Interactions between risk factors may influence disease severity. Knowing this relationship is important for preventive interventions and disease control. The purpose of this study was to determine the interactions effects of obesity and hypertension on the risk of type 2 diabetes mellitus (T2DM).

The data of 9,283 adults 35 to 65 years were examined from the cohort study of Ravansar Non-Communicable Disease (RaNCD). Waist circumference (WC) was used to identify both general and abdominal obesity based on body mass index (BMI). To assess the interaction between hypertension and obesity (general/abdominal) and the risk of T2DM, the additive interaction was calculated.

The adjusted odds ratios for T2DM were 2.38 (1.67, 3.41) in men and 4.02 (2.47, 6.47) in women for the combinations of hypertension and abdominal obesity. The adjusted odds ratios for T2DM were 2.53 (1.63, 3.82) in men and 2.66 (1.92, 3.70) in women for the combinations of hypertension and general obesity. The results of the additive interaction indicators were inconsistent with gender. The relative excess risk due to interaction (interaction between hypertension and central obesity) (RERI), attributable proportion due to interaction (AP) and synergy index (SI) were0.27 (-1.01, 1.54), 0.11 (-0.41, 0.63) and 1.23 (0.41, 3.68) in male and were 0.61 (-1.12, 2.33), 0.23 (0.08, 0.37) and 1.26 (0.60, 2.61) in female, respectively.

General/abdominal obesity and hypertension have a synergistic effect on the risk of T2DM. The recommendation for preventing T2DM is lifestyle modification. Large longitudinal studies are necessary to investigate causal relationships.

Cardiovascular autonomic neuropathy (CAN) associates an abnormal circadian pattern in blood pressure (BP) regulation that might be aggravated by the coexistence of arterial stiffness. We aimed to evaluate the effect of arterial stiffness in the circadian rhythm of BP in patients with type 1 diabetes and CAN.

Cross-sectional study including 56 consecutive patients with type 1 diabetes and CAN, with (n = 28) or without (n = 24) arterial stiffness as defined by an ankle-brachial index above 1.2. CAN was diagnosed by BP and heart rate responses to active standing and cardiovascular autonomic reflex tests. Absence of nocturnal decrease in BP-"non-dipping" pattern- was defined by a daytime to nighttime decrease in mean BP smaller than 10%.

The study's subjects mean age was 40 ± 11 years-old, their mean duration of diabetes was 22 ± 10 years, and their mean A_1c was 7.9 ± 1.5%. A "non-dipping" pattern was observed in 28 patients (54%) regardless of the presence or absence of arterial stiffness. Age, waist circumference, body mass index, and A_1c, were introduced as independent variables into a multiple regression analysis. The stepwise model (R²: 0.113, p = 0.016) retained only A_1c levels (β: ‒ 0.333, 95% confidence interval [CI]: -3.10 to -0.33) as significant predictor of the percentage of nighttime decrease in mean BP.

A non-dipping pattern in BP is very common in patients with type 1 diabetes presenting with subclinical CAN and is associated with a poorer metabolic control. On the contrary, coexistence of arterial stiffness is not associated with abnormalities in circadian BP regulation.

Branch retinal vein occlusion (BRVO) is ocular vascular disease affecting approximately 14 million people worldwide, and is closely associated with high blood pressure (BP). Although macular ischemia is a critical factor in the visual prognosis of BRVO, the relationship between macular ischemia and different patterns of nocturnal BP is unknown. Here, we investigated whether a dipping pattern of nocturnal BP is associated with the development of macular ischemia in patients with BRVO. A total of 273 patients were reviewed; of these, 86 (86 eyes) patients were included. All recruited patients had a macular thickness map by optical coherence tomography and underwent 24-h ambulatory BP monitoring. According to their dipping patterns, the participants were divided into dipper and non-dipper groups. The non-dipper group had worse visual outcomes at the initial and 6-month visits (P = 0.014 and P = 0.003, respectively). Five of 32 eyes (15.6%) in the dipper group and 32 of 54 (59.3%) in the non-dipper group had macular ischemia. In a multivariate analysis, the night-to-day systolic BP ratio was associated with the degree of macular ischemia (β = - 0.313, P = 0.004). Thus, a non-dipping pattern may be a risk factor for macular ischemia in patients with BRVO.

Type 1 diabetes mellitus (T1DM) is a chronic, autoimmune disease that is characterized by total absence of insulin production. Hypertension is a common comorbidity in T1DM with complex pathophysiology, while it is also a well-recognized risk factor for the development of cardiovascular disease (CVD), as well as other microvascular diabetic complications.

The purpose of this review is to present the current definitions, epidemiological data and prevalence rates of hypertension in T1DM, as well as to describe current therapeutic options.

Hypertension affects around a third of the type 1 diabetic population, with higher prevalence rates in older individuals with longer disease duration. Although hypertension affects a substantial proportion of T1DM individuals, blood pressure control rates are disappointingly low. Alongside lifestyle modification, antihypertensive treatment should be initiated in those with blood pressure above 140/90 mmHg, with a systolic blood pressure target of 130 mmHg and lower, if tolerated. In those with established CVD or diabetic nephropathy, systolic blood pressure targets below 130 mmHg should be pursued. Initial pharmacotherapy should consist of a renin-angiotensin-aldosterone system inhibitor. There is an urgent need for good quality data regarding proper antihypertensive treatment initiation, optimal BP targets and optimal antihypertensive treatment for better clinical outcomes.

To examine whether experimentally induced weight gain raises ambulatory blood pressure (BP) in healthy subjects and identify any relationship between changes in BP and changes in regional fat distribution.

Twenty-six normal weight subjects were randomized to 8 weeks of weight gain through overfeeding (n=16; age, 30.4±6.6 years) or to weight maintenance (controls; n=10; age, 27.1±7.7 years) between July 2004 and August 2010. Measures of body composition via dual energy X-ray absorptiometry and computed tomography, circulating biomarkers, and 24-hour ambulatory BP were obtained at baseline and after the 8-week experimental phase.

