Associations of serum D-dimer and glycosylated hemoglobin levels with third-trimester fetal growth restriction in gestational diabetes mellitus

BACKGROUND Gestational diabetes mellitus(GDM)is a special type of diabetes that commonly occurs in women during pregnancy and involves impaired glucose tolerance and abnormal glucose metabolism;GDM is diagnosed for the first time during pregnancy and can affect fetal growth and development.AIM To investigate the associations of serum D-dimer(D-D)and glycosylated hemoglobin(HbA1c)levels with third-trimester fetal growth restriction(FGR)in GDM patients.METHODS The clinical data of 164 pregnant women who were diagnosed with GDM and delivered at the Obstetrics and Gynecology Hospital of Fudan University from January 2021 to January 2023 were analyzed retrospectively.Among these women,63 whose fetuses had FGR were included in the FGR group,and 101 women whose fetuses had normal body weights were included in the normal body weight group(normal group).Fasting venous blood samples were collected from the elbow at 28-30 wk gestation and 1-3 d before delivery to measure serum D-D and HbA1c levels for comparative analysis.The diagnostic value of serum D-D and HbA1c levels for FGR was evaluated by receiver operating characteristic analysis,and the influencing factors of third-trimester FGR in GDM patients were analyzed by logistic regression.RESULTS Serum fasting blood glucose,fasting insulin,D-D and HbA1c levels were significantly greater in the FGR group than in the normal group,while the homeostasis model assessment of insulin resistance values were lower(P<0.05).Regarding the diagnosis of FGR based on serum D-D and HbA1c levels,the areas under the curves(AUCs)were 0.826 and 0.848,the cutoff values were 3.04 mg/L and 5.80%,the sensitivities were 81.0%and 79.4%,and the specificities were 88.1%and 87.1%,respectively.The AUC of serum D-D plus HbA1c levels for diagnosing FGR was 0.928,and the sensitivity and specificity were 84.1%and 91.1%,respectively.High D-D and HbA1c levels were risk factors for third-trimester FGR in GDM patients(P<0.05).CONCLUSION D-D and HbA1c levels can indicate the occurrence of FGR in GDM patients in the third trimester of pregnancy to some extent,and their combination can be used as an important index for the early prediction of FGR.

Cut-off value of glycated hemoglobin A1c for detecting diabetic retinopathy in the Chinese population

BACKGROUND Glycated hemoglobin A1c(HbA1c)is considered the most suitable for diabetes mellitus diagnosis due to its accuracy and convenience.However,the effect of HbA1c on diabetic retinopathy(DR)in the Han and Korean populations in Jilin,China,remains inconclusive.AIM To determine the best cut-off of HbA1c for diagnosing DR among the Chinese.METHODS This cross-sectional study included 1933 participants from the Yanbian area of Jilin Province,China.Trained investigators employed a questionnaire-based survey,physical examination,laboratory tests,and fundus photography for the investigation.The best cut-off value for HbA1c was established via the receiver operating characteristic curve.The factors associated with HbA1c-associated risk factors were determined via linear regression.RESULTS The analysis included 887 eligible Chinese Han and Korean participants,591 of whom were assigned randomly to the training set and 296 to the validation set.The prevalence of DR was 3.27% in the total population.HbA1c of 6.2% was the best cut-off value in the training set,while it was 5.9% in the validation set.In both Chinese Han and Korean populations,an HbA1c level of 6.2% was the best cut-off value.The optimal cut-off values of fasting blood glucose(FBG)≥7 mmol/L and<7 mmol/L were 8.1% and 6.2% respectively in Han populations,while those in Korean populations were 6.9%and 5.3%,respectively.Age,body mass index,and FBG were determined as the risk factors impacting HbA1c levels.CONCLUSION HbA1c may serve as a useful diagnostic indicator for DR.An HbA1c level of 6.2% may be an appropriate cut-off value for DR detection in the Chinese population.

