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Impact of SLC22A1 rs12208357 on therapeutic response to metformin in type 2 diabetes patients. SLC22A1 rs12208357对2型糖尿病患者二甲双胍治疗反应的影响
IF 1.8 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-28 eCollection Date: 2024-12-01 DOI: 10.1007/s40200-024-01486-4
Reza Moazzami, Mohammad Yahya Vahidi Mehrjardi, Ali Miri

Introduction: : Metformin, an oral hypoglycemic agent, is generally used as the first-line treatment in type 2 diabetes mellitus (T2DM) patients. The response to metformin varies between patients, and its mechanisms remain incompletely understood. Genetic variations in proteins involved in the pharmacodynamics and pharmacokinetics of metformin, like OCT1 transporter, are suspected to explain this difference. This study investigated the association of the response to metformin in T2DM patients with the presence of rs12208357 (R61C) variant in the SLC22A1 gene.

Materials and methods: We selected 100 patients who responded and 100 patients who did not respond to metformin monotherapy after 20 weeks according to their HbA1c level change. We investigated the effect of rs12208357 on the structure, function, and stability of OCT1 protein and its interaction with metformin by in silico tools. To determine the genotype of rs12208357 we used the ARMS-PCR technique.

Results: The in silico study indicated that rs12208357 probably changes OCT1 stability, function, interaction site, and binding energy to metformin in the extracellular domain. ARMS-PCR also showed the frequency of T and C alleles were significantly different between responders and non-responders (P-value = 0.014), also there is a significant difference in CC and CT/TT genotype frequency between responders and non-responders (P-value = 0.023).

Conclusion: Based on the in silico study and ARMS-PCR experiment results, the CC genotype has a better response to metformin therapy and the carrier of the T allele (CT and TT genotype) probably has complications in glycemic control by metformin.

二甲双胍是一种口服降糖药,一般作为2型糖尿病(T2DM)患者的一线治疗药物。对二甲双胍的反应因患者而异,其机制尚不完全清楚。与二甲双胍的药效学和药代动力学有关的蛋白质的遗传变异,如OCT1转运蛋白,被怀疑可以解释这种差异。本研究探讨了T2DM患者对二甲双胍的反应与SLC22A1基因中rs12208357 (R61C)变异的关系。材料和方法:我们根据HbA1c水平的变化,选择100例二甲双胍单药治疗20周后有反应的患者和100例无反应的患者。我们利用硅基工具研究了rs12208357对OCT1蛋白结构、功能和稳定性的影响及其与二甲双胍的相互作用。为了确定rs12208357的基因型,我们采用ARMS-PCR技术。结果:硅片研究表明rs12208357可能在胞外区域改变OCT1的稳定性、功能、相互作用位点和对二甲双胍的结合能。应答者与无应答者的T、C等位基因频率差异有统计学意义(p值= 0.014),CC和CT/TT基因型频率差异有统计学意义(p值= 0.023)。结论:基于计算机研究和ARMS-PCR实验结果,CC基因型对二甲双胍治疗有更好的应答,T等位基因携带者(CT和TT基因型)在二甲双胍降糖过程中可能存在并发症。
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引用次数: 0
Predictive modelling of metabolic syndrome in Ghanaian diabetic patients: an ensemble machine learning approach. 加纳糖尿病患者代谢综合征的预测建模:一种集成机器学习方法。
IF 1.8 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-28 eCollection Date: 2024-12-01 DOI: 10.1007/s40200-024-01491-7
Emmanuel Acheampong, Eric Adua, Christian Obirikorang, Enoch Odame Anto, Emmanuel Peprah-Yamoah, Yaa Obirikorang, Evans Adu Asamoah, Victor Opoku-Yamoah, Michael Nyantakyi, John Taylor, Tonnies Abeku Buckman, Maryam Yakubu, Ebenezer Afrifa-Yamoah

Objectives: The burgeoning prevalence of cardiometabolic disorders, including type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) within Africa is concerning. Machine learning (ML) techniques offer a unique opportunity to leverage data-driven insights and construct predictive models for MetS risk, thereby enhancing the implementation of personalised prevention strategies. In this work, we employed ML techniques to develop predictive models for pre-MetS and MetS among diabetic patients.

Methods: This multi-centre cross-sectional study comprised of 919 T2DM patients. Age, gender, novel anthropometric indices along with biochemical measures were analysed using BORUTA feature selection and an ensemble majority voting classification model, which included logistic regression, k-nearest neighbour, Gaussian Naive Bayes, Gradient boosting classification, and support vector machine.

