Alström syndrome (AS) is a rare recessive disorder characterised by diabetes, obesity, insulin resistance (IR), and visual and hearing impairments. Mutations in the ALMS1 gene have been identified as the causative agents of AS. This study aimed to explore the relationship between rare ALMS1 variants and clinical features in Chinese patients with early-onset type 2 diabetes (age at diagnosis ≤40 years; EOD).
Materials and Methods
ALMS1 gene sequencing was performed in 611 Chinese individuals with EOD, 36 with postprandial hyperinsulinemia, and 47 with pre-diabetes and fasting IR. In-silico prediction algorithm and the American College of Medical Genetics Guidelines (ACMG) were used to evaluate the deleteriousness and pathogenicity of the variants.
Results
Sixty-two rare ALMS1 variants (frequency <0.005) were identified in 82 patients with EOD. Nineteen variants were predicted to be deleterious (pD). Patients with EOD carrying pD variants had higher fasting C-peptide, postprandial C-peptide, and HOMA2-IR levels than those without variants. The frequency of ALMS1 pD variants in the subgroup with more insulin-resistant EOD was higher than that in other EOD subgroups. Two patients with EOD, obesity, and IR who carried one heterozygous pathogenic/likely pathogenic rare variant of ALMS1 according to ACMG were identified. Moreover, rare heterozygous pD variants of ALMS1 were found in participants from cohorts of postprandial hyperinsulinemia as well as in pre-diabetes with fasting IR.
Conclusions
ALMS1 rare pD variants are enriched in the populations with significant IR, which is a major hallmark of diabetes pathogenesis. Accordingly, our exploratory study provides insights and hypotheses for further studies of gene function.
目的：阿尔斯特伦综合征（AS）是一种罕见的隐性遗传疾病，以糖尿病、肥胖、胰岛素抵抗（IR）、视力和听力障碍为特征。ALMS1 基因突变已被确定为 AS 的致病因子。本研究旨在探讨中国早发2型糖尿病患者（诊断年龄≤40岁；EOD）中罕见的ALMS1基因变异与临床特征之间的关系：对611名中国EOD患者、36名餐后高胰岛素血症患者和47名糖尿病前期及空腹IR患者进行了ALMS1基因测序。结果发现，有62个罕见的ALMS1基因变异：结果：62个罕见的ALMS1变异体（频率 结论：ALMS1的罕见pD变异体是一种致病性变异体：ALMS1罕见pD变异富集在有明显IR的人群中，而IR是糖尿病发病机制的主要标志。因此，我们的探索性研究为进一步研究基因功能提供了启示和假设。
{"title":"Overburden of rare ALMS1 deleterious variants in Chinese early-onset type 2 diabetes with severe insulin resistance","authors":"Simin Zhang, Siqian Gong, Meng Li, Xiaoling Cai, Wei Liu, Yingying Lou, Yumin Ma, Xiuying Zhang, Qian Ren, Yu Zhu, Jing Wu, Lingli Zhou, Yufeng Li, Xianghai Zhou, Xueyao Han, Linong Ji","doi":"10.1002/dmrr.3788","DOIUrl":"10.1002/dmrr.3788","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Alström syndrome (AS) is a rare recessive disorder characterised by diabetes, obesity, insulin resistance (IR), and visual and hearing impairments. Mutations in the <i>ALMS1</i> gene have been identified as the causative agents of AS. This study aimed to explore the relationship between rare <i>ALMS1</i> variants and clinical features in Chinese patients with early-onset type 2 diabetes (age at diagnosis ≤40 years; EOD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p><i>ALMS1</i> gene sequencing was performed in 611 Chinese individuals with EOD, 36 with postprandial hyperinsulinemia, and 47 with pre-diabetes and fasting IR. In-silico prediction algorithm and the American College of Medical Genetics Guidelines (ACMG) were used to evaluate the deleteriousness and pathogenicity of the variants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Sixty-two rare <i>ALMS1</i> variants (frequency <0.005) were identified in 82 patients with EOD. Nineteen variants were predicted to be deleterious (pD). Patients with EOD carrying pD variants had higher fasting C-peptide, postprandial C-peptide, and HOMA2-IR levels than those without variants. The frequency of <i>ALMS1</i> pD variants in the subgroup with more insulin-resistant EOD was higher than that in other EOD subgroups. Two patients with EOD, obesity, and IR who carried one heterozygous pathogenic/likely pathogenic rare variant of <i>ALMS1</i> according to ACMG were identified. Moreover, rare heterozygous pD variants of <i>ALMS1</i> were found in participants from cohorts of postprandial hyperinsulinemia as well as in pre-diabetes with fasting IR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p><i>ALMS1</i> rare pD variants are enriched in the populations with significant IR, which is a major hallmark of diabetes pathogenesis. Accordingly, our exploratory study provides insights and hypotheses for further studies of gene function.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 4","pages":""},"PeriodicalIF":8.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.3788","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140307450","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}
Previous studies have found that a single liver enzyme may predict gestational diabetes mellitus (GDM), but the results have been inconsistent. This study aimed to explore the associations of liver enzymes in early pregnancy with risk of GDM, as well as to independently rank risk factors.
Methods
This prospective cohort study included 1295 women who underwent liver enzyme measurements during early pregnancy and completed GDM assessment in mid-pregnancy. Logistic regression and restricted cubic spline analyses were conducted to assess the relationship between liver enzymes and risk of GDM. Back-propagation artificial neural network was performed to rank independently risk factors of GDM.
