Circadian Blood Pressure Levels in Normotensive Normoalbuminuric Type 1 Diabetic Patients

Increase in blood pressure and its circadian alterations in Type 1 diabetes are usually associated with diabetic nephropathy. To evaluate if diabetes itself could be responsible for the observed increase in blood pressure levels, we studied a group of 17 normotensive, normoalbuminuric Type 1 diabetic patients with a disease duration more than 15 years, with no clinical evidence of autonomic neuropathy or ischaemic heart disease, and without any known determinant of hypertension, and a control group of 17 normal subjects, normotensive, each matched for sex, age, BMI, albumin excretion rate, and clinical blood pressure to a diabetic subject. In both groups an ambulatory blood pressure monitoring was performed through an oscillometric recorder. The mean systolic and diastolic ambulatory blood pressure values were significantly higher in diabetic patients (p <0.001) in the 24-h analysis and during waking and sleeping periods. The night/day ratio of systolic and diastolic blood pressure were not significantly different in patients and controls, as well as heart rate values and heart rate variability. We conclude that mechanism(s) inherent to the diabetic condition other than diabetic nephropathy or autonomic neuropathy could be responsible for blood pressure evaluation in normotensive Type 1 diabetes with normoalbuminuria.     

Predictors of mortality in patients with type 2 diabetes with or without diabetic nephropathy: a follow-up study

OBJECTIVE: To evaluate the prognostic significance of cardiovascular risk factors including 24-h ambulatory blood pressure level and rhythm for all-cause mortality in type 2 diabetic patients. METHODS: In a prospective observational study, 104 patients with type 2 diabetes were followed: 51 patients with diabetic nephropathy and 53 patients with persistent normoalbuminuria. At baseline, 24-h ambulatory blood pressure, left ventricular hypertrophy, glomerular filtration rate and cardiac autonomic neuropathy were measured. Blood samples were taken and patients answered a World Health Organization questionnaire. Dipping was calculated as the average nocturnal reduction in systolic and diastolic blood pressure. RESULTS: Mean follow-up was 9.2 years (range 0.5-12.9). During follow-up, 54 of 104 patients died. Sixteen patients (15%) had higher blood pressure at night than during the day (reversed pattern); 14 of these patients died (88%), compared to 40 of 88 patients (45%) with reduced dipping or normal dipping; log rank P = 0.001. In a Cox regression analysis, predictors of all-cause mortality were: age, male sex, presence of left ventricular hypertrophy, glycated haemoglobin A1c (HbA1c), daytime systolic blood pressure, cardiac autonomic neuropathy, glomerular filtration rate and dipping (1% increase; hazard ratio 0.97, 95% confidence interval 0.94-0.998, P = 0.033). CONCLUSION: Type 2 diabetes patients with non-dipping of night blood pressure were at higher risk of death as compared to dippers, independent of known cardiovascular risk factors. Since non-dipping has a high prevalence in patients with diabetic nephropathy, 24-h ambulatory blood pressure should be used to assess a full risk profile and blood pressure-lowering therapy in these patients.     

不同阶段糖尿病肾病患者自主神经功能和昼夜血压、心率的变化

探讨自主神经功能和昼夜血压、心率在不同阶段糖尿病肾病患者中的变化。采用 2 4h动态心电图和血压同步监测 38例正常对照组和 84例糖尿病患者 ,包括A组 (正常蛋白尿 ) 4 8例、B组 (微量蛋白尿 ) 2 0例、C组 (大量蛋白尿组 ) 16例。结果 :A组糖尿病患者已有夜间血压和心率增高 ,昼夜血压、心率下降幅度及部分心率变异指标的降低 ;随蛋白尿增多 ,上述指标异常加重 ,并出现白昼血压和心率增高。A、B、C组分别有 5 4 .17%、75 .0 0 %和 87.5 0 %的患者出现昼夜血压节律消失 ,而对照组仅有 2 1.0 5 %。结论 :糖尿病患者普遍存在自主神经病变 ,夜间血压和心率增高可能就是糖尿病肾病早期的临床征象     

Effects of smoking on 24-h ambulatory blood pressure and autonomic function in normoalbuminuric insulin-dependent diabetes mellitus patients

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.     