Results: Distinct metabolic profiles and phenotype clusters were associated with MetS progression. The BORUTA algorithm identified 10 and 16 significant features for pre-MetS and MetS prediction, respectively. For pre-MetS, the top-ranked features were lipid accumulation product (LAP), triglyceride-glucose index adjusted for waist-to-height ratio (TyG-WHtR), coronary risk (CR), visceral adiposity index (VAI) and abdominal volume index (AVI). For MetS prediction, the most influential features were VAI, LAP, waist triglyceride index (WTI), Very low-density cholesterol (VLDLC) and TyG-WHtR. Majority voting ensemble classifier demonstrated superior performance in predicting pre-MetS (AUC = 0.79) and MetS (AUC = 0.87).

Conclusion: Identifying these risk factors reveals the complex interplay between visceral adiposity and metabolic dysregulation in African populations, enabling early detection and treatment. Ethical integration of ML algorithms in clinical decision-making can streamline identification of high-risk individuals, optimize resource allocation, and enable precise, tailored interventions.

Supplementary information: The online version contains supplementary material available at 10.1007/s40200-024-01491-7.

目的:在非洲,包括2型糖尿病(T2DM)和代谢综合征(MetS)在内的心脏代谢疾病的迅速流行令人担忧。机器学习(ML)技术为利用数据驱动的洞察力和构建MetS风险预测模型提供了独特的机会,从而加强了个性化预防策略的实施。在这项工作中,我们采用ML技术来开发糖尿病患者的预MetS和MetS的预测模型。方法:对919例T2DM患者进行多中心横断面研究。使用BORUTA特征选择和集成多数投票分类模型(包括逻辑回归、k近邻、高斯朴素贝叶斯、梯度增强分类和支持向量机)对年龄、性别、新型人体测量指标以及生化指标进行分析。结果:不同的代谢谱和表型簇与MetS进展相关。BORUTA算法分别确定了10个和16个重要特征,用于预MetS和MetS预测。对于pre-MetS,最重要的特征是脂质积累产物(LAP)、经腰高比调整的甘油三酯-葡萄糖指数(TyG-WHtR)、冠状动脉风险(CR)、脏脂肪指数(VAI)和腹容积指数(AVI)。对于MetS的预测,影响最大的特征是VAI、LAP、腰甘油三酯指数(WTI)、极低密度胆固醇(VLDLC)和TyG-WHtR。多数投票集成分类器在预测预MetS (AUC = 0.79)和MetS (AUC = 0.87)方面表现出优越的性能。结论:识别这些危险因素揭示了非洲人群中内脏肥胖和代谢失调之间复杂的相互作用,使早期发现和治疗成为可能。临床决策中ML算法的伦理整合可以简化高风险个体的识别,优化资源分配,并实现精确,量身定制的干预。补充资料:在线版本提供补充资料,网址为10.1007/s40200-024-01491-7。
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引用次数: 0
Managing high disease burden: a study of medication rationality in diabetes and hypertension in Andhra Pradesh. 管理高疾病负担:安得拉邦糖尿病和高血压患者用药合理性研究。
IF 1.8 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-24 eCollection Date: 2024-12-01 DOI: 10.1007/s40200-024-01475-7
Nagasen Dasari, Nisar Ahmed, Sankhanil Panda, Ayushi Kumari, T Thanmayi Sai Lakshmi, Hema Ratna Sai Lakshmi Vemana

Objectives: To assess the burden of chronic Non-communicable diseases (NCDs) such as diabetes and hypertension, and evaluate the utilization of drugs for their treatment among the population of Andhra Pradesh, India.

Methods: A cross-sectional study was conducted to analyse the prevalence of diabetes and hypertension, as well as the pattern of drug usage for their management. Data were collected through surveys and medical records review.

Results: The study revealed a high prevalence of diabetes and hypertension in Andhra Pradesh, with significant proportions of the population remaining untreated despite critical drug utilization. Commonly used antidiabetic drugs included metformin, glipizide, and insulin, while telmisartan, furosemide, and metoprolol were frequently utilized for hypertension treatment. Side effects associated with these drugs were reported, emphasizing the need for better public awareness campaigns, improved access to healthcare, and effective management of side effects.

Conclusions: The findings underscore the importance of early detection and preventive measures for hypertension and diabetes. There is a pressing need for tailored interventions addressing social and economic factors contributing to non-adherence to treatment regimens. While the widespread use of medications indicates significant awareness and proactive healthcare among a substantial portion of the population, the presence of individuals not adhering to their treatment suggests significant gaps in awareness and access to healthcare services. This study provides crucial insights into medication patterns for managing diabetes and hypertension in Andhra Pradesh, laying the groundwork for targeted public health interventions.

