RESUMEN
BACKGROUND: To investigate the added value of elevated urinary albumin excretion (UAE) and high high-sensitive C-reactive protein (hs-CRP) in predicting new-onset type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD) and chronic kidney disease (CKD) in addition to the present metabolic syndrome (MetS) defining criteria. METHODS: The PREVEND Study is a prospective population-based cohort study in the Netherlands, including 8592 participants. The MetS was defined according to the 2004 International Diabetes Federation criteria, elevated UAE as albuminuria ≥ 30 mg/24 h and high hs-CRP as ≥ 3 mg/L. RESULTS: At follow-up, subjects without MetS when compared to subjects with MetS had a lower incidence of T2DM, CVD as well as CKD (2.5 versus 15.5; 4.1 versus 10.3 and 5.8 versus 11.2%, all P < 0.001). In subjects with MetS, the incidence of all three outcomes was higher among subjects with elevated albuminuria versus subjects with normoalbuminuria (all P < 0.01). The incidence of all outcomes was also higher among subjects with high hs-CRP versus subjects without elevated hs-CRP but only significant for CKD (P = 0.002). Multivariate analysis including elevated UAE, hs-CRP and the variables defining the MetS showed that elevated albuminuria was independently associated with the risk for new-onset T2DM, CVD and CKD, whereas high hs-CRP was only independently associated with new-onset CVD and CKD. CONCLUSION: Our data show that elevated UAE has added value to the present MetS defining variables in predicting new-onset T2DM, CVD and CKD, whereas hs-CRP adds to predicting new-onset CVD and CKD, but not T2DM.
Asunto(s)
Albuminuria/diagnóstico , Proteína C-Reactiva/metabolismo , Enfermedades Cardiovasculares/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Fallo Renal Crónico/diagnóstico , Síndrome Metabólico/complicaciones , Síndrome Metabólico/metabolismo , Albuminuria/epidemiología , Albuminuria/etiología , Presión Sanguínea , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Creatinina/sangre , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/etiología , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Incidencia , Agencias Internacionales , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/etiología , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Pronóstico , Estudios Prospectivos , Factores de RiesgoRESUMEN
Screening for albuminuria has been advocated because it is associated with cardiovascular morbidity and all-cause mortality. The "gold standard" to assess albuminuria is 24-hour urinary albumin excretion (UAE). Because 24-hour urine collection is cumbersome, guidelines suggest measuring albuminuria in a first morning void, either as urinary albumin concentration (UAC) or adjusted for creatinine concentration, the albumin:creatinine ratio (ACR). To decide which albuminuria measure to use in clinical practice, it is essential to know which best predicts clinical outcome. In a sample representative of the Groningen (the Netherlands) population (n = 3,414), the authors compared UAC, ACR, and UAE as predictors of cardiovascular events and all-cause mortality. During a median follow-up of 7.5 years, which ended December 31, 2005, they observed 278 events (a major adverse cardiovascular event or mortality). The area under the receiver operating characteristic curve predicting events was 0.65 for UAE, 0.62 for UAC (P = 0.06 vs. UAE), and 0.66 for ACR (P = 0.80 vs. UAE; P = 0.01 vs. UAC). When sex-specific subgroups were considered, UAE was superior to UAC in predicting outcome (P = 0.04) for females, whereas, for males as well as females, no difference was found between ACR and UAE. To predict cardiovascular morbidity and all-cause mortality, measuring ACR in a first-morning-void urine sample is a good alternative to measuring 24-hour UAE.
