Asia Saturnino, Ernesto Maddaloni, Simona Zampetti, Raffaella Buzzetti
Background
Glucagon-like peptide 1 receptor agonists (RA) are novel agents used in the management of type 2 diabetes (T2D) and obesity. Although highly effective, the response to treatment may vary significantly among patients.
Objective
This perspective review aims to summarise the current knowledge about markers of poor or good response to GLP-1 RA, highlighting the possibility of tailoring treatment strategies and reducing costs associated with T2D and obesity treatment.
Methods
A comprehensive literature search was conducted using PubMed, NCBI, and Scopus databases, focussing on studies published between 2016 and 2024 that evaluated factors influencing treatment outcomes with GLP-1 RA.
Results
Several markers, including baseline HbA1c levels, ghrelin and glucose-dependent insulinotropic polypeptide (GIP) levels, specific gut microbiome composition, b-cell function, and genetic markers, were identified as factors associated with treatment response.
Conclusion
Understanding predictive markers of response to therapy can enhance precision-based medicine for the selection of patients eligible for GLP-1 RA, improving clinical outcomes and optimising diabetes management.
{"title":"Searching the Crystal Ball for Tailored GLP-1 Receptor Agonists Treatment in Type 2 Diabetes and Obesity","authors":"Asia Saturnino, Ernesto Maddaloni, Simona Zampetti, Raffaella Buzzetti","doi":"10.1002/dmrr.70017","DOIUrl":"10.1002/dmrr.70017","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Glucagon-like peptide 1 receptor agonists (RA) are novel agents used in the management of type 2 diabetes (T2D) and obesity. Although highly effective, the response to treatment may vary significantly among patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This perspective review aims to summarise the current knowledge about markers of poor or good response to GLP-1 RA, highlighting the possibility of tailoring treatment strategies and reducing costs associated with T2D and obesity treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A comprehensive literature search was conducted using PubMed, NCBI, and Scopus databases, focussing on studies published between 2016 and 2024 that evaluated factors influencing treatment outcomes with GLP-1 RA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Several markers, including baseline HbA1c levels, ghrelin and glucose-dependent insulinotropic polypeptide (GIP) levels, specific gut microbiome composition, b-cell function, and genetic markers, were identified as factors associated with treatment response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Understanding predictive markers of response to therapy can enhance precision-based medicine for the selection of patients eligible for GLP-1 RA, improving clinical outcomes and optimising diabetes management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"41 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824571","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}
Hao Xiang, Chun Zhou, Xiaoqin Gan, Yu Huang, Panpan He, Ziliang Ye, Mengyi Liu, Sisi Yang, Yanjun Zhang, Yuanyuan Zhang, Xianhui Qin
Aims
The association between vitamin D and the risk of venous thromboembolism (VTE) remains inconclusive. We aimed to explore the association of serum 25-hydroxyvitamin D (25OHD) with incident VTE among participants with and without diabetes, and examine the modifying effect of genetic susceptibility of VTE and vitamin D receptor (VDR) gene polymorphisms on this association.
Materials and Methods
A total of 378,082 participants free of VTE at baseline from the UK Biobank were included. Serum 25OHD concentrations were measured by the chemiluminescent immunoassay method. The primary outcome was incident VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE). The genetic risks of VTE were estimated using 297 single nucleotide polymorphisms (SNPs) associated with VTE. The VDR gene polymorphisms included SNPs of rs7975232, rs1544410, rs2228570 and rs731236.
Results
During a median follow-up duration of 12.5 years, 10,645 VTE cases were recorded. Serum 25OHD had a significantly stronger inverse association with incident VTE in participants with diabetes (per SD increment, adjusted HR: 0.87; 95% CI: 0.81–0.93) than in those without diabetes (per SD increment, adjusted HR: 0.97; 95% CI: 0.95–0.99; p-interaction = 0.003). Similar trends were found for incident DVT and PE. Among participants with diabetes, the genetic risk of VTE did not significantly modify the association between serum 25OHD and incident VTE (p-interaction = 0.607). However, a stronger inverse association of serum 25OHD with incident VTE was found in the VDR rs2228570 AA genotype (vs. GG/AG; p-interaction = 0.031).
Conclusions
Serum 25OHD was inversely associated with the risk of VTE, especially among participants with diabetes, regardless of genetic risks of VTE.
