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Association between serum beta-hydroxybutyrate levels and risk of type 2 diabetes mellitus in patients with impaired fasting glucose. 空腹血糖受损患者血清β -羟基丁酸水平与2型糖尿病风险的关系
IF 4.6 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-04-16 DOI: 10.1038/s41387-025-00364-z
Jaehyun Bae, Young-Eun Kim, Keum Ji Jung, Sun Ha Jee, Byung-Wan Lee

Objectives: Ketogenic conditions have gained attention due to their favorable metabolic prognoses. We aimed to investigate the association between blood levels of beta-hydroxybutyrate (βHB), the most abundant form of ketone body, and type 2 diabetes (T2D) incidence in patients with impaired fasting glucose (IFG).

Methods: We randomly selected 500 patients with IFG from the prospective Korean Cancer Prevention Study II biobank. Blood levels of βHB were measured from the stored samples, and the diagnostic data from the Korean National Health Insurance Service were used to determine the probability of T2D-free survival. A multivariable Cox regression analysis was performed to assess the association between blood βHB levels and the incidence of new-onset T2D.

Results: A total of 453 patients with IFG were included, and 105 (23%) developed T2D during a mean follow-up period of 10.9 years. Higher blood βHB levels in patients with IFG were associated with improved T2D-free survival, although it was not statistically significant (log-rank test, p = 0.058). In multivariable Cox regression models, βHB levels showed a tendency toward a lower risk of T2D, but it was not statistically significant (HR 0.70; 95% CI 0.47-1.04; p = 0.07).

Conclusions: In patients with IFG, the blood βHB level showed a tendency to be associated with the risk of new-onset T2D; however, this tendency was not statistically significant.

目的:生酮疾病因其良好的代谢预后而受到关注。我们旨在研究空腹血糖受损(IFG)患者血液中β -羟基丁酸酯(βHB)水平与2型糖尿病(T2D)发病率之间的关系。β -羟基丁酸酯是最丰富的酮体形式。方法:我们从前瞻性韩国癌症预防研究II生物库中随机选择500例IFG患者。从储存的样本中测量血液中βHB的水平,并使用韩国国民健康保险服务的诊断数据来确定无t2d生存的概率。采用多变量Cox回归分析评估血βHB水平与新发T2D发病率之间的关系。结果:共纳入453例IFG患者,其中105例(23%)在平均10.9年的随访期间发生T2D。IFG患者较高的血βHB水平与改善的无t2d生存期相关,但无统计学意义(log-rank检验,p = 0.058)。在多变量Cox回归模型中,βHB水平有降低T2D风险的趋势,但无统计学意义(HR 0.70;95% ci 0.47-1.04;p = 0.07)。结论:IFG患者血βHB水平与新发T2D风险相关;然而,这种趋势在统计上并不显著。
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引用次数: 0
Novel first-trimester serum biomarkers for early prediction of gestational diabetes mellitus. 新的早期妊娠期血清生物标志物用于早期预测妊娠糖尿病。
IF 4.6 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-04-12 DOI: 10.1038/s41387-025-00372-z
Siqi Tian, Mingxi Liu, Shuwen Han, Haiqi Wu, Rencai Qin, Kongyang Ma, Lianlian Liu, Hongjin Zhao, Yan Li

Background: Gestational diabetes mellitus (GDM) is a common obstetric complication worldwide that seriously threatens maternal and fetal health. As the number of women conceiving through in vitro fertilization (IVF) continues to rise, this population is recognized as being at an elevated risk for GDM. However, there is still no consensus on the early prediction of GDM in IVF patients due to the lack of reliable biomarkers.

Methods: We compared the first-trimester serum cytokine and antibody profiles in 38 GDM women and 38 matched controls undergoing IVF treatment, based on the extensive human biobank of our large‑scale assisted reproductive cohort platform. The 76 samples were divided into a training set (n = 53) and a testing set (n = 23) using a 7:3 ratio, and five diverse machine-learning models for predicting GDM were constructed.

Results: By combining the top five differentially expressed first‑trimester serum biomarkers [including total immunoglobulin (Ig)G, total IgM, interleukin (IL)-7, anti‑phosphatidylserine (aPS)-IgG immune complexes (IC), and IL-15], a novel early prediction model was constructed, which achieved superior predictive value [area under the curve (AUC) and 95% confidence interval (CI) 0.906 (0.840-0.971), with a sensitivity of 75% and a specificity of 94.7%] for GDM development. The eXtreme Gradient Boosting (XGBoost) model achieved an AUC of 0.995 (95% CI: 0.995-1.000, P < 0.001) for the training set and 0.867 (95% CI: 0.789-0.952, P < 0.001) for the test set in predicting GDM.

Conclusions: We identified a set of novel first‑trimester serum cytokines and immune-related biomarkers and constructed an efficient first‑trimester prediction model for GDM in IVF population. These findings are expected to aid in the development of early predictive strategies for GDM and offer immunological insights for further mechanistic studies of GDM.

