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The role of long non-coding RNAs in the development of diabetic kidney disease and the involved clinical application 长非编码 RNA 在糖尿病肾病发病过程中的作用及其临床应用
IF 8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-06 DOI: 10.1002/dmrr.3809
Qizhuo Hou, Bin Yi

Diabetic kidney disease (DKD), one of the common microvascular complications of diabetes, is increasing in prevalence worldwide and can lead to End-stage renal disease. However, there are still gaps in our understanding of the pathophysiology of DKD, and both current clinical diagnostic methods and treatment strategies have drawbacks. According to recent research, long non-coding RNAs (lncRNAs) are intimately linked to the developmental process of DKD and could be viable targets for clinical diagnostic decisions and therapeutic interventions. Here, we review recent insights gained into lncRNAs in pathological changes of DKD such as mesangial expansion, podocyte injury, renal tubular injury, and interstitial fibrosis. We also discuss the clinical applications of DKD-associated lncRNAs as diagnostic biomarkers and therapeutic targets, as well as their limitations and challenges, to provide new methods for the prevention, diagnosis, and treatment of DKD.

糖尿病肾病(DKD)是糖尿病常见的微血管并发症之一,在全球的发病率越来越高,并可导致终末期肾病。然而,我们对糖尿病肾病病理生理学的认识仍有差距,目前的临床诊断方法和治疗策略也存在缺陷。根据最新研究,长非编码 RNA(lncRNA)与 DKD 的发展过程密切相关,可以成为临床诊断决策和治疗干预的可行靶点。在此,我们回顾了最近在DKD病理变化(如系膜扩张、荚膜细胞损伤、肾小管损伤和肾间质纤维化)中lncRNA的研究进展。我们还讨论了 DKD 相关 lncRNA 作为诊断生物标志物和治疗靶点的临床应用及其局限性和挑战,以期为 DKD 的预防、诊断和治疗提供新方法。
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引用次数: 0
Correspondence to “association of sleep patterns and cardiovascular disease risk is modified by glucose tolerance status” 通讯:"睡眠模式与心血管疾病风险的关联受葡萄糖耐量状态的影响"
IF 8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-06 DOI: 10.1002/dmrr.3808
Ssu-Yu Chen, Ting-An Lin, Cheuk-Kwan Sun, Renin Chang

After reading the article written by Wang et al., we have encountered several concerns that may compromise the credibility of the article. There are some factors, such as changes in sleep patterns, glucose tolerance status, and the use of hypnotics, which may interfere with the research results. Additionally, the design of the sleep pattern could lead to biased outcomes. Therefore, we are writing this letter to recommend that further research should take these concerns into consideration.

在阅读了 Wang 等人撰写的文章后,我们遇到了几个可能会影响文章可信度的问题。有一些因素,如睡眠模式的变化、葡萄糖耐量状态和催眠药的使用,可能会干扰研究结果。此外,睡眠模式的设计也可能导致结果出现偏差。因此,我们写这封信建议进一步的研究应考虑到这些问题。
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引用次数: 0
Cost-effectiveness of temperature monitoring to help prevent foot ulcer recurrence in people with diabetes: A multicenter randomized controlled trial 通过体温监测预防糖尿病患者足部溃疡复发的成本效益:多中心随机对照试验
IF 8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-04-30 DOI: 10.1002/dmrr.3805
Jaap J. Van Netten, Wouter B. Aan De Stegge, Marcel G. W. Dijkgraaf, Sicco A. Bus

Aims

Diabetes-related foot ulcers are common, costly, and frequently recur. Multiple interventions help prevent these ulcers. However, none of these have been prospectively investigated for cost-effectiveness. Our aim was to evaluate the cost-effectiveness of at-home skin temperature monitoring to help prevent diabetes-related foot ulcer recurrence.

Materials and Methods

Multicenter randomized controlled trial. We randomized 304 persons at high diabetes-related foot ulcer risk to either usual foot care plus daily at-home foot skin temperature monitoring (intervention) or usual care alone (control). Primary outcome was cost-effectiveness based on foot care costs and quality-adjusted life years (QALY) during 18 months follow-up. Foot care costs included costs for ulcer prevention (e.g., footwear, podiatry) and for ulcer treatment when required (e.g., consultation, hospitalisation, amputation). Incremental cost-effectiveness ratios were calculated for intervention versus usual care using probabilistic sensitivity analysis for willingness-to-pay/accept levels up to €100,000.

Results

The intervention had a 45% probability of being cost-effective at a willingness-to-accept of €50,000 per QALY lost. This resulted from (non-significantly) lower foot care costs in the intervention group (€6067 vs. €7376; p = 0.45) because of (significantly) fewer participants with ulcer recurrence(s) in 18 months (36% vs. 47%; p = 0.045); however, QALYs were (non-significantly) lower in the intervention group (1.09 vs. 1.12; p = 0.35), especially in those without foot ulcer recurrence (1.09 vs. 1.17; p = 0.10).

Conclusions

At-home skin temperature monitoring for diabetes-related foot ulcer prevention compared with usual care is at best equally cost-effective. The intervention resulted in cost-savings due to preventing foot ulcer recurrence and related costs, but this came at the expense of QALY loss, potentially from self-monitoring burdens.

目的 与糖尿病有关的足部溃疡很常见,费用高昂,而且经常复发。多种干预措施有助于预防这些溃疡。然而,这些干预措施都没有进行过成本效益的前瞻性调查。我们的目的是评估居家皮肤温度监测在预防糖尿病足溃疡复发方面的成本效益。 材料与方法 多中心随机对照试验。我们将 304 名糖尿病相关足部溃疡高危人群随机分配到常规足部护理加每日居家足部皮肤温度监测(干预)或单纯常规护理(对照)两种方案中。主要结果是基于 18 个月随访期间的足部护理成本和质量调整生命年(QALY)的成本效益。足部护理成本包括溃疡预防成本(如鞋类、足病治疗)和溃疡治疗成本(如咨询、住院、截肢)。采用概率敏感性分析法计算了干预与常规护理的增量成本效益比,支付意愿/接受水平最高为 10 万欧元。 结果 在接受意愿值为每 QALY 损失 50,000 欧元时,干预措施具有成本效益的概率为 45%。这是因为干预组的足部护理成本较低(6067 欧元 vs. 7376 欧元;p = 0.45),因为在 18 个月内溃疡复发的参与者人数较少(36% vs. 47%;p = 0.045);但是,干预组的 QALY 较低(1.09 vs. 1.12;p = 0.35),尤其是没有足部溃疡复发的参与者(1.09 vs. 1.17;p = 0.10)。 结论 在家中进行皮肤温度监测以预防糖尿病相关足部溃疡与常规护理相比,成本效益充其量相当。干预措施可防止足部溃疡复发并节省相关费用,但这是以QALY损失为代价的,QALY损失可能来自于自我监测负担。
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引用次数: 0
Estimating the effect of lipid-lowering agents on novel subtypes of adult-onset diabetes 估算降脂药对成人型糖尿病新亚型的影响
IF 8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-04-25 DOI: 10.1002/dmrr.3793
Jianan Ye, Keyu Guo, Jiaqi Li, Xia Li, Zhiguang Zhou, Lin Yang