{"title":"Relationship of Serum 25-Hydroxyvitamin D Concentrations, Diabetes, Vitamin D Receptor Gene Polymorphisms and Incident Venous Thromboembolism","authors":"Hao Xiang, Chun Zhou, Xiaoqin Gan, Yu Huang, Panpan He, Ziliang Ye, Mengyi Liu, Sisi Yang, Yanjun Zhang, Yuanyuan Zhang, Xianhui Qin","doi":"10.1002/dmrr.70014","DOIUrl":"10.1002/dmrr.70014","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The association between vitamin D and the risk of venous thromboembolism (VTE) remains inconclusive. We aimed to explore the association of serum 25-hydroxyvitamin D (25OHD) with incident VTE among participants with and without diabetes, and examine the modifying effect of genetic susceptibility of VTE and vitamin D receptor (VDR) gene polymorphisms on this association.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>A total of 378,082 participants free of VTE at baseline from the UK Biobank were included. Serum 25OHD concentrations were measured by the chemiluminescent immunoassay method. The primary outcome was incident VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE). The genetic risks of VTE were estimated using 297 single nucleotide polymorphisms (SNPs) associated with VTE. The VDR gene polymorphisms included SNPs of rs7975232, rs1544410, rs2228570 and rs731236.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>During a median follow-up duration of 12.5 years, 10,645 VTE cases were recorded. Serum 25OHD had a significantly stronger inverse association with incident VTE in participants with diabetes (per SD increment, adjusted HR: 0.87; 95% CI: 0.81–0.93) than in those without diabetes (per SD increment, adjusted HR: 0.97; 95% CI: 0.95–0.99; <i>p</i>-interaction = 0.003). Similar trends were found for incident DVT and PE. Among participants with diabetes, the genetic risk of VTE did not significantly modify the association between serum 25OHD and incident VTE (<i>p</i>-interaction = 0.607). However, a stronger inverse association of serum 25OHD with incident VTE was found in the VDR rs2228570 AA genotype (vs. GG/AG; <i>p</i>-interaction = 0.031).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Serum 25OHD was inversely associated with the risk of VTE, especially among participants with diabetes, regardless of genetic risks of VTE.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"41 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814692","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}
Ilaria Barchetta, Sara Dule, Flavia Agata Cimini, Federica Sentinelli, Alessandro Oldani, Giulia Passarella, Tiziana Filardi, Vittorio Venditti, Enrico Bleve, Elisabetta Romagnoli, Susanna Morano, Andrea Lenzi, Olle Melander, Marco Giorgio Baroni, Maria Gisella Cavallo
Context
The mechanisms underlying bone fragility and increased fracture risk observed in individuals with type 2 diabetes (T2D) are not yet fully elucidated. Previous research has suggested a role for neuropeptides in regulating bone metabolism; however, the contribution of the neuropeptide Neurotensin (NT), which is thoroughly implicated in T2D and cardiovascular disease, has not been investigated in this context.
Objective
To study the relationship between circulating levels of the NT precursor proneurotensin (proNT) and bone mineralisation in T2D women.
Materials and Methods
This is a cross-sectional investigation with a longitudinal prospective phase, involving 126 women with T2D who underwent bone density scans and had proNT levels measured. Biomarkers of bone metabolism and inflammation were also assessed. Data on bone mineral density (BMD) after 12 months were available for 49 patients.
Main Outcome Measure
Plasma proNT levels in relation to BMD.
Results
32% of the participants had osteopenia/osteoporosis and exhibited higher proNT than those with normal BMD (200.8 ± 113.7 vs. 161.6 ± 108.8 pg/mL; p = 0.013). ProNT inversely correlated with femur BMD and T-score (p < 0.01) and was associated with degraded bone architecture (TBS, p = 0.02), and higher OPN, P1NP, TNF-α and IL-1β levels. Baseline proNT correlated with further BMD reduction at the 12-month follow-up, independently of potential confounders (p = 0.02).
Conclusions
In women with T2D, greater proNT levels are associated with impaired bone mineralisation and predict mineral density decline overtime. ProNT could potentially serve as a diagnostic tool for identifying patients at higher risk of osteopenia/osteoporosis, suggesting a significant connection between this neuropeptide and bone metabolism in diabetes.
