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Keywords = 1,5-anhydroglucitol

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12 pages, 757 KB  
Article
Metformin Treatment Potentially Modifies Genetically Driven Metabolite-HbA1c Associations: A Gene–Environment Interaction Mendelian Randomization Study
by Najeha Anwardeen, Aleem Razzaq, Asma A. Elashi, Gaurav Thareja, Ilhame Diboun, Khaled Naja, Karsten Suhre and Mohamed A. Elrayess
Pharmaceuticals 2026, 19(5), 780; https://doi.org/10.3390/ph19050780 - 15 May 2026
Viewed by 519
Abstract
Introduction/Background: Metformin is the first-line therapy for type 2 diabetes (T2D); however, a considerable inter-individual variability in glycemic response is observed among patients. This heterogeneity suggests that metformin’s effects depend not only on drug exposure but also on the underlying metabolic and [...] Read more.
Introduction/Background: Metformin is the first-line therapy for type 2 diabetes (T2D); however, a considerable inter-individual variability in glycemic response is observed among patients. This heterogeneity suggests that metformin’s effects depend not only on drug exposure but also on the underlying metabolic and genetic factors. Methods: We applied a Gene–Environment interaction Mendelian Randomization (MR-G×E) in a cohort of 2743 individuals to investigate whether genetically influenced metabolite-HbA1c associations differ by metformin use. Metabolites associated with metformin response were used to establish metabolite-specific polygenic risk scores (PRSs) using metabolome-wide association study (mGWAS) variants. Generated PRS were used as genetic instruments within a one-sample, modified two-stage least squares model. An interaction term between PRS and metformin use was included to assess treatment-dependent genetic effects, adjusting for age, sex, body mass index, and genetic ancestry (principal components). Results: Metformin use significantly modified genetically influenced associations between 18 metabolites and HbA1c. Positive and negative PRS-metformin interaction effects indicated attenuation, strengthening or reversal of baseline genetic associations under treatment. Several amino acid metabolites, palmitoyl sphingomyelin (d18:1/16:0), and carbohydrate-related metabolite 1,5-anhydroglucitol showed specific patterns under metformin use. Interestingly, several metabolites (creatinine, gamma glutamylcitrulline, N-acetylthreonine, 3-methyl-2-oxovalerate, glycerol-3-phosphate, 1-(1-enyl-palmitoyl)-GPC (P-16:0), 1-(1-enyl-palmitoyl)-2-linoleoyl-GPC (P-16:0/18:2), sphingomyelin (d18:1/22:1, d18:2/22:0, d16:1/24:1), fructose, and methyl-glucopyranoside (alpha + beta)) showed no basal causal association with HbA1c but exhibited significant interaction effect with metformin use, suggesting metabolic association only in the presence of metformin. Conclusions: These findings indicate that metformin modifies the genetically influenced metabolite-HbA1c relationships, exhibiting treatment-dependent metabolic effects that are not detectable with standard MR approaches. Incorporating pharmacological context into causal inference provides new insights into the metabolic basis for the variable metformin response and helps inform precision strategies for T2D management. Full article
(This article belongs to the Section Pharmacology)
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18 pages, 1354 KB  
Article
Effects of Balanced Dietary Patterns and/or Integrated Exercise on Serum 1,5-Anhydroglucitol and CVD Risk Factors in Individuals with Prediabetes
by Ting Zhu, Da Pan, Lanlan Gui, Wei Yan, Ligang Yang, Wang Liao, Shaokang Wang and Guiju Sun
Life 2026, 16(2), 198; https://doi.org/10.3390/life16020198 - 25 Jan 2026
Viewed by 866
Abstract
This study aimed to identify metabolomic biomarkers for diabetes progression and validate their response to lifestyle intervention. A two-phase design was employed: first, untargeted metabolomics distinguished normoglycemic, prediabetic (PDM), and diabetic (DM) individuals, identifying 1,5-anhydroglucitol (1,5-AG) as the most significant biomarker for differentiating [...] Read more.
This study aimed to identify metabolomic biomarkers for diabetes progression and validate their response to lifestyle intervention. A two-phase design was employed: first, untargeted metabolomics distinguished normoglycemic, prediabetic (PDM), and diabetic (DM) individuals, identifying 1,5-anhydroglucitol (1,5-AG) as the most significant biomarker for differentiating PDM from DM (apparent AUC = 0.97, 95% CI: 0.95–1.00; corrected AUC = 0.94, 95% CI: 0.83–1.00; q < 0.001). Second, in a 3-month randomized controlled trial involving 300 adults with PDM, the combined diet and exercise intervention significantly improved fasting blood glucose and glycated hemoglobin levels, while concurrently elevating serum 1,5-AG levels compared with the control group, though it did not yield significant improvements in other cardiovascular disease-related risk factors including body mass index, waist circumference, systolic blood pressure, and diastolic blood pressure. The intervention also showed a trend toward reduced diabetes incidence. Integrated analysis establishes 1,5-AG as a sensitive biomarker of dysglycemia that is responsive to lifestyle modification, supporting its potential as a mechanistic tool for monitoring intervention efficacy in diabetes prevention. Full article
(This article belongs to the Section Physiology and Pathology)
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21 pages, 2573 KB  
Article
Application of a Non-Targeted Metabolomics Study in Plasmodium berghei-Infected Rats: Towards Unravelling Metabolic Alterations During Malaria Infection
by Zoxolo Nokulunga Mbuli, Innocent Siyanda Ndlovu, Bubuya Masola and Samson Mukaratirwa
Int. J. Mol. Sci. 2025, 26(21), 10324; https://doi.org/10.3390/ijms262110324 - 23 Oct 2025
Viewed by 1122
Abstract
Falciparum malaria is a life-threatening vector-borne disease prevalent in tropical and subtropical regions. The complexity of severe malaria demands a thorough investigation of host–parasite interactions. Twenty male Sprague Dawley rats were divided into two groups: uninfected controls and Plasmodium berghei-infected rats, infected [...] Read more.