Aims

The aims of the present study were to assess the effects of lipid-lowering drugs [HMG-CoA reductase inhibitors, proprotein convertase subtilisin/kexin type 9 inhibitors, and Niemann–Pick C1-Like 1 (NPC1L1) inhibitors] on novel subtypes of adult-onset diabetes through a Mendelian randomisation study.

Materials and Methods

We first inferred causal associations between lipid-related traits [including high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), apolipoproteins A-I, and apolipoproteins B] and novel subtypes of adult-onset diabetes. The expression quantitative trait loci of drug target genes for three classes of lipid-lowering drugs, as well as genetic variants within or nearby drug target genes associated with LDL-C, were then utilised as proxies for the exposure of lipid-lowering drugs. Mendelian randomisation analysis was performed using summary data from genome-wide association studies of LDL-C, severe autoimmune diabetes, severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), and mild age-related diabetes.

Results

There was an association between HMGCR-mediated LDL-C and the risk of SIRD [odds ratio (OR) = 0.305, 95% confidence interval (CI) = 0.129–0.723; p = 0.007], and there was an association of PCSK9-mediated LDL-C with the risk of SIDD (OR = 0.253, 95% CI = 0.120–0.532; p < 0.001) and MOD (OR = 0.345, 95% CI = 0.171–0.696; p = 0.003). Moreover, NPC1L1-mediated LDL-C (OR = 0.109, 95% CI = 0.019–0.613; p = 0.012) and the increased expression of NPC1L1 gene in blood (OR = 0.727, 95% CI = 0.541–0.977; p = 0.034) both showed a significant association with SIRD. These results were further confirmed by sensitivity analyses.

Conclusions

In summary, the different lipid-lowering medications have a specific effect on the increased risk of different novel subtypes of adult-onset diabetes.

研究目的 本研究旨在通过孟德尔随机研究评估降脂药物[HMG-CoA 还原酶抑制剂、蛋白转换酶枯草酶/kexin 9 型抑制剂和 Niemann-Pick C1-Like 1 (NPC1L1) 抑制剂]对成年型糖尿病新亚型的影响。 材料与方法 我们首先推断了血脂相关性状(包括高密度脂蛋白胆固醇、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)、载脂蛋白 A-I 和载脂蛋白 B)与成年型糖尿病新亚型之间的因果关系。然后利用三类降脂药物靶基因的表达定量性状位点,以及与低密度脂蛋白胆固醇相关的药物靶基因内或附近的遗传变异,作为降脂药物暴露的替代物。利用低密度脂蛋白胆固醇、严重自身免疫性糖尿病、严重胰岛素缺乏性糖尿病(SIDD)、严重胰岛素抵抗性糖尿病(SIRD)、轻度肥胖相关性糖尿病(MOD)和轻度年龄相关性糖尿病的全基因组关联研究的汇总数据进行了孟德尔随机分析。 结果 HMGCR介导的低密度脂蛋白胆固醇(LDL-C)与 SIRD 风险之间存在关联[几率比(OR)= 0.305,95% 置信区间(CI)= 0.129-0.723; p = 0.007],PCSK9介导的LDL-C与SIDD(OR = 0.253,95% CI = 0.120-0.532; p <0.001)和MOD(OR = 0.345,95% CI = 0.171-0.696; p = 0.003)的风险存在关联。此外,NPC1L1 介导的低密度脂蛋白胆固醇(OR = 0.109,95% CI = 0.019-0.613;p = 0.012)和血液中 NPC1L1 基因表达的增加(OR = 0.727,95% CI = 0.541-0.977;p = 0.034)均与 SIRD 有显著关联。敏感性分析进一步证实了这些结果。 结论 总之,不同的降脂药物对不同新型亚型成人型糖尿病风险的增加有特定的影响。
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引用次数: 0
Global, regional, and national burden of blindness and vision loss attributable to high fasting plasma glucose from 1990 to 2019, and forecasts to 2030: A systematic analysis for the Global Burden of Disease Study 2019 1990 年至 2019 年全球、地区和国家因空腹血浆葡萄糖过高导致失明和视力丧失的负担,以及对 2030 年的预测:2019 年全球疾病负担研究的系统分析
IF 8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-04-18 DOI: 10.1002/dmrr.3802
Cong Li, Guangyao Hua, Shunming Liu, Honghua Yu, Xiaohong Yang, Lei Liu

Aims

To systematically clarify the spatiotemporal trends, and age-sex-specific blindness and vision loss (BVL) burden due to high fasting plasma glucose (HFPG) from 1990 to 2019, and project this burden over the next decade.

Materials and Methods

We obtained the number and rate of years lived with disability (YLDs) for the BVL burden attributable to HFPG by age, sex, socio-demographic index (SDI), and location between 1990 and 2019 from the Global Burden of Disease (GBD) 2019 database. The average annual percentage changes (AAPCs) were calculated to assess the temporal trends of HFPG-attributable BVL burden. The Bayesian age-period-cohort model was used to predict the HFPG-attributable BVL burden.

Results

In 2019, the global number and age-standardized rate (ASR) for YLDs of BVL attributable to HFPG were 673.13 (95% UI: 159.52 to 1565.34) thousand and 8.44 (95% UI: 2.00 to 19.63) per 100,000 people, respectively. The highest burdens were found in Oceania, South Asia, and Southeast Asia, and the BVL burden due to HFPG was higher in the elderly and lower SDI regions. From 1990 to 2019, the global ASR of HFPG-attributable BVL gradually increased with AAPC (95% CI) being 0.80 (0.74 to 0.86). In addition, the HFPG-attributable BVL burden will slightly increase in the future decade.