背景：在2型糖尿病（T2D）患者中观察到的骨脆性和骨折风险增加的机制尚未完全阐明。先前的研究表明神经肽在调节骨代谢中的作用；然而，神经肽神经紧张素（NT）在T2D和心血管疾病中的作用尚未在此背景下进行研究。目的：探讨t2dm患者外周血NT前体前神经紧张素（proNT）水平与骨矿化的关系。材料和方法：这是一项纵向前瞻性的横断面研究，涉及126名患有T2D的女性，她们接受了骨密度扫描并测量了proNT水平。还评估了骨代谢和炎症的生物标志物。49例患者12个月后的骨密度（BMD）数据。主要结果测量：血浆proNT水平与BMD的关系。结果：32%的参与者患有骨质减少/骨质疏松症，proNT高于骨密度正常者(200.8±113.7 vs. 161.6±108.8 pg/mL；p = 0.013)。结论：在患有T2D的女性中，较高的ProNT水平与骨矿化受损相关，并预测矿物质密度随时间的下降。ProNT可能作为一种潜在的诊断工具，用于识别骨质减少/骨质疏松症高风险患者，这表明这种神经肽与糖尿病患者的骨代谢之间存在重要联系。
{"title":"Circulating Proneurotensin Levels Predict Impaired Bone Mineralisation in Postmenopausal Women With Type 2 Diabetes Mellitus","authors":"Ilaria Barchetta, Sara Dule, Flavia Agata Cimini, Federica Sentinelli, Alessandro Oldani, Giulia Passarella, Tiziana Filardi, Vittorio Venditti, Enrico Bleve, Elisabetta Romagnoli, Susanna Morano, Andrea Lenzi, Olle Melander, Marco Giorgio Baroni, Maria Gisella Cavallo","doi":"10.1002/dmrr.70018","DOIUrl":"10.1002/dmrr.70018","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Context</h3>\u0000 \u0000 <p>The mechanisms underlying bone fragility and increased fracture risk observed in individuals with type 2 diabetes (T2D) are not yet fully elucidated. Previous research has suggested a role for neuropeptides in regulating bone metabolism; however, the contribution of the neuropeptide Neurotensin (NT), which is thoroughly implicated in T2D and cardiovascular disease, has not been investigated in this context.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To study the relationship between circulating levels of the NT precursor proneurotensin (proNT) and bone mineralisation in T2D women.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This is a cross-sectional investigation with a longitudinal prospective phase, involving 126 women with T2D who underwent bone density scans and had proNT levels measured. Biomarkers of bone metabolism and inflammation were also assessed. Data on bone mineral density (BMD) after 12 months were available for 49 patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Main Outcome Measure</h3>\u0000 \u0000 <p>Plasma proNT levels in relation to BMD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>32% of the participants had osteopenia/osteoporosis and exhibited higher proNT than those with normal BMD (200.8 ± 113.7 vs. 161.6 ± 108.8 pg/mL; <i>p</i> = 0.013). ProNT inversely correlated with femur BMD and <i>T</i>-score (<i>p</i> < 0.01) and was associated with degraded bone architecture (TBS, <i>p</i> = 0.02), and higher OPN, P1NP, TNF-α and IL-1β levels. Baseline proNT correlated with further BMD reduction at the 12-month follow-up, independently of potential confounders (<i>p</i> = 0.02).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In women with T2D, greater proNT levels are associated with impaired bone mineralisation and predict mineral density decline overtime. ProNT could potentially serve as a diagnostic tool for identifying patients at higher risk of osteopenia/osteoporosis, suggesting a significant connection between this neuropeptide and bone metabolism in diabetes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"41 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802840","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}
Dario Pitocco, Duaa Hatem, Alessia Riente, Michele Maria De Giulio, Alessandro Rizzi, Alessio Abeltino, Cassandra Serantoni, Linda Tartaglione, Emanuele Rizzo, Lorenzo Lucacchini Paoli, Marco De Spirito, Giuseppe Maulucci
Aims
This review evaluates the mechanisms underlying red blood cell (RBC) membrane fluidity changes in diabetes mellitus (DM) and explores strategies to assess and address these alterations. Emphasis is placed on developing a comprehensive index for membrane fluidity to improve monitoring and management in diabetic patients.
Materials and Methods
We reviewed current literature on RBC membrane fluidity, focussing on lipid composition, glycation, oxidative stress, and lipid transport alterations in diabetic patients. Key methodologies include lipidomics, multi-scale probe assessment, and machine learning integration for standardized fluidity measurement.
Results
Diabetic RBCs exhibit increased membrane fluidity, primarily due to oxidative stress, increased glycation, and dysregulated lipid composition. These alterations contribute to vascular complications and impair RBC functionality. Assessing membrane composition as a nutritional marker provides insights into the metabolic impacts of glycaemic management.
Conclusions
There is a critical need for a unified and comprehensive membrane fluidity index in DM, which could support personalised interventions through dietary, medicinal, and lifestyle modifications. Future research should prioritise standardising measurement techniques and integrating lipidomic data with machine learning for predictive modelling, aiming to enhance clinical outcomes for diabetic patients.