Preparation,characterization and antioxidant activity analysis of three Maillard glycosylated bone collagen hydrolysates from chicken,porcine and bovine

Bone collagen hydrolysates(peptides)derived from byproduct of animal product processing have been used to produce commercially valuable products due to their potential antioxidant activity.Maillard glycosylated reaction is considered as a promising method to enhance the antioxidant activity of peptides.Hence,this research aims at investigating the Maillard glycosylation activity and antioxidant activity of bone collagen hydrolysates from different sources.In this study,3 glycosylated bone collagen hydrolysates were prepared and characterized,and cytotoxicity and antioxidant activity were analyzed and evaluated.The free amino groups loss,browning intensity,and fluorescence intensity of G-Cbcp(glycosylated chicken bone collagen hydrolysates(peptides))were the heaviest,followed by G-Pbcp(glycosylated porcine bone collagen hydrolysates(peptides))and G-Bbcp(glycosylated bovine bone collagen hydrolysates(peptides)).The results of amino acid analysis showed that amino acid composition of different bone collagen hydrolysates was significantly different and the amino acid decreased to different degrees after Maillard glycosylated reaction,which may lead to differences in Maillard glycosylated reaction activity.Furthermore,the 3 glycosylated hydrolysates showed no significant cytotoxicity.The results showed that glycosylation process significantly increased the antioxidant activity of bone collagen hydrolysates,and G-Cbcp showed the strongest antioxidant activity,followed by G-Pbcp and G-Bbcp.Therefore,compared with the bone collagen hydrolysates,3 glycosylated hydrolysates showed significant characteristic and structural changes,and higher antioxidant activity.

Role of serum β2-microglobulin, glycosylated hemoglobin, and vascular endothelial growth factor levels in diabetic nephropathy

BACKGROUND Diabetic nephropathy(DN)is a common complication of type 1 and type 2 diabetes that can lead to kidney damage and high blood pressure.Increasing evidence support the important roles of microproteins and cytokines,such asβ2-microglobulin(β2-MG),glycosylated hemoglobin(HbA1c),and vascular endothelial growth factor(VEGF),in the pathogenesis of this disease.In this study,we identified novel therapeutic options for this disease.AIM To analyze the guiding significance ofβ2-MG,HbA1c,and VEGF levels in patients with DN.METHODS A total of 107 patients with type 2 diabetes mellitus complicated with nephropathy and treated in our hospital from May 2018 to February 2021 were included in the study.Additionally,107 healthy individuals and 107 patients with simple diabetes mellitus were selected as the control groups.Changes inβ2-MG,HbA1c,and VEGF levels in the three groups as well as the different proteinuria exhibited by the three groups were examined.RESULTS Changes inβ2-MG,HbA1c,and VEGF levels in the disease,healthy,and simple diabetes groups were significantly different(P<0.05).The expression of these factors from high to low were evaluated in different groups by pairwise comparison.In the disease group,high to low changes inβ2-MG,HbA1c,and VEGF levels were noted in the massive proteinuria,microproteinuria,and normal urinary protein groups,respectively.Changes in these factors were positively correlated with disease progression.CONCLUSION The expression of serumβ2-MG,HbA1c,and VEGF was closely correlated with DN progression,and disease progression could be evaluated by these factors.

Glycated hemoglobin A1C and diabetes mellitus in critically ill patients

BACKGROUND:Hyperglycemia has been detected in many critically ill patients in the department of emergency medicine.But its mechanism and prognosis have not been well elucidated.In this study,we measured the serum level of glycated hemoglobin A1C(HbA1c) in critically ill patients to evaluate the effects of hyperglycemia on the prognosis of the patients.METHODS:A total of 826 critically ill patients,who had been treated at the Department of Emergency Medicine of Chaoyang Hospital during October 2006 and November 2007,were divided into a diabetes mellitus group(n=184) and a non-diabetes mellitus group(642) according to whether they had diabetes mellitus.Fasting glucose and HbA1 c were measured in all patients.Those in the diabetes mellitus group were further assigned to a drug therapy subgroup and a non-drug therapy subgroup;the serum level of HbA1 c and its relationship with short-term outcome were evaluated.RESULTS:Fasting glucose increased in 78.8% of the patients(88.6%in the diabetes mellitus group,and 75.9%in the non-diabetes mellitus group,P<0.05),and HbA1 c was elevated in 45.5% of the patients(78.3% in the diabetes mellitus group,and 36.1%in the non-diabetes mellitus group,P<0.01).Fasting glucose,HbA1 c and 28-day mortality were improved more significantly(P<0.01) in the drug therapy subgroup than in the non-drug therapy subgroup.The 28-day mortality was more significantly different in patients with fasting blood glucose >8.33 mmol/L than in those with fasting blood glucose <8.33 mmol/L.CONCLUSIONS:Hyperglycemia of critically ill patients could not totally attribute to stress response,especially in those who have no history of diabetes mellitus.Prognosis of hyperglycemia may vary among critically ill patients.

