Pub Date : 2025-04-16DOI: 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。
{"title":"Association between serum beta-hydroxybutyrate levels and risk of type 2 diabetes mellitus in patients with impaired fasting glucose.","authors":"Jaehyun Bae, Young-Eun Kim, Keum Ji Jung, Sun Ha Jee, Byung-Wan Lee","doi":"10.1038/s41387-025-00364-z","DOIUrl":"https://doi.org/10.1038/s41387-025-00364-z","url":null,"abstract":"<p><strong>Objectives: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"15 1","pages":"16"},"PeriodicalIF":4.6,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031853","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}
Pub Date : 2025-04-12DOI: 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.
{"title":"Novel first-trimester serum biomarkers for early prediction of gestational diabetes mellitus.","authors":"Siqi Tian, Mingxi Liu, Shuwen Han, Haiqi Wu, Rencai Qin, Kongyang Ma, Lianlian Liu, Hongjin Zhao, Yan Li","doi":"10.1038/s41387-025-00372-z","DOIUrl":"https://doi.org/10.1038/s41387-025-00372-z","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"15 1","pages":"15"},"PeriodicalIF":4.6,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005131","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}
Pub Date : 2025-04-11DOI: 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.
{"title":"A comprehensive review on the implications of Yogic/Sattvic diet in reducing inflammation in type 2 diabetes.","authors":"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","doi":"10.1038/s41387-025-00371-0","DOIUrl":"https://doi.org/10.1038/s41387-025-00371-0","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"15 1","pages":"14"},"PeriodicalIF":4.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11992243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972966","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}
Pub Date : 2025-04-01DOI: 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.
{"title":"Magnesium, fibrinolysis and clotting interplay among children and adolescents with type 1 diabetes mellitus; potential mediators of diabetic microangiopathy.","authors":"Dalia N Toaima, Kholoud S Abdel-Maksoud, Heba M Atef, Nouran Y Salah","doi":"10.1038/s41387-025-00368-9","DOIUrl":"10.1038/s41387-025-00368-9","url":null,"abstract":"<p><strong>Background and aim: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"15 1","pages":"13"},"PeriodicalIF":4.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764440","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}
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.
{"title":"Association of habitual glucosamine use with risk of microvascular complications among individuals with type 2 diabetes: a prospective cohort study in UK biobank.","authors":"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","doi":"10.1038/s41387-025-00369-8","DOIUrl":"10.1038/s41387-025-00369-8","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"15 1","pages":"12"},"PeriodicalIF":4.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764433","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}
Pub Date : 2025-03-27DOI: 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.
{"title":"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.","authors":"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","doi":"10.1038/s41387-025-00360-3","DOIUrl":"10.1038/s41387-025-00360-3","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Clinical trial registration: </strong>ID: NCT00924937; URL Clinical trial: https://clinicaltrials.gov/study/NCT00924937?cond=NCT00924937&rank=1 .</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"15 1","pages":"11"},"PeriodicalIF":4.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730956","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}
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.
{"title":"Gestational weight trajectory and early offspring growth differed by gestational diabetes: a population-based cohort study.","authors":"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","doi":"10.1038/s41387-025-00365-y","DOIUrl":"10.1038/s41387-025-00365-y","url":null,"abstract":"<p><strong>Aims: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"15 1","pages":"10"},"PeriodicalIF":4.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11904208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616565","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}
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.
{"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}
Pub Date : 2025-02-22DOI: 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.
{"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}
Pub Date : 2025-02-22DOI: 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).
{"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}