Increased PP and blunted diurnal BP variation are hemodynamic abnormalities associated with micro- and macrovascular complications in type 2 diabetes.

Summary Significant changes in both blood pressure, autonomic function and kidney ultrastructure are observed in insulin-dependent diabetic (IDDM) patients with microalbuminuria. Intervention strategies are evaluated at even earlier stages of disease. Identification of patients at risk of developing microalbuminuria must be based on a thorough knowledge of the relations between key pathophysiological parameters in patients with normoalbuminuria. The aim of the present study was to characterize the interactions of urinary albumin excretion (UAE), 24-h ambulatory blood pressure (AMBP), and sympathovagal balance in a large group of normoalbuminuric IDDM patients. In 117 normoalbuminuric (UAE < 20 m g/min) patients we performed 24-h AMBP (Spacelabs 90 207), with assessment of diurnal blood pressure and heart rate (HR) variation, and short-term (three times 5 min) power spectral analysis of RR interval oscillations, as well as cardiovascular reflex tests (HR variation to deep breathing, postural HR and blood pressure response). Patients with UAE above the median (4.2 m g/min) had significantly higher 24-h systolic and diastolic AMBP (125 ± 10.1/76 ± 7.2 mmHg) compared to the low normoalbuminuric group (120 ± 8.4/74 ± 5.1 mmHg), p < 0.01 and 0.02, respectively. Patients with UAE above the median had significantly reduced short-term RR interval variability including both the high frequency component (5.47 ± 1.36 vs 6.10 ± 1.43 ln ms 2 ), and low frequency component (5.48 ± 1.18 ln ms 2 compared to 5.80 ± 1.41 ln ms 2 ), p < 0.02 and p = 0.04 (ANOVA). In addition, patients with highnormal UAE had reduced mean RR level (faster heart rates) 916 ± 108 compared to 963 ± 140 ms, p < 0.04. These differences were not explained by age, duration of diabetes, gender, level of physical activity, or cigarette smoking. HbA 1 c was significantly higher (8.6 ± 1.2 vs 8.2 ± 1.0 %, p = 0.03) in the group with high normal UAE. Comparing normoalbuminuric IDDM patients with UAE above and below the median value, we found significantly higher AMBP in combination with significant differences in sympathovagal balance and significantly poorer glycaemic control in the group with high-normal albumin excretion. Our data demonstrate interactions between albumin excretion, blood pressure, autonomic function, and glycaemic status, already present in the normoalbuminuric range and may describe a syndrome indicative of later complications. [Diabetologia (1997) 40: 718-725] Keywords Ambulatory blood pressure, autonomic control, heart rate variability, spectral analysis, IDDM, microalbuminuria, diabetic nephropathy

Decreased sympathovagal balance or tone and nocturnal hypertension is present in TS, and N-terminal pro-BNP is elevated. HRT did not modulate the sympathovagal tone, but decreased BP. These changes may be linked to the increased cardiovascular risk and possibly the increased risk of aortic dilatation in TS.

Summary The role of blood pressure elevation in the incidence and progression of diabetic retinopathy is not clearly established and results have been conflicting. Blood pressure and urinary albumin excretion (UAE) are closely related. In order to evaluate the independent relationship between retinopathy and blood pressure elevation, precise information on UAE is essential, as confounding by renal disease (incipient or overt), cannot otherwise be excluded.The aim of the present study was to evaluate the association between diabetic retinopathy and 24-h ambulatory blood pressure (AMBP) in a group of well-characterized normoalbuminuric IDDM patients. In 65 normoalbuminuric (UAE < 20 mg/min) IDDM patients we performed 24-h AMBP (Spacelabs 90 207) with readings at 20-min intervals. Fundus photographs were graded independently by two experienced ophthalmologists. UAE was measured by RIA and expressed as geometric mean of three overnight collections made within 1 week. HbA 1 c was determined by HPLC. Tobacco use and level of physical activity were assessed by questionnaire. Fifteen patients had no detectable retinal changes [grade 1], 35 had grade 2 retinopathy; and 15 had more advanced retinopathy [grade 3--6]. Diastolic night blood pressure was significantly higher in patients with diabetic retinopathy compared to patients without retinopathy (68 ± 8 mmHg [grade 3--6] and 65 ± 6 mmHg [grade 2], compared to 61 ± 4 mmHg [grade 1], p = 0.02). Diurnal blood pressure variation was significantly blunted in the patients with retinopathy as indicated by a higher night/day ratio of diastolic blood pressure (84.6 % ± 4 [grade 3--6], and 81.2 % ± 6 [grade 2] compared to 79.1 % ± 4 [grade 1], p = 0.01). Heart rate tended to be higher in patients in group 2 and 3--6 compared to patients without retinopathy with p values of 0.07 and 0.11 for day-time and 24 h values, respectively. Mean HbA 1 c increased significantly with increasing levels of retinopathy (p < 0.01). Patients were similar regarding sex, age, tobacco use, and level of physical activity. Notably, UAE was almost identical in the three groups (5.0 × /÷1.7 [grade 1], 3.9 × /÷1.8 [grade 2], and 5.1 × /÷1.6 mg/min [grade 3--6]). In conclusion, night blood pressure is higher and circadian blood pressure variation blunted in patients with retinopathy compared to patients without retinopathy despite strict normoalbuminuria and similar UAE levels in the groups compared. Our data suggest that the association between blood pressure and diabetic retinopathy is present also when coexisting renal disease is excluded. Disturbed diurnal variation of blood pressure is a pathophysiological feature related to the development of both retinopathy and nephropathy in IDDM patients. [Diabetologia (1998) 41: 105--110] Keywords Diabetic retinopathy, 24-h ambulatory blood pressure, IDDM, urinary albumin excretion. Abbreviations: IDDM, Insulin-dependent diabetes mellitus; UAE, urinary albumin excretion; AMBP, ambulatory blood pressure; N/D ratio, night/day ratio.