Results
Women diagnosed with GDM exhibited significantly higher levels of liver enzymes than those without GDM (all p < 0.05). The highest quartile of liver enzymes was associated with higher risk of GDM compared with the lowest quartile, with adjusted odds ratio (ORs) ranging from 2.76 to 8.11 (all p < 0.05). Moreover, the ORs of GDM increased linearly with liver enzymes level (all P for overall association <0.001). Furthermore, Back-propagation artificial neural network identified γ-gamma-glutamyl transferase (GGT) as accounting for the highest proportion in the ranking of GDM risk prediction weights (up to 20.8%).
Conclusions
Single or total elevations of liver enzymes in early pregnancy could predict the GDM occurrence, in which GGT, alkaline Phosphatase, and aspartate aminotransferase were the three most important independent risk factors.
{"title":"Elevated liver enzymes in the first trimester are associated with gestational diabetes mellitus: A prospective cohort study","authors":"Lingling Cui, Xiaoli Yang, Zhiqian Li, Yuting Gao, Zhengya Zhang, Dongmei Xu, Xinxin Liu","doi":"10.1002/dmrr.3799","DOIUrl":"10.1002/dmrr.3799","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Previous studies have found that a single liver enzyme may predict gestational diabetes mellitus (GDM), but the results have been inconsistent. This study aimed to explore the associations of liver enzymes in early pregnancy with risk of GDM, as well as to independently rank risk factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This prospective cohort study included 1295 women who underwent liver enzyme measurements during early pregnancy and completed GDM assessment in mid-pregnancy. Logistic regression and restricted cubic spline analyses were conducted to assess the relationship between liver enzymes and risk of GDM. Back-propagation artificial neural network was performed to rank independently risk factors of GDM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Women diagnosed with GDM exhibited significantly higher levels of liver enzymes than those without GDM (all <i>p</i> < 0.05). The highest quartile of liver enzymes was associated with higher risk of GDM compared with the lowest quartile, with adjusted odds ratio (<i>ORs</i>) ranging from 2.76 to 8.11 (all <i>p</i> < 0.05). Moreover, the <i>ORs</i> of GDM increased linearly with liver enzymes level (all <i>P</i> for overall association <0.001). Furthermore, Back-propagation artificial neural network identified γ-gamma-glutamyl transferase (GGT) as accounting for the highest proportion in the ranking of GDM risk prediction weights (up to 20.8%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Single or total elevations of liver enzymes in early pregnancy could predict the GDM occurrence, in which GGT, alkaline Phosphatase, and aspartate aminotransferase were the three most important independent risk factors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 4","pages":""},"PeriodicalIF":8.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.3799","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140307449","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}
Stefano Ciardullo, Laura Savaré, Federico Rea, Gianluca Perseghin, Giovanni Corrao
Aims
To evaluate the impact of adherence to glucagon like peptide-1 receptor agonists (GLP1-RA) and sodium-glucose transporter two inhibitors (SGLT2-I) on clinical outcomes and costs in patients with type 2 diabetes mellitus (T2DM).
Materials and Methods
The 121,115 residents of the Lombardy Region (Italy) aged ≥40 years newly treated with metformin during 2007–2015 were followed to identify those who started therapy with GLP1-RA or SGLT2-I. Adherence to drug therapy over the first year was defined as the proportion of days covered >80%. Within each drug class, for each adherent patient, one non-adherent patient was matched for age, sex, duration, adherence to metformin treatment and propensity score. The primary clinical outcome was a composite of insulin initiation, hospitalisation for micro- and macrovascular complications and all-cause mortality after the first year of drug treatment. Costs were evaluated based on reimbursements from the national healthcare system.
Results
After matching, 1182 pairs of adherent and non-adherent GLP1-RA users and 1126 pairs of adherent and non-adherent SGLT2-I users were included. In both groups, adherent patients experienced a significantly lower incidence of the primary outcome (HR: 0.85, 95% CI 0.72–0.98 for GLP1-RA and HR: 0.69, 95% CI 0.55–0.87 for SGLT2-I). A significant reduction in hospitalizations was found for adherent patients in the GLP1-RA group but not for the SGLT2-I group. Results were consistent when analyses were stratified by age and sex. While higher drug-related costs in the adherent group were counterbalanced by decreased hospitalisation costs in SGLT2-I treated patients, this was not the case for GLP1-RA.
Conclusions
Higher adherence to drug treatment with GLP1-RA and SGLT2-I during the first year of the drug intake is associated with a lower incidence of adverse clinical outcomes in a real-world setting.