Falciparum malaria is a life-threatening vector-borne disease prevalent in tropical and subtropical regions. The complexity of severe malaria demands a thorough investigation of host–parasite interactions. Twenty male Sprague Dawley rats were divided into two groups: uninfected controls and Plasmodium berghei-infected rats, infected via intraperitoneal injection of parasitized red blood cells. Serum samples were analysed using high-resolution untargeted Gas Chromatography–Time-of-Flight Mass Spectrometry. Metabolomic analyses revealed altered metabolites and enriched metabolic pathways. Distinct metabolite profiles were observed between infected and control groups. Infected rats showed elevated urea levels and reduced concentrations of 1,5-anhydroglucitol, D-(+)-Talose, and arachidonic acid. Pathway analysis revealed significant enrichment of the glucose-alanine cycle, alpha-linolenic acid metabolism, and linoleic acid metabolism in infected rats. Minimal enrichment was observed in arachidonic acid metabolism and lactose biosynthesis. The upregulation of the glucose-alanine cycle suggests increased gluconeogenesis in response to parasite-induced glucose depletion and energy demand. Elevated urea indicates enhanced amino acid catabolism. These findings highlight the potential of metabolomics as a diagnostic tool for malaria detection and prognosis. Full article
(This article belongs to the Special Issue Genetic and Molecular Research on the Malaria Parasite)
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17 pages, 1120 KB  
Article
Circulating Levels of SMPDL3B Define Metabolic Endophenotypes and Subclinical Kidney Alterations in Myalgic Encephalomyelitis
by Bita Rostami-Afshari, Wesam Elremaly, Neil R. McGregor, Katherine Jin Kai Huang, Christopher W. Armstrong, Anita Franco, Christian Godbout, Mohamed Elbakry, Rim Abdelli and Alain Moreau
Int. J. Mol. Sci. 2025, 26(18), 8882; https://doi.org/10.3390/ijms26188882 - 12 Sep 2025
Cited by 1 | Viewed by 3680
Abstract
Myalgic Encephalomyelitis (ME) is a complex, multisystem disorder with poorly understood pathophysiological mechanisms. SMPDL3B, a membrane-associated protein expressed in renal podocytes, is essential for lipid raft integrity and glomerular barrier function. We hypothesize that reduced membrane-bound SMPDL3B may contribute to podocyte dysfunction and [...] Read more.
Myalgic Encephalomyelitis (ME) is a complex, multisystem disorder with poorly understood pathophysiological mechanisms. SMPDL3B, a membrane-associated protein expressed in renal podocytes, is essential for lipid raft integrity and glomerular barrier function. We hypothesize that reduced membrane-bound SMPDL3B may contribute to podocyte dysfunction and impaired renal physiology in ME. To investigate this, we quantified soluble SMPDL3B in plasma and urine as a surrogate marker of membrane-bound SMPDL3B status and assessed renal clearance and plasma metabolomic profiles. In a cross-sectional study of 56 ME patients and 16 matched healthy controls, ME patients exhibited significantly lower urine-to-plasma ratios of soluble SMPDL3B and reduced renal clearance, suggesting podocyte-related abnormalities. Plasma metabolomics revealed dysregulation of metabolites associated with renal impairment, including succinic acid, benzoic acid, phenyllactic acid, 1,5-anhydroglucitol, histidine, and citrate. In ME patients, plasma SMPDL3B levels inversely correlated with 1,5-anhydroglucitol concentrations and renal clearance. Multivariable modeling identified the urine-to-plasma SMPDL3B ratio as an independent predictor of clearance. Female ME patients showed more pronounced SMPDL3B alterations, reduced clearance, and greater symptom severity. Non-linear associations between soluble SMPDL3B and lipid species further suggest systemic metabolic remodeling. These findings support soluble SMPDL3B as a potential non-invasive biomarker of renal-podocyte involvement in ME, highlighting sex-specific differences that may inform future therapeutic strategies. Full article
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14 pages, 841 KB  
Article
Evaluation of the Postprandial-Hyperglycemia-Suppressing Effects and Safety of Short-Term Intake of Mulberry Leaf and Water Chestnut Tea: A Randomized Double-Blind Placebo-Controlled Crossover Trial
by Yuya Shinkawa, Midori Yasuda, Yuichiro Nishida, Mikiko Tokiya, Yusuke Takagi, Akiko Matsumoto, Atsushi Kawaguchi and Megumi Hara
Nutrients 2025, 17(14), 2308; https://doi.org/10.3390/nu17142308 - 13 Jul 2025
Cited by 2 | Viewed by 4568
Abstract
Background/Objectives: Postprandial hyperglycemia is a risk factor for diabetes and cardiovascular diseases, even in healthy individuals. Kanzaki mulberry leaf and water chestnut tea (MW tea), a blend of mulberry (Morus alba) leaves and water chestnut (Trapa japonica) leaves [...] Read more.