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Albuminuria/orina , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/orina , Adulto , Factores de Edad , Anciano , Creatinina/orina , Femenino , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Factores de RiesgoRESUMEN
BACKGROUND: The Kidney Disease Outcomes Quality Initiative guidelines aim to define chronic kidney disease (CKD) and classify its stages. Stage 3 CKD generally receives more attention than stage 1 or 2, because the more impaired glomerular filtration rate (GFR) in stage 3 suggests a higher cardiovascular and renal risk. In this study we evaluated cardiovascular and renal outcome in subjects with stage 1 and 2 CKD. For comparison, we also studied these outcomes in stage 3 CKD. METHODS: We used data of 8495 subjects of the PREVEND study, a prospective community-based cohort study, with data on urinary albumin excretion (UAE) and serum creatinine available. As measure of cardiovascular outcome, combined cardiovascular morbidity and mortality was used. As renal outcome, mean annual change of estimated GFR (eGFR) was used. RESULTS: 6905 subjects had no CKD; 243, 856 and 491 subjects had stage 1, 2 and 3 CKD, respectively. During a median follow-up of 7.5 years 565 cardiovascular events occurred. Incidence rates of cardiovascular events were higher (P < 0.001 for all groups) in subjects with stage 1-3 CKD (17.2, 22.2 and 20.9 events/1000 person-years, respectively) than in subjects without CKD (7.0 events/1000 person-years). Using subjects without CKD as reference, age- and sex-adjusted hazard ratios [HR (95% CI)] were 2.2 (1.5-3.3), 1.6 (1.3-2.0) and 1.3 (1.0-1.7), respectively. Compared to subjects without CKD but similar baseline eGFR, subjects with stage 1 or 2 CKD showed a larger decline in eGFR (-1.1 versus -1.5 and -0.2 versus -0.6 ml/min/1.73 m(2)/year, respectively, both P < 0.01). When subjects with stage 3 CKD were stratified according to the absence or presence of a UAE >30 mg/24 h, age- and sex-adjusted HRs for CVD were 1.0 (0.7-1.4) and 1.6 (1.1-2.3) and the change in eGFR was 0.2 versus -0.3 ml/min/1.73 m(2)/year, respectively. CONCLUSION: Subjects with stage 1 or 2 CKD have an increased risk for adverse cardiovascular and renal outcome and should receive equal attention as subjects with stage 3 CKD. Subdividing stage 3 CKD according to the presence or absence of a UAE >30 mg/24 h improves risk stratification within this stage.
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Albuminuria/complicaciones , Enfermedades Cardiovasculares/etiología , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/orina , Adulto , Anciano , Enfermedades Cardiovasculares/mortalidad , Estudios de Cohortes , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Insuficiencia Renal Crónica/clasificación , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
Because urinary albumin excretion (UAE) is a marker of cardiovascular (CV) risk, some have proposed screening the general population; however, it is unknown how the predictive power of a single screening value changes over time. In this study, data of 8496 individuals in a community-based, prospective cohort were used to evaluate this question. For each doubling of baseline UAE, the hazard ratio (HR) for a CV event was 1.36 (95% confidence interval [CI] 1.31 to 1.42). Baseline UAE similarly predicted events occurring >5 yr after baseline, suggesting that it remains a good predictor during at least the first 5 yr after measurement. Approximately 4 yr after baseline, UAE was measured again in 6800 individuals. Once again, high UAE (>75th percentile) predicted subsequent CV events, whether defined using the baseline UAE or follow-up UAE (HR 3.39 [95% CI 2.58 to 4.45] and HR 2.50 [95% CI] 1.90 to 3.29, respectively; P = 0.3 for difference). Finally, compared with individuals with consistently low UAE, individuals who progressed from low to high UAE during follow-up had a significantly higher risk for CV events (HR 3.68; 95% CI 2.45 to 5.53). In conclusion, UAE remains a good predictor of CV events during the first 5 yr after measurement, but repeating the measurement several years later also detects progression of UAE, which is also associated with increased CV risk. Future studies are required to determine the optimal interval of repeat testing and its cost-effectiveness.