背景:妊娠期糖尿病(GDM)是一种常见的产科并发症,严重威胁孕产妇和胎儿的健康。随着通过体外受精(IVF)怀孕的女性数量不断增加,这一人群被认为是GDM的高风险人群。然而,由于缺乏可靠的生物标志物,对于IVF患者GDM的早期预测仍未达成共识。方法:基于我们的大规模辅助生殖队列平台的广泛人类生物库,我们比较了38名GDM妇女和38名匹配对照组接受试管婴儿治疗的妊娠早期血清细胞因子和抗体谱。将76个样本按7:3的比例分为训练集(n = 53)和测试集(n = 23),构建了5种不同的预测GDM的机器学习模型。结果:结合前5个差异表达的妊娠早期血清生物标志物[包括总免疫球蛋白(Ig)G、总IgM、白细胞介素(IL)-7、抗磷脂酰丝氨酸(aPS)-IgG免疫复合物(IC)和IL-15],构建了一种新的早期预测模型,该模型对GDM的发展具有较好的预测价值[曲线下面积(AUC)和95%置信区间(CI) 0.906(0.840-0.971),敏感性为75%,特异性为94.7%]。极端梯度增强(XGBoost)模型的AUC为0.995 (95% CI: 0.995-1.000, P)。结论:我们鉴定了一组新的妊娠早期血清细胞因子和免疫相关生物标志物,并构建了一个有效的妊娠早期预测模型。这些发现有望帮助开发GDM的早期预测策略,并为GDM的进一步机制研究提供免疫学见解。
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引用次数: 0
A comprehensive review on the implications of Yogic/Sattvic diet in reducing inflammation in type 2 diabetes. 瑜伽/ satvic饮食对减少2型糖尿病炎症的影响的综合综述
IF 4.6 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-04-11 DOI: 10.1038/s41387-025-00371-0
Anupama Vallazhath, Pooja Yedehalli Thimmappa, Harshit B Joshi, Krishna Raghava Hebbar, Anupama Nayak, Shashikiran Umakanth, Apar Avinash Saoji, Nandi Krishnamurthy Manjunath, Basavaraj S Hadapad, Manjunath B Joshi

Chronic inflammation in type 2 diabetes (T2D), characterized by constitutively activated immune cells and elevated pro-inflammatory mediators along with hyperglycaemia and increased free fatty acids and branched chain amino acid levels, significantly alters the immuno-metabolic axis. Over the years, dietary intervention has been explored as an effective strategy for managing T2D. Evidence from experimental and clinical studies indicates that various diets, including Mediterranean, Nordic, Palaeolithic and ketogenic diets, increase insulin sensitivity, decrease gluconeogenesis, and adiposity, and exert anti-inflammatory effects, thus preserving immuno-metabolic homeostasis in individuals with T2D. Indian dietary sources are categorized as Sattvic, Rajasic, and Tamasic, depending on their impact on health and behaviour. The Yogic diet, commonly recommended during yoga practice, is predominantly Sattvic, emphasizing plant-based whole foods while limiting processed and high-glycaemic-index items. Yogic diet is also recommended for Mitahara, emphasizing mindful eating, which is attributed to calorie restriction. Adopting a Yogic diet, featuring low-fat vegetarian principles, strongly reduces inflammatory mediator levels. This diet not only ameliorates insulin resistance and maintains a healthy body weight but also regulates immunomodulation, enhances gut microbiome diversity and provides essential phytonutrients, collectively preventing inflammation. Although, preliminary studies show aforementioned beneficial role of Yogic diet in improving diabetes associated metabolic and inflammatory changes, precise cellular and molecular mechanisms are not yet understood. Hence, further studies are warranted to decipher the mechanisms. This review summarizes the multiple roles of Yogic diet and related dietary components in mitigating inflammation and enhancing glycaemic control in T2D.

2型糖尿病(T2D)的慢性炎症,以组成性激活的免疫细胞和升高的促炎介质以及高血糖和增加的游离脂肪酸和支链氨基酸水平为特征,显著改变了免疫代谢轴。多年来,人们一直在探索饮食干预作为控制T2D的有效策略。来自实验和临床研究的证据表明,各种饮食,包括地中海、北欧、旧石器时代和生酮饮食,可以增加胰岛素敏感性,减少糖异生和肥胖,并发挥抗炎作用,从而保持T2D患者的免疫代谢稳态。根据对健康和行为的影响,印度人的饮食来源可分为satvic、Rajasic和Tamasic。瑜伽饮食,通常在瑜伽练习中推荐,主要是satvic,强调植物性全食物,同时限制加工和高血糖指数的食物。瑜伽饮食也被推荐给三原,强调正念饮食,这归因于卡路里限制。采用瑜伽饮食,以低脂素食原则为特色,可大大降低炎症介质水平。这种饮食不仅可以改善胰岛素抵抗,保持健康的体重,还可以调节免疫调节,增强肠道微生物群的多样性,提供必需的植物营养素,共同预防炎症。虽然,初步研究表明瑜伽饮食在改善糖尿病相关代谢和炎症变化方面的有益作用,但确切的细胞和分子机制尚不清楚。因此,有必要进一步研究以解释其机制。本文综述了瑜伽饮食及其相关饮食成分在缓解炎症和促进糖尿病血糖控制方面的多重作用。
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引用次数: 0
Magnesium, fibrinolysis and clotting interplay among children and adolescents with type 1 diabetes mellitus; potential mediators of diabetic microangiopathy. 儿童和青少年1型糖尿病患者镁、纤溶和凝血的相互作用糖尿病微血管病变的潜在介质。
IF 4.6 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-04-01 DOI: 10.1038/s41387-025-00368-9
Dalia N Toaima, Kholoud S Abdel-Maksoud, Heba M Atef, Nouran Y Salah