Background/Objectives: Postprandial hyperglycemia is a risk factor for diabetes and cardiovascular diseases, even in healthy individuals. Kanzaki mulberry leaf and water chestnut tea (MW tea), a blend of mulberry (Morus alba) leaves and water chestnut (Trapa japonica) leaves and husks, is rich in polyphenols and 1-deoxynojirimycin (DNJ) and may suppress postprandial glucose spikes, but evidence regarding its short-term daily intake is limited. This study aimed to evaluate the postprandial glycemic response and safety of two-week MW tea consumption using continuous glucose monitoring (CGM). Methods: We conducted a randomized, double-blind, placebo-controlled, two-period crossover trial involving 31 participants. Each intervention period lasted two weeks, separated by a one-week washout. Participants consumed either MW tea or a placebo before meals. Interstitial glucose levels were measured every 15 min using CGM. Postprandial glucose responses were recorded every 15 min for 180 min after a standardized meal on the first day of each period. The primary outcome was the coefficient of variation (CV) in glucose levels, calculated using data from the central 10 days of each intervention period. Safety was assessed using CGM-derived hypoglycemia metrics and blood test results. Results: The CV of glucose levels during the MW tea period was significantly lower than during the placebo period (mean difference: 0.02, p = 0.0006). A significant reduction in 1 h postprandial glucose area under the curve was also observed. No significant differences were found in hypoglycemia occurrence, liver/renal/inflammatory markers, or self-reported adverse symptoms. Notably, 1,5-anhydroglucitol (1,5-AG) levels significantly increased during MW tea intake, suggesting improved glycemic control. Conclusions: Short-term consumption of Kanzaki MW tea effectively suppressed postprandial glucose variability without safety concerns. These findings support MW tea as a promising natural supplement for glycemic management and the prevention of diabetes. Full article
(This article belongs to the Section Nutrition and Diabetes)
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15 pages, 715 KB  
Article
Salivary 1,5-Anhydroglucitol and AGEs Are Associated with Postural Instability in Diabetic Foot Patients
by Lorenzo Brognara, Mar Sempere-Bigorra and Omar Cauli
Medicina 2025, 61(6), 968; https://doi.org/10.3390/medicina61060968 - 23 May 2025
Cited by 1 | Viewed by 1984
Abstract
Background and Objectives: Gait and posture alterations are reported in patients with diabetic foot. We evaluated whether gait and postural parameters are associated with a well-known parameter, e.g., glycated hemoglobin levels in blood, and the salivary markers 1,5-anhydro-D-glucitol (1,5-AG) and Advanced Glycation [...] Read more.
Background and Objectives: Gait and posture alterations are reported in patients with diabetic foot. We evaluated whether gait and postural parameters are associated with a well-known parameter, e.g., glycated hemoglobin levels in blood, and the salivary markers 1,5-anhydro-D-glucitol (1,5-AG) and Advanced Glycation End-Products (AGEs) measured in saliva samples. Materials and Methods: Gait and postural impairment was assessed using a wearable inertial sensor, and the evaluation of balance/gait and risk of fall was determined by the Tinetti Scale and Downton Index, respectively. Glycemic control was measured by glycated hemoglobin concentration and fasting glycemia. The salivary concentration of 1,5-AG and AGEs was measured using an enzyme-linked immunosorbent assay. Results: Eighty-five patients were evaluated, revealing significant associations (p < 0.05) between salivary 1,5-AG and sway path displacement along the medio-lateral axis (rho = 0.365, p = 0.017) and sway area (rho = 0.334, p = 0.031) during tandem position tests with eyes closed. Salivary AGEs were significantly associated with sway path displacement along the anterior–posterior axis (rho = 0.419, p = 0.004) and medio-lateral axis (rho = 0.436, p = 0.002) in the tests performed with eyes closed, feet close together, and foam pads, as well as with sway area (rho = 0.387, p = 0.007). The concentration of HbA1c was significantly correlated with sway path displacement along the anterior–posterior axis in the tests performed with eyes closed, feet close together, and foam pads (rho = 0.236, p = 0.043), as well as with sway area (rho = −0.236, p = 0.043). A significant difference was observed in the salivary AGE concentration between patients with previous ulcers versus those without (p = 0.035). By applying Bonferroni correction for multiple comparisons, the associations remained significant (p < 0.05) for AGE concentration in saliva and postural instability parameters. Conclusions: The results suggest a link between salivary glycemic control biomarkers, in particular AGEs and postural changes in patients with diabetic foot, indicating a new interesting filed for further studies on fall risk. Full article
(This article belongs to the Special Issue Physical Therapy: A New Perspective)
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17 pages, 2073 KB  
Article
Dynamics of Glycemic Status and Glucose Metabolism Markers 12 Months After Coronary Artery Bypass Grafting and Their Relationship with the Annual Prognosis of Patients
by Alexey N. Sumin, Natalia A. Bezdenezhnykh, Ekaterina V. Belik, Yulia A. Dyleva, Andrey V. Bezdenezhnykh, Olga V. Gruzdeva and Olga L. Barbarash
J. Clin. Med. 2025, 14(2), 351; https://doi.org/10.3390/jcm14020351 - 8 Jan 2025
Viewed by 1646
Abstract
Background and Objectives: We aim to evaluate the dynamics of glycemic status and markers of carbohydrate metabolism 12 months after coronary artery bypass grafting (CABG) and their relationship with the one-year prognosis. Materials and Methods: The analysis of outcomes of 653 patients during [...] Read more.