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Albuminuria/complicaciones , Enfermedades Cardiovasculares/orina , Adulto , Anciano , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Femenino , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Países Bajos/epidemiología , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de TiempoRESUMEN
We sought to identify predictors of the decline in renal function, especially those that are modifiable, in the 5488 participants of the prospective, community-based cohort study PREVEND who completed three visits during a mean follow-up of 6.5 years. The change in renal function was used as the outcome and this was calculated as the linear regression of three estimated GFR measurements obtained during follow-up. Risk factors, known to influence renal outcome in patients with primary renal diseases, were used as potential predictors in multivariate regression analyses. High systolic blood pressure and plasma glucose were found to be independent predictors for an accelerated decline in function for both genders. In males, albuminuria was the strongest independent predictor for renal function decline, whereas in females albuminuria was univariately associated only after adjustment for age. The direction of the association between cholesterol/HDL ratio and decline of renal function differed by gender. Surprisingly, in males, waist circumference was an independent predictor and positively associated with renal function outcome. These studies show that there are gender differences in the standard predictors of the decline in renal function.
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Albuminuria/fisiopatología , Tasa de Filtración Glomerular , Hipertensión/fisiopatología , Riñón/fisiopatología , Caracteres Sexuales , Albuminuria/epidemiología , Glucemia/metabolismo , Índice de Masa Corporal , HDL-Colesterol/sangre , Estudios de Cohortes , Creatinina/sangre , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/fisiopatología , Femenino , Humanos , Hipertensión/epidemiología , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Valor Predictivo de las Pruebas , Estudios Prospectivos , Insuficiencia Renal/epidemiología , Insuficiencia Renal/fisiopatología , Factores de Riesgo , Fenómenos Fisiológicos del Sistema UrinarioRESUMEN
BACKGROUND: Increased levels of albuminuria have been recognized as a feature of obesity and the metabolic syndrome, and to be associated with an increased risk for cardiovascular and renal disease. The impact of weight change on albuminuria and its possible mechanism has not been studied yet in the general population. We investigated this issue in a cohort of the Northern European population. METHODS: A total of 6894 participants of the Prevention of Renal and Vascular Endstage Disease (PREVEND) study were evaluated from baseline to a mean period of follow-up of 4.2 years for weight change (gain/loss), and its impact on albuminuria, renal function and cardiovascular risk factors. Participants were categorized into three groups based on absolute change in weight from baseline to follow-up: significant weight loss (>10 kg reduction in weight), stable weight, or significant weight gain (>10 kg increase). Multivariate regression analysis was used to evaluate the effect of baseline characteristics and time-dependent changes in these characteristics on the relationship of weight change with urine albumin excretion (UAE). RESULTS: At follow-up 101 subjects experienced significant weight loss (mean change = -14.2 kg), 348 had significant weight gain (mean change = +13.4 kg) and the remaining were defined stable in weight (mean change = +1.4 kg). Weight loss was associated with significant improvement in systolic blood pressure (-11 +/- 15 mmHg), diastolic blood pressure (-5 +/- 8 mmHg), and cholesterol (-0.7 +/- 1.3 mmol/l), even after adjustment for the use of medications (P < 0.001). These parameters worsened significantly in those who substantially gained weight (P < 0.001). Similarly, weight loss was significantly associated with a reduction in UAE (mean -2.2 +/- 1.1 mg/24 h), whereas weight gain was associated with a rise in UAE (mean +0.42 +/- 2.0 mg/24 h). Notably, no changes were observed in GFR (assessed as 24 h urinary creatinine clearance) in subjects with weight loss or weight gain. Multivariate regression modelling with changes in UAE as dependent variable-correcting for factors that might explain the association-showed that only part of the relationship between weight changes and changes in UAE was explained by effect of weight change on blood pressure and cholesterol, whereas the association disappeared with changes in CRP in the model (P = 0.50). CONCLUSION: This is the first population-based longitudinal study to show that changes in weight are associated with parallel changes in albuminuria. This relationship cannot be fully explained by the association between weight and classical cardiovascular risk factors and renal function. Based on our data we hypothesize that weight-induced changes in vascular inflammation may cause changes in albuminuria.
