Fasting Glucose Levels in Predicting 1-Year All-Cause Mortality in Patients Who Do Not Have Diabetes and Are on Maintenance Hemodialysis

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1 Fasting Glucose Levels in Predicting 1-Year All-Cause Mortality in Patients Who Do Not Have Diabetes and Are on Maintenance Hemodialysis Dan-Tzu Lin-Tan,* Ja-Liang Lin,* Li-Hua Wang,* Li-Mei Wang,* Lan-Mei Huang, Lily Liu,* Jeng-Yi Huang,* and Yen-Lin Huang* *Lin-Kou Medical Center, Taipei Chang Gung Memorial Hospital, Taoyuan Chang Gung Memorial Hospital, and School of Medicine, Chang Gung University, Taiwan, Republic of China ABSTRACT Chronic inflammation and malnutrition relate to increased risks for cardiovascular death. This study compared fasting glucose levels (FGL) and impaired fasting glucose (IFG) with malnutrition and inflammation in nondiabetic maintenance hemodialysis (MHD) patients to investigate the adverse affects and risks for mortality. In total, 693 MHD patients were enrolled in this study and followed up for 1 yr. Geographic, hematologic, biochemical, and dialysis-related data were collected. According to 1997 and 2003 definitions, all patients were classified into three groups: Diabetic, nondiabetic with IFG, and nondiabetic with normal FGL. More diabetic and nondiabetic with IFG group patients were malnourished ( , P ) and had inflammatory changes ( , P ) than those with normal FGL. The IFG group had higher high-sensitivity C-reactive protein and ferritin and lower serum albumin, creatinine levels, and normalized protein catabolic rate than the normal FGL group. Age and parameters of nutrition and inflammation were associated with FGL. Stepwise multiple regression analysis demonstrated that FGL were negatively associated with serum albumin (P ) and positively correlated with Log high-sensitivity C-reactive protein (P ) in nondiabetic MHD patients. In addition, after 1 yr of follow-up, Cox multivariate analysis demonstrated that, after adjustment for other significant related factors, FGL (relative risk 1.049; 95% confidence interval to 1.093; P ) or presence of IFG (relative risk 3.798; 95% confidence interval to ; P ) was a significant risk factor for 1-yr all-cause mortality of these patients. On the basis of these findings, basal FGL or presence of IFG, a preventive and treatable status, plays an important role in inflammation, malnutrition, and short-term mortality of nondiabetic MHD patients. J Am Soc Nephrol 18: , doi: /ASN Fasting glucose levels (FGL) are important for diagnosis of diabetes and impaired fasting glucose (IFG). 1 Diabetes is associated with increased incidence of cardiovascular disease (CVD) in both men and women in most racial and ethnic groups. 1,2 Individuals with IFG have increased risk for future diabetes and may also have increased risk for CVD. 3 5 Because IFG is associated with increased CVD risk, initiating preventive interventions is important for these patients. However, the clinical significance of FGL and IFG in maintenance hemodialysis (MHD) patients remains unclear. According to the US Renal Data System, the annual mortality rate for MHD patients is 25%, with nearly 50% of all reported MHD patient deaths being attributed to cardiovascular complications. 6 Although traditional risk factors for CVD are common in patients with ESRD, these factors alone may not explain the high prevalence of CVD. 7 Clinical Received December 28, Accepted April 24, Published online ahead of print. Publication date available at. Correspondence: Dr. Ja-Liang Lin, Department of Nephrology and Division of Clinical Toxicology, Chang Gung Memorial Hospital, 199, Tung-Hwa North Road, Taipei, Taiwan, ROC. Phone: ; Fax: ; jllin99@hotmail.com Copyright 2007 by the American Society of Nephrology J Am Soc Nephrol 18: , 2007 ISSN : /