Background and Objectives: We aim to evaluate the dynamics of glycemic status and markers of carbohydrate metabolism 12 months after coronary artery bypass grafting (CABG) and their relationship with the one-year prognosis. Materials and Methods: The analysis of outcomes of 653 patients during 1 year after coronary artery bypass grafting is presented. In those patients who visited the study center after 1 year, markers of carbohydrate metabolism (glucose, glycated hemoglobin, fructosamine, 1.5 anhydroglucitol) were assessed; in 371 of them, they were studied at three points—before surgery, before discharge from the hospital, and one year after surgery. The influence of these indicators on the incidence of cardiovascular events (death from any cause, myocardial infarction, stroke, repeat myocardial revascularization, surgical interventions on non-coronary arteries, amputations due to peripheral atherosclerosis, emergency hospitalizations due to cardiovascular disease, or combined endpoint [CEP]) was assessed during the year after CABG. Groups with (n = 59)/absence (n = 594) of the combined endpoint were formed and compared based on the dynamics of carbohydrate metabolism markers over the course of a year. Additionally, factors associated with the development of major adverse cardiovascular events (MACE) after CABG were assessed. Results: After 1 year, the number of patients with type 2 diabetes increased from 23.9% to 25.6% and prediabetes from 17.2% to 26.6% (p < 0.001). Among patients with diabetes mellitus, the following dynamics of carbohydrate metabolism markers were noted: a decrease in glucose levels in both groups (with or without CEP), glycated hemoglobin in the group without CEP, and fructosamine in the group with CEP. There were no differences in the intergroup comparison of all the described markers (glucose, fructosamine, glycated hemoglobin) and carbohydrate metabolism at all points. The following factors were associated with the development of MACE within a year after CABG: the presence of peripheral arterial disease, preoperative fibrinogen level, the risk of surgery according to the EuroSCORE scale, and off-pump CABG. Conclusions: In patients with diabetes mellitus one year after coronary artery bypass grafting, a decrease in glucose and glycated hemoglobin levels was noted. No differences in the dynamics of carbohydrate metabolism markers were found in the groups of patients with and without cardiovascular complications. The impact of glycated hemoglobin dynamics one year after CABG on long-term prognosis requires further research. Full article
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21 pages, 1153 KB  
Article
Reference Interval for Glycated Albumin, 1,5-AG/GA, and GA/HbA1c Ratios and Cut-Off Values for Type 1, Type 2, and Gestational Diabetes: A Cross-Sectional Study
by Yusra Al-Lahham, Waldemar Volanski, Liana Signorini, Ademir Luiz do Prado, Glaucio Valdameri, Vivian Rotuno Moure, Marciane Welter, Alexessander C. Alves, Marcel Henrique Marcondes Sari, Fabiane Gomes de Moraes Rego and Geraldo Picheth
Biomedicines 2024, 12(12), 2651; https://doi.org/10.3390/biomedicines12122651 - 21 Nov 2024
Cited by 4 | Viewed by 4157 | Correction
Abstract
Background/Objectives: Glycated albumin (GA) serves as a biomarker for short-term glycemic control (2–3 weeks), playing a role in diabetes management. Our goal was to establish reference intervals (RIs) for serum GA, and the ratios of 1,5-anhydroglucitol to GA (AGI) and GA to HbA1c [...] Read more.