Overfeeding resulted in 3.7 kg (95% CI, 2.9-4.5) increase in body weight in weight gainers, with increments in total (46.2 cm²; 95% CI, 27.6-64.9), visceral (13.8 cm²; 95% CI, 5.8-21.9), and subcutaneous fat (32.4 cm²; 95% CI, 13.5-51.3). No changes occurred in the maintenance group. Increases in 24-hour systolic BP (4 mm Hg; 95% CI, 1.6-6.3), mean BP (1.7 mm Hg; 95% CI, 0.3-3.3), and pulse pressure (2.8 mm Hg; 95% CI, 1.1-4.4) were evident after weight gain in the experimental group, whereas BP remained unchanged in controls. Changes in mean BP correlated only with changes in visceral fat (ρ=0.45; P=.02), but not with changes in other body composition measures.

Modest weight gain causes elevation in 24-hour BP in healthy subjects. The association between increased BP and abdominal visceral fat accumulation suggests that visceral deposition of adipose tissue may contribute specifically to the enhanced risk of hypertension associated with weight gain.

Over 50% of patients with diabetes mellitus, either type 1 or 2, ultimately develop hypertension as a complication. In diabetics, this further increases the incidence of cardiovascular disease (CVD) by 2- to 3-fold and accelerates the progression of diabetic nephropathy. Arteriosclerosis, a clinical feature of hypertension in diabetics, develops and advances from a young age. Therefore, in providing treatment, it is necessary to evaluate the degree of arteriosclerosis. Diabetic patients are encouraged to strictly control their blood glucose levels. Recently developed drugs, such as GLP-1 receptor agonists, DPP-4 inhibitors and SGLT2 inhibitors, also have hypotensive actions, making them ideal for use in diabetics with hypertension. SGLT2 inhibitors and GLP-1 receptor agonists reportedly suppress the onset and progression of CVD, as well as diabetic nephropathy. The possibility of hypoglycemia triggering blood pressure elevation and arrhythmia has been noted, so a key point here is not to cause hypoglycemia. In selecting hypotensive agents, we must choose types that do not aggravate insulin resistance and engage in hypotensive treatment that also considers both nocturnal and morning hypertension. In addition, facing the onset of an aging society, there is a growing need for treatments that do not cause excessive blood pressure reduction or hypoglycemia. Favorable lifelong blood pressure and glucose control are increasingly important for the treatment of diabetes accompanied by hypertension.

It remains unclear whether the abnormal circadian blood pressure (BP) rhythm in non-diabetic chronic kidney disease (CKD) is related to hypoalbuminemia. We evaluated relationships between circadian BP rhythm and serum albumin concentration (SAC) and also examined autonomic nervous activities. Non-diabetic CKD patients with proteinuria (n = 197; 105 men, 92 women; aged 47.0 ± 13.3 years; estimated glomerular filtration rate ≥30 ml/min) were divided into nephrotic syndrome (NS: n = 46, SAC ≤ 30 g/l), hypoalbuminemia (n = 65, 30 < SAC < 40 g/l) and normoalbuminemia (n = 86, SAC ≥ 40 g/l) groups. Non-proteinuria subjects (n = 97, urinary protein/creatinine ratio < 30 mg/g creatinine) were enrolled as the non-proteinuria group. Ambulatory 24 h BP monitoring was conducted in all subjects. Simultaneously, power spectral analysis of heart rate was performed to evaluate the sympathovagal balance. Waking BP was lower in the hypoalbuminemia and NS groups than the other groups. Sleeping/waking mean BP ratio was not different between non-proteinuria (0.87 ± 0.07) and normoalbuminemia (0.89 ± 0.08) groups, but increased significantly (p < 0.05) in the hypoalbuminemia (0.92 ± 0.08) and NS groups (0.96 ± 0.08). Significant reverse correlations were observed between SAC and sleeping/waking mean BP ratio (r = -0.274, p < 0.001) in all patients. Multivariate regression analysis identified SAC and sympathovagal balance as predictors of increased sleeping/waking BP ratios as the dependent variable. In non-diabetic CKD patients with proteinuria, disturbed circadian BP rhythms were related to SAC and 24 h sympathovagal imbalance.

Patients with type 1 diabetes (DM-1) have an increased mortality and morbidity risk compared to non-diabetic subjects. Even not recognized clinically at the early period of disease; patients with DM-1 show subtle neurological and cardiovascular abnormalities which is partly responsible for the increased mortality. One of these abnormalities is the disruption of circadian rhythms. Various factors such as autonomic dysfunction, sleep disturbance, smoking, cardiac and kidney function, atherosclerosis, arterial stiffness are suggested to cause these disturbances. Additionally these abnormalities have also implications regarding target organ damage such as microalbuminuria, retinopathy, and structural changes in glomeruli. Surprisingly, there are scarce data regarding the effect of tight blood glucose control and insulin on circadian rhythms in patients with DM-1. By the light of aforementioned data this review will try to summarize causes and consequences of disruption of circadian rhythms and the impact on glycemic control on these issues in patients with DM-1.

Sleep restriction has been associated with deteriorated insulin sensitivity. The effects of short sleep duration have been explored little in patients with type 1 diabetes. This study addresses the question of whether sleep curtailment affects HbA1c levels in patients with type 1 diabetes.

Seventy-nine adult patients with type 1 diabetes (median age 40 years [IQR 23-49]; 47% men) were recruited to wear a wrist actimetry sensor during 3 consecutive days to assess mean sleep duration during normal daily life. A subsample of 37 patients also performed 24-h ambulatory blood pressure monitoring (ABPM). Medical history, sleep questionnaires, and diabetes-related quality of life (DQOL) were assessed.

