Glycated Albumin Research Articles

Glycated albumin in pregnancy correlates negatively with body mass index and contributes to the risk of gestational diabetes mellitus

ObjectivesThe aims of our study were to establish a reference interval for glycated albumin (GA) in gestational week 30, to investigate whether GA can replace or reduce the need for oral glucose tolerance test (OGTT) in pregnancy, and to reassess the usefulness of body mass-index (BMI), age and fasting glucose in detection of gestational diabetes (GDM). Designand methods: We measured GA in 486 healthy pregnant women. Reference interval was calculated using the central 95% of the results. ROC curves were created to assess the ability of GA, fasting glucose and BMI separately to detect GDM, and logistic regression analysis was used to estimate risk of developing GDM given the level of the same markers. Finally, multiple logistic regression analysis based on GA, fasting glucose and BMI was used to find a strategy of predicting a patient’s risk of GDM. ResultsThe reference interval for GA at week 30 of gestation is 6.8-10.3%. The analysis has a low AUC (0.53) with respect to detecting GDM. It increases slightly to 0.64 when corrected for BMI, as GA is inversely correlated to BMI. Combining GA with fasting glucose and BMI at gestational weeks 16-20 could raise the AUC to 0.80. ConclusionGA cannot be recommended to replace OGTT for the diagnosis of GDM. Nor can it be used to identify women at risk of developing GDM. GA combined with fasting glucose and BMI in early pregnancy could be a useful model to estimate risk of GDM.

Cutoff Values for Glycated Albumin, 1,5-Anhydroglucitol, and Fructosamine as Alternative Markers for Hyperglycemia.

Glycated albumin (GA), 1,5-anhydroglucitol (1,5-AG), and fructosamine have attracted considerable interest as markers of hyperglycemia. This study aimed to evaluate the optimal cutoff values for GA, 1,5-AG, and fructosamine and to determine their respective diagnostic efficacies in relation to hyperglycemia. We enrolled 6012 individuals who had undergone fasting blood glucose (FBG) and Hemoglobin A1c (HbA1c) tests along with at least one alternative glycemic marker. Receiver operating characteristic (ROC) curves and the upper or lower limit of the reference range (97.5 or 2.5 percentiles) were used to ascertain the optimal cutoff values. Follow-up data from healthy individuals were used to identify patients who developed diabetes mellitus (DM). The ROC cutoff values for GA, 1,5-AG, and fructosamine were 13.9%, 13.3 μg/mL, and 278 μmol/L, respectively, with corresponding area under the curve (AUC) values of 0.860, 0.879, and 0.834. The upper limits of the reference intervals for GA and fructosamine were 15.1% and 279 μmol/L, respectively, and the lower limit for 1,5-AG was 5.3 μg/mL. Among the GA cutoff values, the ROC cutoff had the highest sensitivity. Analyzing the follow-up data showed that lowering the GA cutoff from 16.0% to 13.9% identified an additional 40 people with DM progression. Lowering the GA cutoff values significantly increased the sensitivity of DM diagnosis and enhanced its potential as a screening marker by identifying more individuals with diabetes progression. Conversely, modifications to the cutoff values for 1,5-AG and fructosamine did not confer any discernible diagnostic or predictive advantages.

6547 Glycated Hemoglobin is a Better Glycemic Indicator than Glycated Albumin in Mothers with Pregestational Diabetes: Preliminary Results of a CGM study in the 2nd and 3rd Trimesters

