Metabolic Syndrome and Diabetes
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Faculty of Medicine, University of Geneva,
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Faculty of Medicine, University of Geneva,
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Faculty of Medicine, University of Geneva,
Diabetes Center, Faculty of Medicine, University of Geneva,
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Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. This condition is associated with various hormonal, reproductive and metabolic alterations, including androgen excess, ovulatory disorders and a hyperinsulinemic state. A personalized therapeutic approach is necessary to improve PCOS, focusing on patients’ main concerns, with the goal of addressing ovarian dysfunction, reducing hyperandrogenism and improving metabolic alterations, particularly through weight reduction. The therapeutic class of glucagon-like peptide-1 receptor analogues (GLP-1 RAs) represents an attractive option for PCOS due to its various beneficial effects, such as weight loss. In this review, we discuss the clinical and pathological aspects of PCOS, as well as the data and potential roles of GLP-1 RAs in managing this condition.
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China Medical University,
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China Medical University,
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Background
Increasing evidence demonstrates that tryptophan metabolism is closely related to the development of nonalcoholic fatty liver disease (NAFLD). This study aimed to identify specific biomarkers of NAFLD associated with tryptophan metabolism and research its functional mechanism.
Methods
We downloaded NAFLD RNA-sequencing data from GSE89632 and GSE24807, and obtained tryptophan metabolism-related genes (TMRGs) from the MsigDB database. The R package limma and WGCNA were used to identify TMRGs–DEGs, and GO, KEGG and Cytoscape were used to analyze and visualize the data. Immune cell infiltration analysis was used to explore the immune mechanism of NAFLD and the biomarkers. We also validated extended levels of biomarkers.
Results
We identified 375 NAFLD differentially expressed genes (DEGs) and 85 TMRGs–DEGs. GO/KEGG analysis revealed that TMRGs–DEGs were mainly enriched in triglyceride and cholesterol metabolism. ROC curves identified CCL20 (AUC = 0.917), CD160 (AUC = 0.933) and CYP7A1 (AUC = 1) as biomarkers of NAFLD. Immune infiltration analysis showed significant differences in ten immune cells, and the activation of dendritic cells and mast cells were highly positively correlated with NAFLD. CCL20, CD160 and CYP7A1 were highly correlated with M2 macrophage, neutrophil and mast cells activation, respectively. Twenty-seven TMRGs correlated with hub genes, and gene set enrichment analysis demonstrated their function in tryptophan- and lysine-containing metabolic process. We identified 41 therapeutic drug matches which corresponded to two hub genes and four drugs which co-targeted CCL20 and CYP7A1. Finally, three hub genes were validated in our mouse model.
Conclusions
CCL20, CD160 and CYP7A1 are tryptophan metabolism-related biomarkers of NAFLD, related to glycerol ester and cholesterol metabolism. We screened four compounds which co-target CCL29 and CYP7A1 to provide potential experimental drugs for NAFLD.
Diabetic Foot Research Center of Central South University, Changsha, Hunan Province, China
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Diabetic Foot Research Center of Central South University, Changsha, Hunan Province, China
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Diabetic Foot Research Center of Central South University, Changsha, Hunan Province, China
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Diabetic Foot Research Center of Central South University, Changsha, Hunan Province, China
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Diabetic Foot Research Center of Central South University, Changsha, Hunan Province, China
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Diabetic Foot Research Center of Central South University, Changsha, Hunan Province, China
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Graphical abstract
Abstract
Oxidative stress is a key driving factor for the progression of vascular disease in diabetes, and is closely related to endothelial dysfunction. The exact mechanism by which glucagon-like peptide-1 (GLP-1) directly protects vascular endothelium by reducing oxidative stress is not yet fully understood. In this study, we investigated the protective effect of GLP-1 on endothelial cells exposed to palmitic acid (PA)/high glucose-induced oxidative stress and further explored the potential mechanisms involved in microRNA-139-5p (miR-139-5p) regulation. We found that miR-139-5p expression was exhibited significantly elevated in HUVECs that were exposed to PA/high glucose or H2O2, which were reversed by glutathione. Interestingly, this expression was significantly attenuated after GLP-1 pretreatment, with reduced reactive oxygen species (ROS), increased GSH/GSSG ratio and amelioration of cell dysfunction. Overexpression of miR-139-5p resulted in increased ROS and apoptosis, decreased GSH/GSSG ratio, damaged migration and proliferation of HUVECs, while inhibition of miR-139-5p significantly restored PA-induced HUVECs impairments. Further investigation revealed that miR-139-5p directly targets superoxide dismutase 1 (SOD1)/glutamate–cysteine ligase catalytic (GCLc) subunit. The upregulation of miR-139-5p abrogated the protective effects of GLP-1 on cells exposed to PA, and GLP-1-induced downregulation of miR-139-5p was counteracted by the GLP-1 receptor antagonist exendin(9–39). These findings demonstrated that GLP-1 ameliorates oxidative stress-induced endothelial dysfunction, at least in part, by suppressing miR-139-5p, which targets SOD1 and GCLc. This provides further evidence for the vascular protective effects of GLP-1 intervention in diabetes.