Patients having shorter sleep duration--less than 6.5 h (n=21)--had higher levels of HbA1c (P=0.01) than patients with longer sleep duration, above 6.5 h (n=58). In a multivariable regression model including shorter versus longer sleep duration, diabetes duration, DQOL score, and daily activity, sleep duration was the only variable independently associated with HbA1c (R2=10%). In patients who performed 24-h ABPM, patients with a nondipping pattern of blood pressure exhibited shorter sleep duration than patients with a dipping pattern of blood pressure.

Shorter sleep duration is associated with higher HbA1c levels in patients with type 1 diabetes, as well as with a nondipping pattern of blood pressure, anticipating a long-term deleterious impact on the risk of microvascular complications. Further studies should test whether extending the duration of sleep may improve both HbA1c and blood pressure in type 1 diabetes.

We aimed to investigate the association between automated office blood pressure (AOBP) readings and urine albumin excretion (UAE), and to assess if this association is as close as that between 24-h ambulatory blood pressure (ABP) and UAE. A strong association would suggest that AOBP may serve as an indicator of early renal impairment.

In a sample of 162 hypertensives, we compared AOBP with ABP measurements and their associations with UAE in two consecutive 24-h urine collections measured by an immunoturbidimetric assay. Microalbuminuria was defined as UAE of 30-300 mg/24 h.

The age of the subjects was 53 ± 13 (mean ± s.d.) years. Twenty-two were microalbuminuric. In those, AOBP and 24-h ABP were higher than in the normoalbuminuric subjects: 152 ± 19 and 147 ± 20 vs. 138 ± 15 and 130 ± 11 mm Hg for systolic blood pressure (SBP), and 97 ± 15 and 92 ± 14 vs. 86 ± 10 and 82 ± 8 mm Hg for diastolic blood pressure (DBP) (P < 0.001). Correlations between AOBP and 24-h ABP with log-transformed urine albumin were 0.30 (P < 0.001) and 0.43 (P < 0.001) for SBP and 0.27 (P < 0.001) and 0.33 (P < 0.001) for DBP. Adjusting for age, sex, body mass index, and estimated glomerular filtration rate, both AOBP and 24-h ABP were independently associated with urine albumin (P < 0.001 for both associations). Receiver operating characteristics curve analysis showed a similar predictive ability for microalbuminuria for AOBP and for 24-h ABP (area under the curve: 0.819 (P < 0.001) for SBP, 0.836 (P < 0.001) for DBP vs. 0.830 (P < 0.001) for SBP and 0.845 (P < 0.001) for DBP).

In this study, microalbuminuria correlated similarly with high-quality AOBP and ABP readings, further supporting the use of AOBP in the clinical setting.

High blood pressure is reported in over two-thirds of patients with type 2 diabetes, and its development coincides with the development of hyperglycaemia. Many pathophysiological mechanisms underlie this association. Of these mechanisms, insulin resistance in the nitric-oxide pathway; the stimulatory effect of hyperinsulinaemia on sympathetic drive, smooth muscle growth, and sodium-fluid retention; and the excitatory effect of hyperglycaemia on the renin-angiotensin-aldosterone system seem to be plausible. In patients with diabetes, hypertension confers an enhanced risk of cardiovascular disease. A blood pressure of lower than 140/85 mm Hg is a reasonable therapeutic goal in patients with type 2 diabetes according to clinical trial evidence. People with controlled diabetes have a similar cardiovascular risk to patients without diabetes but with hypertension. A renin-angiotensin system blocker combined with a thiazide-type diuretic might be the best initial antihypertensive regimen for most people with diabetes. In general, the positive effects of antihypertensive drugs on cardiovascular outcomes outweigh the negative effects of antihypertensive drugs on glucose metabolism.

Hypertension is common in patients with diabetes mellitus and is a main cause of renal and cardiovascular complications. There has been recent controversy on what should be considered the optimal blood pressure goal and the optimal antihypertensive agent. It has become apparent that one blood pressure does not fit all in diabetic patients. Major confounders are preexisting cardiovascular disease and presence or absence of proteinuric kidney disease. In proteinuric diabetic nephropathy, renin-angiotensin system blockade is clearly indicated, but monotherapy is practically always insufficient to achieve target blood pressure values.

To assess whether nocturnal blood pressure dipping status in type 1 diabetes is correlated with specific sleep characteristics and differences in nocturnal glycemic profiles.

Twenty type 1 diabetic adult patients underwent sleep studies with simultaneous 24-h ambulatory blood pressure monitoring and continuous nocturnal glucose monitoring.

Altogether, 55% of patients exhibited blunted blood pressure dipping. They did not differ from the dipper group in age, BMI, or systolic (SBP) and diastolic (DBP) blood pressure. Total sleep period (TSP) was higher in the dipper group (497 +/- 30 vs. 407 +/- 44 min for dippers and nondippers, respectively, P < 0.001). TSP was correlated with SBP and DBP day-night differences (r = 0.44 and 0.49, respectively). Periods of nocturnal hypoglycemia (i.e., % of TSP with glycemia <70 mg/dl) were longer in the dipper group (8.1 +/- 10.7 vs. 0.1 +/- 0.4% for dippers and nondippers, respectively, P = 0.02).

Dipping status in type 1 diabetes was associated with longer sleep duration and with hypoglycemia unawareness.

Blood pressure (BP) varies according to cycles characterized by a reduction during sleep and an increase on awakening. The nighttime decrease is absent or blunted in some patients (termed "non-dippers"). Cross-sectional and prospective data have shown that non-dippers have more target organ damage than have dippers in normotensive and hypertensive subjects. We reviewed the English language literature regarding this association. A non-fortuitous association seems to exist between non-dipper status and cardiovascular risk such as stroke and cardiac events. Among diabetic patients, this phenomenon has been described to occur more often in individuals with autonomic neuropathy and with different degrees of diabetic nephropathy. In normoalbuminuric normotensive type I diabetic patients without any degree of autonomic dysfunction, according to traditional cardiovascular tests, diastolic BP (dBP) night/day ratio is associated with an increased glomerular filtration rate and an increased extracellular volume. The disruption of the circadian rhythm of sympathovagal activity in non-dipper patients was associated with higher levels in systolic BP (sBP) and dBP and with a reduced decline in sBP and dBP levels during the night. Therefore, the prognostic implications of the non-dipper status may be important since the overall 24-h blood pressure load is elevated in these individuals. These data suggest that patients in whom blood pressure decreases during the night incur less damage to their brain, kidneys, heart, and blood vessels than people with elevated nocturnal BP.