Background/Objectives: Glycated albumin (GA) serves as a biomarker for short-term glycemic control (2–3 weeks), playing a role in diabetes management. Our goal was to establish reference intervals (RIs) for serum GA, and the ratios of 1,5-anhydroglucitol to GA (AGI) and GA to HbA1c in a Euro-Brazilian pediatric population (10 y, n = 299), adults (43.5 y; n = 290), and pregnant women (26 y, n = 406; 26.5 ± 3.1 gestation weeks). Methods: Receiver operating characteristic curve analysis was employed to determine RIs for type 1 diabetes (T1D) in children (n = 148) and adults (n = 81), type 2 diabetes (T2D, n = 283), and gestational diabetes mellitus (GDM, n = 177). Results: Both non-pregnant and pregnant women exhibited GA RIs of 10.0–13.3% and 10.6–14.7%, respectively. The AGI ratio varied from 1.2–4.3 in children, 0.9–3.6 in adults, and 0.8–3.1 in pregnant women. Meanwhile, the GA/HbA1c ratio ranged from 1.8–2.6 in children and adults to 2.3–3.6 in pregnant women. GA and AGI ratios accurately differentiated between T1D and T2D, demonstrating high sensitivity (>84%) and specificity (>97%), with AGI showing superior performance (AUC > 0.99). The GA/HbA1c ratio exhibited moderate discriminatory power (AUC > 0.733) but was less effective in distinguishing adult-onset T1D and T2D, suggesting its limited utility in certain groups. Conclusions: The proposed RIs are consistent with those of other Caucasian populations, affirming their relevance for Euro-Brazilian patients. The GA and AGI ratios emerge as valuable diagnostic tools for T1D and T2D, though their reduced sensitivity in diagnosing GDM warrants further investigation. Clinicians might leverage GA and AGI ratios for more tailored diabetes management, especially when HbA1c results are not optimal. Full article
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21 pages, 2950 KB  
Article
An Okinawan-Based Nordic Diet Leads to Profound Effects on Gut Microbiota and Plasma Metabolites Linked to Glucose and Lipid Metabolism
by Lokeshwaran Manoharan, Bodil Roth, Corinna Bang, Hans Stenlund and Bodil Ohlsson
Nutrients 2023, 15(14), 3273; https://doi.org/10.3390/nu15143273 - 24 Jul 2023
Cited by 11 | Viewed by 6864
Abstract
Dietary interventions modify gut microbiota and clinical outcomes. Weight reduction and improved glucose and lipid homeostasis were observed after adopting an Okinawan-based Nordic diet (O-BN) in individuals with type 2 diabetes. The aim of the present study was to explore changes in metabolomics [...] Read more.
Dietary interventions modify gut microbiota and clinical outcomes. Weight reduction and improved glucose and lipid homeostasis were observed after adopting an Okinawan-based Nordic diet (O-BN) in individuals with type 2 diabetes. The aim of the present study was to explore changes in metabolomics and gut microbiota during O-BN and correlate changes with clinical outcomes. A total of 30 patients (17 women), aged 57.5 ± 8.2 years, diabetes duration 10.4 ± 7.6 years, 90% over-weight, were included. Participants were provided an O-BN for 12 weeks. Before and after intervention, and 16 weeks afterwards, anthropometry and clinical data were estimated and questionnaires were collected, as well as samples of blood and stool. Plasma metabolomics were determined by gas- (GC-MS) or liquid- (LC-MS) chromatography-based mass spectrometry and fecal microbiota determination was based on 16S rRNA amplicons from regions V1–V2. During the intervention, weight (6.8%), waist circumference (6.1%), and levels of glucose, HbA1c, insulin, triglycerides, and cholesterol were decreased. Of 602 metabolites, 323 were changed for any or both periods; 199 (101 lipids) metabolites were decreased while 58 (43 lipids) metabolites were increased during the intervention. Changes in glucose homeostasis were linked to changes in, e.g., 1,5-anhydroglucitol, thyroxine, and chiro-inositol. Changes of microbe beta diversity correlated positively with food components and negatively with IL-18 (p = 0.045). Abundance differences at phylum and genus levels were found. Abundances of Actinobacteria, Bacteroidetes, Firmicutes, and Verrucomicrobia correlated with anthropometry, HbA1c, lipids, inflammation, and food. Changes in metabolites and microbiota were reversed after the intervention. The O-BN-induced changes in metabolomics and gut microbiota correspond to clinical outcomes of reduced weight and inflammation and improved glucose and lipid metabolism. Full article
(This article belongs to the Section Nutrition and Metabolism)
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18 pages, 1801 KB  
Review
Treatment of the Neutropenia Associated with GSD1b and G6PC3 Deficiency with SGLT2 Inhibitors
by Maria Veiga-da-Cunha, Saskia B. Wortmann, Sarah C. Grünert and Emile Van Schaftingen
Diagnostics 2023, 13(10), 1803; https://doi.org/10.3390/diagnostics13101803 - 19 May 2023
Cited by 30 | Viewed by 6882
Abstract
Glycogen storage disease type Ib (GSD1b) is due to a defect in the glucose-6-phosphate transporter (G6PT) of the endoplasmic reticulum, which is encoded by the SLC37A4 gene. This transporter allows the glucose-6-phosphate that is made in the cytosol to cross the endoplasmic reticulum [...] Read more.