Twenty-four hour blood pressure and heart rate profiles of diabetic patients with abnormal cardiovascular reflexes

Twenty-four hour ambulatory blood pressure and heart rate profiles of 24 patients with diabetes were monitored in order to assess the effect of autonomic neuropathy on 24-h haemodynamic profiles. Eighteen patients had abnormal cardiovascular reflexes. Mean arterial pressure rose at night in six of the patients with autonomic neuropathy and fell by less than or equal to 5 mmHg in seven. In the remaining five patients with autonomic neuropathy and in the six diabetic patients with normal cardiovascular reflexes, the fall in nocturnal mean arterial pressure was comparable to that of 11 non-diabetic patients with essential hypertension. Median 24-h mean arterial pressure was similar in all four groups of diabetic patients. Prevalence of autonomic symptoms was not related to the change in blood pressure in those with autonomic neuropathy. Twenty-seven months after monitoring, three fatal and five severe non-fatal cardiovascular or renal events had occurred in four of the six patients with a rise in nocturnal blood pressure, compared with one non-fatal event in those with a small fall and no severe events in those with a pronounced fall (p = 0.02). Blood pressure rises at night in certain diabetic patients with abnormal cardiovascular reflexes and the nocturnal rise appears to be associated with a poor prognosis.     

Relationship between autonomic function, 24-h blood pressure, and albuminuria in normotensive, normoalbuminuric patients with Type 1 diabetes

We performed a battery of cardiovascular reflex tests, 24-h ambulatory blood pressure (AMBP) and 24-h urinary albumin excretion (UAE) in 116 normoalbuminuric and normotensive patients with Type 1 diabetes. Tests of heart rate variation (HRV) included the coefficient of variation (CV) and the low-frequency (LF), mid-frequency (MF), and high-frequency (HF) bands of spectral analysis at rest, HRV during deep breathing (CV, mean circular resultant — MCR), Valsalva ratio, and maximum/minimum 30:15 ratio. Autonomic neuropathy, characterized as an abnormality of more than two tests, was found in 33 patients. Patients with neuropathy compared to those without neuropathy showed significantly higher mean day and night diastolic blood pressure (dBP), mean systolic night blood pressure (sBP), and mean day and night heart rate (HR). Mean night dBP was inversely related to MF, HF, and HRV during deep breathing; mean day dBP and mean night sBP to HF; mean night HR to CV at rest, MF, HF, HRV during deep breathing, 30:15 ratio; mean day HR to HF, HRV during deep breathing, Valsalva, and 30:15 ratio. Mean 24-h UAE was not significantly different in neuropathic than in nonneuropathic patients. UAE was inversely related to CV at rest and HF. In the stepwise multiple regression analysis, reduced MF, HF, HRV during deep breathing, and high levels of UAE and HbA1c were associated with high night dBP. Autonomic neuropathy is already present in normotensive Type 1 diabetic patients at the normoalbuminuric stage and related to BP and albuminuria.     

Diurnal blood pressure variations in normoalbuminuric type 1 diabetic patients

Abstract. Objective. To test the hypothesis that normoal-buminuric type 1 diabetic patients segregate into groups with normal and elevated ambulatory blood pressure. To evaluate diurnal variation of blood pressure assessed by individual or fixed night-time periods. Design. Cross-sectional study. Setting. Tertiary referral centre. Subjects. Inclusion criteria for type 1 diabetic patients (n = 33): normal urinary albumin excretion (UAE age < 45 < 20 μg min^?1), diabetes duration ≤ 20 years, age 45 years. Healthy controls (n = 33) were matched for sex and age. Main outcome measure. Twenty-four hour, day-time, night-time and night/day ratio of ambulatory blood pressure. Results. Twenty-four-hour blood pressure in diabetic patients did not differ significantly from a normal distribution. The 24-h systolic blood pressure was higher in diabetic patients than in healthy controls (difference: 6 mmHg, 95% confidence interval (CI) from 1 to 10 mmHg, P < 0.05), while no significant differences were found for diastolic values. The 24-h systolic blood pressure in diabetic patients with UAE above the median value (5.8 μg min^?1) was higher than for those with lower UAE (difference: 7 mmHg, 95% CI from 0.5 to 13 mmHg, P < 0.05). The night/day ratio of diastolic blood pressure based on individual informations of the night period was (mean ± SD) 80 ± 6% in diabetic patients and 78 ± 8% in controls (difference: 2%, 95% CI from ?1 to 5%, not significant [NS]). This ratio increase significantly (P < 0.00001) to 90 ± 5% in diabetes and to 84 ± 7% in controls if a fixed night period from 22.30 hours to 06.30 hours was assumed. Conclusions. It was not possible to identify a well-separated group of normoalbuminuric type 1 diabetic patients with elevated ambulatory blood pressure. Values of UAE above the median in diabetic patients are associated with higher ambulatory blood pressure. Assessment of the night/day variation from fixed time-points should be abandoned because this leads to a serious underestimation of the nocturnal reduction in blood pressure.     