2 evidence has indicated that chronic inflammation, a nontraditional risk factor for CVD, is common in MHD patients and may cause protein-energy malnutrition and progressive atherosclerosis Protein-energy malnutrition and inflammation, two relatively common and concurrent conditions in MHD patients, have been identified as the main cause of poor short-term survival in this population. 11 Correcting malnutrition and/or inflammation has the potential to reduce rates of CVD in MHD patients. Consequently, it is important to identify correctable factors that are associated with malnutrition and/or inflammation in MHD patients. Whether FGL and IFG 12 in patients who do not have diabetes and are on MHD correlates with mortality, inflammation, and/or malnutrition in these patients remains unknown. This multicenter 1-yr longitudinal study investigated the relationship among FGL, IFG, malnutrition, and inflammation by clinically examining nondiabetic MHD patients. Moreover, this study analyzed whether FGL or IFG contributed to the mortality risk for these patients. RESULTS Characteristics of the Study Population A total of 693 MHD patients (329 men and 364 women) with mean MHD duration of yr were enrolled for analysis. Table 1 lists the baseline clinical characteristics, including age, gender, body mass index (BMI), and biologic and hematologic data. Mean patient age was yr (range 14 to 92 yr). The numbers of patients with renal diseases were as follows: Diabetes 189 (27.3%), chronic glomerulonephritis 226 (32.6%), and hypertensive-related nephropathy 121 (17.5%). Table 1 also lists patient characteristics for the three subgroups. The group with diabetes (n 189) had lower values of Kt/V and intact parathyroid hormone (ipth), shorter duration of HD, higher prevalence of CVD, and higher BMI and white blood cell (WBC) counts than the other groups. Meanwhile, the normal FGL group (n 423) were younger; had higher levels of serum albumin, creatinine, and normalized protein catabolism rate (npcr); and had lower values of triglycerides, Table 1. Baseline characteristics of the study group patients who were on MHD (n 693) a Characteristics Total Participants (n 693) Diabetes and with NFG (n 423) Diabetes and with IFG (n 81) Patients with Diabetes (n 189) Age (y) b,c BMI (kg/m 2 ) b b Female gender (n % ) 364 (52.5) 216 (51.1) 39 (48.1) 109 (57.7) Smoking (n % ) 110 (15.9) 67 (15.8) 15 (18.5) 28 (14.8) Viral hepatitis (n % ) 170 (22.5) 118 (27.9) 21 (25.9) 31 (16.4) CVD (n % ) 40 (5.8) 14 (3.3) 4 (4.9) 22 (11.6) Hypertension (n % ) 199 (28.7) 117 (27.7) 20 (24.7) 62 (32.8) HD duration (yr) b b Use of fistula (n % ) 565 (81.5) 352 (83.2) 63 (77.8) 150 (79.4) Use of BCM dialyzers (n % ) 423 (61.0) 286 (67.6) 51 (63.0) 86 (45.5) Erythropoietin (U/kg per wk) FGL (mg/dl) b,c b WBC (10 3 / l) b b Hemoglobin (g/dl) b Albumin (g/dl) b,c Creatinine (mg/dl) b,c b Cholesterol (mg/dl) b Triglyceride (mg/dl) b,c Transferrin saturation (%) c Ferritin ( g/l) c C-Ca (mg/dl) Phosphate (mg/dl) b ipth (pg/dl) b b hscrp (mg/l) 2.68 (0.17 to 97.00) 2.42 (0.17 to 61.37) b,c 3.79 (0.47 to 97.00) 3.13 (0.19 to 95.08) Kt/V urea (Daugirdas) b b npcr (g/kg per d) b,c CTR (%) b,c a BCM, biocompatible membrane dialyzers; BMI, body mass index; C-Ca, corrected calcium; CTR, cardiothoracic ratio; CVD, cardiovascular diseases; FGL, fasting glucose levels; hscrp, high-sensitivity C-reactive protein; IFG, impaired fasting glucose; ipth, intact parathyroid hormone; MHD, maintenance hemodialysis; NFG, normal fasting glucose; npcr, normalized protein catabolism rate; WBC, white blood cells. Patients with hypertension who taking antihypertensive drugs regularly except diuretics. Cardiovascular diseases included cerebrovascular disease, coronary arterial disease, and peripheral vascular disease. b Significant compared with the diabetes group. c Significant compared with the IFG group. P 2386 Journal of the American Society of Nephrology J Am Soc Nephrol 18: , 2007