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Objective
This study aims to investigate the correlation between the levels of hypoxia-inducible factor-1α (HIF-1α) in the peripheral blood of patients with type 2 diabetes (T2D) and early-stage diabetic retinopathy (DR) and to evaluate its potential as a predictor of early DR.
Methods
From November 2021 to December 2023, 70 patients who underwent fundus photography at Zhangzhou Second Hospital were recruited. Based on the results, patients were categorized into a T2D group comprising 25 patients and a DR group comprising 45 patients. In addition, 18 healthy individuals who underwent routine physical examinations during the same period were included as a control group. Serum levels of the HIF-1α protein were measured in all three groups.
Results
The results indicated that patients in the early-stage DR group had significantly higher levels of HIF-1α, albumin (Alb), Ca and blood urea nitrogen (BUN) compared to the T2D group (P < 0.05). In addition, patients in the DR group exhibited higher levels of total cholesterol, high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose (FPG) and glycated hemoglobin (HbA1C) than the control group (P < 0.05). The incidence rates of DR in groups A, B, C and D were 18.18, 31.82, 59.09 and 95.45%, respectively, with statistically significant differences (P < 0.05). Spearman’s correlation analysis revealed significant positive correlations between HIF-1α and age, disease duration (years), systolic blood pressure, Cr, FPG and HbA1c, with a strong positive correlation between HIF-1α and HbA1c (P < 0.05) optimal cutoff value of 2.3855 ng/mL.
Conclusion
Increased levels of HIF-1α in peripheral blood are closely linked to the development of DR, suggesting that HIF-1α may act as a potential biomarker for the early detection and prediction of DR risk.
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Background
The incidence of type 2 diabetes mellitus (T2DM) is rising among young adults, posing challenges for long-term management after discharge.
Methods
This prospective comparative study included 120 newly diagnosed young adults with T2DM admitted between January and December 2023. Participants were randomized into intervention or control groups (n = 60 each). All patients received standard diabetes education and short-term insulin pump intensive therapy during hospitalization. After discharge, the control group received traditional care, while the intervention group utilized an internet-based management system incorporating continuous glucose monitoring, personalized feedback and remote healthcare team consultations. Primary outcomes included HbA1c, fasting blood glucose (FBG), insulin resistance (HOMA-IR) and β-cell function (HOMA-β and fasting C-peptide). Secondary outcomes included lipid profiles, renal function (urine albumin/creatinine ratio (UACR)), blood pressure, quality of life (SF-36) and depression scores (PHQ-9).
Results
At 12 months, the intervention group had significantly lower HbA1c (6.5 vs 7.2%, P < 0.001) and better improvements in FBG, HOMA-IR, HOMA-β, fasting C-peptide, triglycerides and low-density lipoprotein cholesterol (P < 0.01). Improvements in UACR and blood pressure were minimal (P > 0.05). SF-36 and PHQ-9 scores improved more significantly in the intervention group (P < 0.01). Diabetes remission rates were higher in the intervention group (60 vs 37%, P = 0.028) and remained significant after adjusting for baseline variables (P = 0.015).
Conclusion
The internet-based management system with personalized feedback significantly improved glycemic control and quality of life in young adults with T2DM.
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School of Public Health (Shenzhen), Sun Yat-sen University,
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Department of Endocrinology, the Second People’s Hospital of Kashgar Prefecture,
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School of Public Health (Shenzhen), Sun Yat-sen University,
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School of Public Health (Shenzhen), Sun Yat-sen University,
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Graphical abstract
(Created in BioRender; https://BioRender.com/o08n003). Abbreviations: GDM, gestational diabetes mellitus; NGT, normal glucose tolerance; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; LPC, lysophosphatidylcholine; LPE, lysophosphatidylethanolamine.