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Albuminuria/fisiopatología , Aumento de Peso/fisiología , Pérdida de Peso/fisiología , Adulto , Anciano , Albuminuria/epidemiología , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios ProspectivosRESUMEN
An increase or decrease in urinary albumin excretion (UAE) is associated with, respectively, a higher or lower risk for renal and cardiovascular disease, independent of widely known cardiovascular risk factors. This study aimed to identify factors that are associated with changes in UAE in the nondiabetic population using data of the Prevention of Renal and Vascular End stage Disease (PREVEND) Study, a community-based prospective cohort study. Data of the 6647 nondiabetic participants who completed the first (1997 through 2001) and second (2001 through 2003) screening were used. Change in UAE was categorized as regression (n = 650), stable (n = 5240), or progression (n = 757) on the basis of change in class during follow-up, with classes being a UAE <15, 15 to 30, 30 to 300, and >300 mg/24 h. With the use of stepwise forward multinomial regression analysis changes in BP, fasting glucose concentration, and start of antihypertensive drugs were found to be the most important modifiable variables associated with the risk for progression and regression (P < 0.01 for likelihood ratio test). The odds ratios to develop regression or progression of UAE during follow-up were 0.64 (95% confidence interval [CI] 0.57 to 0.73) and 1.91 (95% CI 1.72 to 2.12), respectively, per 10-mmHg increase in BP during follow-up, 0.89 (95% CI 0.80 to 0.98) and 1.09 (95% CI 1.01 to 1.17), respectively, per 1-mmol/L increase of fasting glucose levels during follow-up, and 1.57 (95% CI 1.21 to 2.06) and 0.70 (95% CI 0.51 to 0.95), respectively, for start of antihypertensive drugs during follow-up. These associations were independent of baseline BP, glucose, body mass index, estimated GFR, and UAE and changes in high-sensitivity C-reactive protein during follow-up. In conclusion, changes in glucose concentration and BP and start of antihypertensive drugs (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in >50% of cases) are associated with progression and regression of UAE in the nondiabetic population. Although associations do not necessarily suggest causality, it is hypothesized that in the general population, the most important ways to reduce UAE are by lowering glucose concentration and BP (including start of antihypertensive medication), even in normotensive, nondiabetic individuals.
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Albuminuria/fisiopatología , Fallo Renal Crónico/epidemiología , Albuminuria/prevención & control , Enfermedades Cardiovasculares/epidemiología , Progresión de la Enfermedad , Humanos , Incidencia , Enfermedades Renales/prevención & control , Valor Predictivo de las Pruebas , PrevalenciaRESUMEN
Macroalbuminuria, erythrocyturia, and impaired renal function are strong predictors of poor renal outcome in patients with known renal disease. However, the yield of mass screening for these variables to identify individuals who are at risk for GFR loss is yet unknown in a Western population. With the use of data from the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study, a prospective, population-based cohort study, the cardiovascular and renal prognosis was investigated in patients with classical renal risk markers: Macroalbuminuria (> or =300 mg albumin/24 h urine), erythrocyturia (> or =250 erythrocytes/L, without leukocyturia), and impaired renal function (both 24-h creatinine clearance and Modification of Diet in Renal Disease clearance below the fifth percentile of age- and gender-matched control subjects). The 8592 patients who were included in this study were followed for a 4-yr period. We identified 134 patients with macroalbuminuria, 128 with erythrocyturia, and 103 with impaired renal function. There was only a little overlap among the three groups. The prevalence of macroalbuminuria, erythrocyturia, and impaired renal function was calculated to be in the general population 0.6, 1.3, and 0.9%, respectively. In all three groups, fewer than 30% of patients were known to have this laboratory abnormality before screening. The incidence of cardiovascular disease was high in the macroalbuminuria group (e.g., the age- and gender-adjusted hazard ratio for mortality as a result of cardiovascular disease is 2.6 [1.1 to 6.0]) and for the impaired renal function group (3.4 [1.5 to 8.0]). After a mean follow-up of 4.2 yr, the macroalbuminuria group showed a -7.2 ml/min per 1.73 m2 estimated GFR (eGFR) loss, compared with -2.3 ml/min per 1.73 m2 in the control group (difference P < 0.001), whereas the rate of eGFR loss in the impaired renal function group (-0.2 ml/min per 1.73 m2; P = 0.18) and the erythrocyturia group (-2.6 ml/min per 1.73 m2) was not different from the control group. Macroalbuminuria and impaired renal function both predict a worse prognosis with respect to cardiovascular morbidity and mortality. However, macroalbuminuria is a better risk marker than low eGFR or erythrocyturia to identify in population screening of individuals who are at risk for accelerated GFR loss.