目的：评估坚持使用胰高血糖素样肽-1受体激动剂（GLP1-RA）和钠-葡萄糖转运体二抑制剂（SGLT2-I）对2型糖尿病（T2DM）患者临床疗效和费用的影响：对伦巴第大区（意大利）2007-2015年间新接受二甲双胍治疗的121115名年龄≥40岁的居民进行跟踪调查，以确定开始接受GLP1-RA或SGLT2-I治疗的患者。第一年的药物治疗依从性定义为治疗天数比例大于 80%。在每一类药物中，对每一位坚持治疗的患者和一位未坚持治疗的患者进行年龄、性别、病程、二甲双胍治疗坚持情况和倾向评分匹配。主要临床结果是胰岛素起始、微血管和大血管并发症住院以及药物治疗第一年后的全因死亡率。根据国家医疗系统的报销情况对成本进行了评估：结果：经过配对，共纳入了 1182 对坚持和非坚持 GLP1-RA 使用者，以及 1126 对坚持和非坚持 SGLT2-I 使用者。在这两组患者中，坚持治疗的患者主要结局发生率明显降低（GLP1-RA HR：0.85，95% CI 0.72-0.98；SGLT2-I HR：0.69，95% CI 0.55-0.87）。GLP1-RA组坚持治疗的患者住院率明显降低，而SGLT2-I组患者住院率则没有明显降低。按年龄和性别进行分层分析后，结果一致。SGLT2-I治疗组患者住院费用的减少抵消了坚持治疗组较高的药物相关费用，但GLP1-RA的情况并非如此：结论：在真实世界环境中，GLP1-RA 和 SGLT2-I 服药第一年内较高的依从性与较低的不良临床结果发生率相关。
{"title":"Adherence to GLP1-RA and SGLT2-I affects clinical outcomes and costs in patients with type 2 diabetes","authors":"Stefano Ciardullo, Laura Savaré, Federico Rea, Gianluca Perseghin, Giovanni Corrao","doi":"10.1002/dmrr.3791","DOIUrl":"10.1002/dmrr.3791","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To evaluate the impact of adherence to glucagon like peptide-1 receptor agonists (GLP1-RA) and sodium-glucose transporter two inhibitors (SGLT2-I) on clinical outcomes and costs in patients with type 2 diabetes mellitus (T2DM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>The 121,115 residents of the Lombardy Region (Italy) aged ≥40 years newly treated with metformin during 2007–2015 were followed to identify those who started therapy with GLP1-RA or SGLT2-I. Adherence to drug therapy over the first year was defined as the proportion of days covered >80%. Within each drug class, for each adherent patient, one non-adherent patient was matched for age, sex, duration, adherence to metformin treatment and propensity score. The primary clinical outcome was a composite of insulin initiation, hospitalisation for micro- and macrovascular complications and all-cause mortality after the first year of drug treatment. Costs were evaluated based on reimbursements from the national healthcare system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After matching, 1182 pairs of adherent and non-adherent GLP1-RA users and 1126 pairs of adherent and non-adherent SGLT2-I users were included. In both groups, adherent patients experienced a significantly lower incidence of the primary outcome (HR: 0.85, 95% CI 0.72–0.98 for GLP1-RA and HR: 0.69, 95% CI 0.55–0.87 for SGLT2-I). A significant reduction in hospitalizations was found for adherent patients in the GLP1-RA group but not for the SGLT2-I group. Results were consistent when analyses were stratified by age and sex. While higher drug-related costs in the adherent group were counterbalanced by decreased hospitalisation costs in SGLT2-I treated patients, this was not the case for GLP1-RA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Higher adherence to drug treatment with GLP1-RA and SGLT2-I during the first year of the drug intake is associated with a lower incidence of adverse clinical outcomes in a real-world setting.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 4","pages":""},"PeriodicalIF":8.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.3791","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140319564","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}
Xiaoqin Xu, Jiang Li, Yuefeng Yu, Xiao Tan, Fei Xu, Bin Wang, Ningjian Wang, Yingli Lu
Objective
Prediabetes and lifestyle factors have been associated with the risks of multiple adverse outcomes, but the effect of a healthy lifestyle on prediabetes-related complications remains unknown. We aimed to investigate whether the risks of multiple adverse outcomes including incident type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and chronic kidney disease (CKD) among individuals with prediabetes can be offset by a broad combination of healthy lifestyle factors.
Methods
This prospective study used data from the UK Biobank cohort. An overall lifestyle score ranging from 0 to 6 was created with 1 point for each of the 6 healthy lifestyle factors: no current smoking, moderate alcohol consumption, regular physical activity, healthy diet, no overweight or obese, and adequate sleep duration. T2DM, CVD, and CKD were ascertained during a median follow-up of 14 years. Cox proportional hazard regression models were used to estimate the associations. Sensitivity analyses were performed to test the robustness of the results.
Results
We included 202,993 participants without T2DM, CVD, and CKD at baseline (mean age 55.5 years [SD 8.1]; 54.7% were women). Among these participants, 6,745, 16,961, and 6,260 participants eventually developed T2DM, CVD, and CKD, respectively. Compared with the participants with normoglycaemia, those with prediabetes showed a higher risk of these adverse outcomes. In addition, those prediabetic participants with a lifestyle score of 0-1 had a significantly higher risk of T2DM (hazard ratio [HR] 16.73, 95% CI 14.24, 19.65), CVD (HR 1.96, 95% CI 1.74, 2.21), and CKD (HR 1.92, 95% CI 1.58, 2.34) compared with those with no prediabetes and a score of 5–6. Moreover, among the participants with prediabetes, the HRs for T2DM, CVD, and CKD comparing a lifestyle score of 5–6 versus 0-1 decreased to 0.43 (95% CI 0.36, 0.51), 0.52 (95% CI 0.44, 0.62), and 0.60 (95% CI 0.46, 0.79), respectively.
Conclusions
Combined healthy lifestyle factors were associated with a significantly lower risk of multiple adverse outcomes, including T2DM, CVD, and CKD. This indicates that prioritising multifactorial approaches to behavioural lifestyle modification is crucial for preventing and postponing the development of complications related to prediabetes.