Glycogen storage disease type Ib (GSD1b) is due to a defect in the glucose-6-phosphate transporter (G6PT) of the endoplasmic reticulum, which is encoded by the SLC37A4 gene. This transporter allows the glucose-6-phosphate that is made in the cytosol to cross the endoplasmic reticulum (ER) membrane and be hydrolyzed by glucose-6-phosphatase (G6PC1), a membrane enzyme whose catalytic site faces the lumen of the ER. Logically, G6PT deficiency causes the same metabolic symptoms (hepatorenal glycogenosis, lactic acidosis, hypoglycemia) as deficiency in G6PC1 (GSD1a). Unlike GSD1a, GSD1b is accompanied by low neutrophil counts and impaired neutrophil function, which is also observed, independently of any metabolic problem, in G6PC3 deficiency. Neutrophil dysfunction is, in both diseases, due to the accumulation of 1,5-anhydroglucitol-6-phosphate (1,5-AG6P), a potent inhibitor of hexokinases, which is slowly formed in the cells from 1,5-anhydroglucitol (1,5-AG), a glucose analog that is normally present in blood. Healthy neutrophils prevent the accumulation of 1,5-AG6P due to its hydrolysis by G6PC3 following transport into the ER by G6PT. An understanding of this mechanism has led to a treatment aimed at lowering the concentration of 1,5-AG in blood by treating patients with inhibitors of SGLT2, which inhibits renal glucose reabsorption. The enhanced urinary excretion of glucose inhibits the 1,5-AG transporter, SGLT5, causing a substantial decrease in the concentration of this polyol in blood, an increase in neutrophil counts and function and a remarkable improvement in neutropenia-associated clinical signs and symptoms. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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15 pages, 2101 KB  
Article
An Efficient Electrochemical Biosensor to Determine 1,5-Anhydroglucitol with Persimmon-Tannin-Reduced Graphene Oxide-PtPd Nanocomposites
by Guiyin Li, Zhide Zhou, Zhongmin Wang, Shiwei Chen, Jintao Liang, Xiaoqing Yao and Liuxun Li
Materials 2023, 16(7), 2786; https://doi.org/10.3390/ma16072786 - 30 Mar 2023
Cited by 4 | Viewed by 2922
Abstract
1,5-Anhydroglucitol (1,5-AG) is a sensitive biomarker for real-time detection of diabetes mellitus. In this study, an electrochemical biosensor to specifically detect 1,5-AG levels based on persimmon-tannin-reduced graphene oxide-PtPd nanocomposites (PT-rGO-PtPd NCs), which were modified onto the surface of a screen-printed carbon electrode (SPCE), [...] Read more.
1,5-Anhydroglucitol (1,5-AG) is a sensitive biomarker for real-time detection of diabetes mellitus. In this study, an electrochemical biosensor to specifically detect 1,5-AG levels based on persimmon-tannin-reduced graphene oxide-PtPd nanocomposites (PT-rGO-PtPd NCs), which were modified onto the surface of a screen-printed carbon electrode (SPCE), was designed. The PT-rGO-PtPd NCs were prepared by using PT as the film-forming material and ascorbic acid as the reducing agent. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), ultraviolet–visible spectroscopy (UV–vis), and X-ray diffraction (XRD) spectroscopy analysis were used to characterise the newly synthesised materials. PT-rGO-PtPd NCs present a synergistic effect not only to increase the active surface area to bio-capture more targets, but also to exhibit electrocatalytic efficiency to catalyze the decomposition of hydrogen peroxide (H2O2). A sensitive layer is formed by pyranose oxidase (PROD) attached to the surface of PT-rGO-PtPd NC/SPCE. In the presence of 1,5-AG, PROD catalyzes the oxidization of 1,5-AG to generate 1,5-anhydrofuctose (1,5-AF) and H2O2 which can be decomposed into H2O under the synergistic catalysis of PT-rGO-PtPd NCs. The redox reaction between PT and its oxidative product (quinones, PTox) can be enhanced simultaneously by PT-rGO-PtPd NCs, and the current signal was recorded by the differential pulse voltammetry (DPV) method. Under optimal conditions, our biosensor shows a wide range (0.1–2.0 mg/mL) for 1,5-AG detection with a detection limit of 30 μg/mL (S/N = 3). Moreover, our electrochemical biosensor exhibits acceptable applicability with recoveries from 99.80 to 106.80%. In summary, our study provides an electrochemical method for the determination of 1,5-AG with simple procedures, lower costs, good reproducibility, and acceptable stability. Full article
(This article belongs to the Special Issue Synthesis, Optimization, and Reuse of Sustainable Bio-Based Materials)
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19 pages, 1546 KB  
Article
Association of Alternative Markers of Carbohydrate Metabolism (Fructosamine and 1,5-Anhydroglucitol) with Perioperative Characteristics and In-Hospital Complications of Coronary Artery Bypass Grafting in Patients with Type 2 Diabetes Mellitus, Prediabetes, and Normoglycemia
by Alexey N. Sumin, Natalia A. Bezdenezhnykh, Andrey V. Bezdenezhnykh, Anastasiya A. Kuzmina, Yuliya A. Dyleva and Olga L. Barbarash
Diagnostics 2023, 13(5), 969; https://doi.org/10.3390/diagnostics13050969 - 3 Mar 2023
Cited by 1 | Viewed by 2866
Abstract
Patients with type 2 diabetes make up 25 to 40% of those referred for coronary bypass surgery, and the impact of diabetes on the results of the operation is studied in various aspects. To assess the state of carbohydrate metabolism before any surgical [...] Read more.
