Glycated Albumin Is a Better Glycemic Indicator than Glycated Hemoglobin Values in Hemodialysis Patients with Diabetes: Effect of Anemia and Erythropoietin Injection
Masaaki Inaba*,
Senji Okuno,
Yasuro Kumeda¶,
Shinsuke Yamada*,
Yasuo Imanishi*,
Tsutomu Tabata,
Mikio Okamura¶,
Shigeki Okada||,
Tomoyuki Yamakawa,
Eiji Ishimura*,
Yoshiki Nishizawa* and
and the Osaka CKD Expert Research Group
* Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine; Shirasagi Hospital; Inoue Hospital; ¶ Ohno Memorial Hospital; || Okada Clinic, Osaka, Japan
Address correspondence to: Dr. Masaaki Inaba, Department of Metabolism, Endocrinology and Molecular Medicine, Internal Medicine, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. Phone: +81-6-6645-3806; Fax: +81-6-6645-3808; E-mail: inaba-m{at}med.osaka-cu.ac.jp
Received for publication July 22, 2006.
Accepted for publication December 14, 2006.
The significance of glycated albumin (GA), compared with casualplasma glucose (PG) and glycated hemoglobin (HbA1c), was evaluatedas an indicator of the glycemic control state in hemodialysis(HD) patients with diabetes. The mean PG, GA, and HbA1c levelswere 164.5 ± 55.7 mg/dl, 22.5 ± 7.5%, and 5.85± 1.26%, respectively, in HD patients with diabetes (n= 538), which were increased by 51.5, 31.6, and 17.7%, respectively,compared with HD patients without diabetes (n = 828). HbA1clevels were significantly lower than simultaneous PG and GAvalues in those patients in comparison with the relationshipamong the three parameters in patients who had diabetes withoutrenal dysfunction (n = 365), as reflected by the significantlymore shallow slope of regression line between HbA1c and PG orGA. A significant negative correlation was found between GAand serum albumin (r = –0.131, P = 0.002) in HD patientswith diabetes, whereas HbA1c correlated positively and negativelywith hemoglobin (r = 0.090, P = 0.036) and weekly dose of erythropoietininjection (r = –0.159, P < 0.001), respectively. AlthoughPG and GA did not differ significantly between HD patients withdiabetes and with and without erythropoietin injection, HbA1clevels were significantly higher in patients without erythropoietin.Categorization of glycemic control into arbitrary quartile byHbA1c level led to better glycemic control in a significantlyhigher proportions of HD patients with diabetes than those assessedby GA. Multiple regression analysis demonstrated that the weeklydose of erythropoietin, in addition to PG, emerged as an independentfactor associated with HbA1c in HD patients with diabetes, althoughPG but not albumin was an independent factor associated withGA. In summary, it is suggested that GA provides a significantlybetter measure to estimate glycemic control in HD patients withdiabetes and that the assessment of glycemic control by HbA1cin these patients might lead to underestimation likely as aresult of the increasing proportion of young erythrocyte bythe use of erythropoietin.