Abstract Disclosure: M. Md Amin: None. J. Ratnasingam: None. S.S. Paramasivam: None. L. Ibrahim: None. L. Lim: None. Q. Lim: None. N. Hee Ken Yoong: None. M. Hamdan: None. S. Ganapathy: None. P. Sthaneshwar: None. S.R. Vethakkan: None. Glycemic control is strongly associated with maternofetal outcomes in mothers with pregestational diabetes. Glycated Hemoglobin (HbA1c) is most accurate in the first trimester. The use of HbA1c to monitor glycemia in pregnancy however is controversial, as altered red-cell kinetics and iron deficiency render it less accurate than in the nongravid state, especially in the 2nd or 3rd trimester. Glycated albumin (GA) is an alternative measure of intermediate-term glycemia (2-3 weeks) which is unaffected by red-cell survival that has been used to monitor glycemia in CKD and pregnancy. However, the accuracy of HbA1c as opposed to GA is unclear, especially in later pregnancy and there are no published data comparing it with CGM (Continuous Glucose Monitoring) metrics in pregnancy. We compared the accuracy of HbA1c and GA as a glycemic indicator in later pregnancy using mean glucose from a 6-day CGM as reference, hypothesizing that GA would correlate more strongly with CGM metrics.Twelve pregnant Malaysian mothers with pregestational Type 1 (n=2) and Type 2 DM(n=10) were enrolled in this prospective observational study. Mothers with known hemoglobinopathy, nephrotic syndrome and liver cirrhosis were excluded. Patients underwent blinded 6-day CGM (Medtronic iPro2) followed by blood sampling for GA, HbA1c, albumin and hemoglobin on Day 7 at standardized timepoints in the 2nd and 3rd trimester (20-28 weeks, 30-36 weeks). Mean pre-pregnancy BMI was 28kg/m2(±5). Mean Hb was 12.3g/dL (±1.5), 16.7% of mothers had anemia, while 62.5% had serum albumin < 35g/L. GA did not correlate with mean CGM glucose (2nd trimester: r=0.180 [n=10], 3rd trimester r=0.493 [n=8], p=NS). After excluding obese women (pre-pregnancy BMI>30kg/m2) however, GA correlated well with mean CGM glucose in the 3rd trimester (r=0.870, p<0.05). HbA1c correlated significantly and strongly with mean CGM glucose in later pregnancy (2nd trimester: r=0.621 [n=11], 3rd trimester r=0.718[n=8], p<0.05) and correlated with estimated A1c from CGM (r=0.548, p=0.01). Unexpectedly, our data indicate that HbA1c correlates well with gold standard mean CGM glucose with a strength approximating that observed in the nongravid population with diabetes, thus validating its use as a complementary secondary measure of glycemia to fingerstick-glucose for therapeutic decision-making in later, as well as early pregnancy. Obesity is a known confounder of accuracy of GA, our findings corroborate this. Therefore, utility of GA as an alternative glycemic measure in pregnancy is potentially limited by the increasing prevalence of obesity worldwide and impact of gestational weight gain. A larger sample is needed to confirm these preliminary findings. Presentation: 6/2/2024

Salivary glycated albumin could be as reliable a marker of glycemic control as blood glycated albumin in people with diabetes

AimsMeasurements of diabetes-related biomarkers are necessary to assess glycemic control. The commonly used finger-prick blood glucose and HbA1c measurements are invasive, as is blood glycated albumin (GA) measurement. Therefore, we developed a non-invasive method, namely, measurement of the salivary GA with high accuracy using a high-performance liquid chromatography (HPLC) method. MethodsWe recruited participants with diabetes mellitus admitted to The University of Tokyo Hospital. Blood and saliva samples were collected at three time points (fasting and 2-hour postprandial at admission and fasting at discharge). After partial purification using an antibody-based column, the samples were subjected to GA measurement by HPLC method. ResultsAmong the 56 participants with diabetes mellitus enrolled in the study, there was a correlation between the GA levels measured in blood and saliva at the three time points described above (n = 45, R2 = 0.985, P < 0.001; n = 48, R2 = 0.973, P < 0.001; n = 51, R2 = 0.979, P < 0.001). Multiple regression analysis revealed the associations were maintained even after adjustments for age, BMI, and nephropathy stage. ConclusionsThis exploratory research revealed that the salivary GA levels by this method were accurate and might be able to replace blood GA measurement. The home salivary GA measurement is expected to be developed that may reduce the burden and complications in people with diabetes mellitus and improve the quality of life.

The Relationship Between Computerized Face and Tongue Image Segmentation and Metabolic Parameters in Patients with Type 2 Diabetes Based on Machine Learning.