3 Table 2. Percentage of malnutrition and inflammation in study group patients on MHD (n 693) a Parameter Diabetes and with NFG (n 423) Diabetes and with IFG (n 81) Patients with Diabetes (n 189) Malnutrition (n % ) 21 (5.0) 15 (18.5) 28 (14.8) Inflammation (n % ) 175 (41.4) 46 (56.8) 97 (51.3) a Patients who had malnutrition means that their serum albumin levels were 3.6 g/dl. Patients who had inflammation means that their serum hscrp levels were more than the means of hscrp 3 mg/l. 2 P high-sensitivity C-reactive protein (hscrp), and cardiothoracic ratio (CTR) than the other groups. Furthermore, the IFG group (n 81) had higher levels of triglycerides, hscrp, and ferritin and lower levels of serum albumin, creatinine, and npcr than the normal FGL group. The groups did not differ in terms of gender; smoking status; presence of hypertension or viral hepatitis; values of Ca P; and use of fistula, biocompatible membrane dialyzers, statins, and/or aspirin (data not shown). The IFG and diabetes group patients had significantly higher percentages of malnutrition ( , P ) and inflammatory status ( , P ) than the normal FGL group patients (Table 2). Significant Correlations among FGL, Baseline Data, Nutrition, and Inflammation Markers in Patients Who Did Not Have Diabetes and Were on MHD The Spearman correlation analysis demonstrated that FGL was significantly and positively correlated with age and inflammatory markers, such as hscrp and ferritin levels, but negatively correlated with nutritional parameters, such as albumin, creatinine, and hemoglobin levels in nondiabetic MHD patients (Table 3). Significant Relations between Serum Albumin and FGL in Patients Who Did Not Have Diabetes and Were on MHD The variables that were considered as potential covariates of serum albumin 7,9 11 were age, gender, BMI, HD years, smoking status, CVD, viral hepatitis B and C, use of aspirin or statins, use of antihypertension drugs, using fistula for vascular access, biocompatible membrane dialyzers, Ca P, ipth, Kt/ V urea (Daugirdas), and log hscrp. Simple linear regression analysis indicated that age, gender, smoking, BMI, previous CVD, use of a fistula, log hscrp, CTR, and FGL were associated with serum albumin in the study patients (Table 4). After adjustment for these significant variables, stepwise multiple linear regression analysis revealed a significant inverse correlation between serum albumin levels and FGL (Table 4). A 1-mg/dl increase in FGL was associated with a g/dl decrease in serum albumin level (P ). Significant Relationship between Log hscrp and FGL in Patients Who Did Not Have Diabetes and Were on MHD The variables 7,9 11 that were considered as potential covariates of inflammation were age, gender, BMI, HD years, smoking status, CVD, viral hepatitis B and C, aspirin or statins drugs, antihypertension drugs, using a fistula for vascular access, biocompatible membrane dialyzers, Ca P, ipth, and Kt/V urea (Daugirdas). Simple linear regression analysis indicated that age, smoking, BMI, previous CVD, Kt/V urea (Daugirdas), CTR, and FGL were associated with log hscrp in these patients (Table 5). After adjustment for these significant variables, stepwise multiple linear regression analysis identified a significant correlation between log hscrp levels and FGL (P ; Table 5). Cox Multivariate Analysis for 1-Yr Mortality in MHD Patients At the end of the 12-mo observation period, the following data were obtained: 23 (12.2%) patients in the diabetic group, eight (9.9%) patients in the IFG group, and 10 (2.4%) patients in the normal FGL group died during the 1-yr follow-up. None of IFG group with sugar 110 died. A total of 606 patients completed the 1-yr follow-up. During this period, 34 patients were transferred to other outpatient hemodialysis units, 12 patients received kidney transplantation, and 41 patients died. Among Table 3. Associations between FGL, nutrition, and inflammation markers in patients who did not have diabetes and were on MHD (n 504) at the beginning of study (Spearman rank correlation coefficients) a Parameter Age BMI HD yr Albumin Hemoglobin Creatinine hscrp Ferritin FGL a a b a a b Age b a b a a a BMI a b a a HD yr b a Albumin a a Hemoglobin a b a Creatinine a hscrp b a P b P J Am Soc Nephrol 18: , 2007 Fasting Glucose and Mortality in MHD 2387