Conclusions

The HFPG remains the important cause of BVL worldwide, placing a substantial disease burden. From 1990 to 2019, the age-standardized burden of BVL due to HFPG increased, and will consistently increase in the future decade, particularly in the elderly and in regions with middle SDI or below.

目的 系统地阐明 1990 年至 2019 年期间空腹血浆葡萄糖过高(HFPG)导致失明和视力丧失(BVL)的时空趋势和特定年龄-性别负担,并预测未来十年的负担情况。 材料与方法 我们从全球疾病负担(GBD)2019 数据库中获得了 1990 年至 2019 年期间因高空腹血浆葡萄糖而导致的残疾生活年数(YLD)的数量和比率,并按年龄、性别、社会人口指数(SDI)和地点进行了分类。通过计算年均百分比变化(AAPCs)来评估高频气胸归因于BVL负担的时间趋势。贝叶斯年龄-时期-队列模型用于预测高危人群可归因的BVL负担。 结果 2019年,HFPG所致BVL的全球YLD数量和年龄标准化率(ASR)分别为每10万人673.13(95% UI:159.52至1565.34)千例和8.44(95% UI:2.00至19.63)例。大洋洲、南亚和东南亚的负担最高,老年人和SDI较低的地区因HFPG导致的BVL负担较高。从 1990 年到 2019 年,全球 HFPG 可归因于 BVL 的 ASR 逐渐增加,AAPC(95% CI)为 0.80(0.74 至 0.86)。此外,在未来十年中,HFPG 导致的 BVL 负担将略有增加。 结论 HFPG 仍是全球 BVL 的重要病因,造成了巨大的疾病负担。从 1990 年到 2019 年,HFPG 导致的 BVL 年龄标准化负担有所增加,并将在未来十年持续增加,尤其是在老年人和 SDI 中等或以下的地区。
{"title":"Global, regional, and national burden of blindness and vision loss attributable to high fasting plasma glucose from 1990 to 2019, and forecasts to 2030: A systematic analysis for the Global Burden of Disease Study 2019","authors":"Cong Li,&nbsp;Guangyao Hua,&nbsp;Shunming Liu,&nbsp;Honghua Yu,&nbsp;Xiaohong Yang,&nbsp;Lei Liu","doi":"10.1002/dmrr.3802","DOIUrl":"https://doi.org/10.1002/dmrr.3802","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To systematically clarify the spatiotemporal trends, and age-sex-specific blindness and vision loss (BVL) burden due to high fasting plasma glucose (HFPG) from 1990 to 2019, and project this burden over the next decade.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We obtained the number and rate of years lived with disability (YLDs) for the BVL burden attributable to HFPG by age, sex, socio-demographic index (SDI), and location between 1990 and 2019 from the Global Burden of Disease (GBD) 2019 database. The average annual percentage changes (AAPCs) were calculated to assess the temporal trends of HFPG-attributable BVL burden. The Bayesian age-period-cohort model was used to predict the HFPG-attributable BVL burden.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In 2019, the global number and age-standardized rate (ASR) for YLDs of BVL attributable to HFPG were 673.13 (95% UI: 159.52 to 1565.34) thousand and 8.44 (95% UI: 2.00 to 19.63) per 100,000 people, respectively. The highest burdens were found in Oceania, South Asia, and Southeast Asia, and the BVL burden due to HFPG was higher in the elderly and lower SDI regions. From 1990 to 2019, the global ASR of HFPG-attributable BVL gradually increased with AAPC (95% CI) being 0.80 (0.74 to 0.86). In addition, the HFPG-attributable BVL burden will slightly increase in the future decade.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The HFPG remains the important cause of BVL worldwide, placing a substantial disease burden. From 1990 to 2019, the age-standardized burden of BVL due to HFPG increased, and will consistently increase in the future decade, particularly in the elderly and in regions with middle SDI or below.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 4","pages":""},"PeriodicalIF":8.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.3802","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140606260","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}
引用次数: 0
The unique multidisciplinarity of diabetes-related foot disease 与糖尿病有关的足病具有独特的多学科性
IF 8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-04-14 DOI: 10.1002/dmrr.3804
Jaap J. van Netten, Jan Apelqvist, Sicco A. Bus, Robert Fitridge, Fran Game, Matilde Monteiro-Soares, Eric Senneville, Nicolaas C. Schaper

Few diseases globally require treatment from so many different disciplines as diabetes-related foot disease. At least 25 different professionals may be involved: casting technicians, dermatologists, diabetes (educator) nurses, diabetologists, dieticians, endocrinologists, general practitioners, human movement scientists, infectious diseases experts, microbiologists, nuclear medicine physicians, orthopaedic surgeons, orthotists, pedorthists, physical therapists, plastic surgeons, podiatric surgeons, podiatrists, prosthetists, psychologists, radiologists, social workers, tissue viability physicians, vascular surgeons, and wound care nurses. A shared vocabulary and shared treatment goals and recommendations are then essential. The International Working Group on the Diabetic Foot (IWGDF) has produced guidelines and supporting documents to stimulate and support shared and multidisciplinary evidence-based treatment in diabetes-related foot disease. In this special virtual issue of Diabetes/Metabolism Research and Reviews, all 21 documents of the 2023 update of the IWGDF Guidelines are bundled, added with a further 6 reviews from multidisciplinary experts to drive future research and clinical innovations, based on their contributions to the International Symposium on the Diabetic Foot. We hope the readers will enjoy this special virtual issue, and widely implement the knowledge shared here in their daily clinical practice and research endeavours with the goal to improve the care for people with diabetes-related foot disease.