We aim to examine and reestablish the correlational and linear regression relationships, as well as the predictive value, between the significant facial and tongue features and the metabolic parameters in type 2 diabetes mellitus (T2DM). From March to May 2024, we studied 269 patients with T2DM in the endocrinology department of Shanghai Pudong Hospital. The patients' facial and tongue characteristics were sampling by a tongue imaging device equipped with artificial intelligence (AI) (XiMaLife, Sinology, China) of automated and advanced machine learning algorithms. Then, the imaging features were examined in relation to the blood examination. Multiple facial and tongue features, as well as dimensional facial and tongue color parameters, were significantly correlated with glycated hemoglobin A1c (HbA1c) (r < 0.3, p < 0.05), glycated albumin (GA) (-0.20 < 0.30, p < 0.05), C-peptide (-0.20.20, p < 0.05), plasma insulin (r < 0.30, p < 0.05), fasting plasma glucose (FPG) (r < 0.3, p < 0.05), significant hepatic and renal function indicators (-0.30 < r < 0.20, p<0.05), cardiac injury markers (-0.30 < r < 0.30, p < 0.05), tumor markers (-0.5 < r < 0.5, p < 0.05), thyroid function (-0.15 < r < 0.55, p < 0.05), and blood cell count, including white blood cells (r < 0.2, p < 0.05), and hemoglobin (Hb) (-0.30 < r < 0.3, 0.0001. The correlational results demonstrated that the tongue's characteristics and signsmay be linked with the dynamic of the metabolic status of T2DM. In order to examine the causal relationships, we performed linear regression analyses, which revealed that various facial and tongue imaging parameters partially determined the metabolic indicators. The predictive value of imaging features was evaluated by receiver operating characteristic curve (ROC) to assess metabolic status in T2DM. This study demonstrated that metabolic status, renal and hepatic, cardiac, and thyroid function, the proportion of blood cells, and Hb in T2DM were intimately associated with facial and tongue features. The precise analysis of facial and tongue features through AI and advanced machine learning could be used to predict T2DM's conditions and progression.

Study on the Clinical Application of Nutritional Management Combined with Clinical Monitoring of Glycated Albumin in Diabetic Nephropathy Dialysis Patients

Objective: To explore the clinical application of nutritional management combined with clinical monitoring of glycated albumin (GA) in diabetic nephropathy (DN) dialysis patients. Methods: A total of 20 diabetic nephropathy dialysis patients admitted to the People’s Hospital of Guandu District from January 2022 to February 2023 were included in the study. They were randomly divided into a conventional group (n = 10) and an observation group (n = 10). The study evaluated the blood glucose control, nutritional status, dialysis efficacy, and quality of life scores of both groups. Results: Before the intervention, there were no significant differences in fasting plasma glucose (FPG), GA, serum albumin, body mass index (BMI), dialysis efficiency values, urea clearance rate, or quality-of-life scores between the two groups (P &gt; 0.05). After the intervention, the observation group showed significantly lower FPG and GA levels, higher serum albumin, dialysis efficiency values, urea clearance rate, and improved quality-of-life scores compared to the conventional group (P &lt; 0.05), with no difference in BMI (P &gt; 0.05). Conclusion: Nutritional management combined with clinical monitoring of glycated albumin has a significant effect on the clinical application of diabetic nephropathy dialysis patients. It can effectively improve patients’ blood glucose control and nutritional status, reduce the risk of complications, and enhance the quality of life, demonstrating clinical value for broader application.

Correlation between glycated albumin (GA) and CHA2DS2-VASc score in comparison to GRACE score regarding outcomes in acute coronary syndrome patients undergoing percutaneous coronary intervention

BackgroundAcute coronary syndrome (ACS) is responsible for one-third of total deaths in people older than 35 years old. Number of prognostic models aims to estimate the future risk of mortality, or the combined risk of all-cause mortality or MI has been developed, such as GRACE score.ObjectiveThe aim of our study is to assess the utility of GA and CHA2DS2-VASc score in predicting outcomes in patients admitted with acute coronary syndromes.Patients and methodsThis study was conducted on 90 patients diagnosed with acute coronary syndrome who were admitted receiving PCI, CHA2DS2-VASc score was calculated on admission, and a serum sample for GA was withdrawn within 24 h from admission.ResultsCombined GA and CHA2DS2-VASc score could significantly predict MACCE with sensitivity 100%, specificity 79%, and diagnostic accuracy 80.9% and significantly predict hospital mortality with sensitivity 100%, specificity 75.3%, and diagnostic accuracy 76.7%; on the other hand, GRACE score can predict MACCE using cutoff point 112.5 with sensitivity 75% and specificity 66%.ConclusionIt was concluded that GA and CHADSVASC score can significantly predict major adverse cardiovascular events, in-hospital mortality, and poor clinical outcomes.

