Wei Liu, Wuhao Wang, Fang Sun, Nan Jiang, Liyuan Yuan, Xiaona Bu, Wentao Shu, Qiang Li, Zhiming Zhu
Aims
To examine whether sublingual microcirculation can be used as an effective and noninvasive method for assessing cardiovascular, kidney, and metabolic risks in patients with type 2 diabetes mellitus (T2DM).
Materials and Methods
This cross-sectional observational study enrolled 186 patients with T2DM. All patients were evaluated using the Framingham General Cardiovascular Risk Score (FGCRS) and cardiovascular-kidney-metabolic (CKM) syndrome stage. Side-stream dark-field microscopy was used for sublingual microcirculation, including total and perfused vessel density (TVD and PVD). Multiple machine-learning prediction models have been developed for CKM risk and stage assessment in T2DM patients. Receiver operating characteristic (ROC) curves were generated to determine cutoff points.
Results
Compared to patients with T2DM, diabetic patients with subclinical atherosclerosis (SA) had a greater CV risk, as measured by the FGCRS, accompanied by markedly decreased microcirculation perfusion. Microcirculatory parameters (TVD and PVD), including carotid intima–media thickness (IMT), brachial-ankle pulse wave velocity (ba-PWV), and FGCRS, were closely associated with SA incidence. Microcirculatory parameters, Index (DMSA screen), and cut-off points were used to screen for SA in patients with T2DM. Furthermore, a new set of four factors identified through machine learning showed optimal sensitivity and specificity for detecting CKM risk in patients with T2DM. Decreased microcirculatory perfusion served as a useful early marker for CKM syndrome risk stratification in patients with T2DM without SA.
Conclusions
Sublingual microcirculatory dysfunction is closely correlated with the risk of SA and CKM risk in T2DM patients. Sublingual microcirculation could be a novel tool for assessing the CKM syndrome stage in patients with T2DM.
{"title":"Machine Learning-Assisted Analysis of Sublingual Microcirculatory Dysfunction for Early Cardiovascular Risk Evaluation and Cardiovascular-Kidney-Metabolic Syndrome Stage in Patients With Type 2 Diabetes Mellitus","authors":"Wei Liu, Wuhao Wang, Fang Sun, Nan Jiang, Liyuan Yuan, Xiaona Bu, Wentao Shu, Qiang Li, Zhiming Zhu","doi":"10.1002/dmrr.3835","DOIUrl":"10.1002/dmrr.3835","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To examine whether sublingual microcirculation can be used as an effective and noninvasive method for assessing cardiovascular, kidney, and metabolic risks in patients with type 2 diabetes mellitus (T2DM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This cross-sectional observational study enrolled 186 patients with T2DM. All patients were evaluated using the Framingham General Cardiovascular Risk Score (FGCRS) and cardiovascular-kidney-metabolic (CKM) syndrome stage. Side-stream dark-field microscopy was used for sublingual microcirculation, including total and perfused vessel density (TVD and PVD). Multiple machine-learning prediction models have been developed for CKM risk and stage assessment in T2DM patients. Receiver operating characteristic (ROC) curves were generated to determine cutoff points.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to patients with T2DM, diabetic patients with subclinical atherosclerosis (SA) had a greater CV risk, as measured by the FGCRS, accompanied by markedly decreased microcirculation perfusion. Microcirculatory parameters (TVD and PVD), including carotid intima–media thickness (IMT), brachial-ankle pulse wave velocity (ba-PWV), and FGCRS, were closely associated with SA incidence. Microcirculatory parameters, Index (DM<sub>SA screen</sub>), and cut-off points were used to screen for SA in patients with T2DM. Furthermore, a new set of four factors identified through machine learning showed optimal sensitivity and specificity for detecting CKM risk in patients with T2DM. Decreased microcirculatory perfusion served as a useful early marker for CKM syndrome risk stratification in patients with T2DM without SA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Sublingual microcirculatory dysfunction is closely correlated with the risk of SA and CKM risk in T2DM patients. Sublingual microcirculation could be a novel tool for assessing the CKM syndrome stage in patients with T2DM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 6","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.3835","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856902","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}
Dan Ziegler, Barbara Thorand, Alexander Strom, Gidon J. Bönhof, Birgit Knebel, Erwin Schleicher, Wolfgang Rathmann, Christian Herder, Haifa Maalmi, Christian Gieger, Margit Heier, Christine Meisinger, Michael Roden, Annette Peters, Harald Grallert
Aims
We recently reported that genetic variability in the TKT gene encoding transketolase, a key enzyme in the pentose phosphate pathway, is associated with measures of diabetic sensorimotor polyneuropathy (DSPN) in recent-onset diabetes. Here, we aimed to substantiate these findings in a population-based KORA F4 study.
Materials and Methods
In this cross-sectional study, we assessed seven single nucleotide polymorphisms (SNPs) in the transketolase gene in 952 participants from the KORA F4 study with normal glucose tolerance (NGT; n = 394), prediabetes (n = 411), and type 2 diabetes (n = 147). DSPN was defined by the examination part of the Michigan Neuropathy Screening Instrument (MNSI) using the original MNSI > 2 cut-off and two alternative versions extended by touch/pressure perception (TPP) (MNSI > 3) and by TPP plus cold perception (MNSI > 4).