Strict glycemic control in patients with diabetes decreasesthe incidence of diabetic complications (1), which can determinethe quality of life and prognosis of such patients. Intensivetreatment with insulin or oral hypoglycemic agents has beenestablished to delay the onset and slow the progression of diabeticmicroangiopathy in the patients with types 1 diabetes and type2 diabetes in the Diabetes Control and Complications Trial (2)and the Kumamoto Study (3), respectively. Furthermore, a reductionof the risk for the development of diabetic microangiopathyin patients with type 2 diabetes by strict glycemic controlwas demonstrated in the UK Prospective Diabetes Study (4). Recentclinical evidence has suggested the favorable effects of strictglycemic control on cardiovascular disease, a main cause ofdeath in patients with diabetes (5,6). It has been reportedthat strict glycemic control, as indicated by lower glycatedhemoglobin (HbA1c) levels, has beneficial effects on the prognosisof patients who have diabetes with chronic kidney disease andundergo regular hemodialysis (HD) (7,8). However, some reportsindicate that HbA1c might not provide a relevant assay for glycemiccontrol in HD patients. Although these have been small-scalestudies, because HbA1c is the product of chemical condensationof hemoglobin and glucose, HbA1c values are influenced significantlyin HD patients by either shortening of the life span of erythrocytes(9,10) or the changing proportion of young to old erythrocytesby erythropoietin use (11). Recently, serum glycated albumin(GA) was hypothesized to be an alternative marker for glycemiccontrol in patients with diabetes, which is not affected bychanges in the survival time of erythrocytes in the case oftype 2 diabetes with hemoglobinopathy (12). Furthermore, thenew, improved method, which is free of interference by endogenousglycated amino acids, is unaffected by changes in albumin concentration(13). Therefore, the present study was designed to assess whetherthe new assay method of GA might provide a better indicatorthan HbA1c for glycemic control in HD patients with diabetes.
Patients
HD patients at Inoue Hospital, Shirasagi Hospital, Ohno MemorialHospital, and Okada Clinic and patients with diabetes and normalrenal function at Osaka City University Hospital were enrolledin this study. All patients provided written informed consentbefore participation in this study, which was approved by institutionalethics committees (Osaka City University Graduate School ofMedicine) and was conducted in accordance with the principlesof the Declaration of Helsinki. This study was composed of 538HD patients with type 2 diabetes, 828 HD patients without diabetes,and 365 patients with type 2 diabetes and normal renal function,which was defined as diabetes and non–chronic renal failure(non-CRF) on the basis of serum creatinine levels of <1.2mg/dl. The diagnosis of diabetes was based on a history of diabetesor on the criteria in the Report of the Expert Committee onthe Diagnosis and Classification of Diabetes Mellitus (14).The inclusion of patients with type 1 diabetes was negated bya history of diabetes, because of the very small number of patientswith type 1 diabetic in Japan (15,16). Patients with diabeteswere restricted to those whose diabetes treatment had not beenaltered during the preceding 6 mo before the determination ofGA and HbA1c. Information on weekly doses of erythropoietin,which had not been changed during the 3 mo before determinationof GA and HbA1c, also was obtained.
Assay of GA and HbA1c
GA was measured by an enzymatic method using the Lucica GA-Lkit (Asahi Kasei Pharma Corp., Tokyo, Japan) (13). GA was hydrolyzedto amino acids by albumin-specific proteinase and then oxidizedby ketoamine oxidase to produce hydrogen peroxide, which wasmeasured quantitatively. The GA value was calculated as thepercentage of GA relative to total albumin, which was measuredwith new bromocresol purple method using the same serum sample(13). GA assay was not influenced by the physiologic concentrationsof ascorbic acid, bilirubin, and up to 1000 mg/dl glucose (17).HbA1c was measured by routine HPLC and latex agglutination immunoassay,which was standardized according to the Japan Diabetes Society(18).
Biochemical Measurements
Blood was drawn immediately without overnight fasting, beforethe morning Monday/Tuesday session of HD, to measure serum parametersin HD patients, as described previously (15,16). In patientswith diabetes and without CRF, blood samples were collectedin the morning.
The mean values of the three monthly measurements of casualplasma glucose (PG) that were obtained during the 2 mo beforedetermination of serum GA and HbA1c were used in the analysis.Serum GA and HbA1c were measured once, concomitant with thedetermination of red blood cells, Hb, hematocrit, total protein,albumin, blood urea nitrogen, and creatinine.
Statistical Analyses
Data are expressed as means ± SD. Correlation coefficientswere calculated by simple regression analysis, and the differencesin means between the two groups were analyzed by t test. A 2test was performed to compare the various distributions. Multiplelogistic regression analysis assessed the independent contributionof PG, HbA1c, and GA to the occurrence of diabetes. Multipleregression analyses were performed to explore the associationof PG, hemoglobin, and erythropoietin dose with HbA1c and GA.Comparison of two regression slopes was performed as describedpreviously (16,19). All analyses were performed using statisticalsoftware for Windows (Stat View 5; SAS Institute, Cary, NC).