NIDDM 患者心血管自主神经病变与红细胞山梨醇含量相关性及其影响

用Ｅｗｉｎｇ法和定量ＨＲＰＳ法同时测定９４例ＮＩＤＤＭ患者心血管自主神经病变（ＣＡＮＤ）程度，探讨其与红细胞山梨醇（ＲＢＣＳ）含量的关系。结果表明ＤＭ患者伴ＣＡＮＤ组的ＲＢＣＳ值显著高于无ＣＡＮＤ组，ＲＢＣＳ升高与ＣＡＮＤ严重程度，植物神经的改变，尤以副交感神经更易受影响，且与年龄、病程、ＦＢＧ、ＨｂＡ１Ｃ、血浆Ｆｇ、ＨＤＬＣ及亚类和血浆镁改变也显著相关；多元逐步回归分析显示ＲＢＣＳ是对ＣＡＮＤ有显著影响的重要因素，提示ＤＭ患者ＣＡＮＤ是多因素共同作用结果，其中高血糖所致山梨醇通路活性增高在其发生发展中起重要作用。     

Cardiac repolarization interval in end-stage diabetic and nondiabetic renal disease

Background and hypothesis: QT interval length is influenced by autonomic nervous activity. In patients with diabetic autonomic neuropathy, both prolongation and shortening of ventricular repolarization has been reported. We studied diabetic and nondiabetic uremic patients to assess the effects of autonomic neuropathy on QT interval length. Methods: 24-hour electrocardiogram recordings were performed in 12 diabetic and 11 nondiabetic renal transplantation patients, and in 12 control patients. Mean and corrected QT interval (QTc) during the 24-h period and intervals at predetermined heart rates at day and night periods were determined. The degree of autonomic neuropathy was assessed with cardiovascular autonomic function tests and measurement of heart rate variability. Results: In the diabetic group, severe autonomic neuropathy was present; in nondiabetic uremic patients, abnormalities were less severe. Mean QTc interval during 24 h was 444 ± 24,447 ± 21, and 442 ± 19 ms in the diabetic and nondiabetic uremic patients, and in the control groups, respectively, without any between-group difference. QT and QTc interval length did not differ among the groups when measured at heart rates of 70, 80, 90, or 100 beats/min. Conclusions: In patients with autonomic failure caused by diabetes and/or uremia, QT interval length cannot be used as a diagnostic indicator of cardiac autonomic neuropathy.     