4 Table 4. Determinants of nutrition (albumin) in patients who did not have diabetes and were on MHD (n 504) Parameter these patients, 35 (72.9%) died of CVD, five (12.2%) died of infection, and one died of hepatoma. Cox multivariate regression analysis revealed that after adjustment for other significant related factors presence of abnormal CTR ( 50%) and FGL were significant risk factors for 1-yr mortality of patients who did not have diabetes and were on MHD (Table 6). Similarly, instead of FGL, presence of IFG is a significant risk factor (relative risk 3.798, 95% confidence interval to ; P ) for 1-yr mortality in these patients after adjustment of related significant factors. The Kaplan-Meier survival analysis for all MHD patients showed that diabetic and nondiabetic IFG group patients had higher mortality than those in the normal FGL group (Log rank test, , P ; Figure 1). At the study end, four (4.9%) of 81 patients with IFG had developed diabetes. DISCUSSION Simple Linear The analytical results showed that, similar to MHD patients with diabetes, MHD patients without diabetes and with IFG had higher levels of inflammatory markers, including hscrp and ferritin, and lower levels of nutritional markers, such as serum albumin, creatinine, and npcr, than MHD patients without diabetes and with normal FGL. A significantly larger percentage of the IFG and diabetic group patients had malnutrition and inflammation than did the normal FGL group patients. In addition, FGL are positively associated with inflammatory markers but negatively correlated with nutritional parameters in the Spearman analysis. After adjustment for significantly related variables, stepwise multiple linear regression analysis revealed that FGL is negatively correlated with serum albumin levels but positively associated with log hscrp in MHD patients without diabetes. A 1-mg/dl increase in FGL was associated with a g/dl decrease in serum albumin level (P ). All of these findings indicate that FGL influences nutritional and inflammatory status in MHD patients without diabetes and that IFG is associated with malnutrition and inflammation in such patients. Similar to the findings of this investigation of MHD patients without diabetes, some previous studies 13,14 reported a strong association between hscrp levels and FGL and that hyperglycemia influences plasma TNF-, IL-6, and IL-18 in individuals without diabetes. Cases of IFG may result from insulin resistance. 15 In a survey of 1008 individuals without diabetes, 16 hscrp, fibrinogen, and WBC counts were found to be associated with insulin resistance. The finding is also supported by the Women s Health Study, 17 which found hscrp to be independently associated with fasting hyperinsulinemia in women without diabetes. Because few studies mention the relationship between hyperglycemia and malnutrition in individuals without diabetes and chronic inflammation is a common cause of malnutrition in MHD patients, 8 10 the negative association between FGL and serum albumin identified here may result from hyperglycemia-induced inflammatory changes or oxidative stresses causing malnutrition in MHD patients without diabetes. At the end of the 12-mo observation period, the 1-yr mortality rates for MHD patients with diabetes (12.2%) and MHD patients without diabetes and with IFG (9.9%) were similar, but the rate for the MHD patients without diabetes and with normal FGL was just 2.2%. The main cause of death was CVD in these patients. Cox hazard multivariate analysis demonstrated that basal FGL or the presence of IFG was a significant independent risk factor for predicting 1-yr all-cause mortality in MHD patients without diabetes after adjustment of other related factors. Because IFG may induce subclinical inflammation and chronic inflammation, which in turn may cause protein-energy malnutrition and progressive atherosclerosis, protein-energy malnutrition and inflammation have been identified as the main cause of poor short-term survival in MHD patients 8 11 ; therefore, it is not surprising that basal FGL or the presence of IFG independently predicts the short-term mortality of MHD patients without diabetes in this investigation. Stepwise Multiple Linear r P Coefficient SE P Age (yr) Gender Smoking BMI (kg/m 2 ) CVD Using fistula FGL (mg/dl) Log hscrp (mg/l) CTR (%) Table 5. Determinants of inflammation (Log hscrp) in patients who did not have diabetes and were on MHD (n 504) Parameter Simple Linear Stepwise Multiple Linear r P Coefficient SE P Age (yr) BMI (kg/m 2 ) Smoking CVD FGL (mg/dl) Kt/V urea (Daugirdas) CTR (%) Journal of the American Society of Nephrology J Am Soc Nephrol 18: , 2007