Variation of Casual PG Levels during Study Period of 2 Months
PG from HD patients with diabetes (n = 538) at 2 mo before,1 mo before, and the time of GA and HbA1c measurements were162.7 ± 67.4, 162.1 ± 64.8, and 163.1 ±67.9 mg/dl, respectively. The correlation coefficients for PGbetween 2 and 1 mo before, between 2 and 0 mo before, and between1 and 0 mo before were r = 0.620 (P < 0.001), r = 0.571 (P< 0.001), and r = 0.588 (P < 0.001), respectively. Thesedata suggested that glycemic control of our patients with diabeteswas stable during the study period.
Effect of a Single HD Session on GA and HbA1c
Serum GA values were almost identical between before and aftera single HD session in HD patients (r = 0.998, P < 0.001);serum HbA1c also correlated significantly in a positive manner(r = 0.992, P < 0.001) but to a lesser degree. These dataclearly indicated that the substances that accumulated intouremic serum did not affect GA values at all.
Correlation between PG and GA or HbA1c in HD Patients with Diabetes and in Patients with Diabetes and without CRF
As shown in Figure 1, there were significant and positive correlationsbetween PG and serum GA (r = 0.539, P < 0.001; Figure 1A)or HbA1c (r = 0.520, P < 0.001; Figure 1B) in HD patientswith diabetes. Figure 1, C and D, indicates the correlationof PG with GA (r = 0.498, P < 0.001; Figure 1C) and HbA1c(r = 0.630, P < 0.001; Figure 1D) in patients with diabetesand without CRF. As shown, the relationship between PG and GAwas identical between the HD patients with diabetes and patientswith diabetes and without CRF, although HbA1c values in comparisonwith those of PG seemed to be significantly lower in HD patientswith diabetes than in patients with diabetes and without CRF.In fact, the regression slope between HbA1c and PG was significantlylower in HD patients with diabetes than in patients with diabetesand without CRF (P < 0.001), although the slope between GAand PG did not differ significantly between the two groups ofpatients (P > 0.10).
Figure 1. Correlation between the average plasma glucose (PG) values and glycated albumin (GA) or glycated hemoglobin (HbA1c) in hemodialysis (HD) patients with diabetes and in patients with diabetes and without chronic renal failure (CRF). The PG levels correlated significantly and positively with the GA (r = 0.539, P < 0.001; A) and HbA1c (r = 0520, P < 0.001; B) levels in HD patients with diabetes. In patients with diabetes and without CRF, the PG levels correlated significantly and positively with GA (r = 0.498, P < 0.001; C) and HbA1c (r = 0.630, P < 0.001; D) levels. The regression slope between HbA1c and PG was significantly more shallow in HD patients with diabetes (0.012) compared with patients with diabetes and without CRF (0.021; P < 0.001), although that between GA and PG did not differ significantly between the two groups of patients (0.068 versus 0.058; P > 0.10).
Correlation between Serum GA and HbA1c Levels in HD Patients with Diabetes in Patients with Diabetes and without CRF
There was a significant and positive correlation between serumGA and HbA1c levels in both HD patients with diabetes (r = 0.777,P < 0.001; Figure 2A) and patients with diabetes and withoutCRF (r = 0.732, P < 0.001; Figure 2B). The GA/HbA1c ratioin patients with diabetes and without CRF was 2.93, which wasconsistent with the previous report of GA/HbA1c ratio of approximately3.0 (20). The GA value relative to HbA1c was increased significantlyto 3.81 in the HD patients with diabetes, which also was supportedby a significantly more shallow slope of the regression linecompared with the patients with diabetes and without CRF (P< 0.001).