Abnormal Digital Pressure Measurements in Diabetic Neuropathic Foot Ulceration

The diabetic neuropathic ulcer is typically slow to heal and recurrent. Macrovascular insufficiency is usually excluded as foot pulses are present and ankle:brachial pressure ratios are not decreased. These assessments cannot however exclude more distal vascular disease. Digital pressure measurements enable a reliable assessment of the distal peripheral vascular status to be made. The aim of this study was therefore to use toe pressures to assess the contribution of distal ischaemia in the pathogenesis of the neuropathic ulcer. Sixteen diabetic patients with recurrent neuropathic foot ulceration had their toe pressures compared to 10 neuropathic patients without a history of foot ulceration, 10 diabetic control subjects, and 11 normal subjects. Four non-diabetic patients with neuropathy and foot ulceration were also assessed. All subjects had ankle:brachial pressure indices ≧ 1. Toe pressure was assessed using laser Doppler flowmetry to record the return of skin blood flow. The toe:brachial pressure index (TBI) was then calculated. The diabetic patients with a history of recurrent neuropathic ulceration, had the lowest mean TBI, 0.63 ± 0.14 (SD), compared to the non-ulcerated diabetic neuropathy patients, the diabetic control subjects, and the normal subjects. 0.84 ± 0.11, 0.82 ± 0.1, and 0.81 ± 0.07, p < 0.01, respectively. Three of the four non-diabetic patients with neuropathic foot ulceration also had an abnormally low TBI. Reduced toe pressure measurements are thus found to be associated with neuropathic foot ulceration. The contribution of distal ischaemia in the pathogenesis of the diabetic neuropathic foot ulcer needs to be evaluated. One hundred and eight non-insulin-dependent diabetic patients who had been tested for autonomic dysfunction in 1984/85 were re-evaluated 5 years later. Autonomic function was assessed by means of four cardiovascular tests (heart rate variation during deep breathing and standing, and blood pressure variation after standing and sustained handgrip). Eighteen subjects were lost to follow-up; in the 90 patients who completed the study, both the deep breathing and the handgrip test significantly worsened (respectively from 13.7 ± 7.8 to 11.6 ± 6.3 beats min^?1 p < 0.01, and from 16.9 ± 8.2 to 12.7 ± 7.1 mmHg, p < 0.001), whereas both the 30:15 ratio and the variation of blood pressure on standing did not change. The impairment of a comprehensive evaluation score (from 2.5 ± 1.7 to 3.0 ± 1.5; p < 0.05) also confirmed the gradual deterioration of autonomic function over the study period.     

Ambulatory blood pressure and heart rate in diabetic patients: an assessment of autonomic function

In order to examine the physiological variation in blood pressure and heart rate that occurs during normal activities in patients with diabetes, 24-h profiles were constructed from continuous ambulatory recordings. Isometric and dynamic tests were also performed. The patients were subdivided into 25 uncomplicated cases, 11 with peripheral neuropathy and 6 with autonomic neuropathy. These were compared with a 'control' group of 22 normal subjects. Abnormal 24-h blood pressure profiles were found particularly in the patients with autonomic neuropathy. This group had attenuation or reversal of the usual diurnal rhythm, blood pressure often rising during the night and falling in the early morning. Diurnal heart rate variation was reduced in all three groups of patients. Blood pressure responses to both forms of exercise were also significantly reduced in the autonomic neuropathy group (maximum change in systolic blood pressure during isometric exercise was 10 +/- 4 mmHg vs 36 +/- 3 mmHg in the control group, p less than 0.003). Patients with peripheral neuropathy also had some impairment of exercise-induced blood pressure changes, but to a lesser degree.     

Effects of smoking on blood pressure and proteinuria in patients with diabetic nephropathy

Objectives. To investigate the effects of smoking on blood pressure and proteinuria in hypertensive diabetic patients with nephropathy.
Design. Controlled, randomized, cross-over study.
Setting. Tertiary care centre, University Hospital of Düsseldorf, Germany.
Subjects. A total of 25 subjects were recruited, each of whom smoked at least 20 cigarettes a day: 10 normotensive healthy volunteers and 15 hypertensive type 1 (insulin-dependent) diabetic outpatients with diabetic retinopathy and persistent micro- or macroalbuminuria; 10 diabetic patients had normal autonomic function test, whilst five patients showed signs of autonomic neuropathy.
Interventions. Controlled smoking or nonsmoking over a period of 8 h on separate days.
Main outcome measures. Blood pressure was measured every 10 min with an automatic device and urine samples were collected every 3 h.
Results. Systolic blood pressure increased during smoking in controls (mean) (11.5 mmHg, P= 0.0001) and in diabetic patients without autonomic neuropathy (7.9 mmHg; P=0.018 ), but not in patients with autonomic neuropathy (-2.4 mmHg; P =0.792). Diastolic blood pressure increased during smoking in controls (6.2 mmHg; P= 0.019) but not in diabetic patients (2.5 mmHg; P =0.204. 0.2 mmHg; P= 0.956). During smoking, median proteinuria and albuminuria increased in diabetic patients without autonomic neuropathy (8.1 mg mmol^-1 creatinine, P=0.002; and 2.6 mg mmol creatinine, P= 0.084). No significant changes in albuminuria or proteinuria occurred in the other two groups.
Conclusions. Smoking increases blood pressure values in healthy subjects and in hypertensive patients with diabetic nephropathy and without autonomic neuropathy. This effect of smoking may be partly responsible for the faster progression of diabetic nephropathy in smoking diabetic patients.     