Recent advances in gold nanostructure-based biosensors in detecting diabetes biomarkers.

Diabetes mellitus (DM) is a prevalent disorder with an urgent need for continuous, precise, and on-site biomarker monitoring devices. The continuous monitoring of DM biomarkers from different biological matrices will become routine in the future, thanks to the promising biosensor design. Lately, employing different nanomaterials in biosensor receptor parts has had a great impact on smart DM monitoring. Among them, gold nanostructures (AuNSs) have arisen as highly potential materials in fabricating precise DM biosensors due to their unique properties. The present study provides an update on the applications of AuNSs in biosensors for detecting glucose as well as other DM biomarkers, such as glycated hemoglobin (HbA1c), glycated albumin (GA), insulin, insulin antibodies, uric acid, lactate, and glutamic acid decarboxylase antibodies (GADA), with a focus on the most important factors in biosensor performance such as sensitivity, selectivity, response time, and stability. Specified values of limit of detection (LOD), linear concentrations, reproducibility%, recovery%, and assay time were used to compare studies. In conclusion, AuNSs, owing to the wide electrochemical potential window and low electrical resistivity, are valuable tools in biosensor design, alongside other biological reagents and/or nanomaterials.

Glucose metabolism and smaller hippocampal volume in elderly people with normal cognitive function

We investigated associations of glycemic measures, and insulin resistance and secretion measures with hippocampal and subfield volumes. In this cross-sectional study, 7400 community-dwelling participants underwent brain MRI and health checkups between 2016 and 2018. Hemoglobin A1c (HbA1c), glycated albumin (GA), homeostasis model assessment for insulin resistance (HOMA-IR), and HOMA of percent β-cell function (HOMA-β) were evaluated. The associations of each measure with a smaller volume of the hippocampus and twelve hippocampal subfields were investigated. As a result, higher HbA1c or GA and lower HOMA-β levels were significantly associated with smaller volumes in multiple hippocampal subfields. Furthermore, even when we analyzed non-diabetic individuals, substantial associations remained between higher GA or lower HOMA-β levels and smaller volumes of the whole hippocampus or the fimbria. Our findings indicate that postprandial glucose fluctuations, postprandial hyperglycemia, and low insulin secretion have a specific effect on the development of smaller hippocampal volume, suggesting that primary prevention of diabetes and/or sufficient glucose control are important for the prevention of dementia.

Glycated albumin levels are associated with adverse stroke outcomes in patients with acute ischemic stroke in China.

Glycated albumin (GA) is a biomarker monitoring glycemia 2-4 weeks before stroke onset. This study was designed to explore the association between GA levels with poststroke outcomes in patients with acute ischemic stroke or transient ischemic attack (TIA). Participants with ischemic stroke or TIA who had a baseline GA measurement were included in the Third China National Stroke Registry study. The effect of GA on stroke recurrence, poor functional outcomes, and combined vascular events was examined during the 1-year follow-up period. Multivariate Cox and logistic regression models were performed to evaluate the association. Discrimination tests were used to examine the incremental predictive value of GA when incorporating it into the conventional model. A total of 3861 participants were enrolled. At the 3-month follow-up, the elevated GA level was associated with an increased risk of poor functional outcomes (adjusted odds ratio [OR], 1.45; 95% confidence interval [CI], 1.01-2.09). A similar increase was observed for stroke recurrence (adjusted hazard ratio [HR], 1.56; 95% CI, 1.09-2.24), poor functional outcomes (adjusted OR, 1.62; 95% CI, 1.07-2.45), and combined vascular events (adjusted HR, 1.55; 95% CI, 1.09-2.20) at the 1-year follow-up. In nondiabetic patients, the association between GA and poor functional outcomes was more pronounced (adjusted OR, 1.62; 95% CI, 1.05-2.50). Adding GA into the conventional model resulted in slight improvements in predicting poor functional outcomes (net reclassification improvement [NRI]: 12.30% at 1 year). This study demonstrated that elevated GA levels in serum were associated with stroke adverse outcomes, including stroke recurrence, poor functional outcomes, and combined vascular events, in patients with ischemic stroke or TIA.