Biological transformation,kinetics and dose-response assessments of bound musk ketone hemoglobin adducts in rainbow trout as biomarkers of environmental exposure

Low levels (ng/g) of musk ketone (MK),used as a fragrance additive in the formulation of personal care products,are frequently detected in the water and other environment.Thus,aquatic organisms can be continuously exposed to MK.In this study,kinetics and dose-response assessments of 2-amino-MK (AMK) metabolite,bound to cysteine-hemoglobin (Hb) in rainbow trout,formed by enzymatic nitro-reduction of MK have been demonstrated.Trout were exposed to a single exposure of 0.010,0.030,0.10,and 0.30 mg MK/g fish.Tw...

Hemoglobin Fukuoka caused unexpected hemoglobin A1c results: A case report

BACKGROUND Glycated hemoglobin(Hb)(HbA1c)is an indicator that is used to diagnose and monitor the treatment of diabetes.Many factors can affect the detection of HbA1c.One of the most important of these factors is the Hb variant.Here,we report a rare Hb variant and evaluate its effect on HbA1c.CASE SUMMARY A 35-year-old man was suspected of harboring an Hb variant following the measurement of HbA1c with the Variant II Turbo 2.0 Hb detection system during a routine examination.Subsequently,we used the Arkray HA-8160 and ARCHITECT c4000 system to reanalyze HbA1c.Finally,the Hb variant was detected with a Capillary2FP analyzer that operates on the principle of capillary electrophoresis.We also used gene sequencing to investigate the mutation site.The value of HbA1c detected with the Variant II Turbo 2.0 system was 52.7%.However,the Arkray HA-8160 system did not display a result while the ARCHITECT c16000 system showed a result of 5.4%.The Capillary2FP analyzer did not reveal any abnormal Hb zones.However,gene sequencing identified the presence of a mutation in the Hbβ2 chain[CD2(CAC>TAC),His>Tyr,HBB:c.7C>T];the genotype was Hb Fukuoka.CONCLUSION Hb variants could cause abnormal HbA1c results.For patients with Hb variants,different methods should be used to detect HbA1c.

CATALYTIC REDUCTION OF HEMOGLOBIN AT PHENOTHIAZINE COATED SILVER ELECTRODE

Phenothiazine-coated silver electrode prepared by a simple reaction of phenothiazine with the metal is very stable and can make the reduction of hemoglobin possible.

Hemoglobin Adducts as Biomarkers of Exposure to and metabolic Activation of Carcinogenic Tobacco-Specific Nitrosamines

The carcinogenic tobacco-specific nitrosamines N-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-l-(3-pyridyl)-l-butanone (NNK) form hemoglobin adducts in laboratory animals and humans. These adducts release 4-hydroxy-l-(3-pyridyl)-l-butanone (HPB) upon mild base hydrolysis. HPB released from human hemoglobin can be quantified by gas chromatography-mass spectrometry. It is the only available biochemical marker for determination of exposure to, and metabolic activation of, carcinogens present only in tobacco. Levels of HPB were highest in snuff-dippers, followed by smokers and nonsmokers. Large interindividual variations in adduct levels were observed. The relationship between HPB levels in globin and DNA of rats treated with NNK has been investigated in order to aid in interpretation of the data from humans. These studies have provided the initial database for understanding the metabolic activation of tobacco-specific nitrosamines in humans.