Results
After adjustment for sex, age, BMI, and HbA1c, in type 2 diabetes participants, four out of seven transketolase SNPs were associated with DSPN for all three MNSI versions (all p ≤ 0.004). The odds ratios of these associations increased with extending the MNSI score, for example, OR (95% CI) for SNP rs62255988 with MNSI > 2: 1.99 (1.16–3.41), MNSI > 3: 2.27 (1.26–4.09), and MNSI > 4: 4.78 (2.22–10.26); SNP rs9284890 with MNSI > 2: 2.43 (1.42–4.16), MNSI > 3: 3.46 (1.82–6.59), and MNSI > 4: 4.75 (2.15–10.51). In contrast, no associations were found between transketolase SNPs and the three MNSI versions in the NGT and prediabetes groups.
Conclusions
The link of genetic variation in transketolase enzyme to diabetic polyneuropathy corroborated at the population level strengthens the concept suggesting an important role of pathways metabolising glycolytic intermediates in the evolution of diabetic polyneuropathy.
{"title":"Association of transketolase polymorphisms with diabetic polyneuropathy in the general population: The KORA F4 study","authors":"Dan Ziegler, Barbara Thorand, Alexander Strom, Gidon J. Bönhof, Birgit Knebel, Erwin Schleicher, Wolfgang Rathmann, Christian Herder, Haifa Maalmi, Christian Gieger, Margit Heier, Christine Meisinger, Michael Roden, Annette Peters, Harald Grallert","doi":"10.1002/dmrr.3834","DOIUrl":"10.1002/dmrr.3834","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>We recently reported that genetic variability in the <i>TKT</i> gene encoding transketolase, a key enzyme in the pentose phosphate pathway, is associated with measures of diabetic sensorimotor polyneuropathy (DSPN) in recent-onset diabetes. Here, we aimed to substantiate these findings in a population-based KORA F4 study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>In this cross-sectional study, we assessed seven single nucleotide polymorphisms (SNPs) in the transketolase gene in 952 participants from the KORA F4 study with normal glucose tolerance (NGT; <i>n</i> = 394), prediabetes (<i>n</i> = 411), and type 2 diabetes (<i>n</i> = 147). DSPN was defined by the examination part of the Michigan Neuropathy Screening Instrument (MNSI) using the original MNSI > 2 cut-off and two alternative versions extended by touch/pressure perception (TPP) (MNSI > 3) and by TPP plus cold perception (MNSI > 4).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After adjustment for sex, age, BMI, and HbA1c, in type 2 diabetes participants, four out of seven transketolase SNPs were associated with DSPN for all three MNSI versions (all <i>p</i> ≤ 0.004). The odds ratios of these associations increased with extending the MNSI score, for example, OR (95% CI) for SNP rs62255988 with MNSI > 2: 1.99 (1.16–3.41), MNSI > 3: 2.27 (1.26–4.09), and MNSI > 4: 4.78 (2.22–10.26); SNP rs9284890 with MNSI > 2: 2.43 (1.42–4.16), MNSI > 3: 3.46 (1.82–6.59), and MNSI > 4: 4.75 (2.15–10.51). In contrast, no associations were found between transketolase SNPs and the three MNSI versions in the NGT and prediabetes groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The link of genetic variation in transketolase enzyme to diabetic polyneuropathy corroborated at the population level strengthens the concept suggesting an important role of pathways metabolising glycolytic intermediates in the evolution of diabetic polyneuropathy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.3834","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499377","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}
Jose Juan Almagro Armenteros, Caroline Brorsson, Christian Holm Johansen, Karina Banasik, Gianluca Mazzoni, Robert Moulder, Karoliina Hirvonen, Tomi Suomi, Omid Rasool, Sylvaine F. A. Bruggraber, M. Loredana Marcovecchio, Emile Hendricks, Naba Al-Sari, Ismo Mattila, Cristina Legido-Quigley, Tommi Suvitaival, Piotr J. Chmura, Mikael Knip, Anke M. Schulte, Jeong Heon Lee, Guido Sebastiani, Giuseppina Emanuela Grieco, Laura L. Elo, Simranjeet Kaur, Flemming Pociot, Francesco Dotta, Tim Tree, Riitta Lahesmaa, Lut Overbergh, Chantal Mathieu, Mark Peakman, Søren Brunak, the INNODIA investigators
Aims
Heterogeneity in the rate of β-cell loss in newly diagnosed type 1 diabetes patients is poorly understood and creates a barrier to designing and interpreting disease-modifying clinical trials. Integrative analyses of baseline multi-omics data obtained after the diagnosis of type 1 diabetes may provide mechanistic insight into the diverse rates of disease progression after type 1 diabetes diagnosis.
Methods
We collected samples in a pan-European consortium that enabled the concerted analysis of five different omics modalities in data from 97 newly diagnosed patients. In this study, we used Multi-Omics Factor Analysis to identify molecular signatures correlating with post-diagnosis decline in β-cell mass measured as fasting C-peptide.
Results
Two molecular signatures were significantly correlated with fasting C-peptide levels. One signature showed a correlation to neutrophil degranulation, cytokine signalling, lymphoid and non-lymphoid cell interactions and G-protein coupled receptor signalling events that were inversely associated with a rapid decline in β-cell function. The second signature was related to translation and viral infection was inversely associated with change in β-cell function. In addition, the immunomics data revealed a Natural Killer cell signature associated with rapid β-cell decline.
Conclusions
Features that differ between individuals with slow and rapid decline in β-cell mass could be valuable in staging and prediction of the rate of disease progression and thus enable smarter (shorter and smaller) trial designs for disease modifying therapies as well as offering biomarkers of therapeutic effect.