Plasma Glycated Albumin in Early Pregnancy and Gestational Diabetes Mellitus: A Prospective and Longitudinal Study.

To investigate associations of plasma glycated albumin (GA) concentrations in early and midpregnancy with gestational diabetes mellitus (GDM) risk. We measured GA concentrations using blood samples collected at 10-14 and 15-26 weeks' gestation in 107 GDM case and 214 control participants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Study. We performed generalized linear mixed-effect regression to test the mean GA difference between GDM case and control participants and conditional logistic regression to assess prospective associations between GA concentrations and GDM risk. At 15-26 weeks' gestation mean GA was lower in GDM case participants than in control participants (mean 11.90% [95% CI 6.42-32.76] vs. 12.46% [8.45-38.35], adjusted P value for difference = 0.004). Consistently, women with higher GA concentrations tended to have a lower GDM risk, although the associations were not statistically significant. This study suggests that GA concentrations in midpregnancy might be lower in women who later develop GDM. Further studies are needed to identify the mechanism.

Glycated albumin may have a complementary role to glycated hemoglobin in glucose monitoring in childhood acute leukemia.

Glycated hemoglobin (HbA1c) as a glycemic index may have limited value in pediatric patients with acute leukemia as they often present with anemia and/or pancytopenia. To address this issue, we evaluated the usefulness of glycated albumin (GA) as a glycemic monitoring index in pediatric patients with acute leukemia. Medical records of 25 patients with type 2 diabetes mellitus (T2DM), 63 patients with acute leukemia, and 115 healthy children from Seoul St. Mary's Hospital, The Catholic University of Korea, were retrospectively investigated for serum GA, HbA1c, and fasting blood glucose (FBG) levels, along with demographic data. GA, HbA1c, and FBG levels did not differ between the control and acute leukemia groups. In the T2DM group, positive correlations were observed among GA, HbA1c, and FBG (P<0.01). Although GA level was not associated with the HbA1c level in the control group, GA and HbA1c levels showed a positive correlation in the acute leukemia group (P=0.045). Regression analysis revealed GA and HbA1c levels to be positively correlated in the acute leukemia and T2DM groups even after adjusting for age, sex, and body mass index z-score (P=0.007, P<0.01). GA may be a useful complementary parameter to HbA1c for glycemic monitoring in pediatric patients with acute leukemia, similar to its use in patients with T2DM.

A nomogram including admission serum glycated albumin/albumin ratio to predict mortality in patients with severe fever with thrombocytopenia syndrome

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is a novel tick-borne infectious disease with a high fatality rate. Although several nomograms based on demographic and laboratory data have been reported to predict the prognosis of SFTS in recent studies, baseline serum glycated albumin (GA)/albumin (ALB) ratio included risk model has not been evaluated for the prediction of clinical outcome.MethodsA total of 214 SFTS patients with integral data admitted to our hospital from May, 2020 to November, 2022 were included in this study. SFTS infection was confirmed by real time fluorescent quantitative PCR (qRT-PCR). The demographic characteristics, clinical and laboratory data were collected with in 24 h of admission and 1 to 2 days before discharge and were analysed retrospectively.ResultsFiffty-seven patients (26.6%) died. Multivariate logistic regression analysis showed that age, aspartate aminotransferase (AST), blood glucose (GLU), GA/ALB ratio, neutrophil counts (NEU) and lymphocyte percentage (LYM%) were the independent risk factors for mortality. A nomogram by these factors was created using RMS package in the R program. Area under the receiver operating characteristic (ROC) curve (AUC) of this nomogram was 0.88 (95% CI: 0.83, 0.93). This model showed the excellent net benefit, as revealed by the decision curve analysis. GA/ALB ratios were also independent risk factors for poor out clinical come in subgroups of patients with hyperglycemia on admission and with diabetes history. Nomograms were constructed by the independent risk factors in the subgroups. AUCs of the nomograms in the subgroups showed high predictive values for adverse prognosis.ConclusionsGA/ALB ratios were independent risk factors for mortality in all SFTS patients and subgroups of with hyperglycemia on admission and diabetes history. The nomograms including GA/ALB ratio had high predictive value for adverse clinical outcome.The nomograms provide a basis for clinical decision-making for the treatment of SFTS patients in different clinical settings.