目的：糖尿病前期和生活方式因素与多种不良后果的风险有关，但健康的生活方式对糖尿病前期相关并发症的影响仍然未知。我们的目的是调查糖尿病前期患者发生 2 型糖尿病（T2DM）、心血管疾病（CVD）和慢性肾脏疾病（CKD）等多种不良后果的风险是否可以通过广泛的健康生活方式因素组合来抵消：这项前瞻性研究使用了英国生物库队列的数据。方法：这项前瞻性研究使用了英国生物库队列中的数据，建立了从 0 到 6 分的总体生活方式评分，6 项健康生活方式因素每项得 1 分：当前不吸烟、适量饮酒、定期体育锻炼、健康饮食、不超重或肥胖以及充足的睡眠时间。在中位 14 年的随访期间，确定了 T2DM、心血管疾病和慢性肾脏病。采用 Cox 比例危险回归模型来估计相关性。我们还进行了敏感性分析，以检验结果的稳健性：我们纳入了 202993 名基线时无 T2DM、心血管疾病和慢性肾脏病的参与者（平均年龄 55.5 岁 [SD 8.1]；54.7% 为女性）。在这些参与者中，分别有 6745 人、16961 人和 6260 人最终患上了 T2DM、心血管疾病和慢性肾脏病。与血糖正常的参与者相比，患有糖尿病前期的参与者出现这些不良后果的风险更高。此外，与没有糖尿病且生活方式得分在 5-6 分的参与者相比，生活方式得分在 0-1 分的糖尿病前期参与者患 T2DM（危险比 [HR] 16.73，95% CI 14.24，19.65）、心血管疾病（HR 1.96，95% CI 1.74，2.21）和慢性肾脏病（HR 1.92，95% CI 1.58，2.34）的风险明显更高。此外，在患有糖尿病前期的参与者中，生活方式评分为5-6分与0-1分相比，T2DM、心血管疾病和慢性肾脏病的HR值分别降至0.43（95% CI 0.36，0.51）、0.52（95% CI 0.44，0.62）和0.60（95% CI 0.46，0.79）：综合的健康生活方式因素与多种不良后果风险的显著降低有关，包括 T2DM、心血管疾病和慢性肾脏病。这表明，优先采用多因素方法来改变行为生活方式，对于预防和推迟糖尿病前期并发症的发生至关重要。
{"title":"Association of combined healthy lifestyle with risk of adverse outcomes in patients with prediabetes","authors":"Xiaoqin Xu, Jiang Li, Yuefeng Yu, Xiao Tan, Fei Xu, Bin Wang, Ningjian Wang, Yingli Lu","doi":"10.1002/dmrr.3795","DOIUrl":"10.1002/dmrr.3795","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Prediabetes and lifestyle factors have been associated with the risks of multiple adverse outcomes, but the effect of a healthy lifestyle on prediabetes-related complications remains unknown. We aimed to investigate whether the risks of multiple adverse outcomes including incident type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and chronic kidney disease (CKD) among individuals with prediabetes can be offset by a broad combination of healthy lifestyle factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This prospective study used data from the UK Biobank cohort. An overall lifestyle score ranging from 0 to 6 was created with 1 point for each of the 6 healthy lifestyle factors: no current smoking, moderate alcohol consumption, regular physical activity, healthy diet, no overweight or obese, and adequate sleep duration. T2DM, CVD, and CKD were ascertained during a median follow-up of 14 years. Cox proportional hazard regression models were used to estimate the associations. Sensitivity analyses were performed to test the robustness of the results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We included 202,993 participants without T2DM, CVD, and CKD at baseline (mean age 55.5 years [SD 8.1]; 54.7% were women). Among these participants, 6,745, 16,961, and 6,260 participants eventually developed T2DM, CVD, and CKD, respectively. Compared with the participants with normoglycaemia, those with prediabetes showed a higher risk of these adverse outcomes. In addition, those prediabetic participants with a lifestyle score of 0-1 had a significantly higher risk of T2DM (hazard ratio [HR] 16.73, 95% CI 14.24, 19.65), CVD (HR 1.96, 95% CI 1.74, 2.21), and CKD (HR 1.92, 95% CI 1.58, 2.34) compared with those with no prediabetes and a score of 5–6. Moreover, among the participants with prediabetes, the HRs for T2DM, CVD, and CKD comparing a lifestyle score of 5–6 versus 0-1 decreased to 0.43 (95% CI 0.36, 0.51), 0.52 (95% CI 0.44, 0.62), and 0.60 (95% CI 0.46, 0.79), respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Combined healthy lifestyle factors were associated with a significantly lower risk of multiple adverse outcomes, including T2DM, CVD, and CKD. This indicates that prioritising multifactorial approaches to behavioural lifestyle modification is crucial for preventing and postponing the development of complications related to prediabetes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 4","pages":""},"PeriodicalIF":8.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.3795","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140307448","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}
Chao Deng, Yuting Xie, Juan Li, Hongwei Jiang, Xiaohong Niu, Dewen Yan, Heng Su, Hongyu Kuang, Liming Tian, Jing Liu, Sheng Jiang, Huibiao Quan, Jixiong Xu, Xiaohong Wu, Na Tao, Shuguang Sun, Xiaohan Tang, Yan Chen, Li Fan, Xia Li, Zhiguang Zhou, the CD1S Study Group
Aims
To evaluate the status quo of type 1 diabetes (T1D) management and characteristics of hospitalised patients with T1D in China through a nationwide multicentre registry study, the China Diabetes Type 1 Study (CD1S).
Materials and Methods
Clinical data from the electronic hospital records of all people with T1D were retrospectively collected in 13 tertiary hospitals across 7 regions of China from January 2016 to December 2021. Patients were defined as newly diagnosed who received a diagnosis of diabetes for less than 3 months.