目的：人们对新诊断的1型糖尿病患者β细胞丢失率的异质性知之甚少，这给设计和解释疾病调整临床试验造成了障碍。对1型糖尿病确诊后获得的基线多组学数据进行综合分析，可从机理上深入了解1型糖尿病确诊后疾病进展的不同速度：我们在一个泛欧联盟中收集了样本，对来自 97 名新确诊患者的数据中的五种不同的组学模式进行了协同分析。在这项研究中，我们使用多指标因子分析来确定与诊断后以空腹 C 肽衡量的 β 细胞质量下降相关的分子特征：结果：两个分子特征与空腹 C 肽水平有明显相关性。其中一个特征与中性粒细胞脱颗粒、细胞因子信号、淋巴细胞和非淋巴细胞相互作用以及 G 蛋白偶联受体信号事件相关，这些事件与 β 细胞功能的快速下降成反比。第二个特征与翻译有关，病毒感染与β细胞功能的变化成反比。此外，免疫组学数据显示，自然杀伤细胞特征与β细胞功能快速下降有关：结论：β细胞数量缓慢下降和快速下降的个体之间的特征差异可能对疾病进展速度的分期和预测很有价值，从而使改变疾病疗法的试验设计更智能（更短、更小），并提供治疗效果的生物标志物。
{"title":"Multi-omics analysis reveals drivers of loss of β-cell function after newly diagnosed autoimmune type 1 diabetes: An INNODIA multicenter study","authors":"Jose Juan Almagro Armenteros, Caroline Brorsson, Christian Holm Johansen, Karina Banasik, Gianluca Mazzoni, Robert Moulder, Karoliina Hirvonen, Tomi Suomi, Omid Rasool, Sylvaine F. A. Bruggraber, M. Loredana Marcovecchio, Emile Hendricks, Naba Al-Sari, Ismo Mattila, Cristina Legido-Quigley, Tommi Suvitaival, Piotr J. Chmura, Mikael Knip, Anke M. Schulte, Jeong Heon Lee, Guido Sebastiani, Giuseppina Emanuela Grieco, Laura L. Elo, Simranjeet Kaur, Flemming Pociot, Francesco Dotta, Tim Tree, Riitta Lahesmaa, Lut Overbergh, Chantal Mathieu, Mark Peakman, Søren Brunak, the INNODIA investigators","doi":"10.1002/dmrr.3833","DOIUrl":"10.1002/dmrr.3833","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Heterogeneity in the rate of <i>β</i>-cell loss in newly diagnosed type 1 diabetes patients is poorly understood and creates a barrier to designing and interpreting disease-modifying clinical trials. Integrative analyses of baseline multi-omics data obtained after the diagnosis of type 1 diabetes may provide mechanistic insight into the diverse rates of disease progression after type 1 diabetes diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We collected samples in a pan-European consortium that enabled the concerted analysis of five different omics modalities in data from 97 newly diagnosed patients. In this study, we used Multi-Omics Factor Analysis to identify molecular signatures correlating with post-diagnosis decline in <i>β</i>-cell mass measured as fasting C-peptide.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Two molecular signatures were significantly correlated with fasting C-peptide levels. One signature showed a correlation to neutrophil degranulation, cytokine signalling, lymphoid and non-lymphoid cell interactions and G-protein coupled receptor signalling events that were inversely associated with a rapid decline in <i>β</i>-cell function. The second signature was related to translation and viral infection was inversely associated with change in <i>β</i>-cell function. In addition, the immunomics data revealed a Natural Killer cell signature associated with rapid <i>β</i>-cell decline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Features that differ between individuals with slow and rapid decline in <i>β</i>-cell mass could be valuable in staging and prediction of the rate of disease progression and thus enable smarter (shorter and smaller) trial designs for disease modifying therapies as well as offering biomarkers of therapeutic effect.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.3833","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499378","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}
Gergő Vilmos Szabó, Csenge Szigetváry, Caner Turan, Marie Anne Engh, Tamás Terebessy, Alíz Fazekas, Nelli Farkas, Péter Hegyi, Zsolt Molnár
Fluid resuscitation during diabetic ketoacidosis (DKA) is most frequently performed with 0.9% saline despite its high chloride and sodium concentration. Balanced Electrolyte Solutions (BES) may prove a more physiological alternative, but convincing evidence is missing. We aimed to compare the efficacy of 0.9% saline to BES in DKA management. MEDLINE, Cochrane Library, and Embase databases were searched for relevant studies using predefined keywords (from inception to 27 November 2021). Relevant studies were those in which 0.9% saline (Saline-group) was compared to BES (BES-group) in adults admitted with DKA. Two reviewers independently extracted data and assessed the risk of bias. The primary outcome was time to DKA resolution (defined by each study individually), while the main secondary outcomes were changes in laboratory values, duration of insulin infusion, and mortality. We included seven randomized controlled trials and three observational studies with 1006 participants. The primary outcome was reported for 316 patients, and we found that BES resolves DKA faster than 0.9% saline with a mean difference (MD) of −5.36 [95% CI: −10.46, −0.26] hours. Post-resuscitation chloride (MD: −4.26 [−6.97, −1.54] mmoL/L) and sodium (MD: −1.38 [−2.14, −0.62] mmoL/L) levels were significantly lower. In contrast, levels of post-resuscitation bicarbonate (MD: 1.82 [0.75, 2.89] mmoL/L) were significantly elevated in the BES-group compared to the Saline-group. There was no statistically significant difference between the groups regarding the duration of parenteral insulin administration (MD: 0.16 [−3.03, 3.35] hours) or mortality (OR: −0.67 [0.12, 3.68]). Studies showed some concern or a high risk of bias, and the level of evidence for most outcomes was low. This meta-analysis indicates that the use of BES resolves DKA faster than 0.9% saline. Therefore, DKA guidelines should consider BES instead of 0.9% saline as the first choice during fluid resuscitation.