{"title":"Evaluating Red Blood Cells' Membrane Fluidity in Diabetes: Insights, Mechanisms, and Future Aspects","authors":"Dario Pitocco, Duaa Hatem, Alessia Riente, Michele Maria De Giulio, Alessandro Rizzi, Alessio Abeltino, Cassandra Serantoni, Linda Tartaglione, Emanuele Rizzo, Lorenzo Lucacchini Paoli, Marco De Spirito, Giuseppe Maulucci","doi":"10.1002/dmrr.70011","DOIUrl":"https://doi.org/10.1002/dmrr.70011","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This review evaluates the mechanisms underlying red blood cell (RBC) membrane fluidity changes in diabetes mellitus (DM) and explores strategies to assess and address these alterations. Emphasis is placed on developing a comprehensive index for membrane fluidity to improve monitoring and management in diabetic patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We reviewed current literature on RBC membrane fluidity, focussing on lipid composition, glycation, oxidative stress, and lipid transport alterations in diabetic patients. Key methodologies include lipidomics, multi-scale probe assessment, and machine learning integration for standardized fluidity measurement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Diabetic RBCs exhibit increased membrane fluidity, primarily due to oxidative stress, increased glycation, and dysregulated lipid composition. These alterations contribute to vascular complications and impair RBC functionality. Assessing membrane composition as a nutritional marker provides insights into the metabolic impacts of glycaemic management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>There is a critical need for a unified and comprehensive membrane fluidity index in DM, which could support personalised interventions through dietary, medicinal, and lifestyle modifications. Future research should prioritise standardising measurement techniques and integrating lipidomic data with machine learning for predictive modelling, aiming to enhance clinical outcomes for diabetic patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"41 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764220","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}
Visceral adipose tissue (VAT) accumulation is essential for the occurrence and development of obesity and related metabolic diseases. Currently, the specific mechanism of VAT accumulation is still unclear.
Materials and Methods
We searched the Gene Expression Omnibus database to obtain single-cell RNA sequencing (scRNAseq) data for VAT in patients with a normal body mass index (BMI), obesity, or morbid obesity. By using PCR, WB, immunofluorescence staining, and flow cytometry analysis, we validated the interactions between macrophages, endothelial cells (ECs), and adipocyte progenitor cells (APCs), as well as the underlying mechanism, in VAT. Finally, we tested the findings in obese mice using recombinant proteins and adeno-associated virus infection.
Results
One study with human scRNAseq data was included. This study collected 13-VAT from 5 individuals with obesity and diabetes, 9 individuals with obesity, and 1 individual with a normal BMI. The proportion of inflammatory macrophages is substantially increased in obese and diabetic patients. ECs have the most active interactions with other cells. Notably, the activation of JAK1/STAT3 is one of the reasons for the increase in inflammatory endothelial cells and can promote the secretion of angiopoietin-2 (Angpt2) and induce APCs to transition from mesothelin (MSLN) to complement factor D (CFD) expression via integrin-α5β1 signalling. This phenotypic transition promotes APC differentiation into mature adipocytes and accelerates VAT accumulation. These observations were further validated in an in vitro model and an in vivo study using Angpt2 recombinant proteins and blocking the expression of Angpt2 by adeno-associated virus infection.
Conclusions
ECs are essential for promoting VAT accumulation by facilitating APC differentiation from MSLN to CFD phenotype. This process is driven by Angpt2 from ECs upon JAK1/STAT3 signalling activation under metabolic stress.
{"title":"Endothelial Angpt2 Promotes Adipocyte Progenitor Cells Maturation to Increase Visceral Adipose Tissue Accumulation","authors":"Xianhao Yi, Jiapu Ling, Yan Tang, Jingjing Cai, Shaihong Zhu, Liyong Zhu","doi":"10.1002/dmrr.70012","DOIUrl":"https://doi.org/10.1002/dmrr.70012","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Visceral adipose tissue (VAT) accumulation is essential for the occurrence and development of obesity and related metabolic diseases. Currently, the specific mechanism of VAT accumulation is still unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We searched the Gene Expression Omnibus database to obtain single-cell RNA sequencing (scRNAseq) data for VAT in patients with a normal body mass index (BMI), obesity, or morbid obesity. By using PCR, WB, immunofluorescence staining, and flow cytometry analysis, we validated the interactions between macrophages, endothelial cells (ECs), and adipocyte progenitor cells (APCs), as well as the underlying mechanism, in VAT. Finally, we tested the findings in obese mice using recombinant proteins and adeno-associated virus infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>One study with human scRNAseq data was included. This study collected 13-VAT from 5 individuals with obesity and diabetes, 9 individuals with obesity, and 1 individual with a normal BMI. The proportion of inflammatory macrophages is substantially increased in obese and diabetic patients. ECs have the most active interactions with other cells. Notably, the activation of JAK1/STAT3 is one of the reasons for the increase in inflammatory endothelial cells and can promote the secretion of angiopoietin-2 (Angpt2) and induce APCs to transition from mesothelin (MSLN) to complement factor D (CFD) expression via integrin-α5β1 signalling. This phenotypic transition promotes APC differentiation into mature adipocytes and accelerates VAT accumulation. These observations were further validated in an in vitro model and an in vivo study using Angpt2 recombinant proteins and blocking the expression of Angpt2 by adeno-associated virus infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>ECs are essential for promoting VAT accumulation by facilitating APC differentiation from MSLN to CFD phenotype. This process is driven by Angpt2 from ECs upon JAK1/STAT3 signalling activation under metabolic stress.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"41 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764221","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}
Haifa Maalmi, Phong B. H. Nguyen, Alexander Strom, Gidon J. Bönhof, Wolfgang Rathmann, Dan Ziegler, Michael P. Menden, Michael Roden, Christian Herder, GDS Group
Background
Diabetic sensorimotor polyneuropathy (DSPN) is often asymptomatic and remains undiagnosed. The ability of clinical and anthropometric variables to identify individuals likely to have DSPN might be limited. Here, we aimed to integrate protein biomarkers for reliably predicting present DSPN.
