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.

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.

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.

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.

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.

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.

Detection and localization of the hemoglobin and collagen distribution of the uterine cervix

Changes of the blood vessels and collagen are associated with the development of abnormal cervical cells.Recently,optical coberence tomography and Mueller polarization images were 1used to provide information regarding the presence of collagen fibers in the cervical tissue.However,most of these methods need a lot of time for image recording and are expensive.In addition,the general survey on the absorption and distribution characteristics of collagen and blood in the cervical is still lacking.In this study,we developed a colposcopy combining cross-polarized inage and image procssing algorithm with an fficient analytical model to map the distribution of blood and collagen in the uterine.For this system's proof of concept,we captured and processed the case of cervical ectopy and Nabothian cyst.The results show that the distribution of blood and collagen maps matched with anatomical and physiological when compared with Lugol's iodline images.This technology has some advantages,such as low cost,real time,and can replace the 11se of acetic acid or Lugol's iodine in the future.

Fluorescence Determination of Artemisinin Using Hemoglobin as Catalyst and Pyronine B as Substrate

Fluorescence decrease ratio was applied to determine of arte misinin （qinghaosu, QHS） based on the catalytic effect of hemoglobin （Hb） using tetraethyldiaminoxanthenyl chloride （Pryonine B, PB） as monitor in this work, Experimental results show that the catalytic characteristics of Hb for QHS, being expressed as Michaelis-Menten parameters, Km, Vmax and Kcat are 2.8×10^-5 mol·L^-1, 4.2×10^-5 mol·L^-1·s^-1 and 280 s^-1 , respectively. Like hemin, enzymatic bioactivities of Hb is inhibited by both deactivated agents and high temperature whereas enhanced by ethanol. With the catalytic action of Hb, quantitative method of QHS can be established based on the fluorescence decrease of PB and linear relationship between the fluorescence decrease ratio F0/F and the concentration of QHS is in the range of （0.0-1.1）×10^-6 mol·L^-1 with detection limit （3σ） being 7. 2×10^-9 mol·L^-1, The concentration of QHS in the media of plasma or urine was detected using this method.

Analysis of styrene oxide-hemoglobin adducts at different binding sites

An assay was described for measures of adducts of styrene oxide(SO)with molecules of hemoglobin(Hb)which have been modified at residues containing either carboxylic acid or sulfhydryl groups.The method employs two steps.In the first,SO carboxylic acid adducts are hydrolyzed in basic medium to liberate styrene glycol(SG).Then,the remaining residues are reacted with a reductive catalyst(Raney nickel)to liberate the two positional isomers of SO cysteine adducts,i.e.,1 phenylethanol(1 PE)and 2 phenylethanol(2 PE).The liberated products are derivatized with pentafluorobenzoyl chloride and measured by GC NICI MS.The assay was evaluated with SO adducts of Hb which had been produced in the blood of Sprague Dawley rats following(a)in vitro modification(0-300m mol/L SO)or(b)i.p administration of either SO(0-1 mmol/kg)or styrene(0-3 mmol/kg).Levels of each of the three analytes(SG,1 PE,and 2 PE)increased with dose in hemoglobin.The ratios of cysteine adducts to carboxylic acid adducts varied significantly among experiments.Ratios of 2 PE to 1 PE were much more consistent(2 PE/1 PE=6.9(SE=1.5))suggesting that binding of SO to cysteine residues of blood proteins is greatly preferred at theαposition rather than theβposition both in vitro and in vivo.The lowest detectable adduct concentration,using 10 mg of protein,was 8 pmol/g protein for SG,5 pmol/g protein for 1 PE,and 0.6 pmol/g protein for 2 PE.No significant change of adduct level was found during storage of proteins at-80℃for 1 year.

Fluorescence Spectra and Enzymatic Property of Hemoglobin as Mimetic Peroxidase

Intrinsic fluorescence emission maxima of hemoglobin(Hb) was investigated in relation to peroxidase property of Hb. The peroxidase activity of Hb was based on its ca\| talytic activity for oxidation of o \|phenylenediamine by hydrogen peroxide. Hb was treated in the condition (temperature, ethanol and salt) that tetramer\|dimer equilibrium of Hb is shifted to the dimer state and its fluorescence spectrum was measured . When Hb treated in temperature (60\|70 ℃), ethanol concentration (60%\|70%) and NaCl concentration (2.5\|3.0 mol/L), the fluorescence emission maxima of Hb shifted towards red wavelength and its activity decreased quickly. Experimental results revealed that the activity and stability of Hb as mimetic peroxidase was closely relative to the hydrophobic environment of active center of Hb, and when Hb (Fe Ⅱ ) converted into met Hb (Fe Ⅲ ), its activity was 1.6 times as much as that of Hb.