Background and aim: Hypomagnesemia and clotting disorders have been reported among people with diabetes especially those with type 2 diabetes (T2DM). Magnesium plays a crucial role in hemostasis and hypomagnesemia was found to increase the thrombotic risk. The patho-mechanism linking magnesium, clotting disorders, and diabetic microangiopathy in T1DM remains to be unraveled. Hence this study aimed to assess the magnesium level among children and adolescents with T1DM compared to healthy controls and to correlate it with coagulopathy markers and diabetic microangiopathy.

Methods: Forty-six children and adolescents with T1DM & 46 controls were assessed for serum magnesium, prothrombin time (PT), activated-partial thromboplastin time (aPTT), plasminogen activator inhibitor-1 (PAI-1) and HbA1c. The Toronto clinical scoring system, fundus, urinary microalbumin, and serum fasting lipids were used to assess diabetic microangiopathy.

Results: Children and adolescents with T1DM have significantly lower magnesium, PT, aPTT, and significantly higher PAI-1 than controls (p<0.001), this is more evident in those having microangiopathy than those without (p<0.001). Serum magnesium is positively correlated with PT, aPTT, and HDL and negatively correlated with insulin daily dose, PAI-1, HbA1c, triglycerides, and urinary microalbumin. Multivariate-logistic regression revealed that diabetes duration, HbA1c, PT, aPTT, PAI-1, and urinary microalbumin were independently associated with serum magnesium among children and adolescents with T1DM (p<0.05).

Conclusion: Children and adolescents with T1DM have lower magnesium levels than controls; that is more pronounced among those having microangiopathy. Low serum magnesium is associated with poor glycemic control, coagulopathy, and diabetic microangiopathy among children and adolescents with T1DM. Magnesium supplementation combined with standard insulin therapy in pediatric patients with T1DM is recommended for better glycemic control and prevention of diabetic microangiopathy.

背景和目的:低镁血症和凝血障碍在糖尿病患者,特别是2型糖尿病(T2DM)患者中有报道。镁在止血中起着至关重要的作用,低镁血症被发现会增加血栓形成的风险。在T1DM中,镁、凝血障碍和糖尿病微血管病变之间的病理机制仍有待阐明。因此,本研究旨在评估与健康对照相比,T1DM儿童和青少年的镁水平,并将其与凝血功能标志物和糖尿病微血管病变联系起来。方法:对46例T1DM儿童和青少年及46例对照组进行血清镁、凝血酶原时间(PT)、活化部分凝血活素时间(aPTT)、纤溶酶原激活物抑制剂-1 (PAI-1)和HbA1c的检测。采用多伦多临床评分系统、眼底、尿微量白蛋白和空腹血脂来评估糖尿病微血管病变。结果:儿童和青少年T1DM患者的镁、PT、aPTT水平明显低于对照组,PAI-1水平明显高于对照组(p结论:儿童和青少年T1DM患者的镁水平低于对照组;这在微血管疾病患者中更为明显。在患有T1DM的儿童和青少年中,低血清镁与血糖控制不良、凝血功能障碍和糖尿病微血管病变有关。建议在儿科T1DM患者中补充镁并联合标准胰岛素治疗,以更好地控制血糖并预防糖尿病微血管病变。
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引用次数: 0
Association of habitual glucosamine use with risk of microvascular complications among individuals with type 2 diabetes: a prospective cohort study in UK biobank. 习惯性使用氨基葡萄糖与2型糖尿病患者微血管并发症风险的关系:英国生物银行的一项前瞻性队列研究
IF 4.6 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-04-01 DOI: 10.1038/s41387-025-00369-8
Zi-Jian Cheng, Yu-Feng Luo, Qing-Yun Zhu, Yan-Fei Wang, Wen-Yan Ren, Fei-Yan Deng, Lin Bo, Xi-Yuan Jiang, Shu-Feng Lei, Long-Fei Wu

Background: Glucosamine is a widely used supplement for treating osteoarthritis and joint pain. New evidence suggests a potential association between glucosamine and type 2 diabetes, inflammation and cardiometabolic risk. We aimed to prospectively evaluate the association of habitual glucosamine use with risk of diabetic microvascular complications based on data from the large-scale nationwide prospective UK Biobank cohort study.

Methods: This analysis included 21,171 participants with type 2 diabetes who were free of microvascular complications from the UK Biobank. Incidence of diabetic microvascular complications was ascertained via electronic health records. The Cox proportional hazards model was used to assess the relationship between glucosamine use and the risk of diabetic microvascular complications. Subgroup analyses and sensitivity analyses were performed to explore the potential effect modifications and the robustness of the main findings.