Methods
Using the proximity extension assay, we measured 135 neurological and protein biomarkers of inflammation in blood samples of 423 individuals with recent-onset diabetes from the German Diabetes Study (GDS). DSPN was diagnosed based on the Toronto Consensus Criteria. We constructed (i) a protein-based prediction model using LASSO logistic regression, (ii) an optimised traditional risk model with age, sex, waist circumference, height and diabetes type and (iii) a model combining both. All models were bootstrapped to assess the robustness, and optimism-corrected AUCs (95% CI) were reported.
Results
DSPN was present in 16% of the study population. LASSO logistic regression selected the neurofilament light chain (NFL) and fibroblast growth factor-19 (FGF-19) as the most predictive protein biomarkers for detecting DSPN in individuals with recent-onset diabetes. The protein-based model achieved an AUC of 0.66 (0.59, 0.73), while the traditional risk model had an AUC of 0.66 (0.61, 0.74). However, combined features boosted the model performance to an AUC of 0.72 (0.67, 0.79).
Conclusion
We developed a prediction model for DSPN in recent-onset diabetes based on two protein biomarkers and five standard anthropometric, demographic and clinical variables. The model has a fair discrimination performance and might be used to inform the referral of patients for further testing.
{"title":"Prediction Model for Polyneuropathy in Recent-Onset Diabetes Based on Serum Neurofilament Light Chain, Fibroblast Growth Factor-19 and Standard Anthropometric and Clinical Variables","authors":"Haifa Maalmi, Phong B. H. Nguyen, Alexander Strom, Gidon J. Bönhof, Wolfgang Rathmann, Dan Ziegler, Michael P. Menden, Michael Roden, Christian Herder, GDS Group","doi":"10.1002/dmrr.70009","DOIUrl":"10.1002/dmrr.70009","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Diabetic sensorimotor polyneuropathy (DSPN) is often asymptomatic and remains undiagnosed. The ability of clinical and anthropometric variables to identify individuals likely to have DSPN might be limited. Here, we aimed to integrate protein biomarkers for reliably predicting present DSPN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using the proximity extension assay, we measured 135 neurological and protein biomarkers of inflammation in blood samples of 423 individuals with recent-onset diabetes from the German Diabetes Study (GDS). DSPN was diagnosed based on the Toronto Consensus Criteria. We constructed (i) a protein-based prediction model using LASSO logistic regression, (ii) an optimised traditional risk model with age, sex, waist circumference, height and diabetes type and (iii) a model combining both. All models were bootstrapped to assess the robustness, and optimism-corrected AUCs (95% CI) were reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DSPN was present in 16% of the study population. LASSO logistic regression selected the neurofilament light chain (NFL) and fibroblast growth factor-19 (FGF-19) as the most predictive protein biomarkers for detecting DSPN in individuals with recent-onset diabetes. The protein-based model achieved an AUC of 0.66 (0.59, 0.73), while the traditional risk model had an AUC of 0.66 (0.61, 0.74). However, combined features boosted the model performance to an AUC of 0.72 (0.67, 0.79).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We developed a prediction model for DSPN in recent-onset diabetes based on two protein biomarkers and five standard anthropometric, demographic and clinical variables. The model has a fair discrimination performance and might be used to inform the referral of patients for further testing.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 8","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733766","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}
Zheng Yang, Subei Zhao, Yuhuan Lv, Linyu Xiang, Xiaoru Zhang, Zhengping Feng, Zhiping Liu, Rong Li
Aims
Diabetic peripheral neuropathy (DPN) often coexists with sudomotor dysfunction, resulting in an increased risk of diabetic foot. This study aimed to explore an efficient method for early diagnosis of DPN by establishing a quantitative Neuropad.
Methods
We recruited 518 patients with type 2 diabetes. Neuropathy Symptoms Score (NSS) combined with Neuropathy Disability Score (NDS) was used to assess distal symmetrical peripheral neuropathy (DSPN). The area under the ROC curve (AUROC), sensitivity, and specificity were used to compare the diagnostic efficacy of quantitative Neuropad (the change rate of the chromatic aberration value per minute) and two types of visual Neuropad (visual Neuropad A: whether the time to complete colour change within 10 min, visual Neuropad B: the time to complete colour change) for DPN.