在全球范围内,很少有疾病像糖尿病足病一样需要如此多不同学科的治疗。至少有 25 种不同的专业人员可能参与其中:铸造技师、皮肤科医生、糖尿病(教育)护士、糖尿病专家、营养师、内分泌专家、全科医生、人体运动科学家、传染病专家、微生物学家、核医学医生、矫形外科医生、矫形师、足部矫正师、理疗师、整形外科医生、足外科医生、足病医生、修复师、心理学家、放射科医生、社会工作者、组织存活率医生、血管外科医生和伤口护理护士。因此,共同的词汇、共同的治疗目标和建议至关重要。国际糖尿病足工作组(IWGDF)制定了相关指南和辅助文件,以促进和支持糖尿病足相关疾病的多学科循证治疗。在这期《糖尿病/代谢研究与评论》虚拟特刊中,捆绑了 IWGDF 指南 2023 年更新版的所有 21 份文件,并根据多学科专家在糖尿病足国际研讨会上的贡献,增加了另外 6 篇评论,以推动未来的研究和临床创新。我们希望读者能喜欢这本虚拟特刊,并在日常临床实践和研究工作中广泛应用其中分享的知识,以改善对糖尿病足相关疾病患者的护理。
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引用次数: 0
Multi-feature, Chinese–Western medicine-integrated prediction model for diabetic peripheral neuropathy based on machine learning and SHAP 基于机器学习和 SHAP 的糖尿病周围神经病变多特征中西医结合预测模型
IF 8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-04-14 DOI: 10.1002/dmrr.3801
Aijuan Jiang, Jiajie Li, Lujie Wang, Wenshu Zha, Yixuan Lin, Jindong Zhao, Zhaohui Fang, Guoming Shen
<div> <section> <h3> Background</h3> <p>Clinical studies have shown that diabetic peripheral neuropathy (DPN) has been on the rise, with most patients presenting with severe and progressive symptoms. Currently, most of the available prediction models for DPN are derived from general clinical information and laboratory indicators. Several Traditional Chinese medicine (TCM) indicators have been utilised to construct prediction models. In this study, we established a novel machine learning-based multi-featured Chinese–Western medicine-integrated prediction model for DPN using clinical features of TCM.</p> </section> <section> <h3> Materials and Methods</h3> <p>The clinical data of 1581 patients with Type 2 diabetes mellitus (T2DM) treated at the Department of Endocrinology of the First Affiliated Hospital of Anhui University of Chinese Medicine were collected. The data (including general information, laboratory parameters and TCM features) of 1142 patients with T2DM were selected after data cleaning. After baseline description analysis of the variables, the data were divided into training and validation sets. Four prediction models were established and their performance was evaluated using validation sets. Meanwhile, the accuracy, precision, recall, F1 score and area under the curve (AUC) of ROC were calculated using ten-fold cross-validation to further assess the performance of the models. An explanatory analysis of the results of the DPN prediction model was carried out using the SHAP framework based on machine learning-based prediction models.</p> </section> <section> <h3> Results</h3> <p>Of the 1142 patients with T2DM, 681 had a comorbidity of DPN, while 461 did not. There was a significant difference between the two groups in terms of age, cause of disease, systolic pressure, HbA1c, ALT, RBC, Cr, BUN, red blood cells in the urine, glucose in the urine, and protein in the urine (<i>p</i> < 0.05). T2DM patients with a comorbidity of DPN exhibited diverse TCM symptoms, including limb numbness, limb pain, hypodynamia, thirst with desire for drinks, dry mouth and throat, blurred vision, gloomy complexion, and unsmooth pulse, with statistically significant differences (<i>p</i> < 0.05). Our results showed that the proposed multi-featured Chinese–Western medicine-integrated prediction model was superior to conventional models without characteristic TCM indicators. The model showed the best performance (accuracy = 0.8109, precision = 0.8029, recall = 0.9060, F1 score = 0.8511, and AUC = 0.9002). SHAP analysis revealed that the dominant risk factors that caused DPN were TCM symptoms (limb numbness, thirst with desire for drinks, blurred vision), age
背景 临床研究表明,糖尿病周围神经病变(DPN)呈上升趋势,大多数患者症状严重且呈进行性发展。目前,大多数现有的 DPN 预测模型都是从一般临床信息和实验室指标中得出的。一些中医指标已被用于构建预测模型。在本研究中,我们利用中医临床特征建立了一个基于机器学习的新型多特征中西医结合 DPN 预测模型。 材料与方法 收集安徽中医药大学第一附属医院内分泌科收治的1581例2型糖尿病(T2DM)患者的临床资料。经数据清理后,选取了 1142 名 T2DM 患者的数据(包括一般信息、实验室指标和中医特征)。对变量进行基线描述分析后,将数据分为训练集和验证集。建立了四个预测模型,并使用验证集对其性能进行了评估。同时,通过十倍交叉验证计算准确率、精确率、召回率、F1得分和ROC曲线下面积(AUC),进一步评估模型的性能。利用基于机器学习预测模型的 SHAP 框架对 DPN 预测模型的结果进行了解释性分析。 结果 在 1142 名 T2DM 患者中,681 人合并有 DPN,461 人没有。两组患者在年龄、病因、收缩压、HbA1c、ALT、RBC、Cr、BUN、尿中红细胞、尿中葡萄糖和尿中蛋白方面存在明显差异(p <0.05)。合并 DPN 的 T2DM 患者表现出多种中医症状,包括肢体麻木、肢体疼痛、低动力、口渴欲饮、口干咽燥、视物模糊、面色晦暗、脉象不滑等,差异有统计学意义(p <0.05)。结果表明,所提出的多特征中西医结合预测模型优于无中医特征指标的传统模型。该模型表现出最佳性能(准确率 = 0.8109,精确率 = 0.8029,召回率 = 0.9060,F1 分数 = 0.8511,AUC = 0.9002)。SHAP 分析显示,导致 DPN 的主要风险因素是中医症状(肢体麻木、口渴欲饮、视力模糊)、年龄、病因和糖化血红蛋白。这些风险因素对 DPN 预测模型产生了积极影响。 结论 建立并验证了一个多特征、中西医结合的 DPN 预测模型。该模型提高了 T2DM 诊断和治疗中 DPN 高危人群的早期识别能力,同时也为糖尿病等慢性病的智能管理提供了信息支持。
{"title":"Multi-feature, Chinese–Western medicine-integrated prediction model for diabetic peripheral neuropathy based on machine learning and SHAP","authors":"Aijuan Jiang,&nbsp;Jiajie Li,&nbsp;Lujie Wang,&nbsp;Wenshu Zha,&nbsp;Yixuan Lin,&nbsp;Jindong Zhao,&nbsp;Zhaohui Fang,&nbsp;Guoming Shen","doi":"10.1002/dmrr.3801","DOIUrl":"https://doi.org/10.1002/dmrr.3801","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Clinical studies have shown that diabetic peripheral neuropathy (DPN) has been on the rise, with most patients presenting with severe and progressive symptoms. Currently, most of the available prediction models for DPN are derived from general clinical information and laboratory indicators. Several Traditional Chinese medicine (TCM) indicators have been utilised to construct prediction models. In this study, we established a novel machine learning-based multi-featured Chinese–Western medicine-integrated prediction model for DPN using clinical features of TCM.