5 Table 6. Cox regression analysis of the overall risk for all-cause 1-yr mortality, according to baseline prognostic factors, in patients who did not have diabetes and were on MHD a Variable Univariate Hazard Analysis Multivariate Hazard Analysis RR (95% CI) P RR (95% CI) P Age (yr; each increment of 1 yr) (1.039 to 1.114) (0.996 to 1.104) Using BCM (no) (1.152 to 7.395) (0.996 to ) Albumin (g/dl; each increment of 1 g/dl) (0.149 to 0.741) (0.455 to ) FGL (mg/dl) (each increment of 1 mg/dl) (1.014 to 1.077) (1.007 to 1.093) Creatinine (mg/dl; each increment of 1 mg/dl) (0.588 to 0.889) (0.705 to 1.394) Transferrin (%; each increment of 1%) (1.004 to 1.016) (0.910 to 1.006) WBC count (10 3 / l; each increment of / l) (1.033 to 1.636) (0.840 to 1.665) Log hscrp (mg/l; each increment of 1) (1.783 to ) (0.764 to 8.015) CTR 50% (no) (0.060 to 0.576) (0.041 to 0.929) a CI, confidence interval; RR, relative risk. Figure 1. The Kaplan-Meier survival analysis demonstrated that diabetic and nondiabetic IFG group patients had a higher 1-yr mortality rate than that of the nondiabetic normal FGL group (Log rank test, , P ). Although hyperglycemia can cause oxidative stress and inflammatory changes and is an established risk factor for CVD in patients with diabetes, 1,2 the prognostic significance of IFG for macrovascular complications remains unclear. 18,19 Because this study defines IFG as an FGL between 105 and 125 mg/dl and none of the IFG group with sugar 110 died, the findings of this investigation are supported by other studies A clinical study 20 in 1998 surveyed 20-yr mortality in 17,285 working men who did not have diabetes and were aged 44 to 55 yr. Regarding death from CVD and coronary heart disease (CHD), men with abnormal fasting glucose distributions had higher risk for death from CHD, with age-adjusted hazard ratios for CHD of 2.7. During 2001, a total of 11,853 patients with established CHD, comprising 1258 patients without diabetes and with IFG, were followed up over 7.7 yr. IFG was identified as a consistent predictor of increased all-cause mortality with a hazard ratio of Furthermore, among 2763 postmenopausal women who had established CHD and were followed up for 6.8 yr, 218 women with IFG according to the 1997 definition (FGL 110 to 125 mg/dl) had significantly increased risk for any CHD events, whereas the 698 women with IFG according to 2003 definition (FGL 100 to 125 mg/dl) had no such increased risk. 22 These findings are similar to the analytical results of this investigation and suggest that IFG is also a risk factor for macrovascular complications. Because excess mortality risk of the presence of IFG was demonstrated within 1 yr in this study, there seems to be an urgent need for preventive actions such as smoking cessation, obesity reduction, and so forth for MHD patients who do not have diabetes and have IFG and seem to face a significant survival risk compared with patients without diabetes and with CHD. The finding that basal FGL or the presence of IFG can predict short-term mortality in MHD patients without diabetes is important because hyperglycemia is treatable. Good glycemic control has been demonstrated to reduce the risk for microvascular complications, but equivalent evidence is lacking for CVD risk reduction. 23 However, the Study to Prevent Non-Insulin Dependent Diabetes Mellitus (STOP-NIDDM) found that acarbose can reduce the risk for any cardiovascular event by 49% compared with the placebo. 