Results
We did not observe very good diagnostic efficacy of Neuropad (visual Neuropad A and B: 0.59 and 0.64, quantitative Neuropad AUROC: 0.62–0.64) when using standard DSPN diagnostic criteria (NDS 6–12 or NDS 3–5 combined with NSS 5–9). When DPN was assessed by NSS + NDS ≥ 4, visual Neuropad B improved the specificity (AUROC 0.72, 67.00%, specificity 71.70%) by extending the detection time compared with visual Neuropad A (AUROC 0.62, sensitivity 81.80%, specificity 41.70%). Quantitative Neuropad significantly improved the diagnostic effect (AUROC 0.81, sensitivity 80.0%, specificity 76.3%) and reduced the detection time (4 min).
Conclusions
This study provides a new quantitative Neuropad, which has great potential to be an extremely useful diagnostic tool for early screening of sudomotor dysfunction in the clinical practice.
{"title":"A New Quantitative Neuropad for Early Diagnosis of Diabetic Peripheral Neuropathy","authors":"Zheng Yang, Subei Zhao, Yuhuan Lv, Linyu Xiang, Xiaoru Zhang, Zhengping Feng, Zhiping Liu, Rong Li","doi":"10.1002/dmrr.70010","DOIUrl":"https://doi.org/10.1002/dmrr.70010","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Diabetic peripheral neuropathy (DPN) often coexists with sudomotor dysfunction, resulting in an increased risk of diabetic foot. This study aimed to explore an efficient method for early diagnosis of DPN by establishing a quantitative Neuropad.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We recruited 518 patients with type 2 diabetes. Neuropathy Symptoms Score (NSS) combined with Neuropathy Disability Score (NDS) was used to assess distal symmetrical peripheral neuropathy (DSPN). The area under the ROC curve (AUROC), sensitivity, and specificity were used to compare the diagnostic efficacy of quantitative Neuropad (the change rate of the chromatic aberration value per minute) and two types of visual Neuropad (visual Neuropad A: whether the time to complete colour change within 10 min, visual Neuropad B: the time to complete colour change) for DPN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We did not observe very good diagnostic efficacy of Neuropad (visual Neuropad A and B: 0.59 and 0.64, quantitative Neuropad AUROC: 0.62–0.64) when using standard DSPN diagnostic criteria (NDS 6–12 or NDS 3–5 combined with NSS 5–9). When DPN was assessed by NSS + NDS ≥ 4, visual Neuropad B improved the specificity (AUROC 0.72, 67.00%, specificity 71.70%) by extending the detection time compared with visual Neuropad A (AUROC 0.62, sensitivity 81.80%, specificity 41.70%). Quantitative Neuropad significantly improved the diagnostic effect (AUROC 0.81, sensitivity 80.0%, specificity 76.3%) and reduced the detection time (4 min).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study provides a new quantitative Neuropad, which has great potential to be an extremely useful diagnostic tool for early screening of sudomotor dysfunction in the clinical practice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 8","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666135","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}
Benjamin N. Wadström, Kasper M. Pedersen, Anders B. Wulff, Børge G. Nordestgaard
Aims
Elevated remnant cholesterol (= the cholesterol carried in triglyceride-rich lipoproteins) is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and is common in individuals with diabetes. We tested the hypothesis that ASCVD in individuals with diabetes can be partly attributed to elevated remnant cholesterol.
Materials and Methods
We included 3806 individuals with diabetes identified among 107,243 individuals from the Copenhagen General Population Study and used multivariable adjusted Poisson regression to estimate the fraction of ASCVD attributable to elevated remnant cholesterol. Elevated remnant cholesterol was defined as levels higher than those observed in individuals with non-high-density lipoprotein (non-HDL) cholesterol < 2.6 mmol/L (100 mg/dL), the European guideline goal. Results were replicated in the UK Biobank.
Results
During 15 years of follow-up, 498 patients were diagnosed with ASCVD, 172 with peripheral artery disease, 185 with myocardial infarction and 195 with ischaemic stroke. In individuals with non-HDL cholesterol < 2.6 mmol/L (100 mg/dL) and in all individuals with diabetes, median remnant cholesterol levels were 0.5 mmol/L (20 mg/dL) and 0.8 mmol/L (31 mg/dL). The fraction of events attributable to elevated remnant cholesterol was 19% (95% confidence interval: 10%–28%) for ASCVD, 21% (5%–37%) for peripheral artery disease, 24% (10%–37%) for myocardial infarction and 17% (1%–31%) for ischaemic stroke; in the UK Biobank, corresponding values were 16% (9%–22%), 25% (12%–36%), 17% (8%–25%) and 7% (0%–19%), respectively.