To define the prevalence and describe the natural history of microalbuminuria (MA) in a population-based sample of children with type 1 diabetes mellitus (T1DM).

Children with T1DM diagnosed <or=16 yrs and screened for MA were identified through the Western Australia diabetes register. Three-monthly hemoglobin (HbA1c) was performed from diagnosis. MA screening (albumin excretion rate in three timed overnight samples) was performed yearly after 10 yrs of age or after 5 yrs from diagnosis. Cox proportional model assessed the risk of different variables on the occurrence of MA. Kaplan-Meier survival analyses (log-rank test) estimated the probability of developing MA.

Nine hundred and fifty-five T1DM children (462 male), mean diabetes duration of 7.6 yrs and mean age at onset of diabetes of 8.5 yrs were selected for the study. MA, mean albumin excretion rate >or=20 and <200 microg/min, developed in 128 subjects (13.4%) at mean diabetes duration of 7.6 yrs. Cumulative probability for MA was 16% after 10 yrs. Determinants for MA were HbA1c [hazard ratio (HR) 1.21; 95% confidence interval (CI) 1.05-1.38; p = 0.007], onset of puberty (HR 8.01; 95% CI 3.18-20.16; p < 0.001) and age at diagnosis (HR 1.25; 95% CI 1.18-1.33; p < 0.001). Females had a higher probability for MA during puberty than males (p = 0.03). The total incidence of MA (subjects with MA/100 person-years) was 1.26, 1.85 and 2.44 for those who developed diabetes at ages <5 yrs, 5-11 yrs and >11 yrs, respectively.

Onset of puberty, diabetes duration and metabolic control are major factors predisposing the development of MA. Children diagnosed with T1DM at younger ages have a prolonged time for developing MA.

The relationship between urinary albumin excretion rate (AER) and elevated blood pressure (BP) is unclear as a cause-effect phenomenon in the development of diabetic nephropathy. The aim of this study was to examine the association between AER, HbA1c and BP in children with normoalbuminuria.

24-hour ambulatory BP assessment was performed in 78 children with type 1 diabetes mellitus (DM1), age mean +/- SD 13.4 +/- 2.7 yr, range 7.3-18.3 yr, DM1 duration mean +/- SD 6.6 +/- 2.9 yr, range 2.1-11.9 yr. Using generalised linear mixed models with systolic (SBP) and diastolic (DBP) blood pressure as dependent variables, the effects of AER and HbA1c were examined, adjusting for age, gender, DM1 duration and insulin dose.

Patients with high normal AER (7-20 microg/min) had higher SBP during daytime and night-time compared to the low normal AER (< or = 7 microg/min) (mean +/- SD 118.20 +/- 7.98 and 110.33 +/- 7.08 mm Hg, p = 0.02; mean +/- SD 108.76 +/- 9.21 and 100.20 +/- 7.75 mm Hg, p = 0.03, respectively). DBP was also higher both during day- and night-time when compared to the < or = 7 microg/min group (mean +/- SD 73.40 +/- 6.50 and 64.86 +/- 5.67 mm Hg, p = 0.002; mean +/- SD 62.50 +/- 6.75 and 56.30 +/- 5.56 mm Hg, p = 0.03 day- and night-time, respectively).

A rise in SBP and DBP is associated with increased levels of AER even within the normal range.

Few studies have assessed whether 24-h blood pressure control induced by antihypertensive agents improves macroalbuminuria in hypertensive type 2 diabetic patients with overt nephropathy. We evaluated the effects of losartan and amlodipine on 24-h blood pressure, autonomic nervous activity, and albuminuria in these patients.

In this open-label, parallel-prospective, randomized study, 44 patients were treated with losartan and 43 with amlodipine for a 12-week titration phase and a maintenance phase for a maximum of 12 weeks. Twenty-four-hour blood pressure and urinary albumin excretion were measured before and during treatment. Simultaneously, power spectral analysis of heart rate was performed to evaluate low frequency (LF) and high frequency (HF) components and LF-to-HF ratios as an index of sympathovagal balance.

Losartan decreased (P < 0.001) mean blood pressure from 162/91 to 150/82 mmHg during daytime and from 146/82 to 137/74 mmHg during nighttime (systolic/diastolic). Amlodipine also decreased (P < 0.001) blood pressure from 159/90 to 147/82 mmHg during daytime and from 143/81 to 131/72 mmHg during nighttime. LF and HF components and nighttime-to-daytime ratios for the LF-to-HF ratios did not differ during treatment in two groups, showing no changes in the diurnal autonomic nervous rhythm. Losartan decreased (P < 0.001) 24-h urinary albumin excretion from 810 mg/day (95% CI 780-1,140) to 570 (510-910). Amlodipine, however, did not decrease (P = 0.893) albuminuria (790 mg/day [780-1,170] vs.790 [710-1,260]).

These results suggest that in type 2 diabetes with overt nephropathy, 24-h blood pressure regulation alone is inadequate to reduce macroalbuminuria and additional effects of losartan are crucial for antiproteinuric action.

To determine whether there is a relation between dipping/nondipping status and end-organ damage (measured as renal glomerulopathy) and long-term renal function in order to predict the development of nephropathy in normoalbuminuric patients with type 1 diabetes.