Results: At baseline, 14.5% of the participants reported habitual use of glucosamine supplements. During a median follow-up of 12.3 years, 4399 people developed diabetic microvascular complications, including 2084 cases of incident diabetic nephropathy, 2401 incident diabetic retinopathy, and 831 incident diabetic neuropathy. Glucosamine use was significantly associated with lower risks of composite microvascular complications (hazard ratio (HR) 0.89, 95% CI: 0.81 to 0.97) and diabetic nephropathy (HR 0.87, 95% CI: 0.76 to 0.98) in fully adjusted models. However, there was no significant inverse association between glucosamine use and the risk of diabetic retinopathy (HR 0.94, 95% CI: 0.83 to 1.06) or diabetic neuropathy (HR 0.88, 95% CI: 0.71 to 1.08).

Conclusions: Habitual use of glucosamine supplement was significantly associated with lower risks of composite microvascular complications and diabetic nephropathy but not retinopathy or neuropathy in individuals with type 2 diabetes.

背景:氨基葡萄糖是一种广泛用于治疗骨关节炎和关节疼痛的补充剂。新的证据表明,葡萄糖胺与2型糖尿病、炎症和心脏代谢风险之间存在潜在关联。我们的目的是前瞻性评估习惯性使用氨基葡萄糖与糖尿病微血管并发症风险的关系,基于大规模的全国性前瞻性英国生物银行队列研究的数据。方法:该分析包括21,171名来自英国生物银行的无微血管并发症的2型糖尿病患者。通过电子健康记录确定糖尿病微血管并发症的发生率。采用Cox比例风险模型评估葡萄糖胺使用与糖尿病微血管并发症风险之间的关系。进行亚组分析和敏感性分析,以探讨潜在的效应修改和主要发现的稳健性。结果:在基线时,14.5%的参与者报告习惯性使用氨基葡萄糖补充剂。在中位12.3年的随访期间,4399人出现糖尿病微血管并发症,其中2084例发生糖尿病肾病,2401例发生糖尿病视网膜病变,831例发生糖尿病神经病变。在完全调整的模型中,葡萄糖胺的使用与复合微血管并发症(危险比(HR) 0.89, 95% CI: 0.81至0.97)和糖尿病肾病(HR 0.87, 95% CI: 0.76至0.98)的较低风险显著相关。然而,葡萄糖胺的使用与糖尿病视网膜病变(HR 0.94, 95% CI: 0.83至1.06)或糖尿病神经病变(HR 0.88, 95% CI: 0.71至1.08)的风险之间没有显著的负相关。结论:习惯性使用葡萄糖胺补充剂与2型糖尿病患者复合微血管并发症和糖尿病肾病的风险降低显著相关,但与视网膜病变或神经病变无关。
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引用次数: 0
Effect of long-term Mediterranean versus low-fat diet on neutrophil count, and type 2 diabetes mellitus remission in patients with coronary heart disease: results from the CORDIOPREV study. 长期地中海饮食与低脂饮食对冠心病患者中性粒细胞计数和2型糖尿病缓解的影响:来自CORDIOPREV研究的结果
IF 4.6 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-03-27 DOI: 10.1038/s41387-025-00360-3
Hatim Boughanem, Francisco M Gutierrez-Mariscal, Antonio Pablo Arenas-de Larriva, José D Torres-Peña, Juan L Romero-Cabrera, Oriol Alberto Rangel-Zuñiga, Helena García-Fernández, Alicia Podadera-Herreros, Fernando Rodríguez-Cantalejo, Oliver Soehnlein, Manuel Macias-Gonzalez, Francisco J Tinahones, Elena M Yubero Serrano, Pablo Perez-Martinez, Javier Delgado-Lista, José López-Miranda

Background: Recent evidence links diet and physical activity with type 2 diabetes mellitus (T2DM) remission, but emerging findings suggest that immune system dysregulation may play a crucial role. This study aimed to investigate the associations between neutrophils and T2DM remission.

Methods: We conducted a comprehensive analysis of newly-diagnosed T2DM patients (N = 183) from the CORDIOPREV study, without glucose-lowering treatment, and were randomized to follow either a Mediterranean or low-fat diet. Patients were classified into two groups: Responders, who achieved T2DM remission (n = 73), and Non-Responders, who did not achieve remission during the 5-year dietary intervention (n = 110). Neutrophil count and their related-ratio (NER, NBR, NLR and NHR, normalized with erythrocytes, basophils, lymphocytes, and HDL respectively) were measured at the baseline and 5 years of follow-up.

Results: The lowest baseline tertile of neutrophil count was associated with an increased likelihood of T2DM remission among patients following a Mediterranean diet (but not for low-fat diet) when compared with the highest tertile [adjusted HR of 4.23 (95% CI: 1.53-11.69)], in which similar results were observed for NER and NHR. When considering clinical and neutrophil variables, the predictive capacity of this model yielded an AUC of 0.783 (95% CI: 0.680-0.822). Furthermore, after 5-years, Responders exhibited lower neutrophil count compared to Non-responders (p = 0.006) and a significant decrease in neutrophil count (p = 0.001) compared to baseline. This decrease in neutrophil count in Responders who consumed a Mediterranean diet exhibited a significant increase in Insulin Sensitivity and Disposition Index (p = 0.011 and p = 0.018) after the follow-up period.

Conclusion: These findings suggest that neutrophil count can help in identifying patients that are more likely to achieve T2DM remission following a Mediterranean diet, suggesting a role on insulin sensitivity and β-cell function. Further research holds promise for providing valuable insights into the pathophysiology of T2DM.