Circadian variation of blood pressure in patients with diabetic nephropathy

Summary The association between diurnal blood pressure variation and diabetic nephropathy was assessed in four groups of Type 1 (insulin-dependent) diabetic patients who underwent 24-h ambulatory blood pressure monitoring using an oscillometrie technique. Patients with nephropathy, who had never been treated for hypertension (group D₃,n = 13), were individually matched for age, sex and diabetes duration to a group of microalbuminuric patients (D₂,n = 26), to normoalbuminuric patients (D₁,n = 26) and to healthy control subjects (C,n = 26). Group D3 was also compared to patients with advanced nephropathy receiving treatment for hypertension, mainly a combination of angiotensin converting enzyme inhibitors, metoprolol and diuretics (D₄,n = 11). In group D₃ 24-h diastolic blood pressure (85 ± 8 mm Hg) was comparable to the results obtained in D₄ (85 ± 8 mm Hg) but significantly higher than in D₂ (78 ± 7 mm Hg), D₁ (73 ± 7 mm Hg) and C (73 ± 7 mm Hg,p < 0.05, Tukey's test). The night/day ratio of diastolic blood pressure was higher in D₃ (86 ± 5 %) and D₂ (85 ± 7%) than in C (80 ± 7 %,p < 0.02). This ratio was also elevated in group D₄ (94 ± 8%) compared to D₃ (p < 0.05) corresponding to a marked smoothing of the diurnal blood pressure curve. The 24-h heart rate (beats per min) was significantly elevated in D₃ (84 ± 8) and D₂ (80 ± 10) compared with C (73 ± 11,p < 0.05 Tukey's test), suggesting the presence of parasympathetic neuropathy In conclusion the normal circadian variation of blood pressure was moderately disturbed in a group of microalbuminuric patients and patients with less advanced overt nephropathy. Patients with advanced diabetic nephropathy receiving antihypertensive therapy showed a marked reduction of nocturnal blood pressure fall, which can only be identified by the application of ambulatory blood pressure measurements to verify the 24-h effectiveness of blood pressure control.     

Sequelae of Acute Hypoglycaemia on 24 hour Blood Pressure and Metabolic Parameters in Normal and Type 1 (Insulin-dependent) Diabetic Individuals

This study was performed to assess possible delayed after-effects of acute hypoglycaemia on blood pressure (BP) and heart rate (HR) over a 24-h period. Eleven insulin-dependent diabetic patients and 11 sex, age, and body mass index matched non-diabetic subjects were studied. Blood pressure was measured using a non-invasive ambulatory blood pressure monitor following acutely induced hypoglycaemia in the morning. No significant differences were observed in 24-h systolic and diastolic BP and HR in either groups, between the day when hypoglycaemia was induced and the day when plasma glucose was kept normal. In diabetic patients, hypoglycaemia induced a temporary but significant fall in mean BP (-7 ± 1 mmHg vs -2 ± 2; p < 0.05). Plasma glucose levels were significantly higher in insulin-dependent diabetic patients following hypoglycaemia than in those observed during the reference test. This study demonstrates that acute hypoglycaemia in insulin-dependent diabetic subjects does not cause significant alterations in 24-h BP in either diabetic or normal subjects.     

Postprandial hypotension in patients with non-insulin-dependent diabetes mellitus.