Abnormal glycosylated hemoglobin as a predictive factor for glucose metabolism disorders in antipsychotic treatment

The aim of this study was to observe the changes in glucose metabolism after antipsychotic(APS)therapy,to note the influencing factors,as well as to discuss the relationship between the occurrence of glucose metabolism disorders of APS origin and abnormal glycosylated hemoglobin(HbA1c)levels.One hundred and fifty-two patients with schizophrenia,whose fasting plasma glucose(FPG)and 2-h plasma glucose(2hPG)in the oral glucose tolerance test(2HPG)were normal,were grouped according to the HbA1c levels,one normal and the other abnormal,and were randomly enrolled into risperidone,clozapine and chlorpromazine treatment for six weeks.The FPG and 2hPG were measured at the baseline and at the end of the study.In the group with abnormal HbA1c and clozapine therapy,2HPG was higher after the study[(9.5±1.8)mmol/L]than that before the study[(7.2±1.4)mmol/L]and the difference was statistically significant(P<0.01).FPG had no statistically significant difference before and after the study in any group(P>0.05).HbA1c levels and drugs contributing to 2HPG at the end of study had statistical cross-action(P<0.01).In the abnormal HbA1c group,2HPG after the study was higher in the clozapine treatment group[(9.5±1.8)mmol/L]than in the risperidone treatment group[(7.4±1.7)mmol/L]and the chlorpromazine treatment group[(7.3±1.6)mmol/L].The differences were statistically significant(P<0.01).In the normal HbA1c group there was no statistically significant difference before and after the study in any group(P>0.05).2HPG before[(7.1±1.6)mmol/L]and after the study[(8.1±1.9)mmol/L]was higher in the abnormal HbA1c group than in the normal HbA1c group[(6.2±1.4)mmol/L vs(6.5±1.4)mmol/L]with the difference being statistically significant(P<0.01 vs P<0.001).As compared with normal HbA1c group,the relative risk(RR)of glucose metabolism disease occurrence was 4.7 in the abnormal HbA1c group with the difference being statistically significant(P<0.001).Patients with abnormal HbA1c are more likely to have a higher risk of having glucose metabolism disorders after APS treatment.

Design and Synthesis of Glycosylated Aromatic Nitrogen Mustard Derivatives

Antibody-directed enzyme prodrug therapy（ADEPT） is a new strategy for the treatment of cancer that has arisen in recent twenty years, the main merits of which are that it can improve the selectivity of anticancer drugs and reduce the side effects in remote tissue. In the present study, two prodrugs-glycosylated aromatic nitrogen mustard derivatives were synthesized. Glucose and lactose were converted into glycosyl donors-trichloroacetimidate; the obtained glycosyl donors were glycosylated with p-nitrophenol （ glycosyl donors） to form β-glucosyl p-nitrobenzene and β-lactosyl p-nitrobenzene that were protected by acetyl in a stereoselective manner; the two products were reduced by zinc dust and then treated with ethylene oxide, afforded two glycosylated nitrogen mustard derivatives that were protected by acetyl; the last step was to deacetylate and then afforded the two target compounds that could be used as prodrugs of ADEPT for further Anti-tumor research.

Glycated hemoglobin and its spinoffs: Cardiovascular disease markers or risk factors?

Atherosclerosis is a major complication of diabetes, increasing the risk of cardiovascular related morbidities and mortalities. The hallmark of diabetes is hyperglycemia which duration is best predicted by elevated glycated haemoglobin A1C(Hb A1C) levels. Diabetic complications are usually attributed to oxidative stress associated with glycation of major structural and functional proteins. This non-enzymatic glycation of long lived proteins such as collagen, albumin, fibrinogen, liver enzymes and globulins result in the formation of early and advanced glycation end products(AGEs) associated with the production of myriads of free radicles and oxidants that have detrimental effects leading to diabetic complications. AGEs have been extensively discussed in the literature as etiological factors in the advancement of atherogenic events. Mechanisms described include the effects of glycation on protein structure and function that lead to defective receptor binding, impairment of immune system and enzyme function and alteration of basement membrane structural integrity. Hemoglobin(Hb) is a major circulating protein susceptible to glycation. Glycated Hb, namely Hb A1 C is used as a useful tool in the diagnosis of diabetes progression. Many studies have shown strong positive associations between elevated Hb A1 C levels and existing cardiovascular disease and major risk factors. Also, several studies presented Hb A1 C as an independent predictor of cardiovascular risk. In spite of extensive reports on positive associations, limited evidence is available considering the role of glycated Hb in the etiology of atherosclerosis. This editorial highlights potential mechanisms by which glycated hemoglobin may contribute, as a causative factor, to the progression of atherosclerosis in diabetics.