目标:评估糖尿病和高血压等慢性非传染性疾病(NCDs)的负担,并评估印度安得拉邦(Andhra Pradesh)人口对治疗这些疾病的药物使用情况。方法:采用横断面研究方法,分析糖尿病和高血压的患病率,以及用药模式,为其管理提供参考。数据是通过调查和医疗记录审查收集的。结果:该研究揭示了安得拉邦糖尿病和高血压的高患病率,尽管关键药物使用,但仍有很大比例的人口未接受治疗。常用的降糖药物包括二甲双胍、格列吡嗪和胰岛素,而替米沙坦、呋塞米和美托洛尔常用于治疗高血压。报告了与这些药物有关的副作用,强调需要更好地开展提高公众认识运动,改善获得医疗保健的机会,并有效地管理副作用。结论:研究结果强调了早期发现和预防高血压和糖尿病的重要性。迫切需要有针对性的干预措施,解决导致不遵守治疗方案的社会和经济因素。虽然药物的广泛使用表明相当一部分人口具有高度的认识和积极的保健,但存在不坚持治疗的个人表明在认识和获得保健服务方面存在重大差距。这项研究为安得拉邦管理糖尿病和高血压的药物模式提供了重要见解,为有针对性的公共卫生干预奠定了基础。
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引用次数: 0
Glycemic status and bone health: investigating the impact of glycosylated hemoglobin on bone density in South Indian adults. 血糖状态和骨骼健康:研究糖基化血红蛋白对南印度成年人骨密度的影响。
IF 1.8 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-20 eCollection Date: 2024-12-01 DOI: 10.1007/s40200-024-01473-9
Rohini Bhadra, Sumithra Selvam, Sucharita Sambashivaiah

Objective: To investigate the relationship between glycosylated Hemoglobin (HbA1c) levels and bone mineral density (BMD) in individuals with varying glycemic statuses, including diabetes, prediabetes, and controls.

Methods: This cross-sectional study conducted in Bengaluru, India, included 336 participants aged 20 to 60. Blood samples were taken to assess fasting blood glucose, HbA1c, and lipid profile. Participants were divided into tertiles based on HbA1c levels: low(HbA1c ≤ 5.5%), moderate(HbA1c > 5.5-6.0%), and high(HbA1c ≥ 6.1%).Dual energy-X-ray absorptiometry(DXA) measured hip, spine, and total BMD as indicators of bone health.

Results: Intermediate and high HbA1c tertiles had a significantly higher hip and total BMD compared to low HbA1c tertiles (p < 0.001 and p = 0.006 for hip and total BMD). Spine BMD was comparable between the three groups. After adjusting for age, gender and BMI, a potential independent effect of glycemic control on hip BMD was observed (Low vs. intermediate and high glycemic status: β: 0.041, 95% C.I.: 0.003, 0.078, p = 0.034).

Conclusion: Elevated HbA1c might be associated with higher hip and overall BMD as observed through DXA. Nonetheless, this doesn't necessarily imply better bone health; further evaluation is advised to prevent fractures.

Supplementary information: The online version contains supplementary material available at 10.1007/s40200-024-01473-9.

目的:探讨糖化血红蛋白(HbA1c)水平与不同血糖状态个体(包括糖尿病、糖尿病前期和对照组)骨密度(BMD)之间的关系。方法:这项横断面研究在印度班加罗尔进行,包括336名年龄在20至60岁之间的参与者。采集血样评估空腹血糖、糖化血红蛋白和血脂。参与者根据HbA1c水平分为低(HbA1c≤5.5%)、中(HbA1c bb0 5.5-6.0%)和高(HbA1c≥6.1%)三组。双能x线骨密度仪(DXA)测量髋部、脊柱和总骨密度作为骨骼健康指标。结果:与低HbA1c水平的患者相比,中等和高HbA1c水平的患者髋部和总骨密度明显更高(髋部和总骨密度p = 0.006)。三组间脊柱骨密度具有可比性。在调整了年龄、性别和BMI后,观察到血糖控制对髋部骨密度的潜在独立影响(低、中、高血糖状态:β: 0.041, 95% ci: 0.003, 0.078, p = 0.034)。结论:通过DXA观察到,HbA1c升高可能与髋关节和总体骨密度升高有关。然而,这并不一定意味着更好的骨骼健康;建议进一步评估以防止骨折。补充资料:在线版本提供补充资料,网址为10.1007/s40200-024-01473-9。
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引用次数: 0
Incretin-based therapy: a new horizon in diabetes management. 以肠促胰岛素为基础的治疗:糖尿病管理的新视野。
IF 1.8 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-17 eCollection Date: 2024-12-01 DOI: 10.1007/s40200-024-01479-3
Malek Zarei, Navideh Sahebi Vaighan, Mohammad Hadi Farjoo, Soosan Talebi, Mohammad Zarei