This study attempted to determine whether postprandial hypotension (PPH) is associated with diabetes mellitus by 24-h ambulatory blood pressure monitoring (24-h ABPM) and by monitoring blood pressure during 75-g oral glucose tolerance test (75-g OGTT) in 15 normal subjects and 35 patients with non-insulin-dependent diabetes mellitus. When we defined PPH as a postprandial decrease in systolic blood pressure of greater than 20 mmHg, the incidence of PPH in diabetics was 37% by 24-h ABPM and 20% by 75-g OGTT. The incidence of proliferative retinopathy and proteinuria was greater in diabetics with PPH than in those without PPH. All of the patients with PPH had somatic and autonomic neuropathy. The C-peptide response was lower in diabetics with PPH than in those without PPH. We revealed the presence of PPH in diabetics, and found that PPH was closely related to disease severity, especially diabetic autonomic neuropathy.     

Increased plasma apolipoprotein B levels and blood hyperviscosity in non-insulin-dependent diabetic patients: Role in the occurrence of arterial hypertension

Summary An association between arterial blood pressure and blood viscosity has been suggested in healthy and in diabetic subjects, and that the hemorheological pattern may be influenced by blood lipid alterations. In diabetic patients a relationship between arterial hypertension and blood lipid changes may therefore be suggested. This study concerns 19 type II diabetics with hyperlipidemia (triglycerides=3.2±1 mmol/l; total cholesterol=6.1±1.2 mmol/l; HDL-cholesterol=0.92±0.27 mmol/l; VLDL=29±5%) (group A), and 19 normolipidemic type II diabetics (triglycerides=1.15±0.5 mmol/l; total cholesterol=5.1±1 mmol/l; HDL-cholesterol =1.25±0.38 mmol/l; VLDL=20±5%) (group B). No differences concerning age, body weight, duration of diabetes and glycemic control were found in hyperlipidemic compared to normolipidemic diabetics. On the contrary, higher systolic and diastolic blood pressure levels were demonstrated in group A (167±14 mmHg and 101±5.2 mmHg, respectively) than in group B (144±15 mmHg, p<0.001 and 87±6.9 mmHg, p<0.001, respectively). An increase of plasma apolipoprotein B level (163±27 mg/dlvs 102±21 mg/dl, p<0.001), of plasma viscosity (1.81±0.08 mPasvs 1.51±0.07 mPas, p<0.001) and of blood viscosity (5.37±0.33 mPasvs 5.07±0.04 mPas, p<0.01, at shear-rate of 90 s⁻¹; 18.4±1 mPasvs 14.1±0.9 mPas, p<0.001 at shear-rate of 2.25 s⁻¹) was found in group A, compared to group B. Moreover several positive correlations (p<0.001) between apolipoprotein B level, plasma and blood viscosity were demonstrated in the hyperlipidemic diabetic patients. These findings suggest that blood changes in diabetes might be involved in the occurrence of blood pressure alterations. This study was presented in part at the 22nd Meeting of the European Association for the Study of Diabetes (EASD), Rome September 16–20, 1986.     

Diurnal Variation in Blood Pressure in Insulin-dependent Diabetic Smokers and Non-smokers with and without Microalbuminuria

In subjects with essential hypertension, loss of the normal nocturnal dip in blood pressure is associated with a greater risk of developing end-organ complications. In subjects with diabetes, smoking carries a similar association. To assess whether these factors may have an aetiological and synergistic role in the vascular complications of diabetes, 24-hour blood pressure monitoring was performed in insulin-dependent diabetic (IDDM) patients with normal albumin excretion (n = 19) and microalbuminuria (n = 21) of comparable age and duration of diabetes, and with no evidence of autonomic neuropathy or hypertension. The potential influence of smoking was examined by subdividing the groups, depending on smoking status. Ten of the microalbuminuric group and 9 of the normoalbuminuric group were current smokers, the remaining patients never having smoked. There was a significant difference between mean (±SD) daytime vs nocturnal blood pressure in patients with normal albumin excretion (114 ± 3/70 ± 4 vs 102 ± 3/62 ± 3 mmHg; p < 0.001) and microalbuminuria (109 ± 5/75 ± 5 vs 101 ± 3/65 ± 4 mmHg; p < 0.001) but mean blood pressure values did not differ significantly between the groups. A similar fall in nocturnal blood pressure was found in smokers and non-smokers with and without microalbuminuria (p < 0.001), but there was no difference between the mean blood pressure values in the different subgroups. In conclusion, normotensive IDDM patients, who do not have autonomic neuropathy, retain a significant diurnal variation in blood pressure, irrespective of smoking habit or presence of microalbuminuria. © 1997 by John Wiley & Sons, Ltd.     