difference in heart rate between inspiration and expiration; LF, square root of power of the low frequency oscillation; LF power, power of the low frequency oscillation; Mean RR, mean of all normal RR intervals; Mean RR D-N, difference between awake and sleep time in mean RR; RSA, respiratory sinus arrhythmia; SDANN, standard deviation of the mean RR in all 5 min segments in a 24 h period; SDNN, standard deviation of all normal RR intervals; SDNN index, mean of SD's calculated on 5 min of RR intervals during a 24 h period; SE, standard error; sNN6%, number of successive RR interval differences > 6%, standardized to 24 h; sNN50, number of successive RR interval differences > 50 ms, standardized to 24 h; UAE, urine albumin excretion. AbstractAims/hypothesis. Diabetic nephropathy is associated with a high risk of cardiac mortality including sudden death. This is presumably related to an imbalance between sympathetic and parasympathetic tone resulting in a decreased heart rate variability (HRV). In nondiabetic patients a decreased HRV is known to be a strong predictor of cardiovascular death. Studies in non-diabetic patients have shown that β-blockers improve HRV parameters known to reflect parasympathetic function. The aim of our study was to investigate effects of additional β-blocker treatment on: cardiac autonomic function, blood pressure, and urine albumin excretion in ACE-inhibitor treated Type I (insulin-dependent) diabetes mellitus patients with abnormal albuminuria. Methods. We studied the effects of 6 weeks treatment with metoprolol (100 mg once daily, zero order kinetics formulation) in 20 patients participating in a randomised, placebo controlled, double blind, crossover trial. Patients were simultaneously monitored under ambulatory conditions with 24-h Holter-monitoring, Corresponding author: Dr. E. Ebbehøj, Medical Department M (Diabetes and Endocrinology), Aarhus Kommunehospitalet, DK-8000 Aarhus Denmark, E-mail: e.ebbehoj@dadlnet.dk Abbreviations: AMBP, Ambulatory blood pressure; CCVHF, coefficient of component variance for HF; CCVLF, coefficient of component variance for LF; HF, square root of power of the high frequency oscillation; HF power, power of the high frequency oscillation; HRV, heart rate variability; HRV index, geometric index of total variability in a 24 h period; I-E diff, Diabetologia (2002) 45:965-975 DOI 10.1007 Effects on heart rate variability of metoprolol supplementary to ongoing ACE-inhibitor treatment in Type I diabetic patients with abnormal albuminuria 24-h ambulatory blood pressure recording, and 24-h fractionated urine collections. Heart rate variability was assessed by four different methods; ambulatory HRV analysis was carried out by spectral and time domain analysis, and on days of investigation short-term spectral analysis and bed-side tests were carried out. Results. Metoprolol treatment improved in vagal tone assessed by short-term spectral analysis. The 24-h ambulatory HRV analysis showed improvement in some parameters reflecting vagal function. A minor decrease in...

Clinical Trials No. NCT01538290.