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Materials and Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The clinical data of 1581 patients with Type 2 diabetes mellitus (T2DM) treated at the Department of Endocrinology of the First Affiliated Hospital of Anhui University of Chinese Medicine were collected. The data (including general information, laboratory parameters and TCM features) of 1142 patients with T2DM were selected after data cleaning. After baseline description analysis of the variables, the data were divided into training and validation sets. Four prediction models were established and their performance was evaluated using validation sets. Meanwhile, the accuracy, precision, recall, F1 score and area under the curve (AUC) of ROC were calculated using ten-fold cross-validation to further assess the performance of the models. An explanatory analysis of the results of the DPN prediction model was carried out using the SHAP framework based on machine learning-based prediction models.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Of the 1142 patients with T2DM, 681 had a comorbidity of DPN, while 461 did not. There was a significant difference between the two groups in terms of age, cause of disease, systolic pressure, HbA1c, ALT, RBC, Cr, BUN, red blood cells in the urine, glucose in the urine, and protein in the urine (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). T2DM patients with a comorbidity of DPN exhibited diverse TCM symptoms, including limb numbness, limb pain, hypodynamia, thirst with desire for drinks, dry mouth and throat, blurred vision, gloomy complexion, and unsmooth pulse, with statistically significant differences (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Our results showed that the proposed multi-featured Chinese–Western medicine-integrated prediction model was superior to conventional models without characteristic TCM indicators. The model showed the best performance (accuracy = 0.8109, precision = 0.8029, recall = 0.9060, F1 score = 0.8511, and AUC = 0.9002). SHAP analysis revealed that the dominant risk factors that caused DPN were TCM symptoms (limb numbness, thirst with desire for drinks, blurred vision), age","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 4","pages":""},"PeriodicalIF":8.0,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.3801","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140553116","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}
引用次数: 0
LADA 30th anniversary: A growing form of diabetes with persistent unresolved questions LADA 30 周年:一种不断发展的糖尿病,始终存在悬而未决的问题
IF 8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-04-06 DOI: 10.1002/dmrr.3800
Ivy Lee Jia Jia, Raffaella Buzzetti, Richard David Leslie, Paolo Pozzilli
<p>The 30th anniversary of Latent Autoimmune Diabetes in Adults (LADA) is a remarkable milestone in diabetes mellitus research. Described for the first time in 1993, LADA disputes the traditional binary classification of diabetes, with autoimmune features (autoimmune-mediated <i>β</i>-cell destruction) like that of type 1 diabetes (T1D) yet with an adult-onset pattern not requiring insulin, at least initially and, therefore, resembling type 2 diabetes (T2D).<span><sup>1, 2</sup></span> Thus, commenced an extensive journey of scientific exploration. Although our understanding of LADA has grown substantially over this period, many questions surrounding LADA remain unresolved. Today, LADA patients constitute a significant fraction, that is, up to 12% of T2D patients, highlighting the pressing need to address these questions.<span><sup>3, 4</sup></span> This commentary discusses such questions, the ongoing efforts by scientists/physicians and future directions in search for answers.</p><p>Diagnosing LADA is challenging due to overlaps with other forms of diabetes, also making it hard to define categorical features. In fact, LADA is often initially misdiagnosed as T2D because of the resemblance in their clinical presentation.<span><sup>5</sup></span> Furthermore, heterogeneity within LADA adds to this diagnostic challenge.<span><sup>2, 6</sup></span> Given that LADA people must be identified early to ensure better outcomes in terms of HbA1c, co-morbidity and hypoglycaemia risk, the best strategy for such identification must be resolved.</p><p>Regarding the diagnostic criteria of LADA, the Immunology of Diabetes Society proposed it includes diabetes cases age ≥30 years, positive for at least one diabetes-associated autoantibody, and without insulin requirement for at least the first six months after diagnosis.<span><sup>5</sup></span> There are some weaknesses with this proposal. First, all criteria are non-categorical, and all the cut-off values are arbitrary, as pointed out by Groop et al.<span><sup>2, 6, 7</sup></span> Second, there are many factors relating to diagnostic autoantibodies (e.g., how positivity is defined and which autoantibody, despite the most common being an autoantibody against glutamic acid decarboxylase [GADA]).<span><sup>3, 7</sup></span> This issue is demonstrated by the significant variability in the percentage of LADA diagnosis among different groups of T2D-diagnosed adults, depending on the autoantibody type used for screening and method of ascertainment.<span><sup>3</sup></span> Third, the choice of whether and when to start insulin treatment is highly physician-dependent, as highlighted by Rajkumar et al.<span><sup>5, 8</sup></span> For these reasons, more precise standardised diagnostic criteria for LADA may be needed.</p><p>As for autoantibody testing, there are no current general recommendations for adult-onset diabetes. At present, autoantibody testing is only done if there is a strong suspicion of LADA in patients wit
