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OBJECTIVE: To analyze the role of autonomic function and other possible factors associated with a blunted fall in nocturnal blood pressure. RESEARCH DESIGN AND METHODS: A total of 39 normotensive normnoalbuminuric type 1 diabetic patients were studied. Glomerular filtration rate (51Cr-EDTA technique), extracellular volume (51Cr-EDTA distribution volume), and urinary albumin excretion rate (UAER) (by radioimmunoassay) were measured. The subjects' 24-h ambulatory blood pressure and a 24-h electrocardiogram were recorded simultaneously Heart rate variability was calculated in the time domain for 24 h, in the frequency domain at night, at rest in the supine position, and during tilt. Patients were classified according to diastolic blood pressure (dBP) night/day ratio as dipper patients (< or =0.9) and nondipper patients (>0.9). RESULTS: Nondipper patients presented a higher low-frequency (LF) component (a sympathetic index) and higher LF/high-frequency (HF) ratio during sleep than dipper patients (0.29 +/- 0.12 vs. 0.19 +/- 0.10 normalized units [n.u.], P = 0.008; and 0.98 +/- 0.53 vs. 0.55 +/- 0.45 n.u., P = 0.007, respectively). At rest, the LF component in nondipper patients (0.38 +/- 0.13 n.u.) was higher than in dipper patients (0.27 +/- 0.12 n.u., P = 0.04). After the tilt, nondipper patients did not show an increase in the LF component (P = 0.32), but in dipper patients, the increase was significant (P = 0.001). In both groups, tilting promoted a decrease in the HF component (a parasympathetic index). In a stepwise multiple linear regression analysis, the LF component during sleep and the UAER accounted for 24% of the variability in the dBP night/day ratio. CONCLUSIONS: The predominance of sympathetic activity and increased levels of UAER, although within the normal range, are associated with a blunted fall in nocturnal dBP in normoalbuminuric normotensive type 1 diabetic patients.

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OBJECTIVE: To analyze the changes in glomerular filtration rate (GFR), urinary albumin excretion rate (UAER), and blood pressure (BP) levels in a cohort of normoalbuminuric and normotensive type 1 diabetic patients. RESEARCH DESIGN AND METHODS: This is an 8.4+/-2.1-year prospective study of 33 normotensive normoalbuminuric (24-h UAER <20 microg/min) type 1 diabetic patients. UAER (radioimmunoassay), GFR (51Cr-EDTA single-injection technique), and GHb (ion-exchange chromatography) were measured at baseline and at 1- to 2-year intervals. RESULTS: The GFR decreased (137.6+/-16.5 to 116.4+/-21.3 ml x min(-1) x 1.73 m(-2) P < 0.05) during the follow-up period. GFR reduction (-0.20+/-0.29 ml x min(-1) x month(-1); P < 0.05) was associated with baseline GFR and mean GHb (R2 = 0.30; beta = 0.072; F = 6.54; P = 0.004). UAER was higher at the end of the study (3.7-7.1 microg/min; P = 0.017). Microalbuminuria was observed in two patients, while macroalbuminuria was observed in one. No changes in UAER were observed when these three patients were excluded from the analysis. Mean blood pressure (MBP) increased during the study (85.8+/-9.7 to 99.6+/-11.6 mmHg; P < 0.001). MBP at the end of the study was associated with age and GFR at baseline (R2 = 0.39; beta = 0.074; F = 9.64; P = 0.001). CONCLUSIONS: In this cohort of normoalbuminuric normotensive type 1 diabetic patients, GFR decreased and BP levels increased during the follow-up period. The predictors for the GFR change were baseline GFR level and metabolic control. For end-of-study MBP, the predictor was baseline GFR level.