Diabetes mellitus, a metabolic syndrome characterized by hyperglycemia and insulin dysfunction, often leads to serious complications such as neuropathy, nephropathy, retinopathy, and cardiovascular disease. Incretins, gut peptide hormones released post-nutrient intake, have shown promising therapeutic effects on these complications due to their wide-ranging biological impacts on various body systems. This review focuses on the role of incretin-based therapies, particularly Glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, in managing diabetes and its complications. We also discuss the potential of novel agents like semaglutide, a recently approved oral compound, and dual/triple agonists targeting GLP-1/GIP, GLP-1/glucagon, and GLP-1/GIP/glucagon receptors, which are currently under investigation. The review aims to provide a comprehensive understanding of the beneficial impacts of natural incretins and the therapeutic potential of incretin-based therapies in diabetes management.

糖尿病是一种以高血糖和胰岛素功能障碍为特征的代谢综合征,常导致严重的并发症,如神经病变、肾病、视网膜病变和心血管疾病。肠促胰岛素是营养摄入后释放的肠道肽激素,由于其对各个身体系统的广泛生物学影响,在这些并发症中显示出有希望的治疗效果。本文综述了以肠促胰岛素为基础的治疗方法,特别是胰高血糖素样肽-1 (GLP-1)激动剂和二肽基肽酶-4 (DPP-4)抑制剂在糖尿病及其并发症中的作用。我们还讨论了新药物的潜力,如最近批准的口服化合物semaglutide,以及目前正在研究的针对GLP-1/GIP, GLP-1/胰高血糖素和GLP-1/GIP/胰高血糖素受体的双/三重激动剂。本综述旨在全面了解天然肠促胰岛素的有益影响以及肠促胰岛素为基础的治疗方法在糖尿病管理中的治疗潜力。
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引用次数: 0
Material needs security and mental health outcomes in adults with type 2 Diabetes in Lebanon: A cross-sectional study. 黎巴嫩成人2型糖尿病患者的物质需求安全和心理健康结局:一项横断面研究
IF 1.8 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-16 eCollection Date: 2024-12-01 DOI: 10.1007/s40200-024-01484-6
Ola Sukkarieh, Maya Bassil, Leonard E Egede

Objectives: Despite their documented significance in type 2 diabetes (T2DM) management, social determinants of health (SDOHs) including material needs security and mental health outcomes are understudied in the Middle East and North Africa (MENA) region. This study aims to assess the relation between material needs security and mental health outcomes in Lebanese adults with T2DM.

Methods: Subjects with T2DM (N = 300) were recruited from primary health care centers in Lebanon. Sociodemographic, material need variables, depression measured by Patient Health Questionnaire (PHQ-9), and diabetes fatalism measured by Diabetes Fatalism Scale (DFS) were collected.

Results: Most of the participants were men, married and with lower educational levels. Multivariate analyses revealed that having material needs security was associated with diabetes fatalism (β = -0.63(-1.13; -0.12)), and depression (β = -0.46(-0.78; -0.13)). Also, higher age (β = 3.49(0.91; 6.06)) and education (β = 3.42(1.18; 5.66)), and lower income (β = 3.25(0.62; 5.88)) were independently associated with diabetes fatalism. Being male was the only independent variable associated with less depression (β = -1.56(-2.97; -0.14)).

Conclusion: Our study highlights the importance of material needs security on mental health outcomes for adults with T2DM in the MENA region. Clinicians are encouraged to assess the impact of material needs on mental health outcomes. Further research is needed to understand potential pathways/mechanisms and options for effective interventions and policymaking.