Clinical trial registration: ID: NCT00924937; URL Clinical trial: https://clinicaltrials.gov/study/NCT00924937?cond=NCT00924937&rank=1 .

背景:最近的证据表明,饮食和体育锻炼与2型糖尿病(T2DM)的缓解有关,但新的研究结果表明,免疫系统失调可能起着至关重要的作用。本研究旨在探讨中性粒细胞与 T2DM 缓解之间的关系:我们对 CORDIOPREV 研究中新诊断的 T2DM 患者(N = 183)进行了全面分析,这些患者未接受降糖治疗,被随机分配为地中海饮食或低脂饮食。患者被分为两组:应答者(T2DM 缓解者,人数为 73 人)和非应答者(5 年饮食干预期间未缓解者,人数为 110 人)。中性粒细胞计数及其相关比率(NER、NBR、NLR 和 NHR,分别与红细胞、嗜碱性粒细胞、淋巴细胞和高密度脂蛋白正常化)在基线和 5 年随访时进行了测量:结果:与最高三分位数相比,中性粒细胞计数的最低基线三分位数与地中海饮食(但不包括低脂饮食)患者 T2DM 缓解的可能性增加有关[调整后 HR 为 4.23(95% CI:1.53-11.69)],其中 NER 和 NHR 也观察到类似的结果。考虑到临床和中性粒细胞变量,该模型的预测能力的AUC为0.783(95% CI:0.680-0.822)。此外,5 年后,与非应答者相比,应答者的中性粒细胞计数较低(p = 0.006),与基线相比,中性粒细胞计数显著下降(p = 0.001)。食用地中海饮食的应答者中性粒细胞数量减少,但在随访期后,其胰岛素敏感性和处置指数显著增加(p = 0.011 和 p = 0.018):这些研究结果表明,中性粒细胞计数有助于确定哪些患者更有可能通过地中海饮食获得 T2DM 缓解,这表明中性粒细胞计数对胰岛素敏感性和 β 细胞功能有影响。进一步的研究有望为 T2DM 的病理生理学提供有价值的见解:临床试验注册:ID:NCT00924937; URL 临床试验:https://clinicaltrials.gov/study/NCT00924937?cond=NCT00924937&rank=1 。
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引用次数: 0
Gestational weight trajectory and early offspring growth differed by gestational diabetes: a population-based cohort study. 妊娠期糖尿病对妊娠体重轨迹和早期后代生长的影响:一项基于人群的队列研究。
IF 4.6 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-03-12 DOI: 10.1038/s41387-025-00365-y
Ye Huang, Diliyaer Ainiwan, Yiwen Qiu, Libi Zhang, Xialidan Alifu, Haoyue Cheng, Haibo Zhou, Nuo Xu, Boya Wang, Shuhui Wang, Hui Liu, Danqing Chen, Yunxian Yu

Aims: To investigate the association of gestational weight gain (GWG) trajectory with early children growth, and explore whether this association varies by gestational diabetes mellitus (GDM) status.

Methods: Maternal weight and offspring anthropometric outcomes before 36 months were extracted from Electronic Medical Record of Zhoushan, China. GWG trajectory was modeled using latent-class trajectory analysis. Multiple generalized estimating equations models were applied to analyze associations of GWG trajectory categories with early children growth.

Results: Three GWG trajectory classes were identified in all participants (n = 13 424), the non-GDM (n = 10 984) and GDM (n = 2440) groups, respectively. In all participants, the Slow-Rapid pattern was significantly associated with lower length z-scores of offspring (β = -0.084; se = 0.015), compared to the Moderate pattern, while the Rapid-Slow pattern was significantly associated with higher length z-scores (β = 0.083; se = 0.022), with no significant effects on other anthropometric outcomes. Similar results were also observed in the non-GDM group. However, in the GDM group, offspring of mothers with the Rapid-Slow pattern showed significantly higher weight z-scores (β = 0.093; se = 0.046), BMI z-scores (β = 0.113; se = 0.052), and risk of overweight/obesity (OR = 1.40, 95%CI: 1.11, 1.76).

Conclusion: GWG trajectory significantly impacted offspring growth before 36 months, with different effects observed based on GDM status. GWG trajectory primarily affected offspring length in the non-GDM group, whereas earlier high weight gain appeared to increase offspring weight, BMI, and risk of overweight/obesity in the GDM group.