Analysis of renal biopsy and ambulatory blood pressure measurements was done in relation to renal function tests performed during a 10-year period. Forty unselected patients (16 girls), with a mean age of 17.7 years and a mean duration of 10.7 years, were studied. The renal biopsies were examined by electron microscopy. Ambulatory blood pressure was monitored (Space Labs 90 207). Systolic nondippers were defined as a <7%, diastolic nondippers as a <14%, and mean arterial blood pressure (MAP) nondippers as a <12% fall in blood pressure during the night. Renal function was evaluated every other year by clearances of inulin (glomerular filtration rate [GFR]) and para-amino hippurate (effective renal plasma flow [ERPF]), and filtration fraction (GFR/ERPF) was calculated. Overnight urinary albumin excretion rate and long-term mean HbA(1c) were measured.

MAP (27% of the patients) and diastolic nondippers (12%) had a significantly thicker basement membrane; larger mesangial matrix volume fraction; and higher long-term GFR, nighttime heart rate, and mean HbA(1c) than dippers.

Nondipping status was related to more renal morphological changes and long-term hyperfiltration in normoalbuminuric adolescents and young adults, despite a short duration of type 1 diabetes. Nondipping status may be an early predictor of later nephropathy.

Several clinical trials have consistently shown that antihypertensive treatment, particularly with angiotensin-converting enzyme inhibitors (ACE-I) reduces albuminuria in Type 1 diabetic patients. More recently, data on the beneficial effects of ACE-I on the preservation of glomerular filtration rate and renal ultrastructure have emerged. However, in general, these trials have recruited a wide spectrum of diabetics, including some patients with severe albuminuria. Thus, the question of the ideal stage at which to instigate what is likely to be lifelong therapy in young people still remains unanswered. Exercise is known to significantly increase both blood pressure (BP) and urinary albumin excretion (UAE), both of which are important determinants of progression of nephropathy in diabetes. Thus, it is possible that exercise may have an adverse effect on diabetic renal disease. The effects of ACE-I on exercise-BP and exercise-UAE in microalbuminuric Type 1 diabetic patients has not been examined in long-term placebo-controlled studies. In the second part of this two-part review, we examine the effects of the ACE-I, lisinopril, 20 mg o.d. for two years, in comparison with placebo, on UAE, 24-hour ambulatory BP, exercise-BP, exercise-UAE and renal haemodynamics in 22 patients with Type 1 diabetes and low-grade microalbuminuria. We further discuss the effects of ACE-I on nephropathy and other complications of diabetes.

The cumulative incidence of diabetic nephropathy in Type 1 diabetes mellitus is in the order of 25 30%. The recognition that elevated blood pressure (BP) is a major factor in the progression of these patients to end-stage renal failure has led to the widespread use of antihypertensive therapy in order to preserve glomerular filtration rate and ultimately to reduce mortality. The routine measurement of microalbuminuria allows early identification of the subgroup of patients at increased risk of developing clinical nephropathy. Microalbuminuric Type 1 diabetic patients show a number of characteristic pathological abnormalities. In addition to elevated BP and abnormal circadian rhythm, there are also associated abnormalities of vagal function, lipid profile and endothelial function, as well as an increased prevalence of retinopathy. The first section of this two-part review focusses on the early changes associated with renal involvement in Type 1 diabetes. It addresses the associations between urinary albumin excretion, glycaemic control, smoking, BP, circadian BP variation, QT interval abnormalities and autonomic function in three groups of patients; those with normoalbuminuria, those progressing towards microalbuminuria and those with established low-grade microalbuminuria.

Diabetic nephropathy in type I diabetic patients, as it is currently understood, progresses in a stepwise fashion from normoalbuminuria to microalbuminuria, then to overt proteinuria and progression to chronic renal failure, and ultimately to end-stage renal disease. The role of early blood pressure changes in relation to diabetic nephropathy is now better understood in light of recent data using ambulatory blood pressure monitoring as a means to monitor blood pressure changes noninvasively throughout the day. Cross-sectional studies with type I diabetic patients with microalbuminuria have shown that the normal nocturnal blood pressure often fails to fall normally during sleep. The question of which comes first, microalbuminuria or a rise in blood pressure in patients with type I diabetes, was recently addressed in a prospective study. An increase in systolic blood pressure during sleep precedes the development of microalbuminuria and may play a causative role in its development.

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.

To study the influence of position changes on 24-h ambulatory blood pressure (ABP) in normotensive or mildly hypertensive normoalbuminuric patients with type 1 diabetes.

A cross-sectional evaluation of patients was staged according to the duration of diabetes (DD) and the presence of microangiopathy. We recruited 37 patients (30 men and 7 women), aged 38 +/- 12 years, who were normotensive or mildly hypertensive (diastolic blood pressure [DBP] <105 mmHg) and free of antihypertensive treatment and microalbuminuria. They were included according to DD (group 1, <5 years; group 2, > or =10 years). An additional group of seven diabetic patients with microalbuminuria and mild untreated hypertension was also investigated. We recorded 24-h ambulatory blood pressure every 15 min with a position sensor, which allowed for the discrimination between standing or supine/sitting position in the patient.

Mean daytime (10:00 A.M. to 8:00 P.M.) ABP in supine/sitting position did not significantly differ between groups 1 and 2. However, standing ambulatory systolic blood pressure (ASBP) and ambulatory DBP (ADBP) were significantly higher than supine/sitting ASBP and ADBP in group 1 (DeltaSBP 4 +/- 5, DeltaDPB 4 +/- 6 mmHg, P < 0.01) but not in group 2 (DeltaSBP 2 +/- 8, DeltaDBP 2 +/- 4 mmHg, P = NS). Patients free of microangiopathy presented with significantly higher ABP in standing position than in sitting/lying position, whereas patients with retinopathy and/or nephropathy exhibited no significant increase of ABP during standing.

The monitoring of position during ambulatory measurement of blood pressure in type 1 diabetic patients shows different patterns in relation to disease duration and the presence of microangiopathy.