Circulating glycated albumin levels and gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is characterized by glucose intolerance that is first diagnosed during pregnancy, making it the most common complication associated with this period. Early detection and targeted treatment of GDM can minimize foetal exposure to maternal hyperglycaemia and subsequently reduce the associated adverse pregnancy outcomes. Previous studies have inconsistently suggested that the level of glycated albumin (GA) might predict GDM. To review and synthesize existing evidence to evaluate the relationship between GA levels and the development of GDM. We sought to compare GA levels between GDM and control groups in this meta-analysis by systematically searching the Web of Science, PubMed, Cochrane Library, and Embase databases for articles published up to June 2023. The analysis utilized the weighted mean difference (WMD) as the primary metric. The data were meticulously extracted, and the quality of the included studies was assessed. Additionally, we conducted a subgroup analysis based on study region and sample size. We assessed heterogeneity using I 2 statistics and evaluated publication bias through funnel plots. Additionally, trim-and-fill analysis was employed to detect and address any potential publication bias. The meta-analysis included a total of 11 studies involving 5477 participants, comprising 1900 patients with GDM and 3577 control individuals. The synthesized results revealed a notable correlation between elevated GA levels and increased susceptibility to GDM. The calculated WMD was 0.42, with a 95% confidence interval (95%CI) ranging from 0.11 to 0.74, yielding a P value less than 0.001. Concerning specific GA levels, the mean GA level in the GDM group was 12.6, while for the control group, it was lower, at 11.6. This discrepancy underscores the potential of GA as a biomarker for assessing GDM risk. Moreover, we explored the levels of glycated haemoglobin (HbA1c) in both cohorts. The WMD for HbA1c was 0.19, with a 95%CI ranging from 0.15 to 0.22 and a P value less than 0.001. This observation suggested that both GA and HbA1c levels were elevated in individuals in the GDM group compared to those in the control group. Our meta-analysis revealed a substantial correlation between elevated GA levels and increased GDM risk. Furthermore, our findings revealed elevated levels of HbA1c in GDM patients, emphasizing the significance of monitoring both GA and HbA1c levels for early GDM detection and effective management.

Glycated Albumin to Predict Adverse Neonatal Outcomes among Women with Diabetes and Overweight or Obese Body Mass Index.

Glycated albumin (GA) has shown promise in predicting risk of adverse neonatal outcomes (ANO) in pregnant women with type 2 diabetes (T2DM) and gestational diabetes (GDM). However, previous studies showing a negative correlation between GA and body mass index (BMI) suggest that lower predictive cutoffs may be needed in populations with elevated BMI. We performed a case-control study of prospectively enrolled pregnant women with T2DM or GDM and BMI ≥25 kg/m2 matched to biobanked controls without diabetes. Serum collected during the second and/or third trimesters was used to measure the percentage of GA (% GA). Receiver operating characteristic (ROC) curves were used to examine % GA to predict an ANO composite, including macrosomia, hypoglycemia, respiratory distress syndrome, and/or hyperbilirubinemia for the second and third trimesters. The median BMIs for cases and controls were 34.0 and 31.0 kg/m2, respectively. The area under the ROC curve to predict the ANO composite was significant for second trimester values but ambiguous for third trimester due to its wide 95% CI. A cutoff of 12.3% GA during second trimester showed 100% sensitivity and 73% specificity. Transference of previously published reference ranges did not validate, suggesting lower ranges are needed for women with overweight/obesity. In this pilot study, % GA shows promise to stratify pregnant patients with diabetes and obesity into risk categories for ANO with excellent predictive ability in the second trimester. If this holds in larger studies, using second trimester % GA could allow additional intervention to improve blood glucose control and minimize ANO.

Nuclear Factor-Kappa-B Mediates the Advanced Glycation End Product-Induced Repression of Slc2a4 Gene Expression in 3T3-L1 Adipocytes.

