Depression, heart rate variability, and exercise training in dialysis patients.

BACKGROUND: Functional limitations, altered cardiac autonomic activity, and psychological distress are known disorders in chronic hemodialysis (HD) patients, relating to increased morbidity and mortality. The aim of this study was to examine the influence of an exercise training program on emotional parameters and heart rate variability (HRV) indices, as well as to determine whether emotional stress contributes to autonomic dysfunction in these patients. METHODS: Forty-four HD patients were randomly assigned into group A (24 patients, aged 46.3+/-11.2 years), who participated in a 1-year intradialytic exercise training program and group B (20 patients, aged 45.8+/-10.8 years), who were used as controls. At baseline and a year after, measures of HRV were obtained for the estimation of standard deviation of RR intervals, the mean square successive differences, percentage of RR intervals differing by more than 50 ms from the preceding RR interval (pNN50), and low to high frequency components. Emotional parameters (Beck Depression Inventory - BDI and Hospital Anxiety and Depression Scale - HADS) were also assessed by validated questionnaires. Moreover, all patients performed a spiroergometric study for the estimation of VO2peak. RESULTS: At baseline, all measurements were similar in the two groups and remained almost unchanged after a year in group B. After a year of training, VO2peak increased from 16.79+/-5.24 to 22.33+/-4.90 ml/kg per min (P<0.001) in group A. Trained patients also showed an increase in standard deviation of RR intervals by 58.8% (P<0.001), the mean square successive differences by 68.1% (P<0.001), pNN50 by 23.5% (P<0.001), and a low to high frequency ratio by 17.3% (P<0.001). Finally, at the end of the study, group A showed a decrease in BDI score by 34.5% (P<0.001) and HADS by 23.9% (P<0.001). Canonical correlation revealed significant inverse correlation among depression (in BDI and HADS) and HRV indices before and after exercise training. CONCLUSION: Cardiac autonomic modulation seemed to be sensitive to the experience of persistent depression in HD patients. Significantly, exercise training reduced emotional distress and concomitantly improved HRV.

The effect of rosiglitazone on novel atherosclerotic risk factors in patients with type 2 diabetes mellitus and hypertension. An open-label observational study.

Thiazolidinediones are antidiabetic agents that decrease insulin resistance. Emerging evidence indicates that they present beneficial effects for the vasculature beyond glycemic control. The aim of this open-label observational study was to determine the effect of the thiazolidinedione rosiglitazone on novel cardiovascular risk factors, namely, lipoprotein(a) [Lp(a)], C-reactive protein (CRP), homocysteine, and fibrinogen in patients with type 2 diabetes and hypertension. A total of 40 type 2 diabetic patients already on treatment with 15 mg of glibenclamide daily and with poorly controlled or newly diagnosed hypertension were included in the study. Twenty of them received 4 mg of rosiglitazone daily as added-on therapy, whereas the rest remained on the preexisting antidiabetic treatment for 26 weeks. At baseline and the end of the study, subjects gave blood tests for the determination of Lp(a), CRP, homocysteine, fibrinogen, serum lipids, apolipoprotein (apo) A-I, and apo B. At the end of the study, rosiglitazone treatment was associated with significant reductions in Lp(a) (10.5 [8.9-54.1] to 9.8 [8.0-42.0] mg/dL, P<.05) and CRP levels (0.33 [0.07-2.05] to 0.25 [0.05-1.84] mg/dL, P<.05) vs baseline. Homocysteine levels were not affected but plasma fibrinogen presented a significant increase (303.5+/-75.1 to 387.5+/-70.4 mg/dL, P<.01) with rosiglitazone. Although no significant changes were observed in the rosiglitazone group for triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein (LDL) cholesterol, both apo A-I and apo B presented small significant reductions and the LDL-apo B ratio was significantly increased. None of the above parameters were changed in the control group. In conclusion, rosiglitazone treatment had a beneficial impact on Lp(a), CRP, and LDL particles' lipid content in type 2 diabetic hypertensive patients but not on homocysteine and fibrinogen. The overall effect of rosiglitazone on cardiovascular risk factors seems positive but must be further evaluated.

The effect of rosiglitazone on urine albumin excretion in patients with type 2 diabetes mellitus and hypertension.

BACKGROUND: Thiazolidinediones are antidiabetic agents that improve insulin sensitivity (IS). Accumulating data indicate that these agents provide beneficial effects beyond glycemic control, such as improvement in vascular function. The aim of this study was to determine the effect of rosiglitazone on urine albumin excretion (UAE) in patients with type 2 diabetes mellitus (DM) and hypertension. METHODS: The study involved 20 subjects with type 2 DM who were already on 15 mg glibenclamide daily but were achieving poor glycemic control and who had either poorly controlled or newly diagnosed hypertension. In these patients, rosiglitazone (4 mg daily) was added to the existing therapeutic regimen for 26 weeks. At baseline and the end of the treatment, subjects gave a 24-h urine collection for direct measurement of albumin and a spot specimen for determination of the albumin-to-creatinine ratio (ACR). Subjects also had a hyperinsulinemic euglycemic clamp and an ambulatory blood pressure (BP) monitoring. RESULTS: At the end of the study, UAE was significantly reduced versus baseline, as measured either directly in the 24-h collection (22.4 +/- 4.6 v 13.8 +/- 3.0 mg/day, P < .05) or with ACR (20.9 +/- 3.8 v 14.0 +/- 2.8 mg/g, P < .05). The percentage changes in UAE (DeltaALB for the 24-h collection and DeltaACR for ACR) correlated with the respective changes in IS (r = -0.64, P < .01 for DeltaALB and r = -0.48, P < .05 for DeltaACR), systolic BP (r = 0.63, P < .01 and r = 0.58, P < .01 respectively), and diastolic BP (r = 0.56, P < .05 and r = 0.50, P < .05 respectively). CONCLUSIONS: In this study, treatment of type 2 diabetic hypertensive patients with rosiglitazone significantly decreased UAE. Lowering of BP and improvement of IS should play roles in this UAE reduction.