With the objective to examine patterns of blood pressure (BP) in normotensive and normoalbuminuric Type 1 diabetic patients during 24 h ambulatory blood pressure monitoring (ABPM) we studied 28 Type 1 diabetic patients aged 27+/-7.1 years with a disease duration of 9+/-6.6 years, and 28 non-diabetic normotensive subjects aged 25+/-6.5 years matched to the diabetic group for age, gender, skin color, weight, height, body mass index, clinic BP and absence of microalbuminuria. Systolic BP (sBP) and diastolic BP (dBP) were recorded for 24 h, daytime and nighttime. SBP and dBP burden, night/day BP ratios and percent nighttime BP fall were determined. Subjects with a nocturnal fall in either sBP or dBP of less than 10% of daytime values were classified as non-dippers. Both sBP (111+/-7.1 vs. 104+/-9 mmHg; P=0.003) and dBP nighttime (66+/-6.1 vs. 61+/-5.3 mmHg; P=0.001) were higher in diabetic patients than non-diabetic subjects. Night/day ratios for sBP (0.93+/-0.04 vs. 0.89+/-0.05; P=0.006) and dBP (0.86+/-0.06 vs. 0.82+/-0.06; P=0.007) were higher in diabetics. The loss of a fall in sBP was more prevalent in diabetic subjects (78 vs. 39%; P=0.007). Non-dippers for sBP and dBP in the diabetic group had higher BP burden during the nighttime (21.4+/-16.6 vs. 3.2+/-3.9%; P=0.01 and 21.9+/-10 vs. 3.7+/-5.5%; P<0.001, respectively). Our data demonstrate higher sBP and dBP during the nighttime and loss of the nocturnal fall in BP in Type 1 diabetic patients. Further prospective studies are needed to define if high BP burden in diabetic non-dippers during the night could represent a risk for nephropathy and cardiovascular disease.

The objective of the present study was to characterize the spectrum of circadian blood pressure changes in type I diabetes at different stages of nephropathy by using two monitorings in each patient in order to avoid intra-individual variability.

A total of 80 type I diabetic subjects and the same number of age, sex and awake mean blood pressure (BP)-matched controls were included. According to urinary albumin excretion, there were 57 normoalbuminurics, 15 persistent microalbuminurics and eight proteinurics. Two 24 h ambulatory blood pressure monitorings were performed at the same urinary albumin excretion stage in absence of antihypertensive treatment for each diabetic subject and for their respective control. Blood pressure and heart rate averages during 24 h, awake, sleep, and day: night ratio were calculated.

Seven of the eight proteinuric subjects were hypertensives, whereas hypertension was absent in the normoalbuminuric and microalbuminuric groups. The intraindividual reproducibility in diabetics showed repeatability coefficients for the 24 h systolic and diastolic pressure of 33 and 42%, respectively. This reproducibility for the day: night ratio was generally worse, 57% for systolic and 59% for diastolic. A progressive increment in the mean ambulatory BP was observed across the three groups of diabetics and the differences in BP observed were most evident during the night-time period. Though no differences in the 24 h circadian pattern were present between the normoalbuminurics and their controls, nocturnal differences were observed, not only in microalbuminurics for systolic BP (P < 0.05), but also in proteinurics for both systolic BP (P < 0.01) as well as diastolic BP (P < 0.05). No differences were observed in heart rate among the diabetic groups. The non-dipping pattern in the two monitorings was observed in 80, 58, 18 and 10% of the proteinurics, microalbuminurics, normoalbuminurics and control groups, respectively.

Persistent abnormal circadian variability seems to be an early and frequent characteristic of type I diabetics with an increased urinary albumin excretion. Although present in some normalbuminuric subjects, the frequency of this abnormality increases as the incipient nephropathy progresses. By the time proteinuria is established, nearly all subjects present the abnormal pattern.

To assess the relevance of circadian blood pressure variation to future morbidity and mortality in patients with diabetes mellitus.

A retrospective descriptive 4 year follow-up study of data collected after ambulatory blood pressure monitoring in a clinic setting.

Seventy-five patients (46 male; 29 female) of whom 41 % had Type 1 diabetes and 59% Type 2 were followed up for a median of 42 months (11-56). The median creatinine for the whole group at baseline was 101 (56-501) micromol/l. The median circadian blood pressures for the total study population were 147 (110-194)/87 (66-109) mmHg during daytime and 132 (86-190)/77 (50-122) mmHg during night-time. Half of the patients exhibited a fall in night-time pressures to 10% lower than daytime pressures (dippers). Dippers were younger, 47 (32-75) years, than non-dippers, 57 (35-79) years, P = 0.03. Over time, dippers had a lower mortality than non-dippers, with 8% deaths in the cohort of dippers, 26% deaths in the cohort of non-dippers, P = 0.04. Cox regression analysis revealed significant contributions from age, duration of diabetes and baseline renal function to subsequent mortality in non-dippers. Analysing current degree of renal impairment and original dipper status together revealed that, of those patients whose creatinine remained normal, 7% of patients whose blood pressure dipped had subsequently died and 10% of non-dipping patients had died; of those patients whose creatinine unequivocally rose, 10% of dipping patients had died and 42% of non-dipping patients had died, P = 0.03

Loss of circadian variation in blood pressure is associated with an increased mortality rate, regardless of diabetes type. The combination of non-dipping and subsequent renal impairment leads to the highest mortality rate. The study suggests a role for ambulatory blood pressure monitoring in day-to-day clinical practice to select patients with nephropathy who are at greatest risk, in an effort to alter outcome.