Advanced glycated end products (AGEs) are cytotoxic compounds that are mainly increased in diabetes mellitus (DM), kidney failure, inflammation, and in response to the ingestion of AGE-rich diets. AGEs can also impair glycemic homeostasis by decreasing the expression of the Slc2a4 (solute carrier family 2 member 4) gene and its GLUT4 (solute carrier family 2, facilitated glucose transporter member 4) protein in muscle. However, the mechanisms underlying AGE's effect on adipocytes have not been demonstrated yet. This study investigated the effects of AGEs upon Slc2a4/GLUT4 expression in 3T3-L1 adipocytes, as well as the potential role of NFKB (nuclear factor NF-kappa-B) activity in the effects observed. Adipocytes were cultured in the presence of control albumin (CA) or advanced glycated albumin (GA) at concentrations of 0.4, 3.6, and 5.4 mg/mL for 24 h or 72 h. Slc2a4, Rela, and Nfkb1mRNAs were measured by RT-qPCR, GLUT4, IKKA/B, and p50/p65 NFKB subunits using Western blotting, and p50/p65 binding into the Slc2a4 promoter was analyzed by chromatin immunoprecipitation (ChIP) assay. GA at 0.4 mg/mL increased Slc2a4/GLUT4 expression after 24 h and 72 h (from 50% to 100%), but at 5.4 mg/mL, Slc2a4/GLUT4 expression decreased at 72 h (by 50%). Rela and Nfkb1 expression increased after 24 h at all concentrations, but this effect was not observed at 72 h. Furthermore, 5.4 mg/mL of GA increased the p50/p65 nuclear content and binding into Slc2a4 at 72 h. In summary, this study reveals AGE-induced and NFKB-mediated repression of Slc2a4/GLUT4 expression. This can compromise the adipocyte glucose utilization, contributing not only to the worsening of glycemic control in DM subjects but also the impairment of glycemic homeostasis in non-DM subjects under the high intake of AGE-rich foods.

Facile biotic/abiotic sandwich detection system for the highly sensitive detection of human serum albumin and glycated albumin.

Quantifying glycated albumin (GA) levels in the blood is crucial for diagnosing diabetes because they strongly correlate with blood glucose concentration. In this study, a biotic/abiotic sandwich assay was developed for the facile, rapid, and susceptible detection of human serum albumin (HSA) and GA. The proposed sandwich detection system was assembled using a combination of two synthetic polymer receptors and natural antibodies. Molecularly imprinted polymer nanogels (MIP-NGs) for HSA (HSA-MIP-NGs) were used to mimic capture antibodies, whereas antibodies for HSA or GA were used as primary antibodies and fluorescent signaling MIP-NGs for the Fc domain of IgG (F-Fc-MIP-NGs) were used as a secondary antibody mimic to indicate the binding events. The HSA/anti-HSA/F-Fc-MIP-NGs complex, formed by incubating HSA and anti-HSA antibodies with F-Fc-MIP-NGs, was captured by HSA-MIP-NGs immobilized on the chips for fluorescence measurements. The analysis time was less than 30min, and the limit of detection was 15pM. After changing the anti-HSA to anti-GA (monoclonal antibody), the fluorescence response toward GA exceeded that of HSA, indicating successful GA detection using the proposed sandwich detection system. Therefore, the proposed system could change the detection property by changing a primary antibody, indicating that this system can be applied to various target proteins and, especially, be a powerful approach for facile and rapid analysis methods for proteins with structural similarity.

DNA aptamer-functionalized PDA nanoparticles: from colloidal chemistry to biosensor applications.

Polydopamine nanoparticles (PDA NPs) are widely utilized in the field of biomedical science for surface functionalization because of their unique characteristics, such as simple and low-cost preparation methods, good adhesive properties, and ability to incorporate amine and oxygen-rich chemical groups. However, challenges in the application of PDA NPs as surface coatings on electrode surfaces and in conjugation with biomolecules for electrochemical sensors still exist. In this work, we aimed to develop an electrochemical interface based on PDA NPs conjugated with a DNA aptamer for the detection of glycated albumin (GA) and to study DNA aptamers on the surfaces of PDA NPs to understand the aptamer-PDA surface interactions using molecular dynamics (MD) simulation. PDA NPs were synthesized by the oxidation of dopamine in Tris buffer at pH 10.5, conjugated with DNA aptamers specific to GA at different concentrations (0.05, 0.5, and 5μM), and deposited on screen-printed carbon electrodes (SPCEs). The charge transfer resistance of the PDA NP-coated SPCEs decreased, indicating that the PDA NP composite is a conductive bioorganic material. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) confirmed that the PDA NPs were spherical, and dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), and Raman spectroscopy data indicated the successful conjugation of the aptamers on the PDA NPs. The as-prepared electrochemical interface was employed for the detection of GA. The detection limit was 0.17μg/mL. For MD simulation, anti-GA aptamer through the 5'terminal end in a single-stranded DNA-aptamer structure and NH2 linker showed a stable structure with its axis perpendicular to the PDA surface. These findings provide insights into improved biosensor design and have demonstrated the potential for employing electrochemical PDA NP interfaces in point-of-care applications.