成人潜伏自身免疫性糖尿病(LADA)30 周年纪念是糖尿病研究领域的一个重要里程碑。LADA 于 1993 年首次被描述,它对糖尿病的传统二元分类提出了质疑,其自身免疫特征(自身免疫介导的 β 细胞破坏)与 1 型糖尿病(T1D)相似,但成人发病模式至少在初期不需要胰岛素,因此与 2 型糖尿病(T2D)相似。尽管在此期间我们对 LADA 的认识有了很大提高,但围绕 LADA 的许多问题仍未得到解决。如今,LADA 患者占 T2D 患者的很大一部分,即高达 12%,这凸显了解决这些问题的迫切需要。3, 4 本评论将讨论这些问题、科学家/医生正在进行的努力以及寻找答案的未来方向。事实上,由于临床表现相似,LADA 最初常常被误诊为 T2D、6 鉴于必须及早发现 LADA 患者,以确保在 HbA1c、并发症和低血糖风险方面取得更好的疗效,因此必须解决识别 LADA 的最佳策略问题。关于 LADA 的诊断标准,糖尿病免疫学会建议包括年龄≥30 岁、至少一种糖尿病相关自身抗体阳性、诊断后至少前六个月无胰岛素需求的糖尿病病例。首先,正如 Groop 等人所指出的,所有标准都是非分类性的,所有临界值都是任意设定的、3、7 这一问题的证据是,在不同的 T2D 诊断成人群体中,LADA 诊断比例存在显著差异,这取决于筛查所用的自身抗体类型和确定方法。第三,正如 Rajkumar 等人强调的那样,选择是否以及何时开始胰岛素治疗在很大程度上取决于医生。5, 8 基于这些原因,可能需要更精确的 LADA 标准化诊断标准。9 与自身抗体检测有关的是,一个国际专家小组在其最近关于 LADA 管理的共识声明中建议对所有新诊断的 T2D 患者进行 GADA 检测。专家小组建议,如果成本有限,则应根据一系列增加 LADA 嫌疑的不同临床因素来选择患者进行 GADA 检测,而不是像目前的做法那样仅根据体重指数来选择。对于 GADA 阴性但怀疑患有 LADA 的患者,专家小组建议对他们进行其他胰岛自身抗体的检测。正如其定义一样,LADA 患者在确诊时仍拥有功能正常的 β 细胞,因此及时有效的干预对于保护残余的胰岛素分泌能力和改善代谢控制至关重要。3 要回答上述问题,首先必须了解不同干预措施(包括降糖药物)的作用。3、8、10-13 与许多降糖药物一样,生活方式调整和免疫干预在 LADA 中的作用也不明确。值得注意的是,需要探讨的一个问题是,当β细胞功能仍有残余时,是否应尽早开始胰岛素治疗。 3, 8 此外,由于 LADA 的异质性,LADA 的治疗应针对每位患者的具体情况,以确保最佳疗效。专家小组建议修改美国糖尿病协会/欧洲糖尿病研究协会(EASD)针对 T2D 的算法,用于 LADA 的治疗。他们建议将患者的 C 肽水平分为三类,如表 2.3 所示,三类 C 肽水平可反映患者的 β 细胞功能状态,从而决定治疗方案。3 与这种快速恶化相关的因素包括 GADA 滴度水平、初始 C 肽和血糖控制质量。首先,UKPDS 和其他研究发现,GADA 水平高与胰岛素需求进展的风险较高之间存在关联。这意味着对血糖的最佳控制可防止日后出现并发症的风险。17 重要的是,要找出导致代谢恶化更快的因素,并有针对性地采取措施,以改善长期预后,包括胰岛素依赖性和并发症风险。尚待解答的问题包括 LADA 的最佳名称(最近被描述为缓慢演变型自身免疫性糖尿病 (SAID))、LADA 的病因以及开始对胰腺 β 细胞进行自身免疫攻击的环境诱因。虽然有证据表明 LADA 与遗传因素有关,包括与 T1D 共同的遗传因素,如某些 HLA 单倍型携带者和与 T2D 共同的 HLA 单倍型携带者患 LADA 的风险较高,但仍需进一步证实、19 此外,这些遗传因素如何影响 LADA 易感性和疾病进展仍不清楚。一些研究揭示了 LADA 的免疫学改变,这对于更好地了解 LADA 的自身免疫过程和潜在的免疫调节策略至关重要5 。此外,将 LADA 与 T1D 的部分缓解阶段相比较,可以深入了解自身免疫与免疫代谢调节之间的平衡,这可能有助于更广泛地了解自身免疫性糖尿病,并可共享治疗策略。例如,如果发病率正在上升,那么 T1D 低发病率地区和高发病率地区之间的差异是什么?总之,LADA 30 周年纪念表明我们对糖尿病的认识在不断发展。在庆祝这一里程碑的同时,我们应该回顾过去,认识到我们在了解 LADA 方面存在的知识差距,其中一些差距已在本评论中进行了讨论,并在表 3 中进行了总结。但必须指出的是,本评论只讨论了所有未决问题中的一小部分,如图 1 所示。Ivy Lee Jia、Raffaella Buzzetti、Richard David Leslie 和 Paolo Pozzilli 对本文的构思、写作(原稿)、审阅和编辑以及最终发表版本的批准做出了同样的贡献。Ivy Lee Jia、Raffaella Buzzetti、Richard David Leslie和Paolo Pozzilli均未报告与本文相关的潜在利益冲突。本文是一篇综述性文章,主题具有普遍意义,无需伦理委员会批准。
{"title":"LADA 30th anniversary: A growing form of diabetes with persistent unresolved questions","authors":"Ivy Lee Jia Jia,&nbsp;Raffaella Buzzetti,&nbsp;Richard David Leslie,&nbsp;Paolo Pozzilli","doi":"10.1002/dmrr.3800","DOIUrl":"https://doi.org/10.1002/dmrr.3800","url":null,"abstract":"&lt;p&gt;The 30th anniversary of Latent Autoimmune Diabetes in Adults (LADA) is a remarkable milestone in diabetes mellitus research. Described for the first time in 1993, LADA disputes the traditional binary classification of diabetes, with autoimmune features (autoimmune-mediated &lt;i&gt;β&lt;/i&gt;-cell destruction) like that of type 1 diabetes (T1D) yet with an adult-onset pattern not requiring insulin, at least initially and, therefore, resembling type 2 diabetes (T2D).&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; Thus, commenced an extensive journey of scientific exploration. Although our understanding of LADA has grown substantially over this period, many questions surrounding LADA remain unresolved. Today, LADA patients constitute a significant fraction, that is, up to 12% of T2D patients, highlighting the pressing need to address these questions.&lt;span&gt;&lt;sup&gt;3, 4&lt;/sup&gt;&lt;/span&gt; This commentary discusses such questions, the ongoing efforts by scientists/physicians and future directions in search for answers.&lt;/p&gt;&lt;p&gt;Diagnosing LADA is challenging due to overlaps with other forms of diabetes, also making it hard to define categorical features. In fact, LADA is often initially misdiagnosed as T2D because of the resemblance in their clinical presentation.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; Furthermore, heterogeneity within LADA adds to this diagnostic challenge.&lt;span&gt;&lt;sup&gt;2, 6&lt;/sup&gt;&lt;/span&gt; Given that LADA people must be identified early to ensure better outcomes in terms of HbA1c, co-morbidity and hypoglycaemia risk, the best strategy for such identification must be resolved.&lt;/p&gt;&lt;p&gt;Regarding the diagnostic criteria of LADA, the Immunology of Diabetes Society proposed it includes diabetes cases age ≥30 years, positive for at least one diabetes-associated autoantibody, and without insulin requirement for at least the first six months after diagnosis.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; There are some weaknesses with this proposal. First, all criteria are non-categorical, and all the cut-off values are arbitrary, as pointed out by Groop et al.&lt;span&gt;&lt;sup&gt;2, 6, 7&lt;/sup&gt;&lt;/span&gt; Second, there are many factors relating to diagnostic autoantibodies (e.g., how positivity is defined and which autoantibody, despite the most common being an autoantibody against glutamic acid decarboxylase [GADA]).&lt;span&gt;&lt;sup&gt;3, 7&lt;/sup&gt;&lt;/span&gt; This issue is demonstrated by the significant variability in the percentage of LADA diagnosis among different groups of T2D-diagnosed adults, depending on the autoantibody type used for screening and method of ascertainment.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Third, the choice of whether and when to start insulin treatment is highly physician-dependent, as highlighted by Rajkumar et al.&lt;span&gt;&lt;sup&gt;5, 8&lt;/sup&gt;&lt;/span&gt; For these reasons, more precise standardised diagnostic criteria for LADA may be needed.&lt;/p&gt;&lt;p&gt;As for autoantibody testing, there are no current general recommendations for adult-onset diabetes. At present, autoantibody testing is only done if there is a strong suspicion of LADA in patients wit","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 4","pages":""},"PeriodicalIF":8.0,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.3800","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140351710","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}
引用次数: 0
Associations of birth weight, plasma metabolome in adulthood and risk of type 2 diabetes 出生体重、成年后血浆代谢组与 2 型糖尿病风险的关系
IF 8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-04-06 DOI: 10.1002/dmrr.3803
Wenxiu Wang, Zhenhuang Zhuang, Yimin Zhao, Zimin Song, Ninghao Huang, Yueying Li, Xue Dong, Wendi Xiao, Tao Huang