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Albuminuria/diagnóstico , Biomarcadores , Tasa de Filtración Glomerular , Tamizaje Masivo/métodos , Insuficiencia Renal/diagnóstico , Factores de Riesgo , Adulto , Anciano , Albuminuria/epidemiología , Estudios de Cohortes , Recuento de Eritrocitos , Femenino , Hematuria/diagnóstico , Hematuria/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Estudios Prospectivos , Insuficiencia Renal/epidemiologíaRESUMEN
BACKGROUND: Statins improve cardiovascular outcome, but less is known on the renal outcome. We, therefore, studied the relationship between the use of statins and urinary albumin excretion (UAE) and glomerular filtration rate (GFR) in two settings: a randomized controlled trial (RCT) and an observational cohort study, in which patients were included to study the impact of an elevated UAE on renal and cardiovascular prognosis. METHODS: We used data from the Prevention of REnal and Vascular ENd-stage Disease Intervention trial (PREVEND-IT) and the PREVEND cohort study. The PREVEND-IT subjects (788 with a UAE 15-300 mg/day) received pravastatin 40 mg/day vs placebo and/or fosinopril 20 mg/day vs placebo in a 2x2 factorial-RCT design. Of the 3440 cohort subjects, 469 used statins during the 4-year follow-up period. Multivariate-regression adjusted for confounding factors and the propensity score was used to estimate the relation between statin use and UAE and GFR. RESULTS: In the RCT, pravastatin did not change UAE or GFR, neither in fosinopril yes/no subgroups. In the observational cohort, statin use was associated with a rise in UAE (+12.1%), compared with statin non-use (+3.6%, P<0.001). This rise was most pronounced in those on statins prior to the first screening [+24.8% (95% CI: 11.9-39.2)], those using statins>3 years [+18.5% (7.3-30.8)] and those with >1 or >2 defined daily doses (+15.7 and +17.3%, respectively). These differences remained significant after adjustment for relevant variables and propensity score. The rise in UAE could not be attributed to a higher dose or a specific statin. GFR fell in 4 years in both statin users and non-users (4.6+/-13.5 and 2.4+/-11.2, respectively). The fall in GFR between groups was not different after adjustment (P=0.11). CONCLUSIONS: We conclude from the RCT data that statins do not lower UAE in subjects selected because of an elevated UAE instead of hyperlipidaemia. In the observational cohort study, the use of statins similarly was not associated with a fall in UAE; UAE instead increased. Statin treatment was not associated with a significant change in GFR in these subjects with only modestly impaired GFR.