目的:尽管在2型糖尿病(T2DM)管理中具有文献记载的重要意义,但在中东和北非(MENA)地区,健康的社会决定因素(SDOHs),包括物质需求、安全和精神健康结果,尚未得到充分研究。本研究旨在评估黎巴嫩成年T2DM患者的物质需求安全与心理健康结果之间的关系。方法:从黎巴嫩的初级卫生保健中心招募T2DM患者(N = 300)。收集社会人口学、物质需求变量、患者健康问卷(PHQ-9)测量的抑郁症和糖尿病宿命论量表(DFS)测量的糖尿病宿命论。结果:大多数参与者是男性,已婚,受教育程度较低。多变量分析显示,物质需求安全与糖尿病宿命论相关(β = -0.63(-1.13;-0.12)),抑郁(β = -0.46(-0.78;-0.13))。年龄越大(β = 3.49(0.91;6.06))和教育(β = 3.42(1.18;5.66)),收入越低(β = 3.25(0.62;5.88))与糖尿病宿命论独立相关。男性是唯一与较少抑郁相关的自变量(β = -1.56;-0.14))。结论:我们的研究强调了物质需求安全对中东和北非地区成年T2DM患者心理健康结果的重要性。鼓励临床医生评估物质需求对精神健康结果的影响。需要进一步研究以了解有效干预和决策的潜在途径/机制和选择。
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引用次数: 0
Assessment of fracture risk in diabetic patients. 糖尿病患者骨折风险评估。
IF 1.8 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-13 eCollection Date: 2024-12-01 DOI: 10.1007/s40200-024-01474-8
Zhenpeng Wang, Mei Zhang, Dan Jia

Patients with diabetes often experience reduced bone strength, resulting in a higher fracture risk. This decline and increased susceptibility stem from intricate interactions within the bone microstructure. However, current gold standard methods for assessing bone strength, such as bone mineral density, and widely-used fracture risk assessment tools do not accurately predict fracture risk in diabetic patients. Therefore, it is crucial to incorporate additional indicators that evaluate bone quality and specific markers relevant to diabetes to enhance the accuracy of predictive models. Moreover, the selection of appropriate algorithms for model construction is essential. This review aims to introduce indicators from both imaging examinations and laboratory indicators that hold significant value for inclusion in fracture risk prediction models for diabetic patients. Additionally, this study provides an overview of the research progress in fracture risk prediction models for diabetic patients, serving as a valuable reference for clinical practice.

糖尿病患者经常经历骨强度降低,导致更高的骨折风险。这种下降和易感性的增加源于骨微观结构内部复杂的相互作用。然而,目前评估骨强度的金标准方法,如骨矿物质密度和广泛使用的骨折风险评估工具,并不能准确预测糖尿病患者的骨折风险。因此,纳入评估骨质量的其他指标和与糖尿病相关的特定标志物以提高预测模型的准确性至关重要。此外,选择合适的算法进行模型构建是至关重要的。本文旨在介绍影像学检查和实验室指标在糖尿病患者骨折风险预测模型中具有重要价值的指标。此外,本研究综述了糖尿病患者骨折风险预测模型的研究进展,为临床实践提供有价值的参考。
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引用次数: 0
Evaluation of diabetes care parameters in patients with diabetes: A population-based cross-sectional study in Khuzestan province (southwest of Iran). 糖尿病患者糖尿病护理参数的评估:在胡齐斯坦省(伊朗西南部)进行的一项基于人群的横断面研究。
IF 1.8 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-13 eCollection Date: 2024-12-01 DOI: 10.1007/s40200-024-01483-7
Leila Yazdanpanah, Hajieh Shahbazian, Ali Akbar Shayesteh, Hossein Poustchi, Saeed Ghanbari, Bahman Cheraghian, Zeinab Masoumipoya, Behnam Ahmadi, Amir Mohammad Zamani

Background: Diabetes is becoming a worldwide concern. Optimal diabetes control reduces diabetes complications.

Objectives: We aimed to measure the principal diabetes care parameters to recognize the main deficits in care for patients with diabetes in the region.

Methods: This cross-sectional study is based on the Khuzestan Comprehensive Health Study (KCHS) data. Of all participants, 4673 (15.3%) were identified to have diabetes. We invited the known cases of diabetes to complete a checklist about their diabetes through face-to-face interviews, and we obtained a blood sample to measure their HbA1c.

Results: Of all participants of the KCHS study, 312 patients with diabetes who met the inclusion criteria were identified. Mean (± SD) HbA1c was 8.5% (± 1.8), and 225 (72.1%) of the participants had poor glycemic control. About 45.2% had blood pressure less than 130/80 mmHg, and 24% had FBS lower than 130 mg/dl. Nearly 37.8% of the participants had LDL < 100 mg/dl and 40% TG < 150 mg/dl. Of all participants, 38.5% had undergone retinal examination, 13.8% had their foot examined, and 39.4% had done urine micro-albumin /Cr test. HbA1c level had a statistically significant relationship with gender (P = 0.012), occupation (P = 0.007), nephropathy (P = 0.004) and retinopathy (P < 0.001).