Ambulatory blood pressure reduction after rosiglitazone treatment in patients with type 2 diabetes and hypertension correlates with insulin sensitivity increase.

BACKGROUND: Within the metabolic syndrome, insulin resistance and compensatory hyperinsulinemia are associated with blood pressure (BP) elevation through various potential mechanisms. Thiazolidinediones are antihyperglycemic agents that decrease insulin resistance. OBJECTIVE: To determine the effect of the thiazolidinedione rosiglitazone on BP and insulin resistance in patients with type 2 diabetes and hypertension. METHODS: In 20 subjects (nine men and 11 women) with type 2 diabetes but with a poor glycemic control, and with poorly controlled or newly diagnosed hypertension, rosiglitazone 4 mg daily was added-on therapy for 26 weeks. At baseline and at the end of the treatment period patients underwent ambulatory blood pressure monitoring, a hyperinsulinemic euglycemic clamp, and blood tests for glucose, insulin, HbA1c, lipids, and routine laboratory parameters. RESULTS: Insulin sensitivity estimated with the clamp significantly increased (Mbw/I index changed from 33.9 +/- 2.6 to 41.9 +/- 3.2 micromol/min per kg per nmol/l, P < 0.001) and the HOMA-IR index significantly decreased (6.34 +/- 0.39 versus 4.40 +/- 0.33, P < 0.001) during rosiglitazone treatment. Ambulatory BP presented small but significant reductions for the total 24-h period (135.3 +/- 1.8 versus 129.9 +/- 1.7 mmHg, P < 0.001 for systolic BP and 76.0 +/- 1.6 versus 71.9 +/- 1.6 mmHg, P < 0.001 for diastolic BP), daytime and night-time. The changes in systolic and diastolic BP correlated with the change in insulin sensitivity (r = -0.78, P < 0.01 and r = -0.68, P < 0.01, respectively). There were also significant reductions in fasting plasma glucose (9.39 +/- 0.41 versus 7.55 +/- 0.31 mmol/l, P < 0.001), insulin (94.0 +/- 0.41 versus 79.5 +/- 5.6 pmol/l, P < 0.01) and HbA1c (8.15 +/- 0.24 versus 7.24 +/- 0.19%, P < 0.001). CONCLUSIONS: Treatment of type 2 diabetic hypertensive patients with rosiglitazone significantly increased insulin sensitivity and lowered ambulatory BP. These changes were strongly correlated. Thiazolidinediones may thus possess a BP-lowering effect beyond their antihyperglycemic properties.

Exercise training in patients with end-stage renal disease on hemodialysis: comparison of three rehabilitation programs.

Functional capacity of end-stage renal disease patients is dramatically impaired. Although exercise training programs appear to have beneficial morphological, functional and psychosocial effects in end-stage renal disease patients on hemodialysis (HD), the adherence rate is high. The purpose of this study was to compare the effects of three modes of exercise training on aerobic capacity and to identify the most favourable, efficient and preferable to patients on HD with regard to functional improvements and participation rate in the programs. Fifty-eight volunteer patients were screened for low-risk status and selected from the dialysis population. The 48 patients who completed the study protocol were randomly assigned either to one of the three training groups or to a control group. Sixteen of them (Group A - mean age 46.4+/-13.9 years) completed a 6-month supervised outpatient exercise renal rehabilitation program consisting of three weekly sessions of aerobic and strengthening training on the non-dialysis days; 10 (Group B - mean age 48.3+/-12.1 years) completed a 6-month exercise program during HD; 10 (Group C - mean age 51.4+/-12.5 years) followed an unsupervised moderate exercise program at home, and 12 patients (Group D-mean age 50.2+/-7.9 years) were used as patient controls. The level of anemia, the medications and the HD prescription remained stable during the study. Fifteen sex- and age-matched sedentary individuals (Group E - mean age 46.9+/-6.4 years) comprised a healthy control group for baseline data. All subjects at the beginning and end of the study underwent clinical examination, laboratory tests and a treadmill exercise test to fatigue endpoints with direct measurement of aerobic capacity. Group A had a higher dropout rate (24%) compared to groups B (17%) and C (17%). Peak oxygen consumption (VO2 peak) increased by 43% (p < 0.05), anaerobic threshold (VO2AT) by 37% (p < 0.05) and exercise time by 33% (p < 0.05) after training in Group A; by 24% (p < 0.05), 18% (p < 0.05) and 22% (p < 0.05), respectively, in B; and by 17% (p < 0.05), 8% (p < 0.05) and 14% (p < 0.05), respectively, in C; while both remained almost unchanged in Group D. These results demonstrate that intense exercise training on non-dialysis days is the most effective way of training, whereas exercise during HD is also effective and preferable.