Results
Among the 4993 people with T1D, the median age (range) at diagnosis was 23.0 (1.0-87.0) years and the median disease duration was 2.0 years. The median haemoglobin A1c (HbA1c) level was 10.7%. The prevalence of obesity, overweight, dyslipidemia, and hypertension were 2.5%, 10.8%, 62.5% and 25.9%, respectively. The incidence rate of diabetic ketoacidosis at disease onset was 41.1%, with the highest in children <10 years of age (50.6%). In patients not newly diagnosed, 60.7% were diagnosed with at least one chronic diabetic complication, with the highest proportion (45.3%) of diabetic peripheral neuropathy. Chronic complications were detected in 79.2% of people with T1D duration ≥10 years.
Conclusions
In the most recent years, there were still unsatisfactory metabolic control and high incidence of diabetic ketoacidosis as well as chronic diabetic complications among inpatients with T1D in China. The ongoing CD1S prospective study aims to improve the quality of T1D management nationally.
{"title":"Care, control and complications of hospitalised patients with type 1 diabetes in China: A nationwide-based registry study","authors":"Chao Deng, Yuting Xie, Juan Li, Hongwei Jiang, Xiaohong Niu, Dewen Yan, Heng Su, Hongyu Kuang, Liming Tian, Jing Liu, Sheng Jiang, Huibiao Quan, Jixiong Xu, Xiaohong Wu, Na Tao, Shuguang Sun, Xiaohan Tang, Yan Chen, Li Fan, Xia Li, Zhiguang Zhou, the CD1S Study Group","doi":"10.1002/dmrr.3796","DOIUrl":"10.1002/dmrr.3796","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To evaluate the status quo of type 1 diabetes (T1D) management and characteristics of hospitalised patients with T1D in China through a nationwide multicentre registry study, the China Diabetes Type 1 Study (CD1S).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Clinical data from the electronic hospital records of all people with T1D were retrospectively collected in 13 tertiary hospitals across 7 regions of China from January 2016 to December 2021. Patients were defined as newly diagnosed who received a diagnosis of diabetes for less than 3 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 4993 people with T1D, the median age (range) at diagnosis was 23.0 (1.0-87.0) years and the median disease duration was 2.0 years. The median haemoglobin A<sub>1c</sub> (HbA<sub>1c</sub>) level was 10.7%. The prevalence of obesity, overweight, dyslipidemia, and hypertension were 2.5%, 10.8%, 62.5% and 25.9%, respectively. The incidence rate of diabetic ketoacidosis at disease onset was 41.1%, with the highest in children <10 years of age (50.6%). In patients not newly diagnosed, 60.7% were diagnosed with at least one chronic diabetic complication, with the highest proportion (45.3%) of diabetic peripheral neuropathy. Chronic complications were detected in 79.2% of people with T1D duration ≥10 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In the most recent years, there were still unsatisfactory metabolic control and high incidence of diabetic ketoacidosis as well as chronic diabetic complications among inpatients with T1D in China. The ongoing CD1S prospective study aims to improve the quality of T1D management nationally.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 3","pages":""},"PeriodicalIF":8.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140289364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lede Lin, Kang Ning, Liyuan Xiang, Liao Peng, Xiang Li
Objective
To identify the causal role of sodium-glucose cotransporter 2 (SGLT2) inhibition on three urological cancers.
Methods
Six single nucleotide polymorphisms associated with the expression level of SLC5A2, a proxy for SGLT2 inhibition, from a recent publication were extracted. Three common urological cancers, including bladder cancer, prostate cancer and kidney cancer, were analysed. The main cohort of bladder cancer was derived from UK Biobank (1279 cases and 372,016 controls). The prostate cancer cohort was from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium (79,148 cases and 61,106 controls). The kidney cancer phenotype was from the UK Biobank cohort of 463,010 individuals (1114 cases and 461,896 controls). Primary and sensitivity analysis were performed to validate the results. In vitro analysis was also incorporated to validate the Mendelian randomisation results.
Results
In primary analysis, SGLT2 inhibition was associated with reduced risk of bladder cancer (OR: 0.98, 95% CI: 0.97–0.99) per unit lowering of HbA1c level. A protective association was also observed for prostate cancer with odds ratio = 0.31 (95% CI = 0.21–0.47). However, we did not discover a causal relationship between SGLT2 inhibition and kidney cancer (OR: 1.00, 95% CI: 0.99–1.00). Sensitivity analysis and in vitro validation did not support the causal role of SGLT2 inhibition in increasing cancer risk.
Conclusions
We did not find any evidence that SGLT2 inhibition could increase the risk of the three cancers. Even in some analysis, SGLT2 inhibition tended to show protective effects on the three urological cancers.
{"title":"SGLT2 inhibition and three urological cancers: Up-to-date results","authors":"Lede Lin, Kang Ning, Liyuan Xiang, Liao Peng, Xiang Li","doi":"10.1002/dmrr.3797","DOIUrl":"10.1002/dmrr.3797","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To identify the causal role of sodium-glucose cotransporter 2 (SGLT2) inhibition on three urological cancers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Six single nucleotide polymorphisms associated with the expression level of SLC5A2, a proxy for SGLT2 inhibition, from a recent publication were extracted. Three common urological cancers, including bladder cancer, prostate cancer and kidney cancer, were analysed. The main cohort of bladder cancer was derived from UK Biobank (1279 cases and 372,016 controls). The prostate cancer cohort was from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium (79,148 cases and 61,106 controls). The kidney cancer phenotype was from the UK Biobank cohort of 463,010 individuals (1114 cases and 461,896 controls). Primary and sensitivity analysis were performed to validate the results. In vitro analysis was also incorporated to validate the Mendelian randomisation results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In primary analysis, SGLT2 inhibition was associated with reduced risk of bladder cancer (OR: 0.98, 95% CI: 0.97–0.99) per unit lowering of HbA1c level. A protective association was also observed for prostate cancer with odds ratio = 0.31 (95% CI = 0.21–0.47). However, we did not discover a causal relationship between SGLT2 inhibition and kidney cancer (OR: 1.00, 95% CI: 0.99–1.00). Sensitivity analysis and in vitro validation did not support the causal role of SGLT2 inhibition in increasing cancer risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We did not find any evidence that SGLT2 inhibition could increase the risk of the three cancers. Even in some analysis, SGLT2 inhibition tended to show protective effects on the three urological cancers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 3","pages":""},"PeriodicalIF":8.0,"publicationDate":"2024-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140208067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Weixiang Wu, Dan Luo, Cunwei Ji, Fuqiang Diao, Lihong Wu, Xiaolin Ruan, Chunming Gu, Mingyong Luo
Aims
The role of maternal genetic factors in the association between high glycated haemoglobin (HbA1c) levels and adverse birth outcomes remains unclear.