目的:探讨妊娠期体重增加(GWG)轨迹与儿童早期生长发育的关系,并探讨这种关系是否因妊娠期糖尿病(GDM)状况而异。方法:从舟山电子病历中提取36个月前的母亲体重和子代人体测量结果。采用潜级弹道分析对GWG弹道进行建模。应用多元广义估计方程模型分析了GWG轨迹类别与幼儿生长发育的关系。结果:在所有参与者(n = 13 424)、非GDM组(n = 10 984)和GDM组(n = 2440)中分别确定了三种GWG轨迹类别。在所有参与者中,慢速模式与后代较低的长度z分数显著相关(β = -0.084;se = 0.015),而快速-缓慢模式与较高的长度z分数显著相关(β = 0.083;Se = 0.022),对其他人体测量结果无显著影响。在非gdm组中也观察到类似的结果。然而,在GDM组中,快-慢模式母亲的后代体重z分数显著高于GDM组(β = 0.093;se = 0.046), BMI z-评分(β = 0.113;se = 0.052),超重/肥胖风险(OR = 1.40, 95%CI: 1.11, 1.76)。结论:GWG轨迹对36月龄前子代生长有显著影响,不同GDM状态对子代生长有不同影响。在非GDM组中,GWG轨迹主要影响后代长度,而在GDM组中,早期的高体重增加似乎增加了后代体重、BMI和超重/肥胖的风险。
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引用次数: 0
Multi-omics integration analysis and association study reveal the potential of ADIPOQ function in gestational diabetes mellitus. 多组学整合分析和相关研究揭示了ADIPOQ在妊娠糖尿病中的潜在功能。
IF 4.6 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-03-01 DOI: 10.1038/s41387-025-00356-z
Xiaoying Li, Tianshuang Jia, Yingnan Wu, Yanqing Peng, Yanan Feng, Liping Gong, Shuang Dong, Jiawei Tian, Litao Sun

Aim: To investigate the role of ADIPOQ gene in gestational diabetes mellitus (GDM).

Methods: We genotyped single nucleotide polymorphisms (SNPs) rs266729 and rs1501299 within the ADIPOQ gene in a cohort of 1157 pregnant women of north Chinese Han ethnicity. This cohort comprised 560 pregnant women diagnosed with GDM and 597 pregnant women who exhibited normal oral glucose tolerance test at 24-28 weeks' gestation. All participants were recruited from the Department of Obstetrics and Gynecology at the Second Affiliated Hospital of Harbin Medical University. Additionally, we used conventional bioinformatics analysis methods to conduct multi-omics analysis (transcriptome, epigenome, and single-cell level) of ADIPOQ-regulated GDM.

Results: The systolic blood flow velocity/diastolic blood flow velocity (S/D) ratio of the umbilical artery in GDM patients with CC genotype of rs266729 and GG genotype of rs1501299 was higher than control. Single-cell analysis suggested that ADIPOQ was expressed in extravillous trophoblast (EVT), T cell, monocytes, myelocyte, NK cell and syncytiotrophoblast (SCT). Functional enrichment analysis showed ADIPOQ gene was associated with response to nutrient levels, fat cell differentiation.

Conclusion: The findings of our study indicate a correlation between SNPs of ADIPOQ in GDM patients, and ADIPOQ is involved in the transcriptional regulation of GDM.

目的:研究ADIPOQ基因在妊娠糖尿病(GDM)中的作用:我们对 1157 名中国北方汉族孕妇的 ADIPOQ 基因中的单核苷酸多态性(SNPs)rs266729 和 rs1501299 进行了基因分型。该队列由 560 名确诊为 GDM 的孕妇和 597 名在妊娠 24-28 周时口服葡萄糖耐量试验正常的孕妇组成。所有参与者均来自哈尔滨医科大学附属第二医院妇产科。此外,我们还采用传统的生物信息学分析方法,对ADIPOQ调控的GDM进行了多组学分析(转录组、表观基因组和单细胞水平):结果:rs266729基因型为CC型和rs1501299基因型为GG型的GDM患者脐动脉收缩期血流速度/舒张期血流速度(S/D)比值高于对照组。单细胞分析表明,ADIPOQ在绒毛外滋养层细胞(EVT)、T细胞、单核细胞、骨髓细胞、NK细胞和合胞滋养层细胞(SCT)中均有表达。功能富集分析表明,ADIPOQ基因与营养水平反应、脂肪细胞分化有关:我们的研究结果表明,GDM 患者 ADIPOQ 的 SNPs 之间存在相关性,ADIPOQ 参与了 GDM 的转录调控。
{"title":"Multi-omics integration analysis and association study reveal the potential of ADIPOQ function in gestational diabetes mellitus.","authors":"Xiaoying Li, Tianshuang Jia, Yingnan Wu, Yanqing Peng, Yanan Feng, Liping Gong, Shuang Dong, Jiawei Tian, Litao Sun","doi":"10.1038/s41387-025-00356-z","DOIUrl":"10.1038/s41387-025-00356-z","url":null,"abstract":"<p><strong>Aim: </strong>To investigate the role of ADIPOQ gene in gestational diabetes mellitus (GDM).</p><p><strong>Methods: </strong>We genotyped single nucleotide polymorphisms (SNPs) rs266729 and rs1501299 within the ADIPOQ gene in a cohort of 1157 pregnant women of north Chinese Han ethnicity. This cohort comprised 560 pregnant women diagnosed with GDM and 597 pregnant women who exhibited normal oral glucose tolerance test at 24-28 weeks' gestation. All participants were recruited from the Department of Obstetrics and Gynecology at the Second Affiliated Hospital of Harbin Medical University. Additionally, we used conventional bioinformatics analysis methods to conduct multi-omics analysis (transcriptome, epigenome, and single-cell level) of ADIPOQ-regulated GDM.</p><p><strong>Results: </strong>The systolic blood flow velocity/diastolic blood flow velocity (S/D) ratio of the umbilical artery in GDM patients with CC genotype of rs266729 and GG genotype of rs1501299 was higher than control. Single-cell analysis suggested that ADIPOQ was expressed in extravillous trophoblast (EVT), T cell, monocytes, myelocyte, NK cell and syncytiotrophoblast (SCT). Functional enrichment analysis showed ADIPOQ gene was associated with response to nutrient levels, fat cell differentiation.</p><p><strong>Conclusion: </strong>The findings of our study indicate a correlation between SNPs of ADIPOQ in GDM patients, and ADIPOQ is involved in the transcriptional regulation of GDM.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"15 1","pages":"9"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537506","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
ZHX2 inhibits diabetes-induced liver injury and ferroptosis by epigenetic silence of YTHDF2. ZHX2通过YTHDF2的表观遗传沉默抑制糖尿病诱导的肝损伤和铁下沉。
IF 4.6 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-02-22 DOI: 10.1038/s41387-025-00355-0
Wei Meng, Linghua Li