{"title":"Fluid resuscitation with balanced electrolyte solutions results in faster resolution of diabetic ketoacidosis than with 0.9% saline in adults – A systematic review and meta-analysis","authors":"Gergő Vilmos Szabó, Csenge Szigetváry, Caner Turan, Marie Anne Engh, Tamás Terebessy, Alíz Fazekas, Nelli Farkas, Péter Hegyi, Zsolt Molnár","doi":"10.1002/dmrr.3831","DOIUrl":"10.1002/dmrr.3831","url":null,"abstract":"<p>Fluid resuscitation during diabetic ketoacidosis (DKA) is most frequently performed with 0.9% saline despite its high chloride and sodium concentration. Balanced Electrolyte Solutions (BES) may prove a more physiological alternative, but convincing evidence is missing. We aimed to compare the efficacy of 0.9% saline to BES in DKA management. MEDLINE, Cochrane Library, and Embase databases were searched for relevant studies using predefined keywords (from inception to 27 November 2021). Relevant studies were those in which 0.9% saline (Saline-group) was compared to BES (BES-group) in adults admitted with DKA. Two reviewers independently extracted data and assessed the risk of bias. The primary outcome was time to DKA resolution (defined by each study individually), while the main secondary outcomes were changes in laboratory values, duration of insulin infusion, and mortality. We included seven randomized controlled trials and three observational studies with 1006 participants. The primary outcome was reported for 316 patients, and we found that BES resolves DKA faster than 0.9% saline with a mean difference (MD) of −5.36 [95% CI: −10.46, −0.26] hours. Post-resuscitation chloride (MD: −4.26 [−6.97, −1.54] mmoL/L) and sodium (MD: −1.38 [−2.14, −0.62] mmoL/L) levels were significantly lower. In contrast, levels of post-resuscitation bicarbonate (MD: 1.82 [0.75, 2.89] mmoL/L) were significantly elevated in the BES-group compared to the Saline-group. There was no statistically significant difference between the groups regarding the duration of parenteral insulin administration (MD: 0.16 [−3.03, 3.35] hours) or mortality (OR: −0.67 [0.12, 3.68]). Studies showed some concern or a high risk of bias, and the level of evidence for most outcomes was low. This meta-analysis indicates that the use of BES resolves DKA faster than 0.9% saline. Therefore, DKA guidelines should consider BES instead of 0.9% saline as the first choice during fluid resuscitation.</p>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.3831","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141460112","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}
Due to the high cost and complexity, the oral glucose tolerance test is not adopted as the screening method for identifying diabetes patients, which leads to the misdiagnosis of patients with isolated post-challenge hyperglycemia (IPH), that is., patients with normal fasting plasma glucose (<7.0 mmoL/L) and abnormal 2-h postprandial blood glucose (≥11.1 mmoL/L). We aimed to develop a model to differentiate individuals with IPH from the normal population.
Methods
Data from 54301 eligible participants were obtained from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a longitudinal (REACTION) study in China. Data from 37740 participants were used to develop the diagnostic system. External validation was performed among 16561 participants. Three machine learning algorithms were used to create the predictive models, which were further evaluated by various classification algorithms to establish the best predictive model.
Results
Ten features were selected to develop an IPH diagnosis system (IPHDS) based on an artificial neural network. In external validation, the AUC of the IPHDS was 0.823 (95% CI 0.811–0.836), which was significantly higher than the AUC of the Taiwan model [0.799 (0.786–0.813)] and that of the Chinese Diabetes Risk Score model [0.648 (0.635–0.662)]. The IPHDS model had a sensitivity of 75.6% and a specificity of 74.6%. This model outperformed the Taiwan and CDRS models in subgroup analyses. An online site with instant predictions was deployed at https://app-iphds-e1fc405c8a69.herokuapp.com/.
Conclusions
The proposed IPHDS could be a convenient and user-friendly screening tool for diabetes during health examinations in a large general population.