Figure 2. Correlation between the GA and HbA1c levels in HD patients with diabetes and in patients with diabetes and without CRF. The GA values correlated significantly and positively with the HbA1c values in HD patients with diabetes (r = 0.777, P < 0.001; A) and patients with diabetes and without CRF (r = 0.732, P < 0.001; B). The regression slope between GA and HbA1c levels was significantly more shallow in HD patients with diabetes (slope 0.141) compared with patients with diabetes and without CRF (slope 0.197; P < 0.001).
Comparison of the Degrees of Glycemic Control on the Basis of HbA1c and GA Values
The mean PG, GA, and HbA1c levels in the HD patients with diabeteswere 164.5 ± 55.7 mg/dl, 22.5 ± 7.50%, and 5.85± 1.26%, respectively, all of which were significantlyhigher than the corresponding values of 108.6 ± 26.8mg/dl, 17.1 ± 4.35%, and 4.97 ± 0.83% in the HDpatients without diabetes (Figure 3). The mean PG, GA, and HbA1clevels in the patients with diabetes were increased by 51.5,31.6, and 17.7%, respectively, of the corresponding values inpatients without diabetes. The mean weekly doses of erythropoietinwere significantly greater in HD patients with diabetes comparedwith the HD patients without diabetes (5385.7 ± 3182.3versus 4955.7 ± 3270.7 U, P < 0.05), although Hb andalbumin did not differ significantly between the two groupsof patients (HD patients with diabetes versus HD patients withoutdiabetes 9.95 ± 1.30 g/dl versus 9.89 ± 1.25 g/dl[P = 0.387]; 3.55 ± 0.42 g/dl versus 3.54 ± 0.36g/dl [P = 0.836]).
Figure 3. Mean PG, GA, and HbA1c levels in patients with and without diabetes. The means of the average PG, GA, and HbA1c levels all were significantly higher in patients with diabetes that without diabetes by t test (P < 0.001). The mean PG, GA, and HbA1c levels in patients with diabetes were increased by 51.5, 31.6, and 17.7%, respectively, of the corresponding value in patients without diabetes.
Logistic Regression Analysis of PG, GA, and HbA1c with Diabetes in HD Patients
The independent contribution of PG, GA, and HbA1c to the probabilityof diabetes in HD patients was assessed after adjustment forserum albumin and Hb by multiple logistic regression analysis.PG (per 10 mg/dl; odds ratio [OR] 1.486; P < 0.001), GA (per1.0%; OR 1.242; P < 0.001), and HbA1c (per 1.0%; OR 2.479;P < 0.001) were independent risk factors associated withdiabetes in HD patients (Table 1).
Table 1. Logistic regression analysis of PG, GA, and HbA1c and other factors associated with diabetes in HD patientsa
Distribution of the Degrees of Glycemic Control on the Basis of the HbA1c and GA Values
The HD patients with diabetes were divided into four arbitrarycategories according to serum HbA1c values: Excellent (HbA1c6.0%), good (6.0 < HbA1c 7.0%), fair (7.0 < HbA1c 8.0%),and poor (HbA1c >8.0%). There were 307 (57.1%), 128 (23.7%),65 (12.1%), and 38 (7.1%) of 538 patients in each group, respectively(Table 2). On the basis of previous reports and our data (Figure 2)that GA values were approximately three times greater than HbA1cvalues, glycemic control also was assessed according to theGA values: Excellent (GA 18.0%), good (18.0 < GA 21.0%),fair (21.0 < GA 24.0%), and poor (GA >24.0%). There were152 (28.3%), 106 (19.7%), 84 (15.6%), and 196 (36.4%) patientsin each of the respective groups. The proportions of glycemiccontrol that were based on the HbA1c values were significantlydifferent from those that were based on the GA values (P <0.001 by 2 test).