Correlation Analysis between Mean Corpuscular Hemoglobin and Mean Corpuscular Volume for Thalassemia Screening in Large Population

Correlation analysis between the hematological parameters mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) for thalassemia screening in large population was discussed. A total of 4920 peripheral blood samples of reproductive age persons were collected from Guangdong province of China. The hematological parameters MCH and MCV values of samples were first measured, and then the DNA analyses for thalassemia were conducted. All samples were composed by 4463 non-thalassemia and 457 thalassemia, and among 457 thalassemia samples, 311 were α-thalassemia, 133 were β-thalassemia, and 13 were α & β-thalassemia. In accordance with non-thalassemia, thalassemia, α-thalassemia, β-thalassemia, α & β-thalassemia and the entire group itself, a total of six sample groups were divided. The corresponding correlation coefficients between the measured MCH and MCV values for the six sample groups were 0.880, 0.968, 0.966, 0.962, 0.980 and 0.965 respectively. For the thalassemia carriers, highly significant correlation between MCH and MCV were observed. The fitting equations between MCH and MCV values were also obtained. The results indicated that the feasibility for thalassemia screening using MCV or MCH independently as parameter, and provided suitable strategy to select parameters and models for thalassemia screening in large population.

Investigation on Low Hemoglobin and Ascaris Infection among Primary and Secondary School Students in Hohhot

Introduction: Anemia and Ascaris infection are important indicators to reflect the health status of students. In this study, by investigating the current situation of low hemoglobin and positive rate of Ascaris eggs of primary and secondary school students in Hohhot, the health status of local primary and secondary school students is actually reflected. Objectives: To understand the prevalence of Low Hemoglobin and Ascaris infection among primary and secondary school students in Hohhot in 2015 and to give some suggestions on the health status of primary and secondary school students in Hohhot. Study Design: This project uses a cross-sectional study to investigate the distribution of disease and health status of primary and middle school students in Hohhot at a specific time, and to provide a clue to the cause of the hypothesis test. Methods: A stratified cluster random sampling method was used to select 4 districts, 4 counties and 1 flag in Hohhot, a total of 36 primary and secondary schools for sample survey. Cyanine HiCN and smear method is to detect hemoglobin and ascaris eggs positive. Results: In 2015, the positive rate of low hemoglobin in primary and secondary school students was 21.45% in urban and rural areas, 33.17% in urban and rural areas, 43.69% in rural areas, 13.59% in ascaris eggs, 10.69% in urban and rural areas, 7.81% in rural areas. There are geographical differences and gender differences between cities, urban-rural junctions and rural areas (p Conclusion: The prevalence of low hemoglobin in primary and secondary school students in Hohhot is high in rural areas. The detection rate of ascaris egg positive rate in the city is high. Monitoring, publicity and education should continue to be strengthened.

The effect of weight loss on fasting blood sugars and hemoglobin A1c in overweight and obese diabetics and non-diabetics

BACKGROUND: Diet and exercise are recommended first line treatment for overweight, obese, and diabetic patients with the goal of decreasing weight and improving glycemic control. The goal of this study was to determine the effect that a low calorie diet and behavioral modification program, as implemented by a medically supervised weight loss program, would have on the fasting blood sugar and hemoglobin A1c in overweight or obese diabetic and over-weight or obese non-diabetic participants. METHODS: Charts from 2009 to 2010 were reviewed for 310 diabetic and non-diabetic patients enrolled in the Via Christi Weight Management (VCWM) program in Wichita, Kansas. Data were collected before and after patients underwent a program of meal replacements and weekly physical activity lasting 12 weeks. Variables included pre and post treatment fasting blood sugars, hemoglobin A1c, body mass index, percent body weight lost, and diabetes status. RESULTS: Diabetic participants lost an average of 11.7% of their initial body weight (IBW), and non-diabetic patients lost 12.5% of their IBW over the treatment course. Post-treatment average fasting blood glucose (FBG) decreased in both diabetics and non-diabetics by 15.53 mg/dL and 8.46 mg/dL, respectively (p = 0.08). Diabetic patients experienced a significant decrease of 0.83% from pre to post-treatment in hemoglobin A1c. For diabetic and non-diabetic groups, the changes in FBG were correlated with the change in weight. CONCLUSIONS: Diet and exercise, as prescribed by the VCWM program, is effective in reducing hemoglobin A1c in diabetics and reducing fasting blood sugars in both diabetic and non-diabetic patients.