Conclusions
One in five ASCVD events in individuals with diabetes can be attributed to elevated remnant cholesterol. It remains to be determined in clinical trials if remnant cholesterol-lowering therapy may prevent ASCVD.
{"title":"One in Five Atherosclerotic Cardiovascular Disease Events in Individuals With Diabetes Attributed to Elevated Remnant Cholesterol","authors":"Benjamin N. Wadström, Kasper M. Pedersen, Anders B. Wulff, Børge G. Nordestgaard","doi":"10.1002/dmrr.70005","DOIUrl":"10.1002/dmrr.70005","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Elevated remnant cholesterol (= the cholesterol carried in triglyceride-rich lipoproteins) is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and is common in individuals with diabetes. We tested the hypothesis that ASCVD in individuals with diabetes can be partly attributed to elevated remnant cholesterol.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We included 3806 individuals with diabetes identified among 107,243 individuals from the Copenhagen General Population Study and used multivariable adjusted Poisson regression to estimate the fraction of ASCVD attributable to elevated remnant cholesterol. Elevated remnant cholesterol was defined as levels higher than those observed in individuals with non-high-density lipoprotein (non-HDL) cholesterol < 2.6 mmol/L (100 mg/dL), the European guideline goal. Results were replicated in the UK Biobank.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>During 15 years of follow-up, 498 patients were diagnosed with ASCVD, 172 with peripheral artery disease, 185 with myocardial infarction and 195 with ischaemic stroke. In individuals with non-HDL cholesterol < 2.6 mmol/L (100 mg/dL) and in all individuals with diabetes, median remnant cholesterol levels were 0.5 mmol/L (20 mg/dL) and 0.8 mmol/L (31 mg/dL). The fraction of events attributable to elevated remnant cholesterol was 19% (95% confidence interval: 10%–28%) for ASCVD, 21% (5%–37%) for peripheral artery disease, 24% (10%–37%) for myocardial infarction and 17% (1%–31%) for ischaemic stroke; in the UK Biobank, corresponding values were 16% (9%–22%), 25% (12%–36%), 17% (8%–25%) and 7% (0%–19%), respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>One in five ASCVD events in individuals with diabetes can be attributed to elevated remnant cholesterol. It remains to be determined in clinical trials if remnant cholesterol-lowering therapy may prevent ASCVD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 8","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649061","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}
Glucose metabolism abnormalities are prevalent in acute ischaemic stroke (AIS) patients and are associated with poor prognosis. The continuous glucose monitoring (CGM) system can provide detailed information on glucose levels and glycaemic excursions. This study aimed to evaluate the feasibility and accuracy of CGM application in the acute phase of AIS patients.
Methods
This single-centre, prospective, and observational study consecutively enrolled patients with AIS with anterior circulation large vessel occlusion (AC-LVO) and received mechanical thrombectomy (MT) within 24 h of symptom onset. A user-retrospectively calibrated iPro2 CGM system was implanted right before the MT procedure started and removed on the fifth day after MT or at discharge. Fingertip glucose was measured as a reference. Accuracy evaluation included the Bland–Altman plot (with a proportion of CGM values within 15/15, 20/20 and 30/30), the absolute relative difference (ARD) and error grid analysis (EGA). The safety and glucose profiles were also evaluated.
Results
Of the 183 patients screened, 141 were included, with a median monitoring duration of 4.49 days. Compared to reference measurements, 3097 CGM readings were matched with a mean bias of −4.16 mg/dL. The proportions of sensor readings meeting the 15/15, 20/20 and 30/30 criteria were 64.55%, 76.07% and 87.21%, respectively. The overall mean and median ARD were 14.60% ± 14.62% and 9.77% (4.15, 20.00). EGA showed that 98.97%, 99.42% and 99.06% values fall within clinically accurate zones in Clarke, Parkes and continuous glucose EGA, respectively.
Conclusion
The CGM system was feasible, safe and accurate for in-hospital use among AIS patients who received MT.