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common complication of type 2 diabetes mellitus (DM). The transcription factor zinc fingers and homeoboxes 2 (ZHX2) has been implicated in the pathogenesis of chronic liver diseases, yet its precise role and underlying mechanism in DM-induced hepatic injury remain poorly elucidated.

Methods: To investigate this, we used a high-fat diet (HFD) and streptozotocin (STZ) administration to create a DM model in mice, while high glucose (HG) exposure was used to simulate DM in vitro. Through various experiments such as luciferase reporter assay, chromatin immunoprecipitation, RNA immunoprecipitation, and rescue experiments, we aimed to uncover the mechanisms involving ZHX2.

Results: Our findings revealed that ZHX2 was lower and YTHDF2 was higher in the livers of DM mice and HG-induced Huh7 cells. ZHX2 overexpression rescued DM-induced liver injury. ZHX2 overexpression also reversed DM-induced hepatic ferroptosis in vivo and in vitro. Mechanistically, YTHDF2 recognized m6A-modified ZHX2 mRNA and promoted its degradation. In turn, ZHX2 inhibited the transcription of YTHDF2 by binding to its promoter region. Knockdown of ZHX2 led to increased ferroptosis in Huh7 cells through activating YTHDF2-induced GPX4 and SLC7A11 degradation.

Conclusion: These findings highlight the involvement of the ZHX2-YTHDF2-ferroptosis pathway in DM-induced liver injury and suggest that targeting this pathway may hold therapeutic potential for improving such injuries.

目的:代谢功能障碍相关脂肪变性肝病(MASLD)是2型糖尿病(DM)的常见并发症。转录因子锌指和同源盒2 (ZHX2)与慢性肝病的发病机制有关,但其在dm诱导的肝损伤中的确切作用和潜在机制尚不清楚。方法:采用高脂肪饮食(HFD)和链脲佐菌素(STZ)建立小鼠DM模型,采用高糖(HG)暴露体外模拟DM。通过荧光素酶报告基因测定、染色质免疫沉淀、RNA免疫沉淀、抢救实验等多种实验,我们旨在揭示ZHX2的作用机制。结果:我们发现DM小鼠和hg诱导的Huh7细胞肝脏中ZHX2较低,YTHDF2较高。ZHX2过表达可挽救dm诱导的肝损伤。在体内和体外,ZHX2过表达也能逆转dm诱导的肝铁下垂。在机制上,YTHDF2识别m6a修饰的ZHX2 mRNA并促进其降解。反过来,ZHX2通过结合YTHDF2的启动子区域抑制YTHDF2的转录。敲低ZHX2通过激活ythdf2诱导的GPX4和SLC7A11降解,导致Huh7细胞铁凋亡增加。结论:这些发现突出了zhx2 - ythdf2 -铁下沉通路参与dm诱导的肝损伤,提示靶向该通路可能具有改善此类损伤的治疗潜力。
{"title":"ZHX2 inhibits diabetes-induced liver injury and ferroptosis by epigenetic silence of YTHDF2.","authors":"Wei Meng, Linghua Li","doi":"10.1038/s41387-025-00355-0","DOIUrl":"10.1038/s41387-025-00355-0","url":null,"abstract":"<p><strong>Objective: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common complication of type 2 diabetes mellitus (DM). The transcription factor zinc fingers and homeoboxes 2 (ZHX2) has been implicated in the pathogenesis of chronic liver diseases, yet its precise role and underlying mechanism in DM-induced hepatic injury remain poorly elucidated.</p><p><strong>Methods: </strong>To investigate this, we used a high-fat diet (HFD) and streptozotocin (STZ) administration to create a DM model in mice, while high glucose (HG) exposure was used to simulate DM in vitro. Through various experiments such as luciferase reporter assay, chromatin immunoprecipitation, RNA immunoprecipitation, and rescue experiments, we aimed to uncover the mechanisms involving ZHX2.</p><p><strong>Results: </strong>Our findings revealed that ZHX2 was lower and YTHDF2 was higher in the livers of DM mice and HG-induced Huh7 cells. ZHX2 overexpression rescued DM-induced liver injury. ZHX2 overexpression also reversed DM-induced hepatic ferroptosis in vivo and in vitro. Mechanistically, YTHDF2 recognized m6A-modified ZHX2 mRNA and promoted its degradation. In turn, ZHX2 inhibited the transcription of YTHDF2 by binding to its promoter region. Knockdown of ZHX2 led to increased ferroptosis in Huh7 cells through activating YTHDF2-induced GPX4 and SLC7A11 degradation.</p><p><strong>Conclusion: </strong>These findings highlight the involvement of the ZHX2-YTHDF2-ferroptosis pathway in DM-induced liver injury and suggest that targeting this pathway may hold therapeutic potential for improving such injuries.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"15 1","pages":"6"},"PeriodicalIF":4.6,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476779","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
Triglyceride-glucose index and the risk of in-hospital and ICU all-cause mortality: a systematic review and meta-analysis of observational studies. 甘油三酯-葡萄糖指数与院内和重症监护病房全因死亡风险:观察性研究的系统回顾和荟萃分析。
IF 5.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-02-22 DOI: 10.1038/s41387-025-00366-x
Elham Sharifi-Zahabi, Nooshin Nasiri, Fatemeh Hajizadeh-Sharafabad, Maryam Sharifi, Amir Saber