Materials and Methods
In this study, the maternal HbA1c levels of 5108 normoglycemic pregnant women in China were measured, and A1298C and C677T polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene were genotyped.
Results
Elevated HbA1c levels during the second trimester were associated with increased risks of macrosomia, large-for-gestational age (LGA), preterm birth (PTB), and reduced gestational age (p < 0.05). Pregnant women with MTHFR A1298C AA or C677T CT + TT genotypes were susceptible to adverse pregnancy outcomes related to HbA1c levels. Among pregnant women with the A1298C AA genotype, each standard deviation (SD) increase in HbA1c levels increased the risk of PTB by 1.32-times and reduced the gestational age by 0.11 weeks (p < 0.05). For MTHFR C677T CC + TT genotype carriers, higher HbA1c levels were associated with 1.49-, 1.24-, and 1.23-times increased risks of macrosomia, LGA, and PTB, respectively (p < 0.05). A U-shaped curve for PTB risk in relation to HbA1c levels was observed among the C677T CC + TT participants, with a cut-off value of 4.58%. Among subjects with the A1298C AA genotype combined with the C677T CT + TT genotype, each SD increase in HbA1c levels was associated with 1.40 and 1.37-times increased risks of LGA and PTB, respectively.
Conclusions
Our findings highlight the importance of glycaemic control during pregnancy and the potential impact of genetic factors on birth outcomes. However, further large-scale studies are required to confirm these findings.
{"title":"Interaction effects of MTHFR C677T and A1298C polymorphisms with maternal glycated haemoglobin levels on adverse birth outcomes","authors":"Weixiang Wu, Dan Luo, Cunwei Ji, Fuqiang Diao, Lihong Wu, Xiaolin Ruan, Chunming Gu, Mingyong Luo","doi":"10.1002/dmrr.3794","DOIUrl":"10.1002/dmrr.3794","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The role of maternal genetic factors in the association between high glycated haemoglobin (HbA1c) levels and adverse birth outcomes remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>In this study, the maternal HbA1c levels of 5108 normoglycemic pregnant women in China were measured, and A1298C and C677T polymorphisms in the <i>methylenetetrahydrofolate reductase</i> (<i>MTHFR</i>) gene were genotyped.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Elevated HbA1c levels during the second trimester were associated with increased risks of macrosomia, large-for-gestational age (LGA), preterm birth (PTB), and reduced gestational age (<i>p</i> < 0.05). Pregnant women with <i>MTHFR</i> A1298C AA or C677T CT + TT genotypes were susceptible to adverse pregnancy outcomes related to HbA1c levels. Among pregnant women with the A1298C AA genotype, each standard deviation (SD) increase in HbA1c levels increased the risk of PTB by 1.32-times and reduced the gestational age by 0.11 weeks (<i>p</i> < 0.05). For MTHFR C677T CC + TT genotype carriers, higher HbA1c levels were associated with 1.49-, 1.24-, and 1.23-times increased risks of macrosomia, LGA, and PTB, respectively (<i>p</i> < 0.05). A U-shaped curve for PTB risk in relation to HbA1c levels was observed among the C677T CC + TT participants, with a cut-off value of 4.58%. Among subjects with the A1298C AA genotype combined with the C677T CT + TT genotype, each SD increase in HbA1c levels was associated with 1.40 and 1.37-times increased risks of LGA and PTB, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings highlight the importance of glycaemic control during pregnancy and the potential impact of genetic factors on birth outcomes. However, further large-scale studies are required to confirm these findings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 3","pages":""},"PeriodicalIF":8.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.3794","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190262","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}
Karsten Buschard, Knud Josefsen, Lars Krogvold, Ivan Gerling, Knut Dahl-Jørgensen, Flemming Pociot
Aims
Sulfatide is a chaperone for insulin manufacturing in beta cells. Here we explore whether the blood glucose values normally could be associated with this sphingolipid and especially two of its building enzymes CERS2 and CERS6. Both T1D and T2D have low blood sulfatide levels, and insulin resistance on beta cells at clinical diagnosis. Furthermore, we examined islet pericytes for sulfatide, and beta-cell receptors for GLP-1, both of which are related to the insulin production.
Materials and Methods
We examined mRNA levels in islets from the DiViD and nPOD studies, performed genetic association analyses, and histologically investigated pericytes in the islets for sulfatide.