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Albuminuria/tratamiento farmacológico , Tasa de Filtración Glomerular/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Glomérulos Renales/efectos de los fármacos , Adulto , Anciano , Albuminuria/orina , Enfermedades Cardiovasculares/fisiopatología , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/orina , Estudios de Cohortes , Método Doble Ciego , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Fallo Renal Crónico/fisiopatología , Fallo Renal Crónico/prevención & control , Fallo Renal Crónico/orina , Masculino , Persona de Mediana Edad , Países Bajos , Estudios ProspectivosRESUMEN
The hypothesis that high urinary albumin excretion (UAE; indicating mild renal damage) may precede development of hypertension was tested, and the relation among UAE, GFR, and development of hypertension was investigated. Data of 4635 patients of a prospective cohort study who participated in an extensive screening in 1997 to 1998 and 2001 to 2003 at our outpatient unit and were normotensive at baseline were used. Hypertension was defined according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure criteria, UAE was measured in two consecutive 24-h urine samples, and GFR was calculated with the modified Modification of Diet in Renal Disease formula. Mean follow-up was 4.3 yr. Baseline UAE was significantly associated with the risk for developing hypertension (odds ratio 2.29; 95% confidence interval 1.77 to 2.95 per 10-fold increase of UAE). This association was independent of potential confounders. An interaction between UAE and GFR was found (P = 0.030), indicating that with elevated UAE and lowered GFR, but still within the normal range, the risk for developing hypertension was highest. In conclusion, these findings support the hypothesis that mild renal damage may precede the development of hypertension.
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Albuminuria/fisiopatología , Hipertensión/epidemiología , Hipertensión/orina , Adulto , Albuminuria/complicaciones , Estudios de Casos y Controles , Femenino , Tasa de Filtración Glomerular , Humanos , Hipertensión/fisiopatología , Incidencia , Riñón/fisiopatología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Medición de RiesgoAsunto(s)
Fístula Arteriovenosa/terapia , Embolización Terapéutica , Rechazo de Injerto/patología , Trasplante de Riñón/patología , Arteria Renal/anomalías , Venas Renales/anomalías , Adulto , Angiografía de Substracción Digital , Fístula Arteriovenosa/diagnóstico , Fístula Arteriovenosa/etiología , Biopsia/efectos adversos , Diabetes Mellitus Tipo 1/cirugía , Estudios de Seguimiento , Humanos , Masculino , Trasplante de Páncreas , Arteria Renal/diagnóstico por imagen , Venas Renales/diagnóstico por imagen , Ultrasonografía DopplerRESUMEN
OBJECTIVE: To investigate urinary albumin excretion (UAE) and its relation with C-reactive protein (CRP) and the metabolic syndrome in the prediction of the development of type 2 diabetes. RESEARCH DESIGN AND METHODS: We used data from the Prevention of Renal and Vascular End Stage Disease (PREVEND) study, an ongoing, community-based, prospective cohort study initiated in 1997 in the Netherlands. The initial cohort consisted of 8,592 subjects. After 4 years, 6,894 subjects participated in a follow-up survey. Subjects with diabetes at baseline or missing data on fasting glucose were excluded, leaving 5,654 subjects for analysis. The development of type 2 diabetes, defined as a fasting glucose > or = 7.0 mmol/l and/or the use of antidiabetic medication, was used as the outcome measure. UAE was calculated as the mean UAE from two consecutive 24-h urine collections. Logistic regression models were used, with the development of type 2 diabetes as the dependent variable. RESULTS: Of the 5,654 subjects for whom data were analyzed, 185 (3.3%) developed type 2 diabetes during a mean follow-up period of 4.2 years. UAE, CRP, and the presence of the metabolic syndrome at baseline were significantly associated with the incidence of type 2 diabetes (P < 0.001 for all variables). In a univariate model, the odds ratio (OR) for UAE was 1.59 (95% CI 1.42-1.79). In our full model, adjusted for age, sex, number of criteria of metabolic syndrome, and other known risk factors for the development of type 2 diabetes (including fasting insulin), the association between UAE and type 2 diabetes remained significant (OR 1.53, 95% CI 1.25-1.88, P < 0.001). There was a significant interaction between UAE and CRP (P = 0.002). After CRP was stratified into tertiles, the ORs for the association between baseline UAE and the development of type 2 diabetes were 2.2 (1.47-3.3), 1.33 (0.96-1.84), and 1.04 (0.83-1.31) for the lowest to highest tertiles, respectively. CONCLUSIONS: UAE predicts type 2 diabetes independent of the metabolic syndrome and other known risk markers of development of type 2 diabetes. The predictive value of UAE was modified by the level of CRP.