Conclusions: This study showed that less than half of the participants achieved the optimal ADA goals for diabetes care, therefore it is necessary to revise the basic protocols of diabetes care in the region to improve diabetes management.

背景:糖尿病正成为全球关注的问题。最佳的糖尿病控制可以减少糖尿病并发症。目的:我们旨在测量糖尿病护理的主要参数,以识别该地区糖尿病患者护理的主要缺陷。方法:本横断面研究基于胡齐斯坦综合健康研究(KCHS)数据。在所有参与者中,4673人(15.3%)被确定患有糖尿病。我们邀请已知的糖尿病患者通过面对面的访谈来完成一份关于他们糖尿病的清单,我们获得了他们的血液样本来测量他们的HbA1c。结果:在KCHS研究的所有参与者中,确定了312例符合纳入标准的糖尿病患者。平均(±SD) HbA1c为8.5%(±1.8),225名(72.1%)参与者血糖控制不良。45.2%的患者血压低于130/80 mmHg, 24%的患者FBS低于130 mg/dl。结论:本研究表明,不到一半的参与者达到了ADA糖尿病护理的最佳目标,因此有必要修改该地区糖尿病护理的基本方案,以改善糖尿病管理。
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引用次数: 0
Circulating mannose-binding lectin in diabetic patients and risk of vascular complications: a systematic review and meta-analysis. 糖尿病患者循环甘露糖结合凝集素与血管并发症的风险:一项系统综述和荟萃分析。
IF 1.8 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-05 eCollection Date: 2024-12-01 DOI: 10.1007/s40200-024-01478-4
Mohammad Sedghi, Ali Ranjbaran, Mahtab Forouhi, Mahdi Nejatianfar, Nazanin Azmi-Naei, Parian Pourmoafi Esfahani, Mahdi Tavakoli, Fatemeh Sadat Hashemi Javaheri, Nazanin Shakibi, Elham Mirzaee, Akram Mirzaee, Hannaneh Nejati, Mansoureh Makarem, Tahereh Parishan Kordiani, Gita Pourshahikhaneh, Rasoul Shavaleh, Kazem Rahmani, Molood Foogerdi

Objectives: Recent studies have confirmed the involvement of mannose-binding lectin (MBL) in the pathogenesis of vascular complications in individuals with diabetes. Due to the discrepancy between the results of studies, a meta-analysis was conducted to evaluate MBL levels in patients with diabetes and its vascular complications.

Methods: We reviewed all observational studies published in PubMed/Medline, Scopus, EMBASE, and Web of Science Core Collection databases to identify relevant studies up to 1 April 2024. To account for describing heterogeneity among the studies, I2 and χ2 statistics were utilized. Also, a random-effects model was employed to combine the studies. The Newcastle Ottawa Scale (NOS) checklist was applied for quality assessment of each study.

Results: Twenty-eight papers were encompassed in this meta-analysis. The mean difference in MBL levels between patients with diabetic nephropathy and diabetic retinopathy differed significantly compared with the healthy control group and the diabetic group without vascular complications (P-value < 0.05). Moreover, the pooled results revealed a significant relationship between MBL levels and the incidence of vascular complications (pooled HR = 1.44, 95% CI: 1.07-1.95, P-value < 0.05) and disease-related mortality (pooled HR = 1.52, 95% CI: 1.07-2.16, P-value < 0.05) among diabetic patients. Also, there was a direct association between incidence of nephropathy in diabetics and higher levels of MBL (pooled HR = 2.16, 95% CI: 1.52-3.08, P-value < 0.05).

Conclusion: Diabetic patients with elevated MBL levels are potentially at increased risk of vascular complications such as nephropathy and retinopathy. Therefore, by determining MBL status in diabetic patients, it is possible to predict the progress and possible consequences of the disease.