Patients with type 2 diabetes make up 25 to 40% of those referred for coronary bypass surgery, and the impact of diabetes on the results of the operation is studied in various aspects. To assess the state of carbohydrate metabolism before any surgical interventions, including CABG, daily glycemic control, and the determination of glycated hemoglobin (HbA1c) is recommended. Glycated hemoglobin reflects the glucose concentration for the 3 months prior to the measurement, but alternative markers that reflect glycemic fluctuations over a shorter period of time may be useful in preoperative preparation. The aim of this study was to study the relationship between the concentration of alternative markers of carbohydrate metabolism (fructosamine and 1,5-anhydroglucitol) with patients’ clinical characteristics and the rate of hospital complications after coronary artery bypass grafting (CABG). Method. In the cohort of 383 patients, besides the routine examination, additional markers of carbohydrate metabolism were determined before and on days 7–8 after CABG: glycated hemoglobin (HbA1c), fructosamine, and 1,5-anhydroglucitol. We evaluated the dynamics of these parameters in groups of patients with diabetes mellitus, prediabetes, and normoglycemia, as well as the association of these parameters with clinical parameters. Additionally, we assessed the incidence of postoperative complications and factors associated with their development. Results. In all groups of patients (diabetes mellitus, prediabetes, normoglycemia), there was a significant decrease in the level of fructosamine on the 7th day after CABG compared with baseline (p1st–2nd point 0.030, 0.001, and 0.038 in groups 1, 2, and 3, respectively), whereas the level of 1,5-anhydroglucitol did not change significantly. The preoperative level of fructosamine was associated with the risk of surgery according to the EuroSCORE II scale (p = 0.002), as were the number of bypasses (p = 0.012), body mass index and overweightness (p < 0.001 in both cases), triglyceride (p < 0.001) and fibrinogen levels (p = 0.002), preoperative and postoperative glucose and HbA1c levels (p < 0.001 in all cases), left atrium size (p = 0.028), multiplicity of cardioplegia, cardiopulmonary bypass duration and aortic clamp time (p < 0.001 in all cases). The preoperative level of 1,5-anhydroglucitol showed an inverse correlation with fasting glucose and fructosamine levels before surgery (p < 0.001 in all cases), intima media thickness (p = 0.016), and a direct correlation with LV end-diastolic volume (p = 0.020). The combined endpoint (presence of significant perioperative complications + extended hospital stay after surgery >10 days) was identified in 291 patients. In binary logistic regression analysis patient age (p = 0.005) and fructosamine level (p = 0.022) were independently associated with the development of this composite endpoint (presence of significant perioperative complications + extended hospital stay after surgery >10 days). Conclusions: This study demonstrated that in patients after CABG there was the significant decrease in the level of fructosamine compared with baseline, whereas the level of 1,5-anhydroglucitol did not change. Preoperative fructosamine levels were one of the independent predictors of the combined endpoint. The prognostic value of preoperative assessment of alternative markers of carbohydrate metabolism in cardiac surgery deserves further study. Full article
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19 pages, 510 KB  
Article
Dietary and Animal Strategies to Reduce the Environmental Impact of Pastoral Dairy Systems Result in Altered Nutraceutical Profiles in Milk
by Cameron Joel Marshall, Konagh Garrett, Stephan Van Vliet, Matthew Raymond Beck and Pablo Gregorini
Animals 2022, 12(21), 2994; https://doi.org/10.3390/ani12212994 - 31 Oct 2022
Cited by 8 | Viewed by 3327
Abstract
The objective of this study was to evaluate and provide further insights into how dairy cows genetically divergent for milk urea N breeding values [MUNBV, high (2.21 ± 0.21) vs. low (−1.16 ± 0.21); µ ± SEM], consuming either fresh cut Plantain ( [...] Read more.