{"title":"Development and validation of a machine learning-based model to predict isolated post-challenge hyperglycemia in middle-aged and elder adults: Analysis from a multicentric study","authors":"Rui Hou, Jingtao Dou, Lijuan Wu, Xiaoyu Zhang, Changwei Li, Weiqing Wang, Zhengnan Gao, Xulei Tang, Li Yan, Qin Wan, Zuojie Luo, Guijun Qin, Lulu Chen, Jianguang Ji, Yan He, Wei Wang, Yiming Mu, Deqiang Zheng","doi":"10.1002/dmrr.3832","DOIUrl":"https://doi.org/10.1002/dmrr.3832","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Due to the high cost and complexity, the oral glucose tolerance test is not adopted as the screening method for identifying diabetes patients, which leads to the misdiagnosis of patients with isolated post-challenge hyperglycemia (IPH), that is., patients with normal fasting plasma glucose (<7.0 mmoL/L) and abnormal 2-h postprandial blood glucose (≥11.1 mmoL/L). We aimed to develop a model to differentiate individuals with IPH from the normal population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data from 54301 eligible participants were obtained from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a longitudinal (REACTION) study in China. Data from 37740 participants were used to develop the diagnostic system. External validation was performed among 16561 participants. Three machine learning algorithms were used to create the predictive models, which were further evaluated by various classification algorithms to establish the best predictive model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ten features were selected to develop an IPH diagnosis system (IPHDS) based on an artificial neural network. In external validation, the AUC of the IPHDS was 0.823 (95% CI 0.811–0.836), which was significantly higher than the AUC of the Taiwan model [0.799 (0.786–0.813)] and that of the Chinese Diabetes Risk Score model [0.648 (0.635–0.662)]. The IPHDS model had a sensitivity of 75.6% and a specificity of 74.6%. This model outperformed the Taiwan and CDRS models in subgroup analyses. An online site with instant predictions was deployed at https://app-iphds-e1fc405c8a69.herokuapp.com/.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The proposed IPHDS could be a convenient and user-friendly screening tool for diabetes during health examinations in a large general population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.3832","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141439644","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}
Evangelia Baldimtsi, Salvador Amezcua, Martin Ulander, Lars Hyllienmark, Håkan Olausson, Johnny Ludvigsson, Jeanette Wahlberg
Aims
We have evaluated long-term weighted mean HbA1c (wHbA1c), HbA1c variability, diabetes duration, and lipid profiles in relation to the development of diabetic peripheral neuropathy (DPN), nephropathy, and retinopathy in childhood-onset type 1 diabetes.
Materials and Methods
In a longitudinal cohort study, 49 patients (21 women) with childhood-onset type 1 diabetes were investigated with neurophysiological measurements, blood tests, and clinical examinations after a diabetes duration of 7.7 (±3.3) years (baseline) and followed with repeated examinations for 30.6 (±5.2) years. We calculated wHbA1c by integrating the area under all HbA1c values since the diabetes diagnosis. Lipid profiles were analysed in relation to the presence of DPN. Long-term fluctuations of HbA1c variability were computed as the standard deviation of all HbA1c measurements. Data regarding the presence of other diabetes complications were retrieved from medical records.
Results
In this follow-up study, 51% (25/49) of the patients fulfilled electrophysiological criteria for DPN. In nerve conduction studies, there was a deterioration in the amplitudes and conduction velocities for the median, peroneal, and sural nerves over time. Patients with DPN had a longer duration of diabetes, higher wHbA1c, and increased HbA1c variability. The lowest wHbA1c value associated with the development of DPN was 62 mmol/mol (7.8%). The presence of albuminuria and retinopathy was positively correlated with the presence of neuropathy.
Conclusions
More than half of the patients had developed DPN after 30 years. None of the patients who developed DPN had a wHbA1c of less than 62 mmol/mol (7.8%).
{"title":"HbA1c and the risk of developing peripheral neuropathy in childhood-onset type 1 diabetes: A follow-up study over 3 decades","authors":"Evangelia Baldimtsi, Salvador Amezcua, Martin Ulander, Lars Hyllienmark, Håkan Olausson, Johnny Ludvigsson, Jeanette Wahlberg","doi":"10.1002/dmrr.3825","DOIUrl":"10.1002/dmrr.3825","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>We have evaluated long-term weighted mean HbA<sub>1c</sub> (wHbA<sub>1c</sub>), HbA<sub>1c</sub> variability, diabetes duration, and lipid profiles in relation to the development of diabetic peripheral neuropathy (DPN), nephropathy, and retinopathy in childhood-onset type 1 diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>In a longitudinal cohort study, 49 patients (21 women) with childhood-onset type 1 diabetes were investigated with neurophysiological measurements, blood tests, and clinical examinations after a diabetes duration of 7.7 (±3.3) years (baseline) and followed with repeated examinations for 30.6 (±5.2) years. We calculated wHbA<sub>1c</sub> by integrating the area under all HbA<sub>1c</sub> values since the diabetes diagnosis. Lipid profiles were analysed in relation to the presence of DPN. Long-term fluctuations of HbA<sub>1c</sub> variability were computed as the standard deviation of all HbA<sub>1c</sub> measurements. Data regarding the presence of other diabetes complications were retrieved from medical records.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In this follow-up study, 51% (25/49) of the patients fulfilled electrophysiological criteria for DPN. In nerve conduction studies, there was a deterioration in the amplitudes and conduction velocities for the median, peroneal, and sural nerves over time. Patients with DPN had a longer duration of diabetes, higher wHbA<sub>1c,</sub> and increased HbA<sub>1c</sub> variability. The lowest wHbA<sub>1c</sub> value associated with the development of DPN was 62 mmol/mol (7.8%). The presence of albuminuria and retinopathy was positively correlated with the presence of neuropathy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>More than half of the patients had developed DPN after 30 years. None of the patients who developed DPN had a wHbA<sub>1c</sub> of less than 62 mmol/mol (7.8%).</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 5","pages":""},"PeriodicalIF":8.0,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.3825","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141328009","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}
Christian Herder, Barbara Thorand, Alexander Strom, Wolfgang Rathmann, Margit Heier, Wolfgang Koenig, Helen Morrison, Dan Ziegler, Michael Roden, Annette Peters, Gidon J. Bönhof, Haifa Maalmi
Aims
The aim of this study was to assess associations between neurological biomarkers and distal sensorimotor polyneuropathy (DSPN).