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OBJECTIVE: To analyze the blood pressure patterns in normoalbuminuric IDDM patients with glomerular hyperfiltration. RESEARCH DESIGN AND METHODS: A controlled cross-sectional study of 38 normotensive normoalbuminuric (urinary albumin excretion rate < 20 micrograms/min) IDDM patients (18 hyperfiltering [glomerular filtration rate > 134 ml.min-1 1.73 m-2] and 20 normofiltering) and 20 normal individuals matched for age, sex, and BMI was performed. The 24-h ambulatory blood pressure was monitored using an auscultatory technique (Pressurometer IV, Del Mar Avionics), the glomerular filtration rate was measured by 51Cr-labeled EDTA method, extracellular volume by the distribution volume of 51Cr-labeled EDTA, and the 24-h urinary albumin excretion rate by radioimmunoassay. RESULTS: Mean nocturnal diastolic blood pressure was higher in hyperfiltering IDDM patients (70.4 +/- mmHg), when compared with the control group (65.1 +/- 5.3 mmHg, P = 0.04). Diastolic blood pressure night:day ratio was higher in hyperfiltering IDDM patients (92.0 +/- 8.6%), when compared with normofiltering IDDM patients (85.9 +/- 4.8%) and control subjects (87.0 +/- 6.8%, P = 0.02). In IDDM patients, the glomerular filtration rate significantly correlated with the diastolic blood pressure night:day ratio (r = 0.5, P = 0.002), extracellular volume (r = 0.04, P = 0.002), and HbA1 (r = 0.3, P = 0.03). In stepwise multiple regression analysis, factors associated with glomerular filtration rate were diastolic blood pressure night:day ratio, extracellular volume, and HbA1 (adjusted r2 = 0.27, P = 0.003). CONCLUSIONS: Glomerular hyperfiltration is associated with higher nocturnal diastolic blood pressure and with a blunted nocturnal decrease in diastolic blood pressure levels in normotensive and normoalbuminuric IDDM patients.

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The aim of this study was to evaluate gallbladder dynamics in insulin-dependent diabetic patients with and without autonomic neuropathy. Gallbladder dynamics was studied by a scintigraphic method after a test meal in 26 insulin-dependent diabetic patients and 10 normal individuals. The presence and severity of autonomic neuropathy were defined according to the number of abnormal cardiovascular reflex tests: absent (no abnormal test), mild (1-3 abnormal tests), and severe (4-5 abnormal tests). The time from the moment when the patient started to take the test meal to the beginning of gallbladder emptying was longer (P = 0.01) in diabetic patients with mild (N = 11, 12.1 +/- 7.6 min) and severe neuropathy (N = 8, 11.0 +/- 10.6 min) than diabetic patients without autonomic neuropathy (N = 7, 3.9 +/- 4.4 min) and controls (N = 10, 4.8 +/- 4.2 min). The ejection rate was higher (P = 0.02) in the group with severe autonomic neuropathy (N = 8, 5.1 +/- 3.3%/min) than diabetic patients with mild (N = 11, 2.0 +/- 1.0%/min) or without autonomic neuropathy (N = 7, 1.8 +/- 0.8%/min) and controls (N = 10, 2.6 +/- 1%/min). Thirty-two percent of the diabetic patients with autonomic neuropathy presented increased perspiration, nausea and urgency to defecate after the ingestion of the test meal. A significant positive correlation of ejection rate with the presence of these symptoms (biserial point correlation test = 0.67, P < 0.01) was also observed. These data suggest that insulin-dependent diabetic patients with autonomic neuropathy present abnormalities of gallbladder emptying that could be related to specific gastrointestinal symptoms.

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The aim of this study was to evaluate gallbladder dynamics in insulin-dependent diabetic patients with and without autonomic neuropathy. Gallbladder dynamics was studied by a scintigraphicmethod after a test meal in 26 insulin-dependent diabetic patients and 10 normal individuals. The presence and severity of autonomic neuropathy were defined according to the number of abnormal cardiovascular reflex tests: absent (no abnormal test), mild (1-3 abnormal tests), and severe (4-5 abnormal tests). The time from the moment when the patient started to take the test meal to the begnning of gallbladder emptying was longer (P = 0.01) in diabetic patients with mild (N = 11,12.1 ñ 7.6 min) and severe neuropathy (N = 8,11.0 ñ 10.6 min) than diabetic patients without autonomic neuropathy (N = 7,3.9 ñ 4.4 min) and controls (N = 10,4.8 ñ 4.2 min). The ejection rate was higher (P = 0.02) in the group with severe autonomic neuropathy (N = 8,5.1 ñ 3.3 percent/min) than diabetic patients with mild (N = 11,2.) ñ 1.0 percent/min) or without autonomic neuropathy (N = 7,1.8 ñ 0.8 por cento/min) and controls (N = 10,2.6 ñ 1 percent/min). Thirty-two percent of the diabetic patients with autonomic neurpathy presented increased perspiration, nausea and urgency to defecate after the ingestion of the test meal. A significant positive correlation of ejection rate with the presence of these symptoms (biserial point correlation test = 0.67,P<0.01) was also observed. These data suggest that insulin-dependent diabetic patients with autonomic neuropathy present abnormalities of gallbladder emptying that could be related to specific gastrointestinal sumptoms