Results
Polymorphisms of the gene encoding the CERS6 enzyme responsible for synthesising dihydroceramide, a precursor to sulfatide, are associated with random blood glucose values in non-diabetic persons. This fits well with our finding of sulfatide in pericytes in the islets, which regulates the capillary blood flow in the islets of Langerhans, which is important for oxygen supply to insulin production. In the islets of newly diagnosed T1D patients, we observed low levels of GLP-1 receptors; this may explain the insulin resistance in their beta cells and their low insulin production. In T2D patients, we identified associated polymorphisms in both CERS2 and CERS6.
Conclusions
Here, we describe several polymorphisms in sulfatide enzymes related to blood glucose levels and HbA1c in non-diabetic individuals. Islet pericytes from such persons contain sulfatide. Furthermore, low insulin secretion in newly diagnosed T1D may be explained by beta-cell insulin resistance due to low levels of GLP-1 receptors.
{"title":"Influence of sphingolipid enzymes on blood glucose levels, development of diabetes, and involvement of pericytes","authors":"Karsten Buschard, Knud Josefsen, Lars Krogvold, Ivan Gerling, Knut Dahl-Jørgensen, Flemming Pociot","doi":"10.1002/dmrr.3792","DOIUrl":"10.1002/dmrr.3792","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Sulfatide is a chaperone for insulin manufacturing in beta cells. Here we explore whether the blood glucose values normally could be associated with this sphingolipid and especially two of its building enzymes CERS2 and CERS6. Both T1D and T2D have low blood sulfatide levels, and insulin resistance on beta cells at clinical diagnosis. Furthermore, we examined islet pericytes for sulfatide, and beta-cell receptors for GLP-1, both of which are related to the insulin production.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We examined mRNA levels in islets from the DiViD and nPOD studies, performed genetic association analyses, and histologically investigated pericytes in the islets for sulfatide.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Polymorphisms of the gene encoding the CERS6 enzyme responsible for synthesising dihydroceramide, a precursor to sulfatide, are associated with random blood glucose values in non-diabetic persons. This fits well with our finding of sulfatide in pericytes in the islets, which regulates the capillary blood flow in the islets of Langerhans, which is important for oxygen supply to insulin production. In the islets of newly diagnosed T1D patients, we observed low levels of GLP-1 receptors; this may explain the insulin resistance in their beta cells and their low insulin production. In T2D patients, we identified associated polymorphisms in both <i>CERS2</i> and <i>CERS6</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Here, we describe several polymorphisms in sulfatide enzymes related to blood glucose levels and HbA1c in non-diabetic individuals. Islet pericytes from such persons contain sulfatide. Furthermore, low insulin secretion in newly diagnosed T1D may be explained by beta-cell insulin resistance due to low levels of GLP-1 receptors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 3","pages":""},"PeriodicalIF":8.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.3792","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190261","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}
Pam Chen, Nalini Campillo Vilorio, Ketan Dhatariya, William Jeffcoate, Ralf Lobmann, Caroline McIntosh, Alberto Piaggesi, John Steinberg, Prash Vas, Vijay Viswanathan, Stephanie Wu, Fran Game
Background
It is critical that interventions used to enhance the healing of chronic foot ulcers in diabetes are backed by high-quality evidence and cost-effectiveness. In previous years, the systematic review accompanying guidelines published by the International Working Group of the Diabetic Foot performed 4-yearly updates of previous searches, including trials of prospective, cross-sectional and case-control design.
Aims
Due to a need to re-evaluate older studies against newer standards of reporting and assessment of risk of bias, we performed a whole new search from conception, but limiting studies to randomised control trials only.
Materials and Methods
For this systematic review, we searched PubMed, Scopus and Web of Science databases for published studies on randomised control trials of interventions to enhance healing of diabetes-related foot ulcers. We only included trials comparing interventions to standard of care. Two independent reviewers selected articles for inclusion and assessed relevant outcomes as well as methodological quality.
Results
The literature search identified 22,250 articles, of which 262 were selected for full text review across 10 categories of interventions. Overall, the certainty of evidence for a majority of wound healing interventions was low or very low, with moderate evidence existing for two interventions (sucrose-octasulfate and leucocyte, platelet and fibrin patch) and low quality evidence for a further four (hyperbaric oxygen, topical oxygen, placental derived products and negative pressure wound therapy). The majority of interventions had insufficient evidence.
Conclusion
Overall, the evidence to support any other intervention to enhance wound healing is lacking and further high-quality randomised control trials are encouraged.
