validated using clinical samples, confirming the reliability of our findings in clinical practice.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;By integrating machine learning, MR and experimental validation, we successfully identified and validated &lt;i&gt;CA2&lt;/i&gt; as a promising biomarker for DN with excellent predictive performance. The biomarker may play a role in the pathogenesis and progression of DN via immune-related pathways. These findings provide important insights into the molecular mechanisms underlying DN and may inform the development of personalized treatment strategies for this disease.&lt;/p&gt;\u0000 ","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"26 12","pages":"5646-5660"},"PeriodicalIF":5.4,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}