Materials and Methods
Cross-sectional analyses were based on 1032 participants aged 61–82 years from the population-based KORA F4 survey, 177 of whom had DSPN at baseline. The prevalence of type 2 diabetes was 20%. Prospective analyses used data from 505 participants without DSPN at baseline, of whom 125 had developed DSPN until the KORA FF4 survey. DSPN was defined based on the examination part of the Michigan Neuropathy Screening Instrument. Serum levels of neurological biomarkers were measured using proximity extension assay technology. Associations between 88 biomarkers and prevalent or incident DSPN were estimated using Poisson regression with robust error variance and are expressed as risk ratios (RR) and 95% CI per 1-SD increase. Results were adjusted for multiple confounders and multiple testing using the Benjamini–Hochberg procedure.
Results
Higher serum levels of CTSC (cathepsin C; RR [95% CI] 1.23 (1.08; 1.39), pB-H = 0.044) and PDGFRα (platelet-derived growth factor receptor A; RR [95% CI] 1.21 (1.08; 1.35), pB-H = 0.044) were associated with prevalent DSPN in the total study sample. CDH3, JAM-B, LAYN, RGMA and SCARA5 were positively associated with DSPN in the diabetes subgroup, whereas GCP5 was positively associated with DSPN in people without diabetes (all pB-H for interaction <0.05). None of the biomarkers showed an association with incident DSPN (all pB-H>0.05).
Conclusions
This study identified multiple novel associations between neurological biomarkers and prevalent DSPN, which may be attributable to functions of these proteins in neuroinflammation, neural development and myelination.
{"title":"Associations between multiple neurological biomarkers and distal sensorimotor polyneuropathy: KORA F4/FF4 study","authors":"Christian Herder, Barbara Thorand, Alexander Strom, Wolfgang Rathmann, Margit Heier, Wolfgang Koenig, Helen Morrison, Dan Ziegler, Michael Roden, Annette Peters, Gidon J. Bönhof, Haifa Maalmi","doi":"10.1002/dmrr.3807","DOIUrl":"10.1002/dmrr.3807","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The aim of this study was to assess associations between neurological biomarkers and distal sensorimotor polyneuropathy (DSPN).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Cross-sectional analyses were based on 1032 participants aged 61–82 years from the population-based KORA F4 survey, 177 of whom had DSPN at baseline. The prevalence of type 2 diabetes was 20%. Prospective analyses used data from 505 participants without DSPN at baseline, of whom 125 had developed DSPN until the KORA FF4 survey. DSPN was defined based on the examination part of the Michigan Neuropathy Screening Instrument. Serum levels of neurological biomarkers were measured using proximity extension assay technology. Associations between 88 biomarkers and prevalent or incident DSPN were estimated using Poisson regression with robust error variance and are expressed as risk ratios (RR) and 95% CI per 1-SD increase. Results were adjusted for multiple confounders and multiple testing using the Benjamini–Hochberg procedure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Higher serum levels of CTSC (cathepsin C; RR [95% CI] 1.23 (1.08; 1.39), <i>p</i><sub>B-H</sub> = 0.044) and PDGFRα (platelet-derived growth factor receptor A; RR [95% CI] 1.21 (1.08; 1.35), <i>p</i><sub>B-H</sub> = 0.044) were associated with prevalent DSPN in the total study sample. CDH3, JAM-B, LAYN, RGMA and SCARA5 were positively associated with DSPN in the diabetes subgroup, whereas GCP5 was positively associated with DSPN in people without diabetes (all <i>p</i><sub>B-H</sub> for interaction <0.05). None of the biomarkers showed an association with incident DSPN (all <i>p</i><sub>B-H</sub>>0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study identified multiple novel associations between neurological biomarkers and prevalent DSPN, which may be attributable to functions of these proteins in neuroinflammation, neural development and myelination.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 5","pages":""},"PeriodicalIF":8.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.3807","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141318689","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}
Metabolic/bariatric surgery as a treatment for obesity and related diseases, such as type 2 diabetes mellitus (T2DM), has been increasingly recognised in recent years. However, compared with conventional pharmacologic therapy, the long-term effect (≥ 5 years) of metabolic surgery in T2DM patients is still unclear. This study aimed to evaluate the diabetes remission rate, incidence of diabetic microvascular complications, incidence of macrovascular complications, and mortality in T2DM patients who received metabolic surgery versus pharmacologic therapy more than 5 years after the surgery. Searching the database, including PubMed, Embase, Web of Science, and Cochrane Library from the inception to recent (2024), for randomised clinical trials (RCTs) or cohort studies comparing T2DM patients treated with metabolic surgery versus pharmacologic therapy reporting on the outcomes of the diabetes remission rate, diabetic microvascular complications, macrovascular complications, or mortality over 5 years or more. A total of 15 articles with a total of 85,473 patients with T2DM were eligible for review and meta-analysis in this study. There is a significant long-term increase in diabetes remission for metabolic surgery compared with conventional medical therapy in the overall pooled estimation and RCT studies or cohort studies separately (overall: OR = 4.58, 95% CI: 1.89–11.07, P < 0.001). Significant long-term decreases were found in the pooled results of microvascular complications incidence (HR = 0.57, 95% CI: 0.41–0.78, P < 0.001), macrovascular complications incidence (HR = 0.59, 95% CI: 0.50–0.70, P < 0.001) and mortality (HR = 0.53, 95% CI: 0.53–0.79, P = 0.0018). Metabolic surgery showed more significant long-term effects than pharmacologic therapy on diabetes remission, macrovascular complications, microvascular complications incidence, and all-cause mortality in patients with T2DM using currently available evidence. More high-quality evidence is needed to validate the long-term effects of metabolic surgery versus conventional treatment in diabetes management.