The objective of this study was to evaluate and provide further insights into how dairy cows genetically divergent for milk urea N breeding values [MUNBV, high (2.21 ± 0.21) vs. low (−1.16 ± 0.21); µ ± SEM], consuming either fresh cut Plantain (Plantago lanceolata L., PL) or Ryegrass (Lolium perenne L., RG) herbage, impacted the nutraceutical profile of whole milk by investigating amino and fatty acid composition and applying metabolomic profiling techniques. Both diet and MUNBV, and their interaction term, were found to affect the relative abundance of alanine, glycine, histidine, and phenylalanine in the milk (p < 0.05), but their minor absolute differences (up to ~0.13%) would not be considered biologically relevant. Differences were also detected in the fatty acid profile based on MUNBV and diet (p < 0.05) with low MUNBV cows having a greater content of total unsaturated fatty acids (+16%) compared to high MUNBV cows and cows consuming PL having greater content of polyunsaturated fatty acids (+92%), omega 3 (+101%) and 6 (+113%) compared to RG. Differences in the metabolomic profile of the milk were also detected for both MUNBV and dietary treatments. Low MUNBV cows were found to have greater abundances of choline phosphate, phosphorylethanolamine, N-acetylglucosamine 1-phosphate, and 2-dimethylaminoethanol (p < 0.05). High MUNBV cows had a greater abundance of methionine sulfoxide, malate, 1,5-anhydroglucitol (1,5-AG), glycerate, arabitol/xylitol, 3-hydroxy-3-methylglutarate, 5-hydroxylysine and cystine (p < 0.05). Large differences (p < 0.05) were also detected as a result of diet with PL diets having greater abundances of the phytochemicals 4-acetylcatechol sulfate, 4-methylcatechol sulfate, and p-cresol glucuronide whilst RG diets had greater abundances of 2,6-dihydroxybenzoic acid, 2-acetamidophenol sulfate, and 2-hydroxyhippurate. The results of this study indicate the potential to alter the nutraceutical value of milk from dietary and genetic strategies that have been previously demonstrated to reduce environmental impact. Full article
(This article belongs to the Special Issue Advanced Grazing Management: Applied Nutritional and Foraging Ecology)
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12 pages, 652 KB  
Article
Correlation between BMI and Oral Health Status (DMFT, PI, mSBI, and Salivary 1,5-AG) among the Pediatric Population in Saudi Arabia: A Clinico-Biochemical Study
by Sara Ayid Alghamdi, Aziza Aljohar, Basim Almulhim, Abdullah Alassaf, Smita Singh Bhardwaj, Julie Toby Thomas, Abdullah Almalki, Areej Owaid Aljuaid and Sreekanth Kumar Mallineni
Children 2022, 9(7), 1017; https://doi.org/10.3390/children9071017 - 8 Jul 2022
Cited by 22 | Viewed by 4599
Abstract
The study aimed to investigate the association of varying body mass index (BMI) with oral health status among children aged 5–14 years and correlate the concentration of salivary levels of 1,5-AG with varying BMI, dental caries, and periodontal disease. This cross-sectional study was [...] Read more.
The study aimed to investigate the association of varying body mass index (BMI) with oral health status among children aged 5–14 years and correlate the concentration of salivary levels of 1,5-AG with varying BMI, dental caries, and periodontal disease. This cross-sectional study was conducted on subjects aged 5 to 14 years. The children were recruited from the Pediatric Dental Clinic, College of Dentistry, Majmaah University, by convenient sampling method. Sociodemographic details and clinical parameters, including body mass index (BMI), DMFT/def (deciduous decayed tooth (d), deciduous extracted tooth (e), deciduous filled tooth (f), permanent tooth decayed (D), permanent missing tooth (M), and permanent filled tooth (F)), plaque index (PI), and modified sulcular bleeding index (mSBI), were evaluated. Salivary 1,5-anhydroglucitol (1,5-AG) was analyzed using an enzyme-linked immunosorbent assay (ELISA) for all the subjects. Statistical analyses performed using SPSS v. 27 (IBM Statistics, Chicago, IL, USA) and the Kruskal–Wallis and chi-square tests were used for comparisons. The Spearman rank correlation coefficient was used to examine the association between the study subjects’ independent variables, BMI, and caries activity. The mean def score, PI, and mSBI scores were higher in obese children. PI score, mSBI score, and salivary concentrations of 1,5-AG between the BMI categories were statistically significant (p < 0.001). The study emphasizes promoting preventive oral health regimes, health awareness campaigns, and nutritional educational programs among the pediatric population. Full article
(This article belongs to the Special Issue Advance Research in Pediatric Dental Disease)
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15 pages, 576 KB  
Review
Metabolomic Biomarkers in Gestational Diabetes Mellitus: A Review of the Evidence
by Simon Alesi, Drishti Ghelani, Kate Rassie and Aya Mousa
Int. J. Mol. Sci. 2021, 22(11), 5512; https://doi.org/10.3390/ijms22115512 - 24 May 2021
Cited by 100 | Viewed by 11471
Abstract
Gestational diabetes mellitus (GDM) is the fastest growing type of diabetes, affecting between 2 to 38% of pregnancies worldwide, varying considerably depending on diagnostic criteria used and sample population studied. Adverse obstetric outcomes include an increased risk of macrosomia, and higher rates of [...] Read more.
Gestational diabetes mellitus (GDM) is the fastest growing type of diabetes, affecting between 2 to 38% of pregnancies worldwide, varying considerably depending on diagnostic criteria used and sample population studied. Adverse obstetric outcomes include an increased risk of macrosomia, and higher rates of stillbirth, instrumental delivery, and birth trauma. Metabolomics, which is a platform used to analyse and characterise a large number of metabolites, is increasingly used to explore the pathophysiology of cardiometabolic conditions such as GDM. This review aims to summarise metabolomics studies in GDM (from inception to January 2021) in order to highlight prospective biomarkers for diagnosis, and to better understand the dysfunctional metabolic pathways underlying the condition. We found that the most commonly deranged pathways in GDM include amino acids (glutathione, alanine, valine, and serine), carbohydrates (2-hydroxybutyrate and 1,5-anhydroglucitol), and lipids (phosphatidylcholines and lysophosphatidylcholines). We also highlight the possibility of using certain metabolites as predictive markers for developing GDM, with the use of highly stratified modelling techniques. Limitations for metabolomic research are evaluated, and future directions for the field are suggested to aid in the integration of these findings into clinical practice. Full article
(This article belongs to the Special Issue Identification of Metabolites of Xenobiotics 2.0)
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