目的:最近的研究已经证实甘露糖结合凝集素(MBL)参与糖尿病患者血管并发症的发病机制。由于研究结果之间存在差异,我们对糖尿病患者及其血管并发症的MBL水平进行了meta分析。方法:我们回顾了PubMed/Medline、Scopus、EMBASE和Web of Science Core Collection数据库中截至2024年4月1日发表的所有观察性研究。为了解释研究间的异质性,采用I2和χ2统计。同时,采用随机效应模型对研究进行组合。采用纽卡斯尔渥太华量表(NOS)检查表对每项研究进行质量评估。结果:本荟萃分析纳入了28篇论文。糖尿病肾病和糖尿病视网膜病变患者MBL水平的平均差异与健康对照组和无血管并发症的糖尿病组相比有显著差异(p值)。结论:糖尿病患者MBL水平升高可能增加肾病和视网膜病变等血管并发症的风险。因此,通过确定糖尿病患者的MBL状态,可以预测疾病的进展和可能的后果。
{"title":"Circulating mannose-binding lectin in diabetic patients and risk of vascular complications: a systematic review and meta-analysis.","authors":"Mohammad Sedghi, Ali Ranjbaran, Mahtab Forouhi, Mahdi Nejatianfar, Nazanin Azmi-Naei, Parian Pourmoafi Esfahani, Mahdi Tavakoli, Fatemeh Sadat Hashemi Javaheri, Nazanin Shakibi, Elham Mirzaee, Akram Mirzaee, Hannaneh Nejati, Mansoureh Makarem, Tahereh Parishan Kordiani, Gita Pourshahikhaneh, Rasoul Shavaleh, Kazem Rahmani, Molood Foogerdi","doi":"10.1007/s40200-024-01478-4","DOIUrl":"10.1007/s40200-024-01478-4","url":null,"abstract":"<p><strong>Objectives: </strong>Recent studies have confirmed the involvement of mannose-binding lectin (MBL) in the pathogenesis of vascular complications in individuals with diabetes. Due to the discrepancy between the results of studies, a meta-analysis was conducted to evaluate MBL levels in patients with diabetes and its vascular complications.</p><p><strong>Methods: </strong>We reviewed all observational studies published in PubMed/Medline, Scopus, EMBASE, and Web of Science Core Collection databases to identify relevant studies up to 1 April 2024. To account for describing heterogeneity among the studies, I<sup>2</sup> and χ<sup>2</sup> statistics were utilized. Also, a random-effects model was employed to combine the studies. The Newcastle Ottawa Scale (NOS) checklist was applied for quality assessment of each study.</p><p><strong>Results: </strong>Twenty-eight papers were encompassed in this meta-analysis. The mean difference in MBL levels between patients with diabetic nephropathy and diabetic retinopathy differed significantly compared with the healthy control group and the diabetic group without vascular complications (P-value < 0.05). Moreover, the pooled results revealed a significant relationship between MBL levels and the incidence of vascular complications (pooled HR = 1.44, 95% CI: 1.07-1.95, P-value < 0.05) and disease-related mortality (pooled HR = 1.52, 95% CI: 1.07-2.16, P-value < 0.05) among diabetic patients. Also, there was a direct association between incidence of nephropathy in diabetics and higher levels of MBL (pooled HR = 2.16, 95% CI: 1.52-3.08, P-value < 0.05).</p><p><strong>Conclusion: </strong>Diabetic patients with elevated MBL levels are potentially at increased risk of vascular complications such as nephropathy and retinopathy. Therefore, by determining MBL status in diabetic patients, it is possible to predict the progress and possible consequences of the disease.</p>","PeriodicalId":15635,"journal":{"name":"Journal of Diabetes and Metabolic Disorders","volume":"23 2","pages":"2131-2142"},"PeriodicalIF":1.8,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Recognition of GCK Homozygote missense (His424Tyr) variant in a female patient with neonatal hyperglycemia. 1例女性新生儿高血糖患者GCK纯合子错义(His424Tyr)变异的识别
IF 1.8 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-01 eCollection Date: 2024-12-01 DOI: 10.1007/s40200-024-01480-w
Amirreza Pashapour Yeganeh, Marjan Rahimi Farahani, Nekoo Panahi, Mahsa Mohammad Amoli, Zeynab Nickhah Klashami, Hamid Reza Aghaei Meybodi, Akbar Soltani

Introduction: Heterozygous mutations in the GCK gene result in mildly elevated glucose levels from birth, and the homozygous loss-of-function mutations leads to permanent neonatal diabetes. In the present study we aim to investigate the cause of diabetes in an adult female patient with unusual course of diabetes.