Aims

We aimed to examine the longitudinal associations of birth weight with plasma metabolites in adulthood, and further quantify the proportions of the links between birth weight and incident adult type 2 diabetes (T2D) that were mediated by plasma metabolites.

Materials and Methods

A total of 62,033 participants with complete nuclear magnetic resonance metabolomics and birth weight data from the UK Biobank were included in this study. Linear regression was used to assess the associations between birth weight and metabolites. Cox regression was used to estimate hazard ratios for T2D associated with metabolites. We further performed mediation analyses to estimate the extent to which metabolites might mediate the association between birth weight and T2D risk.

Results

Low birth weight was associated with the adverse metabolic responses across multiple metabolic pathways, including lipoprotein subclasses, amino acids, fatty acids (FA), and inflammation. Metabolites associated with higher birth weight tended to be associated with a lower risk of T2D (Pearson correlation coefficient: −0.85). A total of 62 metabolites showed statistically significant mediation effects in the protective association of higher birth weight and T2D risk, including large-sized very low-density lipoprotein particles and triglyceride concentrations as well as saturated, and monounsaturated FA and glycoprotein acetyls.

Conclusions

We identified a range of metabolites that reflect the adult metabolic response to birth weight, some of which might lie on the pathway between birth weight and adult T2D risk.

目的 我们旨在研究出生体重与成年后血浆代谢物之间的纵向联系,并进一步量化出生体重与成年后 2 型糖尿病(T2D)之间的联系中由血浆代谢物介导的比例。 材料与方法 本研究共纳入了 62033 名来自英国生物库、具有完整核磁共振代谢组学数据和出生体重数据的参与者。线性回归用于评估出生体重与代谢物之间的关系。Cox 回归用于估算与代谢物相关的 T2D 危险比。我们还进一步进行了中介分析,以估计代谢物可能在多大程度上中介出生体重与 T2D 风险之间的关系。 结果 低出生体重与多种代谢途径的不良代谢反应有关,包括脂蛋白亚类、氨基酸、脂肪酸和炎症。与较高出生体重相关的代谢物往往与较低的 T2D 风险相关(皮尔逊相关系数:-0.85)。共有 62 种代谢物在出生体重较高与 T2D 风险的保护性关联中显示出具有统计学意义的中介效应,其中包括大尺寸极低密度脂蛋白颗粒和甘油三酯浓度以及饱和和单不饱和脂肪酸和糖蛋白乙酰。 结论 我们发现了一系列反映成人代谢对出生体重反应的代谢物,其中一些可能位于出生体重与成人 T2D 风险之间的路径上。
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引用次数: 0
Clusters of adipose tissue dysfunction in adults with type 2 diabetes identify those with worse lipidomic profile despite similar glycaemic control 成人 2 型糖尿病患者脂肪组织功能障碍群组可识别出那些血糖控制相似但脂质组学特征较差的患者。
IF 8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-04-01 DOI: 10.1002/dmrr.3798
Giuseppe Della Pepa, Fabrizia Carli, Silvia Sabatini, Samantha Pezzica, Marco Russo, Marilena Vitale, Maria Masulli, Gabriele Riccardi, Angela A. Rivellese, Olga Vaccaro, Lutgarda Bozzetto, Amalia Gastaldelli

Aims

To investigate clusters of adipose tissue dysfunction, that is, with adipose tissue insulin resistance (ADIPO-IR) and large waist circumference (WC), identify a worse lipidomic profile characterised by a high proportion of lipids rich in saturated fatty acids (SFA).

Materials and Methods

Hierarchical clustering based on WC and ADIPO-IR (calculated as fasting plasma non-esterified fatty acids times fasting plasma insulin, FFA×INS), was performed in 192 adults with overweight/obesity and type 2 diabetes (T2D) treated with metformin (HbA1c = 7.8%). Free fatty acid composition and lipidomic profile were measured by mass spectrometry (GC-MS and LC-MSQTOF). Indexes of fatty acid desaturation (stearoyl-coA desaturase-1 activity, SCD116 = palmitoleic acid/palmitic acid and SCD118 = oleic acid/stearic acid) and of insulin resistance (HOMA-IR) were also calculated.