The Splanchnic Circulation and Postural Hypotension in Diabetic Autonomic Neuropathy

Postural hypotension results from sympathetic failure to cause superior peripheral vasoconstriction. The importance of the splanchnic circulation was studied by measuring mesenteric artery blood flow with duplex Doppler scanning. Nine normal and 9 Type 1 diabetic controls were compared to 8 Type 1 patients with autonomic neuropathy whose pressure fell 40–113 mmHg (range) on tilting. Measurements were made supine and after vertical tilt, fasting without insulin and after a 550 kcal meal. Superior mesenteric artery diameter decreased on tilting in normal controls but not in diabetic control or neuropathy groups (supine vs tilted: controls. 6.3 ± 0.9 to 5 ± 0.9 mm, p = 0.004, diabetic controls: 6.0 ± 0.6 to 6.0 ± 1.0 mm, and neuropathy group: 6.4 ± 0.9 to 5.6 ± 0.9 mm), but proportional blood flow changes were similar in all subjects (controls: 407 ± 154 to 255 ± 67 ml min^?1 (-31%, p = 0.03), diabetic controls: 379 ± 140 to 306 ± 149 ml min^?1 (-8%, p = 0.28), neuropathy group: 639 ± 371 to 435 ± 142 ml min^?1 (-23%, p = 0.10). Postprandially supine superior mesenteric artery flow increased in all subjects but this did not affect the degree of systolic blood pressure drop on tilting (fasting vs postprandial blood flow: controls: 407 ± 154 to 775 ± 400 ml min^?1 (p = 0.04), diabetic controls: 379 ± 140 to 691 ± 262 ml min^?1 (p = 0.01), neuropathy group: 639 ± 371 to 943 ± 468 ml min^?1 (p < 0.06)). The similarity of superior mesenteric artery responses to tilting in the three groups, and the lack of exacerbation of postural hypotension in the presence of postprandial hyperaemia indicates that control of splanchnic blood flow is less important in the aetiology of diabetic autonomic postural hypotension than previously thought.     

24-h ambulatory blood pressure and retinopathy in normoalbuminuric IDDM patients

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 μg/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 μg/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] Received: 27 May 1997 and in revised form: 5 September 1997     

Latent overhydration and nocturnal hypertension in diabetic nephropathy

Summary With the aim of studying the diurnal variation in blood pressure in relation to degree of fluid retention, 24-h ambulatory blood pressure monitoring was performed in 31 insulin-dependent diabetic patients with nephropathy. The extracellular volume was calculated from the distribution volume of ⁵¹Cr-EDTA after a single injection. The study population was arbitrarily divided into two groups, depending on their extracellular volume. Group 1 included 15 patients with a lower extracellular volume and group 2, 16 patients with a higher extracellular volume. Ambulatory blood pressure was measured with a portable monitor using an oscillometric technique. In all patients, the mean ±SD 24-h ambulatory blood pressure was 135/79±14/7 mm Hg. Day and night-time blood pressures were 136/81±14/7 and 133/75±17/8, respectively (p<0.02). The ambulatory blood pressure was 135/80±14/7 in group 1 and 136/78±15/6 mm Hg in group 2. The nocturnal change in blood pressure was significantly greater in group 1 than in group 2, –9/–9±10/5 mm Hg and 1/–3±10/6 mm Hg, respectively (p=0.005/0.01). There were no other significant differences between the groups than the diurnal blood pressure pattern. There were significant correlations between day ambulatory blood pressure and night ambulatory blood pressure and 24-h ambulatory blood pressure and urinary albumin excretion. There was no correlation between auscultatory clinic blood pressure on the one hand and albuminuria on the other. Latent fluid retention therefore may contribute to nocturnal hypertension in diabetic nephropathy.Abbreviations ECV Extracellular volume - IDDM insulin-dependent diabetes mellitus - ABP ambulatory blood pressure