Case presentation: We evaluate a female patient who previously encountered significant hyperglycemia during the infancy and subsequently experienced a relatively uneventful childhood. In later years, she faced significant hyperglycemia and retinopathy that required laser photocoagulation. Her treatment history included periods of oral hypoglycemic agents or insulin, which occasionally led to hypoglycemia, as well as extended intervals without treatment. However, she never required hospitalization for diabetic ketoacidosis. The patient's family history was significant, with her parents being cousins and having a history of prediabetes and gestational diabetes in several family members. Autoantibody tests for type 1 diabetes were negative. Next-generation sequencing analysis of the coding regions and conserved splice sites of several genes identified a homozygous GCK (T/T) missense (His424Tyr) variant, which was validated by Sanger sequencing. Heterozygous C/T mutations were revealed in the parents.

Discussion and conclusion: This case highlights the importance of considering homozygous GCK mutations as a potential cause of persistent neonatal diabetes, especially in patients with a history of elevated glucose levels from infancy, a family history of early-onset non-progressive diabetes and gestational diabetes, and parental consanguinity. Genetic testing can help identify the underlying genetic etiology in such cases. Early diagnosis is crucial to guide appropriate treatment and management strategies.

GCK基因的杂合突变导致出生时血糖水平轻度升高,纯合功能丧失突变导致永久性新生儿糖尿病。在本研究中,我们的目的是探讨糖尿病的原因在一个成年女性患者的异常病程。病例介绍:我们评估了一位女性患者,她以前在婴儿期遇到过明显的高血糖,随后经历了一个相对平静的童年。在后来的几年里,她面临着严重的高血糖和视网膜病变,需要激光光凝。她的治疗史包括口服降糖药或胰岛素,偶尔导致低血糖,以及不治疗的时间间隔延长。然而,她从未因糖尿病酮症酸中毒而住院。患者的家族史很重要,她的父母是表兄妹,有几个家庭成员有前驱糖尿病和妊娠糖尿病史。1型糖尿病自身抗体测试呈阴性。新一代测序分析了多个基因的编码区和保守剪接位点,发现了一个纯合子GCK (T/T)错义(His424Tyr)变体,并通过Sanger测序验证了这一结果。在亲本中发现杂合C/T突变。讨论和结论:本病例强调了考虑纯合GCK突变作为持续新生儿糖尿病的潜在原因的重要性,特别是在婴儿期血糖水平升高、早发性非进行性糖尿病和妊娠糖尿病家族史以及父母有血缘关系的患者中。基因检测可以帮助确定这些病例的潜在遗传病因。早期诊断对于指导适当的治疗和管理策略至关重要。
{"title":"Recognition of GCK Homozygote missense (His424Tyr) variant in a female patient with neonatal hyperglycemia.","authors":"Amirreza Pashapour Yeganeh, Marjan Rahimi Farahani, Nekoo Panahi, Mahsa Mohammad Amoli, Zeynab Nickhah Klashami, Hamid Reza Aghaei Meybodi, Akbar Soltani","doi":"10.1007/s40200-024-01480-w","DOIUrl":"10.1007/s40200-024-01480-w","url":null,"abstract":"<p><strong>Introduction: </strong>Heterozygous mutations in the GCK gene result in mildly elevated glucose levels from birth, and the homozygous loss-of-function mutations leads to permanent neonatal diabetes. In the present study we aim to investigate the cause of diabetes in an adult female patient with unusual course of diabetes.</p><p><strong>Case presentation: </strong>We evaluate a female patient who previously encountered significant hyperglycemia during the infancy and subsequently experienced a relatively uneventful childhood. In later years, she faced significant hyperglycemia and retinopathy that required laser photocoagulation. Her treatment history included periods of oral hypoglycemic agents or insulin, which occasionally led to hypoglycemia, as well as extended intervals without treatment. However, she never required hospitalization for diabetic ketoacidosis. The patient's family history was significant, with her parents being cousins and having a history of prediabetes and gestational diabetes in several family members. Autoantibody tests for type 1 diabetes were negative. Next-generation sequencing analysis of the coding regions and conserved splice sites of several genes identified a homozygous GCK (T/T) missense (His424Tyr) variant, which was validated by Sanger sequencing. Heterozygous C/T mutations were revealed in the parents.</p><p><strong>Discussion and conclusion: </strong>This case highlights the importance of considering homozygous GCK mutations as a potential cause of persistent neonatal diabetes, especially in patients with a history of elevated glucose levels from infancy, a family history of early-onset non-progressive diabetes and gestational diabetes, and parental consanguinity. Genetic testing can help identify the underlying genetic etiology in such cases. Early diagnosis is crucial to guide appropriate treatment and management strategies.</p>","PeriodicalId":15635,"journal":{"name":"Journal of Diabetes and Metabolic Disorders","volume":"23 2","pages":"2401-2405"},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Journal of Diabetes and Metabolic Disorders
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