{"title":"Performance of Continuous Glucose Monitoring System Among Patients With Acute Ischaemic Stroke Treated With Mechanical Thrombectomy","authors":"Jie Shi, Jiahao Weng, Yu Ding, Yue Xia, Yongwen Zhou, Xulin Wang, Feng Zhang, Pan Zhang, Sihui Luo, Xueying Zheng, Xinfeng Liu, Chaofan Wang, Wen Sun, Jianping Weng","doi":"10.1002/dmrr.70001","DOIUrl":"10.1002/dmrr.70001","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Glucose metabolism abnormalities are prevalent in acute ischaemic stroke (AIS) patients and are associated with poor prognosis. The continuous glucose monitoring (CGM) system can provide detailed information on glucose levels and glycaemic excursions. This study aimed to evaluate the feasibility and accuracy of CGM application in the acute phase of AIS patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This single-centre, prospective, and observational study consecutively enrolled patients with AIS with anterior circulation large vessel occlusion (AC-LVO) and received mechanical thrombectomy (MT) within 24 h of symptom onset. A user-retrospectively calibrated iPro2 CGM system was implanted right before the MT procedure started and removed on the fifth day after MT or at discharge. Fingertip glucose was measured as a reference. Accuracy evaluation included the Bland–Altman plot (with a proportion of CGM values within 15/15, 20/20 and 30/30), the absolute relative difference (ARD) and error grid analysis (EGA). The safety and glucose profiles were also evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 183 patients screened, 141 were included, with a median monitoring duration of 4.49 days. Compared to reference measurements, 3097 CGM readings were matched with a mean bias of −4.16 mg/dL. The proportions of sensor readings meeting the 15/15, 20/20 and 30/30 criteria were 64.55%, 76.07% and 87.21%, respectively. The overall mean and median ARD were 14.60% ± 14.62% and 9.77% (4.15, 20.00). EGA showed that 98.97%, 99.42% and 99.06% values fall within clinically accurate zones in Clarke, Parkes and continuous glucose EGA, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The CGM system was feasible, safe and accurate for in-hospital use among AIS patients who received MT.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 8","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630975","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}
Yutang Wang, Yan Fang, Andreas J. R. Habenicht, Jonathan Golledge, Edward L. Giovannucci, Antonio Ceriello
Aims
This study investigated the association of postprandial plasma glucose (PPG) with cancer mortality using a general cohort of US adults.
Materials and Methods
This cohort study included 14,860 US adults who attended the third National Health and Nutrition Examination Survey from 1988 to 1994, with mortality being followed up until December 31, 2019. The explanatory variable was the level of plasma glucose, including PPG with a fasting time of 0–3.9 h (PPG0–3.9h) and 4–7.9 h (PPG4–7.9h), plasma glucose with a fasting time ≥8 h (PGfasting), and plasma glucose at 2 h after oral glucose tolerance test (PG2hOGTT). Plasma glucose-associated cancer mortality risk was assessed using Cox proportional hazard models.
Results
A 1-natural-log-unit increase in PPG4–7.9h was associated with a higher multivariate-adjusted risk for cancer mortality [hazard ratio (HR), 3.24; 95% confidence interval (CI), 1.50–7.00]. However, PPG0–3.9h, PGfasting, PG2hOGTT, haemoglobin A1c, and insulin were not significantly associated with cancer mortality. The positive association of PPG4–7.9h with cancer mortality remained in those without a prior diagnosis of cancer.
Conclusions
High PPG4–7.9h is associated with a higher cancer mortality risk in US adults. Lowering PPG4–7.9h may reduce cancer mortality.
{"title":"Postprandial Plasma Glucose With a Fasting Time of 4–7.9 h Is Positively Associated With Cancer Mortality in US Adults","authors":"Yutang Wang, Yan Fang, Andreas J. R. Habenicht, Jonathan Golledge, Edward L. Giovannucci, Antonio Ceriello","doi":"10.1002/dmrr.70008","DOIUrl":"10.1002/dmrr.70008","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study investigated the association of postprandial plasma glucose (PPG) with cancer mortality using a general cohort of US adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This cohort study included 14,860 US adults who attended the third National Health and Nutrition Examination Survey from 1988 to 1994, with mortality being followed up until December 31, 2019. The explanatory variable was the level of plasma glucose, including PPG with a fasting time of 0–3.9 h (PPG<sub>0–3.9h</sub>) and 4–7.9 h (PPG<sub>4–7.9h</sub>), plasma glucose with a fasting time ≥8 h (PG<sub>fasting</sub>), and plasma glucose at 2 h after oral glucose tolerance test (PG<sub>2hOGTT</sub>). Plasma glucose-associated cancer mortality risk was assessed using Cox proportional hazard models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A 1-natural-log-unit increase in PPG<sub>4–7.9h</sub> was associated with a higher multivariate-adjusted risk for cancer mortality [hazard ratio (HR), 3.24; 95% confidence interval (CI), 1.50–7.00]. However, PPG<sub>0–3.9h</sub>, PG<sub>fasting</sub>, PG<sub>2hOGTT</sub>, haemoglobin A<sub>1c</sub>, and insulin were not significantly associated with cancer mortality. The positive association of PPG<sub>4–7.9h</sub> with cancer mortality remained in those without a prior diagnosis of cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>High PPG<sub>4–7.9h</sub> is associated with a higher cancer mortality risk in US adults. Lowering PPG<sub>4–7.9h</sub> may reduce cancer mortality.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 8","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631002","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}
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