Urinary Albumin Excretion Rate Is Associated with Increased Ambulatory Blood Pressure in Normoalbuminuric Type 2 Diabetic Patients
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Pathophysiology/Complications ORIGINAL ARTICLE Urinary Albumin Excretion Rate Is Associated With Increased Ambulatory Blood Pressure in Normoalbuminuric Type 2 Diabetic Patients 1 1 CRISTIANE B. LEITAO˜ , MD MARCEL P. MOLON emerging evidence that patients with dia- 1 2 LU´IS H. CANANI, MD ANTONIOˆ F. PINOTTI, MD betes in the high-normal range of UAER 1 1 PATR´ICIA B. POLSON JORGE L. GROSS, MD are already at high risk for progressing to microalbuminuria or even more ad- vanced stages of renal disease (6–9). Arterial hypertension follows the es- tablishment of microalbuminuria in pa- OBJECTIVE — To evaluate the 24-h blood pressure profile in normoalbuminuric type 2 tients with type 1 diabetes (10). In type 2 diabetic patients. diabetes, this relationship is not that clear because hypertension is a common fea- RESEARCH DESIGN AND METHODS — A cross-sectional study was conducted in 90 type 2 diabetic patients with a urinary albumin excretion rate (UAER) Ͻ20 g/min on two ture in these patients, regardless of renal occasions, 6 months apart (immunoturbidimetry). Patients underwent clinical and laboratory status (11). Ambulatory 24-h blood pres- evaluations. Ambulatory blood pressure monitoring and echocardiograms were also performed. sure monitoring has a better correlation with target organ damage than doctor’s RESULTS — UAER was found to correlate positively with systolic doctor’s office blood pres- office blood pressure measurements (12) sure measurements (r ϭ 0.243, P ϭ 0.021) and ambulatory blood pressure (24 h: r ϭ 0.280, P ϭ and allows the evaluation of blood pres- 0.008) and left ventricular posterior wall thickness (r ϭ 0.359, P ϭ 0.010). Patients were divided sure parameters, such as circadian blood Ͻ Ն Ն Ն into four groups according to UAER ( 5, 5–10, 10–15, and 15–20 g/min). Systolic pressure rhythm and blood pressure blood pressure parameters for the 1st, 2nd, 3rd, and 4th groups, respectively, were 123.0 Ϯ Ϯ Ϯ Ϯ loads. Nondiabetic healthy subjects in the 10.6, 132.5 15.0, 139.0 23.4, and 130.7 8.0 mmHg for 24-h blood pressure (ANOVA high-normal range of UAER (15–20 P ϭ 0.004) and 48.4 Ϯ 6.0, 54.5 Ϯ 11.2, 58.8 Ϯ 15.6, and 57.6 Ϯ 8.0 mmHg for 24-h pulse pressure (ANOVA P ϭ 0.003). A progressive increase in the prevalence of diabetic retinopathy mg/24 h) have higher blood pressure lev- was observed from the 1st to the 4th UAER group: 27.3, 43.8, 45.5, and 66.7% (P ϭ 0.029 for els than nondiabetic individuals in the trend). lower ranges of UAER (13). The same seems to be true for patients with type 1 CONCLUSIONS — In type 2 diabetic patients, UAER in the normoalbuminuric range is diabetes and UAER above the median (4.2 positively associated with systolic ambulatory blood pressure indexes, left ventricular posterior g/min) (14), suggesting that high- wall thickness, and diabetic retinopathy, suggesting that intensive blood pressure treatment may normal albuminuria is associated with an prevent diabetes complications in these patients. increase in blood pressure values. Never- theless, no information is available con- Diabetes Care 28:1724–1729, 2005 cerning the relationship between UAER and 24-h ambulatory blood pressure in type 2 diabetes. Therefore, we hypothe- icroalbuminuria is a known risk fine microalbuminuria (urinary albumin sized that patients with type 2 diabetes in factor for the development of clin- excretion rate [UAER] Ͼ20 g/min or the high-normal range of UAER would M ical nephropathy in type 1 and Ͼ30 mg/24 h) (5) was defined by consen- have higher blood pressure levels than pa- type 2 diabetes (1–4), and it is also an sus, based on studies performed in pa- tients in the lower ranges. The aim of this independent risk factor for cardiovascular tients with type 1 and type 2 diabetes in study was to evaluate the blood pressure disease (4). The cutoff value used to de- the 1980s (1–4). However, there is patterns and the clinical and laboratory ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● profile of normoalbuminuric patients From the 1Endocrine Division, Hospital de Clı´nicas de Porto Alegre, Universidade Federal do Rio Grande do with type 2 diabetes according to their Sul, Porto Alegre, Brazil; and the 2Cardiology Division, Hospital de Clı´nicas de Porto Alegre, Universidade UAER levels. Federal do Rio Grande do Sul, Porto Alegre, Brazil. Address correspondence and reprint requests to Jorge L. Gross, Servic¸o de Endocrinologia do Hospital de Clı´nicas de Porto Alegre, Rua Ramiro Barcelos 2350, Pre´dio 12, 4° andar, 90035-003, Porto Alegre, RS, Brazil. E-mail: [email protected]. RESEARCH DESIGN AND Received for publication 10 December 2004 and accepted in revised form 4 April 2005. METHODS — A cross-sectional study Abbreviations: UAER, urinary albumin excretion rate. was performed in normoalbuminuric A table elsewhere in this issue shows conventional and Syste`me International (SI) units and conversion type 2 diabetic patients regularly attend- factors for many substances. ing the diabetes outpatient clinic at Hos- © 2005 by the American Diabetes Association. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby pital de Clı´nicas de Porto Alegre. Type 2 marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. diabetes was defined based on World 1724 DIABETES CARE, VOLUME 28, NUMBER 7, JULY 2005 Leita˜o and Associates Health Organization criteria (i.e., Ͼ30 years of age at onset of diabetes, no previ- ous episode of ketoacidosis or docu- mented ketonuria, and treatment with insulin only after 5 years of diagnosis) (15). Patients with other renal diseases, cardiac arrhythmia, or postural hypoten- sion were excluded. Normoalbuminuric patients were selected based on UAER values Ͻ20 g/min on at least two occa- sions over the preceding 6 months while on their usual antihypertensive drugs. Pa- tients using ACE inhibitors had these medications suspended for 1 week, after which a 3rd UAER measurement was per- formed. Of the 92 patients recruited, 2 had UAER Ͼ20 g/min and were not in- cluded in the study. Therefore, UAER was consistently within the normoalbumin- uric range for all of the patients included. The study protocol was approved by the hospital’s research ethics committee, and Figure 1—Correlation between UAER (logarithmic scale) and 24-h systolic blood pressure. informed consent was obtained from all patients. the percentage of 24-h and daytime blood colorimetric method. The glomerular fil- pressure Ն140/90 mmHg and of night- tration rate was determined in 67 patients Clinical, blood pressure, and time blood pressure Ն120/80 mmHg. by the single-injection 51Cr-EDTA tech- echocardiographic evaluation Pulse pressure was the difference between nique (18). Demographic and anthropometric data the systolic and diastolic blood pressure were collected by means of an interview means. Patients with a night/day blood Statistical analysis and clinical examination, as previously pressure ratio Ͼ0.9 were considered to be One-way ANOVA or the 2 test were used described (16). Indirect ophthalmoscopy nondippers. to compare clinical and laboratory data. was performed through dilated pupils by Echocardiograms (n ϭ 60) were ob- The Bonferroni test was used to determine an ophthalmologist. For the purpose of tained according to the recommendations differences between groups. Quantitative this study, patients were classified only of the American Society of Echocardiog- variables without normal distribution according to the presence or absence of raphy (17), using standard parasternal were submitted to logarithmic transfor- any degree of diabetic retinopathy. and apical views with subjects in the par- mation. Data are expressed as the blood pressure evaluations were per- tial left decubitus position and using a means Ϯ SD, except for triglycerides, se- formed 1 week after withdrawal from all commercially available instrument (So- rum creatinine, and blood pressure loads, antihypertensive medications. Office nus 1000; Hewellet Packard). Left ven- which are expressed as the median blood pressure was measured with a mer- tricular mass was calculated based on wall (range). Correlations were performed cury sphygmomanometer, using the left thickness (end-diastolic ventricular inter- with the Pearson’s 2 (log-UAER versus arm and with the patient in a sitting posi- nal diameter, end-diastolic interventricu- blood pressure means and left ventricular tion, after a 5-min rest. The mean of two lar septum, and posterior wall) and was posterior wall thickness) or Spearman’s measurements was considered. The pa- adjusted to body surface area. The cardi- rank correlation (log-UAER versus blood tient was classified as hypertensive based ologist who performed the echocardio- pressure loads) tests, depending on the on use of antihypertensive drugs and/or grams was unaware of the subjects’ distribution of variables. Multiple linear office blood pressure Ն140/90 mmHg. clinical and laboratory characteristics. regression was performed with log-UAER Ambulatory 24-h blood pressure moni- as the dependent variable. P values Ͻ0.05 toring was performed by oscillometry Laboratory methods (two tailed) in the univariate analysis were (Spacelabs 90207), with a 15-min inter- UAER was measured in sterile 24-h timed considered to be significant. val during the daytime and a 20-min in- urine samples by immunoturbidimetry terval during the nighttime. Patients were (Microlab; Ames, Tarrytown, NY). HbA1c RESULTS — There was a positive and advised to maintain their usual daily ac- (AlC) was measured by a high-perfor- significant correlation found between tivities. Sleep time was recorded as the mance liquid chromatography system log-UAER and systolic office (r ϭ 0.243, period between the time when the patient (normal range 2.7–4.3%, Merck-Hitachi P ϭ 0.021), systolic 24-h (r ϭ 0.280, P ϭ went to bed and the time when the patient 9100).