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OBJECTIVE: To compare the effect of a normal protein diet (test diet) in which chicken and fish were substituted for red meat with a low-protein diet (LPD) on glomerular filtration rate (GFR) in normoalbuminuric insulin-dependent-diabetes mellitus (IDDM) patients. RESEARCH DESIGN AND METHODS: A crossover randomized clinical trial was performed in 15 normoalbuminuric IDDM patients, 9 normofiltering, and 6 hyperfiltering patients. They followed three diets for a 3-week period each: a usual diet (UD), an LPD (0.5 g.kg-1.day-1 of proteins, 7% calories as protein, 33% as fat, and 60% as carbohydrates), and a normoproteic isocaloric test diet in which white meat (chicken and fish) was substituted for red meat of the UD. At the end of each diet, a clinical evaluation and measurements of GFR (51Cr-ethylenediaminetetraacetate (EDTA) single injection technique), urinary albumin excretion (UAE), and plasma amino acids were performed. Dietary compliance was assessed by a 24-h urinary urea and weekly interviews with the dietitian. RESULTS: In all diabetic patients, GFR after the LPD (114.9 +/- 16.5 ml.min-1 x 1.73 m-2) and after the test diet (122.7 +/- 16.7 ml.min-1 x 1.73 m-2) was significantly lower than after the UD (132.0 +/- 27.7 ml.min-1 x 1.73 m-2) (P = 0.001). Similar results were found in the hyperfiltering group: after UD = 161.1 +/- 15.4 ml.min-1 x 1.73 m-2, after LPD = 129.8 +/- 9.0 ml.min-1 x 1.73 m-2, and after the test diet = 136.5 +/- 3.1 ml.min-1 x 1.73 m-2, (P < 0.001). In the normofiltering group, no significant changes in GFR were observed after the three diets. Metabolic control, nutritional indexes, blood pressure (BP), and UAE did not change after the three diets in all patients. CONCLUSIONS: A normoproteic diet with chicken and fish as the only meat protein source decreases the GFR in the hyperfiltering normoalbuminuric IDDM patients. The GFR reduction after this diet is similar to that observed after an LPD.

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1. The effect of age and sex on glomerular filtration rate (GFR) was measured by the 51Cr-EDTA radioisotopic method in 76 normal individuals (43 women and 33 men). 2. Age has a significant effect on GFR. Subjects aged 41 to 60 years have GFR values [104.5 +/- 16.5 ml min-1 (1.73 m2)-1, N = 43] lower than younger individuals aged 20 to 40 years [116.6 +/- 11.2 ml min-1 (1.73 m2)-1, N = 33]. GFR decreases after 40 years of age by approximately 6.0 ml min-1 (1.73 m2)-1 per decade. 3. GFR values in women [105.9 +/- 16.0 ml min-1 (1.73 m2)-1, N = 43] were lower when compared to men [114.8 +/- 14.3 ml min-1 (1.73 m2)-1, N = 33]. 4. We conclude that the effect of sex and age must be taken into account when establishing reference values for GFR.

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The effect of age and sex on glomerular filtration rate (GFR) was measured by the 51 Cr-EDTA radioisotopic method in 76 normal individuals (43 women and 33 men). Age has a significant effect on GFR. Subjects aged 41 to years have GFR values [104,5 ñ 16.5 ml min-1 (1.73 m2)-1, N=43] lower than younger individuals aged 20 to 40 years [116.6 ñ 11.2 ml min-1 (1.73 m2)-1, N=33]. GFR decreases after 40 years of age by approximately 6.0 ml min-1 (1.73 m2)-1 per decade. GFR values in women [105.9 ñ 16.0 ml min-1 (1.73 m2)-1, N=43] were lower when compared to men [114.8 ñ 14.3 ml min-1 (1.73 m2)-1, N=33]. We conclude that the effect of sex and age must be taken into account when establishing reference values for GFR

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