背景：用于促进糖尿病慢性足部溃疡愈合的干预措施必须有高质量的证据和成本效益的支持。目的：由于需要根据新的报告标准和偏倚风险评估标准重新评估旧的研究，我们从概念开始进行了全新的检索，但仅限于随机对照试验：为了进行此次系统性综述，我们在 PubMed、Scopus 和 Web of Science 数据库中搜索了已发表的有关促进糖尿病足溃疡愈合的干预措施的随机对照试验研究。我们只纳入了将干预措施与标准护理进行比较的试验。两位独立审稿人对文章进行筛选，并对相关结果和方法学质量进行评估：文献检索发现了 22250 篇文章，其中 262 篇被选中进行全文审阅，涉及 10 类干预措施。总体而言，大多数伤口愈合干预措施的证据确定性较低或很低，其中两项干预措施（蔗糖-辛硫酸盐和白细胞、血小板和纤维蛋白贴片）的证据确定性中等，另外四项干预措施（高压氧、局部供氧、胎盘衍生产品和负压伤口疗法）的证据质量较低。大多数干预措施的证据不足：总体而言，目前还缺乏证据支持任何其他促进伤口愈合的干预措施，因此鼓励进一步开展高质量的随机对照试验。
{"title":"Effectiveness of interventions to enhance healing of chronic foot ulcers in diabetes: A systematic review","authors":"Pam Chen, Nalini Campillo Vilorio, Ketan Dhatariya, William Jeffcoate, Ralf Lobmann, Caroline McIntosh, Alberto Piaggesi, John Steinberg, Prash Vas, Vijay Viswanathan, Stephanie Wu, Fran Game","doi":"10.1002/dmrr.3786","DOIUrl":"10.1002/dmrr.3786","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>It is critical that interventions used to enhance the healing of chronic foot ulcers in diabetes are backed by high-quality evidence and cost-effectiveness. In previous years, the systematic review accompanying guidelines published by the International Working Group of the Diabetic Foot performed 4-yearly updates of previous searches, including trials of prospective, cross-sectional and case-control design.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Due to a need to re-evaluate older studies against newer standards of reporting and assessment of risk of bias, we performed a whole new search from conception, but limiting studies to randomised control trials only.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>For this systematic review, we searched PubMed, Scopus and Web of Science databases for published studies on randomised control trials of interventions to enhance healing of diabetes-related foot ulcers. We only included trials comparing interventions to standard of care. Two independent reviewers selected articles for inclusion and assessed relevant outcomes as well as methodological quality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The literature search identified 22,250 articles, of which 262 were selected for full text review across 10 categories of interventions. Overall, the certainty of evidence for a majority of wound healing interventions was low or very low, with moderate evidence existing for two interventions (sucrose-octasulfate and leucocyte, platelet and fibrin patch) and low quality evidence for a further four (hyperbaric oxygen, topical oxygen, placental derived products and negative pressure wound therapy). The majority of interventions had insufficient evidence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Overall, the evidence to support any other intervention to enhance wound healing is lacking and further high-quality randomised control trials are encouraged.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 3","pages":""},"PeriodicalIF":8.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.3786","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140177345","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}
Yu Yuan, Liping Huang, Lulu Yu, Xingxu Yan, Siyu Chen, Chenghao Bi, Junjie He, Yiqing Zhao, Liu Yang, Li Ning, Hua Jin, Rongrong Yang, Yubo Li
Aims
Diabetic Kidney Disease (DKD), one of the major complications of diabetes, is also a major cause of end-stage renal disease. Metabolomics can provide a unique metabolic profile of the disease and thus predict or diagnose the development of the disease. Therefore, this study summarises a more comprehensive set of clinical biomarkers related to DKD to identify functional metabolites significantly associated with the development of DKD and reveal their driving mechanisms for DKD.
Materials and Methods
We searched PubMed, Embase, the Cochrane Library and Web of Science databases through October 2022. A meta-analysis was conducted on untargeted or targeted metabolomics research data based on the strategy of standardized mean differences and the process of ratio of means as the effect size, respectively. We compared the changes in metabolite levels between the DKD patients and the controls and explored the source of heterogeneity through subgroup analyses, sensitivity analysis and meta-regression analysis.
Results
The 34 clinical-based metabolomics studies clarified the differential metabolites between DKD and controls, containing 4503 control subjects and 1875 patients with DKD. The results showed that a total of 60 common differential metabolites were found in both meta-analyses, of which 5 metabolites (p < 0.05) were identified as essential metabolites. Compared with the control group, metabolites glycine, aconitic acid, glycolic acid and uracil decreased significantly in DKD patients; cysteine was significantly higher. This indicates that amino acid metabolism, lipid metabolism and pyrimidine metabolism in DKD patients are disordered.
Conclusions
We have identified 5 metabolites and metabolic pathways related to DKD which can serve as biomarkers or targets for disease prevention and drug therapy.
{"title":"Clinical metabolomics characteristics of diabetic kidney disease: A meta-analysis of 1875 cases with diabetic kidney disease and 4503 controls","authors":"Yu Yuan, Liping Huang, Lulu Yu, Xingxu Yan, Siyu Chen, Chenghao Bi, Junjie He, Yiqing Zhao, Liu Yang, Li Ning, Hua Jin, Rongrong Yang, Yubo Li","doi":"10.1002/dmrr.3789","DOIUrl":"10.1002/dmrr.3789","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Diabetic Kidney Disease (DKD), one of the major complications of diabetes, is also a major cause of end-stage renal disease. Metabolomics can provide a unique metabolic profile of the disease and thus predict or diagnose the development of the disease. Therefore, this study summarises a more comprehensive set of clinical biomarkers related to DKD to identify functional metabolites significantly associated with the development of DKD and reveal their driving mechanisms for DKD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We searched PubMed, Embase, the Cochrane Library and Web of Science databases through October 2022. A meta-analysis was conducted on untargeted or targeted metabolomics research data based on the strategy of standardized mean differences and the process of ratio of means as the effect size, respectively. We compared the changes in metabolite levels between the DKD patients and the controls and explored the source of heterogeneity through subgroup analyses, sensitivity analysis and meta-regression analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The 34 clinical-based metabolomics studies clarified the differential metabolites between DKD and controls, containing 4503 control subjects and 1875 patients with DKD. The results showed that a total of 60 common differential metabolites were found in both meta-analyses, of which 5 metabolites (<i>p</i> < 0.05) were identified as essential metabolites. Compared with the control group, metabolites glycine, aconitic acid, glycolic acid and uracil decreased significantly in DKD patients; cysteine was significantly higher. This indicates that amino acid metabolism, lipid metabolism and pyrimidine metabolism in DKD patients are disordered.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We have identified 5 metabolites and metabolic pathways related to DKD which can serve as biomarkers or targets for disease prevention and drug therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"40 3","pages":""},"PeriodicalIF":8.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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