23 Whether good glycemic control is beneficial for MHD patients without diabetes and with IFG requires further assessment. At the end of 1-yr of follow-up, Four (4.9%) of 81 patients with IFG had developed diabetes. The results are similar to a previous study 24 that analyzed six prospective studies and demonstrated the incidence rates of type 2 diabetes among patients with impaired glucose tolerance ranging from 3.6 to 8.7 per 100 person-years. Further studies are needed to clarify the risk factors that influence the progression from IFG to overt diabetes in MHD patients without diabetes and with IFG. This study has some limitations. Two-hour postchallenge glucose levels were not checked; therefore, we could not compare the strength of the association of IFG with impaired glucose tolerance for mortality. In addition, the baseline prevalence of diabetes was probably underestimated, and some patients with diabetes were misclassified as having IFG. Although this may have biased the study results and increased J Am Soc Nephrol 18: , 2007 Fasting Glucose and Mortality in MHD 2389

6 mortality risk in the IFG group, strict selection criteria were used and three FGL checks were performed at 1-mo intervals to determine whether the study patients had IFG or diabetes, thereby minimizing the bias that resulted from this problem. This study showed that FGL influences nutritional and inflammatory status in MHD patients without diabetes and that IFG is associated with malnutrition and inflammation in these patients. Furthermore, basal FGL or the presence of IFG independently predicts 1-yr mortality of MHD patients without diabetes. The analytical results of this investigation are important for MHD patients without diabetes because IFG is a preventive and treatable condition and correcting hyperglycemia has the potential to reduce short-term mortality in these patients. Further study is required to confirm this observation and hypothesis. CONCISE METHODS Patients All study patients came from three HD centers: Chang Gung Memorial Hospitals (CGMH) in Taipei, Lin-Kou, and Toayuan. All MHD patients were enrolled, after exclusion of those with malignancies and obvious infectious diseases, as well as those who were hospitalized or underwent surgery or renal transplantation during the 3 mo before the study. Patients who were currently using FG-elevating drugs, such as postmenopausal replacement hormones, steroids, thyroid hormone; who could not tolerate fasting time; or who had been receiving regular HD for 6 mo were also excluded. This longitudinal observational study enrolled a total of 693 patients. Most HD patients had been undergoing 4 h of HD three times per week. HD for these patients used single-use hollow-fiber dialyzers equipped with modified cellulose-based polyamide or polysulfone membranes. The dialysate used was a standard ionic composition, and a bicarbonate-based buffer was used in all cases. Presence of diabetes and CVD, including cerebrovascular disease, coronary arterial disease, congestive heart failure, and peripheral vascular disease, were recorded. Smoking behavior and use of drugs that effect inflammatory properties, such as statins and aspirin, were also recorded. This clinical study followed the Declaration of Helsinki and was approved by the Medical Ethics Committee of CGMH, Taipei. Study Groups Patients who met the inclusion criteria were classified into three groups according to their FGL, which were checked at least three times at 1-mo intervals. All values had to be within the classification of the IFG and normal FGL ranges, based on the 1997 and 2003 definitions. 12 The three patient classification groups were as follows: The nondiabetic with normal FGL group (fasting glucose 105 mg/dl; n 423), the nondiabetic with IFG group (fasting glucose 126 and 105 mg/dl; n 81), and the diabetic group (twice subsequent fasting glucose 126 mg/dl or diabetes was diagnosed by a physician in the history; n 189). All patients were followed up for 1 yr, and mortality during this period was the primary end point. Laboratory, Nutritional, and Inflammatory Parameters Laboratory data for each patient were obtained within a few days of the clinical examination during stable outpatient HD sessions to minimize any effects of acute events. Blood samples were drawn from the arterial end of the vascular access immediately before initiation of a 2-d interval HD, centrifuged, and