{"title":"The long-term effect of bariatric/metabolic surgery versus pharmacologic therapy in type 2 diabetes mellitus patients: A systematic review and meta-analysis","authors":"Yumeng Yang, Chuhan Miao, Yingli Wang, Jianxun He","doi":"10.1002/dmrr.3830","DOIUrl":"10.1002/dmrr.3830","url":null,"abstract":"<p>Metabolic/bariatric surgery as a treatment for obesity and related diseases, such as type 2 diabetes mellitus (T2DM), has been increasingly recognised in recent years. However, compared with conventional pharmacologic therapy, the long-term effect (≥ 5 years) of metabolic surgery in T2DM patients is still unclear. This study aimed to evaluate the diabetes remission rate, incidence of diabetic microvascular complications, incidence of macrovascular complications, and mortality in T2DM patients who received metabolic surgery versus pharmacologic therapy more than 5 years after the surgery. Searching the database, including PubMed, Embase, Web of Science, and Cochrane Library from the inception to recent (2024), for randomised clinical trials (RCTs) or cohort studies comparing T2DM patients treated with metabolic surgery versus pharmacologic therapy reporting on the outcomes of the diabetes remission rate, diabetic microvascular complications, macrovascular complications, or mortality over 5 years or more. A total of 15 articles with a total of 85,473 patients with T2DM were eligible for review and meta-analysis in this study. There is a significant long-term increase in diabetes remission for metabolic surgery compared with conventional medical therapy in the overall pooled estimation and RCT studies or cohort studies separately (overall: OR = 4.58, 95% CI: 1.89–11.07, <i>P</i> < 0.001). Significant long-term decreases were found in the pooled results of microvascular complications incidence (HR = 0.57, 95% CI: 0.41–0.78, <i>P</i> < 0.001), macrovascular complications incidence (HR = 0.59, 95% CI: 0.50–0.70, <i>P</i> < 0.001) and mortality (HR = 0.53, 95% CI: 0.53–0.79, <i>P</i> = 0.0018). Metabolic surgery showed more significant long-term effects than pharmacologic therapy on diabetes remission, macrovascular complications, microvascular complications incidence, and all-cause mortality in patients with T2DM using currently available evidence. More high-quality evidence is needed to validate the long-term effects of metabolic surgery versus conventional treatment in diabetes management.</p>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 5","pages":""},"PeriodicalIF":8.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.3830","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141318690","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}
Alexandra Rabotin, Yair Schwarz, Orit Pinhas-Hamiel, Ofer Amir, Estela Derazne, Dorit Tzur, Gabriel Chodick, Arnon Afek, Avishai M. Tsur, Gilad Twig
Aims
To investigate the association between stuttering during adolescence and the onset of dysglycemia (prediabetes or type 2 diabetes) in early adulthood among men and women.
Materials and Methods
This cohort study included Maccabi Health Services members assessed for mandatory military service at ages 16–19 during 1990–2019 and followed until 31 December 2020. Stuttering status was recorded in the baseline medical evaluation. Incident cases of dysglycemia were identified systematically using prediabetes and diabetes registries. Cox proportional hazard models were applied for men and women separately, adjusting for sociodemographics and medical status.
Results
The study cohort comprised 866,304 individuals (55% men; 0.21% with stuttering) followed for a total of 12,696,250 person-years. During the study period, 7.6% (n = 36,603) of men and 9.0% (n = 34,723) of women were diagnosed with dysglycemia. The mean ages at diagnosis were 34 and 32 years for men and women, respectively. Women with stuttering exhibited the highest dysglycemia incidence rate (102.3 per 10,000 person-years) compared with the other groups (61.4, 69.0, and 51.9 per 10,000 person-years for women without stuttering, men with stuttering, and men without stuttering, respectively). For both men and women, those with stuttering showed an increased risk of being diagnosed with dysglycemia compared with those without (adjusted hazard ratios 1.18 [1.01–1.38] and 1.61 [1.15–2.26], respectively). The associations persisted in extensive sub-analyses.
Conclusions
Stuttering in adolescence is associated with a higher risk of dysglycemia in early adulthood for men and women. Screening and targeted prevention in this population, especially women, may be beneficial.