Table 2. Proportion of glycemic control of HD patients with diabetes when assessed by HbA1c and GAa
Correlation between GA and Serum Albumin and between HbA1c and Hemoglobin Levels in HD Patients with Diabetes
The serum albumin and HbA1c in HD patients with diabetes rangedfrom 1.5 to 4.8 g/dl and from 4.9 to 14.8 g/dl, respectively.A significant and negative correlation was found between GAand serum albumin levels (r = –0.131, P = 0.002; Figure 4A),although HbA1c did not correlate with serum albumin levels (r= 0.010, P = 0.853). In contrast, there was a significant andpositive correlation between HbA1c and hemoglobin levels (r= 0.090, P = 0.036; Figure 4B), although GA did not correlatewith serum hemoglobin levels (r = 0.037, P = 0.397).
Figure 4. Correlation between serum albumin and GA and between Hb and HbA1c. In patients with diabetes, the GA values correlated significantly and negatively with serum albumin values (r = –0.131, P = 0.002; A) and HbA1c values correlated positively with hemoglobin (r = 0.090, P = 0.036; B).
Correlation of the Weekly Erythropoietin Dose with HbA1c but Not with GA in HD Patients with Diabetes
As shown in Figure 5, there was a significant and negative correlationbetween HbA1c and the weekly dose of erythropoietin (r = –0.159,P < 0.001) in HD patients with diabetes, although GA didnot correlate well (r = 0.055, P = 0.201). The average PG andGA levels in the HD patients with diabetes and without erythropoietin(n = 73) were 157.3 ± 60.1 mg/dl and 21.8 ± 7.8%,which were not significantly different from the respective valuesof 162.8 ± 57.9 mg/dl and 23.0 ± 7.1% in thosewho received erythropoietin (n = 465). However, the HbA1c valueswere significantly higher in those who were not treated witherythropoietin compared with those who were treated with erythropoietin(6.26 ± 1.46 versus 5.94 ± 1.25%, P < 0.05).
Figure 5. Correlation of weekly doses of recombinant human erythropoietin with GA and HbA1c levels. Although serum GA did not correlate significantly with weekly doses of recombinant human erythropoietin in the HD patients with diabetes (r = 0.065, P = 0.201; A), HbA1c correlated significantly in a negative manner (r = –0.159, P < 0.001; B).
Multiple Regression Analysis of Factors for HbA1c and GA in HD Patients with Diabetes Table 3 represents the results of multiple regression analysisof various clinical variables to evaluate their independentassociation with HbA1c and GA values in HD patients with diabetes.In model 1, which included average PG, serum albumin, serumcreatinine, and hemoglobin, only average PG and hemoglobin wereindependent factors associated with HbA1c. In model 2, whichincluded the weekly dose of erythropoietin in place of hemoglobin,it emerged as a significant and independent factor associatedwith HbA1c, in addition to average PG. In model 3, which simultaneouslyincluded hemoglobin and erythropoietin dose, erythropoietindose but not hemoglobin retained a significant and independentassociation with HbA1c. In fact, the HbA1c values were significantlylower in HD patients who had diabetes and were treated witherythropoietin (5.94 ± 1.25%) than in those without (6.26± 1.46%; P < 0.05), although PG (162.8 ± 57.9versus 157.3 ± 60.1 mg/dl) and GA (23.0 ± 7.1versus 21.8 ± 7.8%) did not differ significantly betweenthose with and without erythropoietin. In the same model asmodel 3 for HbA1c to evaluate the independent factors that wereassociated with GA, the average PG alone exhibited a significantand independent association with GA, although the associationwith serum albumin was NS.