stored at 70 C until they were used in assays. Serum albumin, creatinine levels, transferrin saturation, npcr, triglycerides, and total cholesterol were assayed and recorded as nutritional markers. Moreover, WBC and hemoglobin were measured as the hematologic indicators. This study used both serum ferritin and hscrp as inflammation markers. Serum hscrp concentrations were measured using immunonephelometry (Nanopia CRP; Daiichi, Tokyo. Japan). The lowest detection limit was 0.15 mg/l. All other markers were measured using standard laboratory approaches with an automatic analyzer. npcr in HD patients was calculated via validated equations and normalized to actual body weight. 25 Dialysis clearance of urea was expressed as Kt/V urea, using the method described by Daugirdas 26 in HD patients. Serum calcium, phosphate, and ipth were also detected. Corrected calcium serum calcium (mg/dl) [0.8(4.0 serum albumin [g/dl])]. Definition of Malnutrition and Inflammation To determine whether FGL reflects the inflammation and/or malnutrition status of MHD patients, this work investigated serum albumin and hscrp levels in different population subgroups on the basis of the absence or presence of malnutrition and inflammation. The presence of inflammation in MHD patients was defined as an hscrp level 3 mg/dl, a level that is correlated with raised cardiovascular risk in the general population. 27 This work defined albumin levels 3.6 g/dl ( 36 g/l) as a state of malnutrition, levels that represent the 10th percentile of the Third National Health and Nutrition Examination Survey. 28,29 Statistical Analyses Unless otherwise stated, continuous variables are expressed as means SEM, and categorical variables are expressed as numbers or percentages for each item. Comparisons among the three study groups of patients were analyzed via one-way ANOVA using Bonferroni test for post hoc analysis. The Kruskal-Wallis test and Mann- Whitney U test were used to detect significant differences among nonnormally distributed variables, and logarithmic conversion was conducted for hscrp levels. The 2 test was used for categorical variables, including gender, smoking status, CVD, and the presence of malnutrition and inflammation. Moreover, Spearman correlation analysis was conducted to assess the relations between variables. To identify factors that were associated with inflammation and nutrition, this investigation used multiple linear regression models with backward stepwise procedures for biochemical and demographic variables, 7,9 11 such as age, gender, BMI, HD years, smoking status, CVD, viral hepatitis B and C, use of aspirin or statins, use of antihypertension drugs, using fistula for vascular access, biocompatible membrane dialyzers, Ca P, ipth, and Kt/V urea (Daugirdas). The Cox proportional hazards model was applied to determine the significance of variables for predicting 1-yr mortality (the primary end point). This model included all of the variables that were identified in the litera Journal of the American Society of Nephrology J Am Soc Nephrol 18: , 2007

7 ture 7,9 11 as related to HD mortality. The level of significance was set at P All statistical calculations were performed using StatView 2.0 for Windows (SAS Institute, Cary, NC). ACKNOWLEDGMENTS We appreciate the help provided by the HD staff of Taipei, Lin-Kou, and Toayuan CGMH. DISCLOSURES None. REFERENCES 1. Lim SC, Tai ES, Tan BY, Chew SK, Tan CE: Cardiovascular risk profile in individuals with borderline glycemia: The effect of the 1997 American Diabetes Association diagnostic criteria and the 1998 World Health Organization Provisional Report. Diabetes Care 23: , Davidson MB, Landsman PB, Alexander CM: Lowering the criterion for impaired fasting glucose will not provide clinical benefit. Diabetes Care 26: , Glucose tolerance and mortality: Comparison of WHO and American Diabetes Association diagnostic criteria. The DECODE study group. European Diabetes Epidemiology Group. Diabetes Epidemiology: Collaborative analysis of diagnostic criteria in Europe. 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