Results

Three clusters were identified: CL1 (ADIPO-IR = 4.9 ± 2.4 and WC = 96±7 cm, mean ± SD), CL2 (ADIPO-IR = 6.5 ± 2.5 and WC = 114 ± 7 cm), and CL3 (ADIPO-IR = 15.0 ± 4.7 and WC = 107 ± 8 cm). Insulin concentrations, ADIPO-IR, and HOMA-IR significantly increased from CL1 to CL3 (all p < 0.001), while fasting glucose concentrations, HbA1c, dietary lipids and caloric intake were similar. Moreover, CL3 showed significantly higher concentrations of monounsaturated free fatty acids, oleic and palmitoleic acids, triglycerides (TAG) rich in saturated FA and associated with de novo lipogenesis (i.e., TAG 46–50), higher SCD116, SCD118, ceramide (d18:0/18:0), and phosphatidylcholine aa(36:5) compared with CL1/CL2 (all p < 0.005).

Conclusions

High ADIPO-IR and large WC identify a worse lipid profile in T2D characterised by complex lipids rich in SFA, likely due to de novo synthesis given higher plasma monounsaturated FFA and increased desaturase activity indexes.

Registration Number Trial

ID NCT00700856 https://clinicaltrials.gov.

目的:研究脂肪组织功能障碍的聚类,即脂肪组织胰岛素抵抗(ADIPO-IR)和腰围(WC)较大的聚类,确定以富含饱和脂肪酸(SFA)的脂质比例较高为特征的较差脂质组学特征。材料与方法:对 192 名超重/肥胖并接受二甲双胍治疗(HbA1c = 7.8%)的 2 型糖尿病(T2D)成人进行了基于腰围和 ADIPO-IR(计算方法为空腹血浆非酯化脂肪酸乘以空腹血浆胰岛素,FFA×INS)的分层聚类。采用质谱法(气相色谱-质谱联用仪和液相色谱-质谱联用仪)测量了游离脂肪酸组成和脂质组谱。此外,还计算了脂肪酸不饱和指数(硬脂酰-CoA 不饱和酶-1 活性、SCD116 = 棕榈油酸/棕榈酸和 SCD118 = 油酸/硬脂酸)和胰岛素抵抗指数(HOMA-IR):结果:确定了三个群组:CL1(ADIPO-IR = 4.9 ± 2.4,WC = 96 ± 7 cm,平均值 ± SD)、CL2(ADIPO-IR = 6.5 ± 2.5,WC = 114 ± 7 cm)和 CL3(ADIPO-IR = 15.0 ± 4.7,WC = 107 ± 8 cm)。与 CL1/CL2 相比,CL1 至 CL3 的胰岛素浓度、ADIPO-IR 和 HOMA-IR 显著增加(均为 p 16),SCD118、神经酰胺(d18:0/18:0)和磷脂酰胆碱 aa(36:5)也显著增加(均为 p 结论:高 ADIPO-IR 和大 WC 表明 T2D 患者的血脂状况较差,其特征是富含 SFA 的复杂脂质,这可能是由于血浆中单不饱和 FFA 较高和去饱和酶活性指数增加导致的从头合成:ID NCT00700856 https://clinicaltrials.gov。
{"title":"Clusters of adipose tissue dysfunction in adults with type 2 diabetes identify those with worse lipidomic profile despite similar glycaemic control","authors":"Giuseppe Della Pepa,&nbsp;Fabrizia Carli,&nbsp;Silvia Sabatini,&nbsp;Samantha Pezzica,&nbsp;Marco Russo,&nbsp;Marilena Vitale,&nbsp;Maria Masulli,&nbsp;Gabriele Riccardi,&nbsp;Angela A. Rivellese,&nbsp;Olga Vaccaro,&nbsp;Lutgarda Bozzetto,&nbsp;Amalia Gastaldelli","doi":"10.1002/dmrr.3798","DOIUrl":"10.1002/dmrr.3798","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To investigate clusters of adipose tissue dysfunction, that is, with adipose tissue insulin resistance (ADIPO-IR) and large waist circumference (WC), identify a worse lipidomic profile characterised by a high proportion of lipids rich in saturated fatty acids (SFA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Hierarchical clustering based on WC and ADIPO-IR (calculated as fasting plasma non-esterified fatty acids times fasting plasma insulin, FFA×INS), was performed in 192 adults with overweight/obesity and type 2 diabetes (T2D) treated with metformin (HbA1c = 7.8%). Free fatty acid composition and lipidomic profile were measured by mass spectrometry (GC-MS and LC-MSQTOF). Indexes of fatty acid desaturation (stearoyl-coA desaturase-1 activity, SCD1<sub>16</sub> = palmitoleic acid/palmitic acid and SCD1<sub>18</sub> = oleic acid/stearic acid) and of insulin resistance (HOMA-IR) were also calculated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Three clusters were identified: CL1 (ADIPO-IR = 4.9 ± 2.4 and WC = 96±7 cm, mean ± SD), CL2 (ADIPO-IR = 6.5 ± 2.5 and WC = 114 ± 7 cm), and CL3 (ADIPO-IR = 15.0 ± 4.7 and WC = 107 ± 8 cm). Insulin concentrations, ADIPO-IR, and HOMA-IR significantly increased from CL1 to CL3 (all <i>p</i> &lt; 0.001), while fasting glucose concentrations, HbA1c, dietary lipids and caloric intake were similar. Moreover, CL3 showed significantly higher concentrations of monounsaturated free fatty acids, oleic and palmitoleic acids, triglycerides (TAG) rich in saturated FA and associated with de novo lipogenesis (i.e., TAG 46–50), higher SCD1<sub>16,</sub> SCD1<sub>18</sub>, ceramide (d18:0/18:0), and phosphatidylcholine aa(36:5) compared with CL1/CL2 (all <i>p</i> &lt; 0.005).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>High ADIPO-IR and large WC identify a worse lipid profile in T2D characterised by complex lipids rich in SFA, likely due to de novo synthesis given higher plasma monounsaturated FFA and increased desaturase activity indexes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Registration Number Trial</h3>\u0000 \u0000 <p>ID NCT00700856 https://clinicaltrials.gov.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 4","pages":""},"PeriodicalIF":8.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.3798","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337292","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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Diabetes/Metabolism Research and Reviews
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