Ambulatory blood pressure monitoring (ABPM) has now become an established clinical tool. It is appropriate to take stock and assess the situation of this technique. UPDATE ON EQUIPMENT: Important improvements in equipment have occurred, with reductions in weight, in awkwardness and in noisiness of the machines, better acceptability and tolerance by the patients, and better reliability. Validation programmes have been proposed and should be referred to. Limitations of the technique persist with intermittent recording in current practice. The reproducibility is limited in the short-term while recording over 24 h is acceptable. DIAGNOSIS AND PROGNOSIS: White-coat effect (WCE) is manifested as a transient elevation in blood pressure during the medical visit The frequency of this phenomenon, the size of the effect, age, sex and level of blood pressure (BP) or the situation of occurrence (general practitioner, specialist or nurse) have been interpreted differently. It does not seem that WCE predicts cardiovascular morbidity or mortality. White-coat hypertension (WCH) is diagnosed on the evidence of abnormal clinical measures of BP and normal ABPM. The latest upper limits of normality by ABPM recommended by the JNCVI are < 135/85 mmHg while patients are awake and < 120/75 mmHg while patients are asleep. If we accept these upper limits of normality in ABPM, WCH does not appear to be a real problem as regards risk factors or end-organ effects. In terms of prognosis, data are limited. Cardiovascular morbidity seems low in WCH but identical to that of hypertensive subjects in these studies. However, further studies are needed to confirm these results. WCH does not appear to benefit from anti-hypertensive treatment. It is obvious that the lower the BP regarded as the limit of normality, the less likely the occurrence of secondary effects of metabolism, or end-organ effects or complications in those classified as hypertensive. 24 HOUR CYCLE: One of the most specific characteristics of ABPM is the possibility of being able to discover modification or alteration of the 24 h cycle of BP. Non-dippers are classically defined as those who show a reduction in BP of less than 10/5 mmHg or 10% between the day (06.00-22.00 h) and the night, or an elevation in BP. In contrast, extreme dippers are those in whom the BP reduction is greater than 20%. CARDIOVASCULAR SYSTEM: The data remain inconclusive with regard to the existence of a consistent relationship between the lack of a nocturnal dip in blood pressure and target organ damage. As regards prognosis, it seems that an inversion of the day-night cycle is of pejorative significance. CEREBROVASCULAR SYSTEM: Almost all studies have shown that non-dippers had a significantly higher frequency of stroke than dippers. In contrast, too great a fall in nocturnal BP may be responsible for more marked cerebral ischaemia. RENAL SYSTEM: Non-dippers have a significantly elevated median urinary excretion of albumin. There is a significant correlation between the systolic BP and nocturnal diastolic BP, and urinary excretion of albumin. Various studies have confirmed the increased frequency of change in the 24 h cycle in hypertensive subjects at the stage of renal failure.

BP abnormalities should be considered as markers of an elevated risk in diabetic subjects but cannot be considered at present as predictive of the appearance of micro-albuminuria or other abnormalities. ABPM is thus of interest in type I or type II diabetes both in the initial assessment and in the follow-up and adaptation of treatment. PHARMACO-THERAPEUTIC USES: The introduction of ABPM has truly changed the means and possibilities of approach to the study of the effects of anti-hypertensive medications, with new possibilities of analysis such as trough-peak ratio smoothness index, etc.

To determine the relationship of day- and night-time blood pressure (BP) with the degree of albuminuria in subjects with non-insulin-dependent diabetes (NIDDM).

BP was determined hourly for 24 h in 27 NIDDM normotensive patients, and 10 age- and BMI-matched controls. Diabetic subjects were separated into normo- and microalbuminuric groups according to the urinary albumin excretion rate (AER < 15 and > or = 15 micrograms/min), respectively.

Non-dippers defined by a nocturnal fall in BP of less then 10/5 mmHg represented 68.8% of the normo- and 81.8% of the microalbuminuric patients. Microalbuminuric diabetics demonstrated a significantly higher ratio of night:day BP in comparison to controls, but not to normoalbuminuric diabetics. AER was significantly correlated with BP ratio in the normoalbuminuric, but not in microalbuminuric group.

Ambulatory 24-h BP monitoring is useful to find blunted nocturnal fall in BP even in normotensive NIDDM subjects with or without microalbuminuria. However, whether or not an increase in the night-time BP and/or the night:day ratio in NIDDM patients plays a pathogenetic role in the progression of diabetic nephropathy remains to be clarified.

Lack of the physiological nocturnal fall in blood pressure (BP) has been found in diabetics and it seems to be related to the presence of diabetic complications. The present study examined the changes in the nocturnal BP pattern of 8 normotensive insulin-dependent diabetic adolescents without nephropathy following improvement in glycemic control induced by an 8-day program of adequate diet and exercise. The same number of age- and sex-matched control subjects were studied. During the first and eighth nights of the program, BP was obtained by ambulatory BP monitoring. After a 10-min rest, 3 BP and heart rate (HR) recordings were taken and the mean values were considered to represent their awake values. The monitor was programmed to cuff insufflation every 20 min from 10:00 p.m. to 7:00 a.m. The glycemic control of diabetics improved since glycemia (212.0 +/- 91.5 to 140.2 +/- 69.1 mg/dl, P < 0.03), urine glucose (12.7 +/- 11.8 to 8.6 +/- 6.4 g/24 h, P = 0.08) and insulin dose (31.1 +/- 7.7 to 16.1 +/- 9.7 U/day, P < 0.01) were reduced on the last day. The mean BP of control subjects markedly decreased during the sleeping hours of night 1 (92.3 +/- 6.4 to 78.1 +/- 5.0 mmHg, P < 0.001) and night 8 (87.3 +/- 6.7 to 76.9 +/- 3.6 mmHg, P < 0.001). Diabetic patients showed a slight decrease in mean BP during the first night. However, the fall in BP during the nocturnal period increased significantly on the eighth night. The average awake-sleep BP variation was significantly higher at the end of the study (4.2 vs 10.3%, P < 0.05) and this ratio turned out to be similar to that found in the control group (10.3 vs 16.3%). HR variation also increased on the eighth night in the diabetics. Following the metabolic improvement obtained at the end of the period, the nocturnal BP variation of diabetics was close to the normal pattern. We suggest that amelioration of glycemic control may influence the awake-sleep BP and HR differences. This effect may be due at least in part to an attenuated insulin stimulation of sympathetic activity.