In this study, the measurement of GA was shown to provide amore relevant method to assess glycemic control in HD patientswith diabetes. Although PG was measured without overnight fasting,a previous report showed that nonfasting, rather than fasting,PG was a better marker of glycemic control in type 2 diabetes(21). Because the mean values of monthly-determined PG essentiallywere the same throughout the study period, it was suggestedthat glycemic control had been stable during the 2 mo beforethe determination of GA and HbA1c and that a single determinationjust before the Monday/Tuesday HD session might be representativeof glycemic control in HD patients with diabetes. Although HbA1cand GA reflect glycemic control during the preceding 4 to 6wk and 1 to 2 wk (11), the stable glycemic control during thepreceding 2 mo can negate the different impact of acute changesof glycemic control between HbA1c and GA in this study. Supportiveof this notion is that the correlation coefficient between PGand HbA1c was similar with that between PG and GA. The correlationcoefficients of PG at 2, 1, or 0 mo before with HbA1c were verysimilar to those with GA (data not shown).
Although the seven-point PG profile during a single day is hypothesizedto be ideal as a measure of glycemic control, HD patients showeda higher day-to-day variation of diet intake and physical stressas a result of the HD session three times a week. Although theprevious report used the PG sampling scheme to a 14-point schemeduring a 7-d period in a small number of HD patients (10), thisscheme cannot apply to almost 1400 patients. The degree withwhich serum GA correlated with PG was identical between theHD patients with diabetes and patients with diabetes and withoutCRF (Figure 1, A and C). The significantly lower value of HbA1crelative to PG and GA in HD patients with diabetes comparedwith the patients with diabetes and without CRF (Figure 1, Band D) might suggest that the measurement of HbA1c would resultin the underestimation of glycemic control in HD patients withdiabetes. On the basis of the regression line between GA andPG in HD patients with diabetes (Figure 1, A and B), it wasshown that a "fair" category of GA of 21.0% and HbA1c of 7.0%results in a PG of 130 and 247 mg/dl, respectively. Therefore,the GA value of 21.0% was reasonably categorized into a faircategory, as reflected by the PG value of 130 mg/dl. However,categorization of the HbA1c value of 7.0% into a fair categorydefinitely was an underestimation, as reflected by PG valuesas high as 247 mg/dl.
The mechanism for the significantly lower HbA1c value in thosepatients was explained by anemia and/or erythropoietin injection,as reflected by a significant correlation of HbA1c with hemoglobinand the weekly dose of erythropoietin (Figures 4 and 5). Multipleregression analysis demonstrated that erythropoietin use, ratherthan hemoglobin reduction, was an independent factor that wasassociated significantly with the HbA1c values (Table 3). Infact, the HbA1c values were significantly lower in HD patientswho had diabetes and were treated with erythropoietin comparedwith those without, although PG and GA did not differ significantlybetween two groups of patients. The differences of the meanHbA1c values between the HD patients with diabetes and HD patientswithout diabetes were smaller than those of PG and GA, whichis explained partly by a significantly greater erythropoietindose in the HD patients with diabetes. Importantly, althoughserum albumin correlated negatively with GA (Figure 4), it failedto be a significant factor associated with GA (Table 3). Theonly factor that associated independently with GA value wasthe average PG, which associated to a greater degree with GAcompared with HbA1c. Multiple logistic regression analysis showedthat PG glucose, GA, and HbA1c were independent risk factorsassociated with the prevalence of diabetes after adjustmentfor serum albumin and Hb. A 1% increase of GA value is indicativeof 1.242-fold increase to have diabetes in contrast to a 2.479-foldincrease per 1% increase of HbA1c value. Because a 3% increaseof GA is equal to a 1% increase of HbA1c, it was suggested thatan increase of GA might be more highly indicative of diabetesthan that of HbA1c.