Abstract
Objective
Women with gestational diabetes mellitus (GDM) often develop a metabolic memory that increases the risk of future metabolic disorders, even after blood glucose levels normalize following clinical intervention. However, the impact of this metabolic memory on susceptibility to SARS-CoV-2 remains unclear. Therefore, we aim to investigate the potential association between metabolic memory in GDM and susceptibility to SARS-CoV-2 infection.
Methods
We conducted a prospective cohort study with 1,675 pregnant women, including 197 (11.8%) with GDM. Postpartum SARS-CoV-2 infections were tracked via telephone follow-up and categorized into negative and positive groups. Logistic regression was used to explore risk factors for SARS-CoV-2 infection. Peripheral blood samples were collected from 30 GDM and 30 normal glucose-tolerant (NGT) pregnant women in three trimesters (T1, T2 and T3) for longitudinal untargeted metabolomics to identify GDM and SARS-CoV-2-associated metabolites. Limma package was applied to find differential expressed metabolites associated with SARS-CoV-2 infection and GDM.
Results
Among 1,675 women, 1,348 (80.5%) tested positive for SARS-CoV-2. GDM postpartum women had higher SARS-CoV-2 infection rates (88.3 vs 79.4%, P = 0.003) than NGT women. GDM was associated with SARS-CoV-2 infection (T2: OR (95% CI): 2.17 (1.26–3.54), P = 0.005; T3: OR (95% CI): 1.70 (1.03–2.82), P = 0.040). Compared to the SARS-CoV-2 negative group, the positive group exhibited elevated levels of allantoic acid, LPE (0:0/22:6), LPC (15:0/0:0) and 1-linoleoyl-sn-glycero-3-phosphorylcholine in T1 and T2, before clinical intervention. In T3, allantoic acid remained elevated post-intervention. A similar increase as described above was observed in the GDM compared to the NGT group. The tricarboxylic acid cycle was the sole overlapping enriched pathway in the SARS-CoV-2 positive versus negative group and the GDM versus NGT group. Cis-aconitic acid, a metabolite from this pathway, was elevated in T3 in the GDM group.
Conclusion
Compared to NGT, women with GDM are at a higher risk of postnatal SARS-CoV-2 infection. Metabolic memory from GDM may heighten susceptibility to SARS-CoV-2.
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Background
Transition describes preparing children with chronic illnesses for adult healthcare and gradually transferring their care, starting late adolescence. Joint meetings and visits are recommended during this process. This study examines an 8-year transition experience in our clinic, focusing on the differences between adult and pediatric endocrinology practices and the rates of loss to follow-up in specific disease groups.
Methods
Three hundred thirty-five patients evaluated in transition meetings were included. The frequency of visits 1 year before transition, during the first and second years after transition, the number of patients lost to follow-up and disease groups were analyzed.
Results
Among the patients discussed in the transition meetings, 56.3% participated in joint visits. Post-transition, 82.5% of patients continued their follow-up care, while 17.5% were lost to follow-up. There was a statistically significant difference in the number of visits before and after the first year of transition (P = 0.000).
Conclusion
To increase adaptation during the transition, informing patients and families about the process at every visit after late adolescence is beneficial. Moreover, scheduling joint visits on flexible dates and increasing the number of joint visits per patient could substantially enhance patient participation and follow-up rates. We observed that patient follow-up frequency was higher in pediatric endocrinology due to differences in pediatric and internal medicine practices.
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Objective
Obesity and insulin resistance carry a high risk of progressing to type 2 diabetes mellitus. A lot of evidence has tightly associated insulin resistance with chronic inflammation. Besides, it has been reported that the activation of amphiregulin epidermal growth factor receptor pathways is involved in chronic inflammation. The aim of this study was to evaluate the relationship between insulin resistance and amphiregulin.
Methods
Data from 203 volunteers were collected from November 2020 to June 2023 visiting the Affiliated Suzhou Hospital of Nanjing Medical University, Jiangsu, China. The serum levels of amphiregulin and diabetes-related parameters were measured in all participants. The correlation analysis and multiple stepwise regression of amphiregulin and some diabetes indicators were performed in all groups.