Diabetes epidemic in the Asia pacific region:has hemoglobin A1C finally earned its place as a diagnostic tool?

Two-third of the world's population lives in the Asia Pacific region where prevalence of diabetes has reached epidemic proportion.With China and India being the most populous nations on the globe,it is believed that over 150 million diabetes reside in the region with more than 95%being of type 2 diabetes mellitus(T2DM).Furthermore,other Pacific islands in the region have high rales of T2DM including Tonga.Fiji.French Polynesia,and Nauru.The latter has the highest prevalence of T2DM per population in the world.Over the past two decades,in Australia and New Zealand,the prevalence of T2DM has more than doubled,mainly amongst the Aboriginal and Torres Strait Islander and Maori peoples respectively.With the increasing prevalence of dialietes in the Asia Pacific region coupled with the limited number of resources,use of a reliable and effective mode of diagnosis for T3DVI is warranted.Yet to date,only New Zealand has adopted the American Diabetes Association recommendation of using hemoglobin A1C in the diagnosis of the disease.The aim of this review is to discuss the clinical usefulness of hemoglobin A1C and highlight its diagnostic role in the Asia Pacific region where T2DM is increasingly encountered.

Metabolic syndrome does not affect sustained virologic response of direct-acting antivirals while hepatitis C clearance improves hemoglobin A1c

AIM To determine whether successful treatment with direc-tacting antivirals(DAA) is associated with improvements in hemoglobin A1 c(HbA1 c) and if type 2 diabetes mellitus(T2 DM) or metabolic syndrome affects sustained virologic response(SVR).METHODS We performed a retrospective analysis of all hepatitis C virus(HCV) patients at the VA Greater Los Angeles Healthcare System treated with varying DAA therapy between 2014-2016. Separate multivariable logistic regression was performed to determine predictors of HbA1 c decrease ≥ 0.5 after DAA treatment and predictors of SVR 12-wk post treatment(SVR12).RESULTS A total of 1068 patients were treated with DAA therapy between 2014-2016. The presence of T2 DM or metabolic syndrome did not adversely affect SVR12. 106 patients had both HCV and T2 DM. Within that cohort,patients who achieved SVR12 had lower mean HbA1 c pre treatment(7.35 vs 8.60,P = 0.02),and lower mean HbA1 c post-treatment compared to non-responders(6.55 vs 8.61,P = 0.01). The mean reduction in HbA1 c after treatment was greater for those who achieved SVR12 than for non-responders(0.79 vs 0.01,P = 0.03). In adjusted models,patients that achieved SVR12 were more likely to have a HbA1 c decrease of ≥ 0.5 than those that did not achieve SVR12(adjusted OR = 7.24,95%CI: 1.22-42.94). CONCLUSION In HCV patients with T2 DM,successful treatment with DAA was associated with a significant reduction in HbA1 c suggesting that DAA may have a role in improving insulin sensitivity. Furthermore,the presence of T2 DM or metabolic syndrome does not adversely affect SVR12 rates in patients treated with DAA.