The nonenzymatic glycation of various proteins is increasedin patients with diabetes as a result of sustained higher PG(22). The rate of production also depends on the half-life ofeach protein (23). HbA1c provides an integrated measure of PGduring the previous 2 to 3 mo as a result of the long life spanof erythrocytes (120 d) (24,25), whereas GA has been hypothesizedto be a glycemic indicator during the immediately previous 2wk (23). Although a rapid change in glycemic control may reflecta greater change of GA than HbA1c, this study examined the significanceof GA compared with HbA1c under stationary state of diabeticcontrol, without any change of antidiabetic drugs during thestudy period, and compared GA and HbA1c values in patients withdiabetes and with and without renal dysfunction. Therefore,the better correlation of average PG during the preceding 2mo with GA compared with HbA1c cannot be accounted for by arapid fluctuation of glycemic control in the HD patients withdiabetes. Although the HbA1c values correlated significantlywith PG and GA in both HD patients with diabetes and patientswith diabetes and without CRF, the ratios of HbA1c/PG and HbA1c/GAwere significantly lower in the HD patients with diabetes, asindicated by the significantly more shallow slope between theHbA1c and PG or GA in those patients, although the GA/PG ratioretained the same relationship between two groups of patients.A previous report (11) showed that after erythropoietin treatment,HbA1c levels decreased with the increase of hematocrit in 15HD patients without diabetes, although PG did not change. Conversely,after stopping erythropoietin treatment, HbA1c levels increased.Because erythropoietin accelerates the production of new erythrocytesand the proportion of young erythrocytes in peripheral bloodmust increase after erythropoietin administration. HbA1c isthe product of the chemical condensation of hemoglobin and glucose,and the glycated rate of just-produced young erythrocytes isreported to be lower than that of old cells (26). Therefore,it seems that the decrease of HbA1c levels relative to PG orGA in HD patients who have diabetes and are treated with erythropoietinmight be due to the increasing proportion of young erythrocytesover old erythrocytes in peripheral blood of those patients(11). Anemia that results from shorter life span of erythrocytestheoretically suppresses HbA1c values. Withdrawal of erythropoietinadministration increases HbA1c values, although it suppressesHb levels (11). Therefore, a relationship between HbA1c andHb could be controversial. These data may suggest that HbA1cis not an ideal index for glycemic control in HD patients whohave diabetes and receive erythropoietin. Because approximately90% of dialysis patients undergo erythropoietin treatment, HbA1cmight be an unsuitable marker to reflect glycemic control inHD patients with diabetes because of the false reduction ofHbA1c values as a result of the increasing proportion of youngerythrocytes over old erythrocytes in peripheral blood of thosewho receive erythropoietin; however, this was not due to improvementof glycemic control, leading to the underestimation of integratedhyperglycemia when assessed by HbA1c value. Among 12 countriesin the Dialysis Outcomes and Practice Patterns (DOPPS) study,Japanese HD patients received the lowest weekly dosages of erythropoietin,which was less than one third of the highest dosage in the UnitedStates (27). Therefore, it is possible that the seeming erythropoietin-inducedreduction of HbA1c values might be greater in the other countries.
GA acquires biologic properties that are linked to the pathogenesisof diabetic vascular complications (28,29), suggesting thatGA not only is significant as an indicator of hyperglycemia(30,31) but also contributes directly to vascular injury. Assuch, GA is better than HbA1c in predicting the developmentof vascular complications in HD patients with diabetes. However,a limitation of the GA assay also exists. Albumin turnover shouldchange in patients who are maintained on peritoneal dialysisand in patients who have CRF with massive proteinuria, in whomGA values theoretically should be reduced as a result of shorterexposure to plasma albumin.
It was suggested that GA provides a significantly better measureto estimate glycemic control in HD patients with diabetes andthat the assessment of glycemic control by HbA1c in those patientsmight lead to underestimation.
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Abstract
Introduction
2 test was performed to compare the various distributions. Multiple logistic regression analysis assessed the independent contribution of PG, HbA1c, and GA to the occurrence of diabetes. Multiple regression analyses were performed to explore the association of PG, hemoglobin, and erythropoietin dose with HbA1c and GA. Comparison of two regression slopes was performed as described previously (16,19). All analyses were performed using statistical software for Windows (Stat View 5; SAS Institute, Cary, NC). 
6.0%), good (6.0 < HbA1c 