Several studies have illustrated the association of the triglyceride glucose (TyG) index with in-hospital and intensive care unit (ICU) mortality. However, no studies have compiled this evidence and reached a conclusion. This study aimed to quantify the association of the TYG index with the risk of in-hospital and ICU mortality. An extensive search of databases including PubMed, Scopus, and Web of Science, was performed up to 21 Jan 2024. Nineteen studies were included in the meta-analysis. The outcomes were in-hospital mortality in 18 studies and ICU mortality in 8 studies. Among the 42,525 participants, 5233 in-hospital and 1754 ICU mortality cases were reported. The pooled analysis revealed that each unit increase in the TYG index was associated with a 33% and 45% increase in the risk of in-hospital (RR = 1.33; 95% CI: 1.23, 1.43; I squared = 90.3%) and ICU (RR: 1.45; 95% CI: 1.25, 1.67; I squared = 44.8%) mortality, respectively. Subgroup analysis revealed a stronger association between the TYG index and the risk of in-hospital mortality in patients with cardiovascular diseases than in those with cerebrovascular diseases (Pheterogeneity between Groups = 0.014). The findings of this study showed a positive association between the TyG index and the risk of in-hospital and ICU mortality. (PROSPERO registration ID: CRD420245414390).

多项研究表明,甘油三酯血糖(TyG)指数与院内和重症监护室(ICU)死亡率有关。但是,还没有研究对这些证据进行汇总并得出结论。本研究旨在量化 TYG 指数与院内和重症监护室死亡风险的关系。截至 2024 年 1 月 21 日,对包括 PubMed、Scopus 和 Web of Science 在内的数据库进行了广泛检索。19项研究被纳入荟萃分析。18项研究的结果为院内死亡率,8项研究的结果为重症监护室死亡率。在42525名参与者中,共报告了5233例院内死亡病例和1754例重症监护室死亡病例。汇总分析显示,TYG指数每增加一个单位,院内(RR=1.33;95% CI:1.23,1.43;I平方=90.3%)和ICU(RR:1.45;95% CI:1.25,1.67;I平方=44.8%)死亡风险分别增加33%和45%。亚组分析显示,与脑血管疾病患者相比,心血管疾病患者的 TYG 指数与院内死亡风险之间的关系更为密切(组间异质性 = 0.014)。该研究结果表明,TyG指数与住院和重症监护室死亡风险呈正相关。(PROSPERO注册编号:CRD420245414390)。
{"title":"Triglyceride-glucose index and the risk of in-hospital and ICU all-cause mortality: a systematic review and meta-analysis of observational studies.","authors":"Elham Sharifi-Zahabi, Nooshin Nasiri, Fatemeh Hajizadeh-Sharafabad, Maryam Sharifi, Amir Saber","doi":"10.1038/s41387-025-00366-x","DOIUrl":"10.1038/s41387-025-00366-x","url":null,"abstract":"<p><p>Several studies have illustrated the association of the triglyceride glucose (TyG) index with in-hospital and intensive care unit (ICU) mortality. However, no studies have compiled this evidence and reached a conclusion. This study aimed to quantify the association of the TYG index with the risk of in-hospital and ICU mortality. An extensive search of databases including PubMed, Scopus, and Web of Science, was performed up to 21 Jan 2024. Nineteen studies were included in the meta-analysis. The outcomes were in-hospital mortality in 18 studies and ICU mortality in 8 studies. Among the 42,525 participants, 5233 in-hospital and 1754 ICU mortality cases were reported. The pooled analysis revealed that each unit increase in the TYG index was associated with a 33% and 45% increase in the risk of in-hospital (RR = 1.33; 95% CI: 1.23, 1.43; I squared = 90.3%) and ICU (RR: 1.45; 95% CI: 1.25, 1.67; I squared = 44.8%) mortality, respectively. Subgroup analysis revealed a stronger association between the TYG index and the risk of in-hospital mortality in patients with cardiovascular diseases than in those with cerebrovascular diseases (P<sub>heterogeneity between Groups</sub> = 0.014). The findings of this study showed a positive association between the TyG index and the risk of in-hospital and ICU mortality. (PROSPERO registration ID: CRD420245414390).</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"15 1","pages":"8"},"PeriodicalIF":5.2,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476778","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
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Nutrition & Diabetes
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