Editorial on hemoglobin A1c, blood pressure, and lowdensity lipoprotein cholesterol goals in diabetics

The American Diabetes Association (ADA) 2013 guidelines state that a reasonable hemoglobin A1c goal for many nonpregnant adults with diabetes is less than 7.0% a hemoglobin A1c level of less than 6.5% may be considered in adults with short duration of diabetes, long life expectancy, and no significant cardiovascular disease if this can be achieved without significant hypoglycemia or other adverse effects of treatment. A hemoglobin A1c level less than 8.0% may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced macrovascular and microvascular complications, extensive comorbidities, and long-standing diabetes in whom the hemoglobin A1c goal is difficult to attain despite multiple glucoselowering drugs including insulin. The ADA 2013 guidelines recommend that the systolic blood pressure in most diabetics with hypertension should be reduced to less than 140 mmHg. These guidelines also recommend use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in the treatment of hypertension in diabetics unless they are pregnant. Diabetics at high risk for cardiovascular events should have theirserum low-density lipoprotein (LDL) cholesterol lowered to less than 70 mg/dL with statins. Lower-risk diabetics should have their serum LDL cholesterol reduced to less than 100 mg/dL. Combination therapy of a statin with either a fibrate or niacin has not been shown to provide additional cardiovascular benefit above statin therapy alone and is not recommended. Hypertriglyceridemia should be treated with dietary and lifestyle changes. Severe hypertriglyceridemia should be treated with drug therapy to reduce the risk of acute pancreatitis.

The Electrochemical Characteristics of Multilayer Assembly of Hemoglobin and Polystyrene Sulfonate at Self-assembled MonolayerSurface

A multilayer film of hemoglobin (Hb) molecules and polyelectrolyte sulfonate were fabricated on a thiol self-assembled monolayers (SAMs) by electrostatic force. The Hb maintains electroactive property in the multilayer film, methylene blue (MB) incorporated into the multilayer can enhance the electron transfer rate between the Hb and the electrode surface.

Study on the Intermediate in the o-Phenylenediamine Oxidative Reaction Using Hemoglobin as A Mimetic Peroxidase in Aqueous-Organic Two Phase

Hemoglobin was used as a mimetic enzyme for peroxidase to catalyze the oxidative reaction of o-phenylenediamine with H2O2 which functioned as an oxidant. The relationship between physicochemical properties of the intermediate and enzymatic activity of hemoglobin was studied. Since the solubility of the intermediate in the reaction is higher in butanol phase than in water phase, the intermediate itself diffused from the aqueous phase to the butanol phase. The experimental results showed that the rate of product and the stability of intermediate were associated with the temperature and the pH value of the buffer. The formation rate of intermediate and half-life period reveal the maximal in pH7, nevertheless, the whole rate of the catalytic reaction is the greatest in pH5, which the ratio of the initial rate in final product formation compared to that intermediate formation is the greatest.

INTERACTION BETWEEN THE SURFACE GLYCOSYLATED POLYPROPYLENE MEMBRANE AND LECTIN

A glycopolymer bearing glucose residues was tethered onto the surface of polypropylene microporous membrane by UV-induced graft polymerization ofα-allyl glucoside.Concanavalin A (Con A),a glucose recognizing lectin,could be specifically adsorbed to the membrane surface.On the other hand,the membrane surface showed no recognition ability to another lectin peanut agglutinin.Moreover,the recognition complex between the glycosylated membrane surface and Con A could be inhibited by glucose and mannose solution.T...

Direct Electrochemistry and Electrocatalysis of Hemoglobin at PAMAM Dendrimer-MWNTs-Au Nanoparticles Composite Film Modified Glassy Carbon Electrode

The direct electron transfer of hemoglobin at the PAMAM-MWNTs-AuNPs composite film modified glassy carbon electrode was studied. In a phosphate buffer solution（PBS, pH=7.0）, the formal potential（E^0） of Hb was -0.105 V versus SCE, the electron transfer rate constant was 4.66 s-1. E^0＇ of Hb at the modified electrode was linearly varied in a pH range of 5.0-8.0 with a slope of-49.2 mV/pH. The Hb/PAMAM-MWNTs-AuNPs/GCE gave an excellent electrocatalytic response to the reduction of hydrogen peroxide. The catalytic current increased linearly with H2O2 concentration in a range of 1.0× 10^-6 to 2.2× 10^-3 mol/L. The detection limit was 2.0× 10^-7 mol/L at a signal to noise ratio of 3. The Michaelis-Menten constant（Km^app） was 2.95 mmol/L.