Smoking is an important risk factor for the development and progression of diabetic nephropathy. The mechanisms by which smoking increases albuminuria and promotes nephropathy are unknown. Considering the acute pressor effect of smoking and the close association between blood pressure elevation and development of diabetic nephropathy, blood pressure increase might be implicated in the association between smoking and diabetic nephropathy. However, among nondiabetics, smokers have repeatedly been found to have lower blood pressure than nonsmokers. This is possibly mediated by an autonomic adjustment to sustained sympathetic stimulation by nicotine. Impaired modulation of the sympathovagal activity has been described in diabetes. In diabetic patients, the effect of smoking on blood pressure and autonomic function remains unclarified. We examined 24-h ambulatory blood pressure (oscillometric technique) and autonomic function (short-term power spectral analysis as well as conventional tests) in 24 smokers and 24 nonsmokers matched for sex, age, and diabetes duration. All patients were normoalbuminuric insulin-dependent diabetes mellitus patients. Smoking status was assessed by questionnaire with confirmatory determinations of urinary cotinine. Diabetic smokers had significantly higher 24-h mean arterial blood pressure (94+/-6.7 mm Hg compared to diabetic nonsmokers 90+/-5.8 mm Hg, P = .04) including higher diastolic nighttime blood pressure (68+/-7.3 mm Hg v 64+/-5.2 mm Hg, P = .03). Smokers also had significantly higher 24-h heart rate (80+/-7.2 compared to 72+/-9.2 beats/min, P < .001). In addition, smoking was associated with significantly reduced short-term RR interval variability (supine low frequency component) (5.45+/-1.29 ln ms2 in smokers compared to 6.31+/-1.11 ln ms2 in nonsmokers, P < .02), as well as reduced brake index (33.5+/-14.5 in smokers v 42.1+/-16.0 in nonsmokers, P < .05). Diabetic smokers have significantly higher 24-h blood pressure compared to diabetic nonsmokers. This finding, contrasting the effect of smoking among nondiabetics, is possibly mediated by coexisting abnormal postural responses in autonomic cardiac regulation in diabetic smokers. Blood pressure elevation, persisting throughout 24 h, might be operative in the association between smoking and development of diabetic nephropathy.

During the past decades, several studies in different populations have suggested that nighttime blood pressure (BP) is a stronger predictor of cardiovascular (CV) events than daytime BP. [1][2][3][4][5] Indeed, a recent meta-analysis concluded that nighttime BP is superior to daytime BP in predicting CV events and total mortality in both patients and general populations. 6 Consequently, treatment strategies to target nighttime BP have come into focus.Bedtime administration (BA) of different classes of antihypertensive drugs has been shown to reduce nighttime BP, although results are not unequivocal. 7 Moreover, a recent prospective study concluded that BA of ≥1 antihypertensive drugs resulted in a significantly lower relative risk of total events and major CV events.8 Consequently, the American Diabetes Association now recommends administering ≥1 antihypertensive drugs at bedtime. 9Diabetes mellitus is a condition in which CV risk is markedly increased. 10 The predictive role of nighttime BP has also been established in patients with diabetes mellitus.3 Nocturnal hypertension is more frequent in diabetic compared with that in nondiabetic patients, in part, because of autonomic dysfunction. Only a few studies have investigated the effect of BA of antihypertensive drugs in diabetes mellitus, 11,12 and these studies applied BA irrespective of the level of nighttime BP.Hence, it was our aim to conduct a randomized crossover study on the effect of change of administration time of oncedaily antihypertensive drugs in a population of patients with type 2 diabetes mellitus and nocturnal hypertension, defined as nighttime systolic BP (SBP) ≥120 mm Hg. Our primary end point was changes in ambulatory BP parameters, with specific focus on nighttime BP. MethodsThe study was approved by the Central Denmark Region Committees on Health Research Ethics and the Danish Data Protection Agency. All patients provided informed consent. The study was registered at ClinicalTrials.gov with ID NCT01158625. Study PopulationInclusion criteria included (1) type 2 diabetes mellitus, (2) antihypertensive treatment including ≥1 once-daily renin-angiotensin system Abstract-Several studies in different populations have suggested that nighttime blood pressure (BP) is a stronger predictor of cardiovascular events than daytime BP. Consequently, treatment strategies to target nighttime BP have come into focus. The aim of the present study was to investigate the effect of change of administration time of antihypertensive drugs. We included 41 patients with type 2 diabetes mellitus and nocturnal hypertension (nighttime systolic BP >120 mm Hg) in an open-label, crossover study. Patients were randomized to 8 weeks of either morning or bedtime administration of all of the individual's once-daily antihypertensive drugs, followed by 8 weeks of switched dosing regimen. Bedtime administration of antihypertensive drugs resulted in a significant reduction in nighttime (7.5 mm Hg; P<0.001) and 24-hour (3.1 mm Hg; P=0.014) systolic BP, with a nonsignificant reduct...