Association between glycated albumin and adverse outcomes in patients with heart failure.

Diabetes mellitus is a traditional risk factor for heart failure (HF), and glycated albumin (GA) is a marker to assess short-term glycemic control. Whether GA has prognostic significance in patients with HF remains unclear. A total of 717 patients with HF were enrolled in the prospective cohort study. Patients were grouped by the normal upper limit of GA (17%). Kaplan-Meier analysis and Cox proportional hazards regression were used to evaluate the association between GA and prognosis. During a mean follow-up of 387 days, 232 composite endpoint events of hospitalization for HF or all-cause death occurred. Kaplan-Meier analysis showed a higher rate of adverse events in the higher GA group (GA >17%; log-rank test P < 0.001). GA was an independent predictor of adverse events, both as a continuous variable (per 1% change: hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.00-1.06, P = 0.030) and as a categorical variable (GA >17%: HR 1.36, 95% CI 1.03-1.80, P = 0.032). Restricted cubic splines showed a linear association between GA and adverse events (P for non-linearity = 0.231). There was no significant difference in adverse outcome risk between those with diabetes and GA ≤17% and those without diabetes, whereas the prognosis was worse in those with diabetes and GA >17% (HR 1.56, 95% CI 1.16-2.11, P = 0.004). Compared to the group with normal levels of GA and glycated hemoglobin, the group with GA >17% and glycated hemoglobin >6.5% had a higher risk of adverse events (HR 1.49, 95% CI 1.06-2.10, P = 0.022). GA was an independent predictor of HF prognosis. Combining GA and glycated hemoglobin might improve the predictive power of adverse outcomes in patients with HF.

Efficacy of Self-Review of Lifestyle Behaviors with Once-Weekly Glycated Albumin Measurement in People with Type 2 Diabetes: A Randomized Pilot Study.

Lifestyle management, including appropriate modifications of nutrition, exercise, and medication behaviors, is essential for optimal glycemic control. The absence of appropriate monitoring methods to validate the lifestyle change may hinder the modification and continuation of behaviors. In this study, we evaluated whether once-weekly glycated albumin (GA) measurement received via a smartphone application could improve glycemia management in patients with type 2 diabetes mellitus by supporting self-review and modification of lifestyle behaviors. This open-label, randomized controlled, single-center study in Japan with an 8-week intervention period was conducted in individuals with type 2 diabetes mellitus and HbA1c levels between 7.0 and 9.0% (53‒75mmol/mol). The intervention was once-weekly home monitoring of GA with a daily self-review of lifestyle behaviors using a smartphone application, in addition to conventional treatment. A total of 98 participants (72.0% males; age 63.2 ± 11.4years; HbA1c 7.39 ± 0.39% [57.3 ± 4.3mmol/mol]) were randomly assigned to the intervention or control group. Significant decreases of the GA and HbA1c levels from the baseline to the last observation day were observed in the intervention group (- 1.71 ± 1.37% [- 39.1 ± 31.3mmol/mol] and - 0.32 ± 0.32% [- 3.5 ± 3.5mmol/mol], respectively). Significant decreases of the body weight, waist circumference, and caloric expenditure (p < 0.0001 and p = 0.0003, p = 0.0346, respectively), but not of the caloric intake (p = 0.678), were also observed in the intervention group as compared with the control group. Self-review of lifestyle behaviors in combination with once-weekly GA home testing received via a smartphone application might potentially benefit glycemic management in people with type 2 diabetes mellitus. jRCTs042220048.