Results
The concentrations of amphiregulin were 143.29, 163.29, 158.92, 171.89 and 155.03 pg/mL in the normal, obesity, nonobese diabetes, obese diabetes and obese diabetes after therapy groups (P < 0.01), respectively, and the homeostasis model assessment index were 1.6, 4.01, 3.93, 6.67 and 3.4, respectively (P < 0.01). Moreover, amphiregulin positively correlated with the homeostasis model assessment index in each separated group and the total sample (r = 0.644, P < 0.01). Meanwhile, the regression analysis showed a strong, positive association between amphiregulin and the homeostasis model assessment index (P < 0.01). More importantly, this correlation remained after obese diabetes patients were treated with drugs to relieve insulin resistance.
Conclusion
Amphiregulin is upregulated in obese individuals than in normal size people, whether diabetic or not, and positively correlates with the homeostasis model assessment index, suggesting early signs of insulin resistance and abnormal glucose metabolism.
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Amsterdam Cardiovascular Sciences Research Institute, Amsterdam UMC,
Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC,
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Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC,
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Amsterdam Public Health Research Institute, Amsterdam UMC,
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Amsterdam Public Health Research Institute, Amsterdam UMC,
Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC,
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Introduction
Glucagon-like peptide-1 receptor agonists reduce insulin requirements and improve glucose control when administered before cardiac surgery. An increase in endogenous insulin release is the most likely mechanism, but this has never been studied in the setting of cardiac surgery. We hypothesized that liraglutide increases pancreatic insulin secretion during cardiac surgery with cardiopulmonary bypass (CPB).
Methods
We performed a planned prospective substudy of a multicenter randomized-controlled trial (GLOBE trial, NTR6323). Patients undergoing cardiac surgery with CPB were randomized to receive either two preoperative subcutaneous injections of liraglutide or a matching placebo. We measured hormone concentrations before and after surgery, including insulin, glucagon, C-peptide and free fatty acid (FFA), and calculated HOMA-B, HOMA-IR and insulin/glucagon ratios. We compared between-group and before and after surgery differences in outcomes.
Results
Metabolic hormone concentrations were measured in 37 participants. HOMA-B revealed that liraglutide increased insulin secretion relative to glycemia (258 ± 179 vs 116 ± 180, difference (95% CI): 142 (24–261), P = 0.004). While insulin, C-peptide and glucagon levels did not differ significantly between groups, the insulin/glucagon ratios were significantly higher in the liraglutide group (preoperatively: 1.09 ± 0.45 vs 0.79 ± 0.35 difference (95% CI): −0.30 (−0.57 to −0.03), P = 0.039). Overall, postoperative insulin levels decreased >60% from preoperative insulin levels (55 ± 31 to 21 ± 9.8, difference (95% CI): −29 (−36 to −22), P < 0.001).
Conclusion
Preoperative liraglutide administration increased beta-cell function, measured as HOMA-B, and higher insulin/glucagon ratios. These results could explain the lower glucose and FFA concentrations in the liraglutide-treated patients. Interestingly, in both groups, we observed a remarkable drop in insulin and other hormone levels over the course of surgery.
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Background
Thyroid dysfunctions, such as hypothyroidism and hyperthyroidism, are known to influence metabolism, but their long-term impact on the development of type 2 diabetes (T2D) mellitus in humans remains elusive. Thus, this study aimed to assess the cumulative incidence and association between thyroid disorders and T2D development.
Methods
We conducted a retrospective cohort study using data from the Disease Analyzer database (IQVIA™, USA) from 2005 to 2022. The study included 158,674 patients with thyroid disorders and an equal number of matched patients without thyroid disorders. Propensity score matching was performed to balance age, sex and codiagnoses between the cohorts. Kaplan–Meier curves and Cox regression models were used to assess the cumulative incidence and hazard ratios (HRs) for new-onset T2D.
Results
After a 10-year follow-up period, the cumulative incidence of T2D was higher in patients with thyroid disorders compared to the non-thyroid disorder cohort (P < 0.001). The HRs for T2D were 1.34 (95% CI: 1.28–1.39) for hypothyroidism and 1.30 (95% CI: 1.21–1.39) for hyperthyroidism. The strongest associations were observed in younger age groups for both hypothyroidism and hyperthyroidism.
Conclusion
Thyroid disorders, including hypothyroidism and hyperthyroidism, are associated with an increased incidence of new-onset T2D. These findings suggest the need for proactive screening and management of glucose metabolism in patients with thyroid dysfunctions, particularly in younger individuals, independent of metabolic risk factors.