{"title":"Stuttering in adolescence and the risk for dysglycemia in early adulthood","authors":"Alexandra Rabotin, Yair Schwarz, Orit Pinhas-Hamiel, Ofer Amir, Estela Derazne, Dorit Tzur, Gabriel Chodick, Arnon Afek, Avishai M. Tsur, Gilad Twig","doi":"10.1002/dmrr.3828","DOIUrl":"10.1002/dmrr.3828","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To investigate the association between stuttering during adolescence and the onset of dysglycemia (prediabetes or type 2 diabetes) in early adulthood among men and women.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This cohort study included Maccabi Health Services members assessed for mandatory military service at ages 16–19 during 1990–2019 and followed until 31 December 2020. Stuttering status was recorded in the baseline medical evaluation. Incident cases of dysglycemia were identified systematically using prediabetes and diabetes registries. Cox proportional hazard models were applied for men and women separately, adjusting for sociodemographics and medical status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study cohort comprised 866,304 individuals (55% men; 0.21% with stuttering) followed for a total of 12,696,250 person-years. During the study period, 7.6% (<i>n</i> = 36,603) of men and 9.0% (<i>n</i> = 34,723) of women were diagnosed with dysglycemia. The mean ages at diagnosis were 34 and 32 years for men and women, respectively. Women with stuttering exhibited the highest dysglycemia incidence rate (102.3 per 10,000 person-years) compared with the other groups (61.4, 69.0, and 51.9 per 10,000 person-years for women without stuttering, men with stuttering, and men without stuttering, respectively). For both men and women, those with stuttering showed an increased risk of being diagnosed with dysglycemia compared with those without (adjusted hazard ratios 1.18 [1.01–1.38] and 1.61 [1.15–2.26], respectively). The associations persisted in extensive sub-analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Stuttering in adolescence is associated with a higher risk of dysglycemia in early adulthood for men and women. Screening and targeted prevention in this population, especially women, may be beneficial.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 5","pages":""},"PeriodicalIF":8.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.3828","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301939","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}
Amir H. Sam, Adam J. Buckley, Brian Y. H. Lam, Gavin A. Bewick, Paul R. Bech, Karim Meeran, Maha T. Barakat, Stephen R. Bloom, Giles S. H. Yeo, Nader G. Lessan, Kevin G. Murphy
Aims
Pancreatic polypeptide (PP) is elevated in people with vascular risk factors such as type 2 diabetes or increased visceral fat. We investigated potential relationships between PP and microvascular and macrovascular complications of diabetes.
Materials and Methods
Animal study: Subcutaneous PP infusion for 4 weeks in high fat diet mouse model. Retinal mRNA submitted for Ingenuity Pathway Analysis. Human study: fasting PP measured in 1478 participants and vascular complications recorded over median 5.5 (IQR 4.9–5.8) years follow-up.
Results
Animal study: The retinal transcriptional response to PP was indicative of cellular stress and damage, and this footprint matched responses described in previously published studies of retinal disease. Of mechanistic importance the transcriptional landscape was consistent with upregulation of folliculin, a recently identified susceptibility gene for diabetic retinopathy. Human study: Adjusting for established risk factors, PP was associated with prevalent and incident clinically significant retinopathy (odds ratio (OR) 1.289 (1.107–1.501) p = 0.001; hazard ratio (HR) 1.259 (1.035–1.531) p = 0.0213), albuminuria (OR 1.277 (1.124–1.454), p = 0.0002; HR 1.608 (1.208–2.141) p = 0.0011), and macrovascular disease (OR 1.021 (1.006–1.037) p = 0.0068; HR 1.324 (1.089–1.61), p = 0.0049), in individuals with type 2 diabetes, and progression to diabetes in non-diabetic individuals (HR 1.402 (1.081–1.818), p = 0.0109).
Conclusions
Elevated fasting PP is independently associated with vascular complications of diabetes and affects retinal pathways potentially influencing retinal neuronal survival. Our results suggest possible new roles for PP-fold peptides in the pathophysiology of diabetes complications and vascular risk stratification.
{"title":"Fasting pancreatic polypeptide predicts incident microvascular and macrovascular complications of type 2 diabetes: An observational study","authors":"Amir H. Sam, Adam J. Buckley, Brian Y. H. Lam, Gavin A. Bewick, Paul R. Bech, Karim Meeran, Maha T. Barakat, Stephen R. Bloom, Giles S. H. Yeo, Nader G. Lessan, Kevin G. Murphy","doi":"10.1002/dmrr.3829","DOIUrl":"10.1002/dmrr.3829","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Pancreatic polypeptide (PP) is elevated in people with vascular risk factors such as type 2 diabetes or increased visceral fat. We investigated potential relationships between PP and microvascular and macrovascular complications of diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p><i>Animal study</i>: Subcutaneous PP infusion for 4 weeks in high fat diet mouse model. Retinal mRNA submitted for Ingenuity Pathway Analysis. <i>Human study</i>: fasting PP measured in 1478 participants and vascular complications recorded over median 5.5 (IQR 4.9–5.8) years follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>Animal study</i>: The retinal transcriptional response to PP was indicative of cellular stress and damage, and this footprint matched responses described in previously published studies of retinal disease. Of mechanistic importance the transcriptional landscape was consistent with upregulation of folliculin, a recently identified susceptibility gene for diabetic retinopathy. <i>Human study</i>: Adjusting for established risk factors, PP was associated with prevalent and incident clinically significant retinopathy (odds ratio (OR) 1.289 (1.107–1.501) <i>p</i> = 0.001; hazard ratio (HR) 1.259 (1.035–1.531) <i>p</i> = 0.0213), albuminuria (OR 1.277 (1.124–1.454), <i>p</i> = 0.0002; HR 1.608 (1.208–2.141) <i>p</i> = 0.0011), and macrovascular disease (OR 1.021 (1.006–1.037) <i>p</i> = 0.0068; HR 1.324 (1.089–1.61), <i>p</i> = 0.0049), in individuals with type 2 diabetes, and progression to diabetes in non-diabetic individuals (HR 1.402 (1.081–1.818), <i>p</i> = 0.0109).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Elevated fasting PP is independently associated with vascular complications of diabetes and affects retinal pathways potentially influencing retinal neuronal survival. Our results suggest possible new roles for PP-fold peptides in the pathophysiology of diabetes complications and vascular risk stratification.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 5","pages":""},"PeriodicalIF":8.0,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.3829","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288718","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}
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