The aim of our study was to compare ambulatory blood pressure monitoring (ABPM) measures (mean systolic/diastolic blood pressure, diurnal rhythm, and pressure burden) in matched normo- and microalbuminuric (IDDM) adolescents and healthy controls. Twenty-four hour monitoring was undertaken in 39 normotensive (normal clinic blood pressure measurements) IDDM adolescents (22 normo- and 17 microalbuminuric subjects) and 23 controls. Subjects were matched for age, bodymass index, gender, and IDDM duration. Microalbuminuria was diagnosed on the basis of a urinary albumin excretion rate greater than 15 but less than 200 micrograms/min in two of the three 24-h urine collections. The microalbuminuric patients differed from the normoalbuminuric subjects and controls in having higher mean 24-h and overnight systolic pressure, loss of systolic diurnal rhythm and increased systolic and diastolic pressure burden. There were no differences between the three groups in diastolic blood pressure. The normoalbuminuric group differed from the controls only with respect to an increased systolic pressure burden. Microalbuminuric IDDM adolescents show similar, albeit milder changes in ABPM, to those reported in adults with microalbuminuria. We postulate that these milder changes represent an earlier phase to that observed in the adult population and that taken together, the adolescent and adult data suggests a specific order in the development of ABPM changes in diabetic subjects.

Twenty-four hour ambulatory blood pressure (ABP) was evaluated in 150 teenage and young adults with insulin-dependent diabetes mellitus (IDDM) to define high-risk subjects who are likely to develop early diabetic nephropathy. Their age range was 16-28 years with diabetes of 3.5-25.8 years duration. All subjects had office blood pressure (BP) measured, wore an ABP monitor for 24 h, and collected two or more timed urine samples for albumin excretion rates (AERs). Eighty-six subjects had no elevation of AER (< 7.6 micrograms/min), 29 subjects had borderline elevations (7.6-20 micrograms/min), 24 subjects had microalbuminuria (20.1-200 micrograms/min), and 11 had macroalbuminuria (> 200 micrograms/min). Age, gender, duration of diabetes, and single office BP readings were similar in the four groups (p > 0.05, logistic regression). All 24-h ABP parameters were significantly higher in subjects with diabetes having AER values greater than 7.6 micrograms/min when compared with healthy age- and gender-matched nondiabetic controls (p < 0.05, Dunnett's t test). The percent of nighttime systolic and diastolic ABP readings above the 90th percentile of normal for age, gender, and race and the percent of readings in the hypertensive range (> 140/90) were significantly related with AERs (p < 0.01; logistic regression). A higher percentage of ABP values above the 90th percentile for age, gender, and ethnic group or of ABP readings above hypertensive levels (> or = 140/90) are associated with diabetic renal disease.

In order to assess the characteristics of day-night blood pressure (BP) variation in normotensive and hypertensive non-insulin-dependent diabetic (NIDDM) patients with asymptomatic autonomic neuropathy, 54 NIDDM patients and 13 healthy control subjects were studied by casual BP measurements and 24-h ambulatory blood pressure monitoring. Signs but not symptoms of autonomic neuropathy were documented by results of standard cardiovascular function tests in each patient. Daytime (06:00-22:00) and nighttime (22:00-06:00) BP values were separately analyzed and delta day-night BP values and diurnal index were determined. Patients were classified as being normotensive or having hypertension according to the casual BP values and medical history. In normotensive NIDDM patients (n = 30), nighttime systolic BP was significantly higher, whereas delta day-night systolic and delta day night diastolic BP values as well as diurnal index were considerably lower than those in control subjects (n = 13). In hypertensive NIDDM patients (n = 24), similar alterations were found at higher BP levels. No significant difference was found in BP values if normoalbuminuric and microalbuminuric NIDDM patients were compared. 'Non-dipper' phenomenon could be found in normotensive and hypertensive NIDDM patients with asymptomatic autonomic neuropathy, suggesting that relative sympathetic overdrive due to incipient and predominantly parasympathetic impairment of cardiovascular innervation might play a role in early alterations of circadian BP variation.

Ambulatory blood pressure (AMBP) is of particular interest in diabetes because of the close association between elevated BP and diabetic nephropathy and the attenuated night drop in some diabetic subgroups: (1) Normoalbuminuric patients: If standardized for type of day (work or day off), coefficient of variation (CV) for 24 h AMBP is 2%-3% and 5%-6% for night/day ratio. The male-female difference in AMBP seen in healthy subjects is reduced in diabetes. Smoking did not significantly affect AMBP. AMBP is increased in patents with high normal urinary albumin excretion (UAE). Night/day ratio of AMBP and night heart rate is higher in long than short term diabetic patients. This difference in night/day ratio is not significant if the slightly higher UAE in long-term patients is accounted for. (2) Microalbuminuric patients: Diastolic night/day ratio is increased compared with healthy controls, with the value for normoalbuminuric patients in between. A large overlap between groups is evident. Thus the prognostic value of a single abnormal night/day ratio is doubtful. If divided into dippers and nondippers, no difference in extracellular- or plasma volume is found, but nondippers have a lower plasma aldosterone and arginine vasopressin level, possibly to counteract volume expansion. (3) Patients with overt nephropathy: A marked increased in AMBP and a clear reduction of the nocturnal blood pressure fall is seen. In conclusion, AMBP (but not night/day ratio) is highly reproducible. The association between elevated AMBP, elevated night/day ratio, and pathological UAE is detectable even in normoalbuminuric patients. The prognostic importance of abnormal circadian variation of BP is unsettled.

We studied 24-h ambulatory blood pressure (SBP, DBP), actual glycemic control assessed from seven blood glucose measurements, 16-h daytime and 8-h nighttime urinary excretion of albumin (UAE) and retinol-binding protein (URBP) in 20 normoalbuminuric (group A, nighttime UAE < 20 micrograms/min) and 20 microalbuminuric and low-proteinuric type I diabetic patients (group B, nighttime UAE 20-500 micrograms/min) matched for age and diabetes duration. Glycemic control was similar in the two groups. Daytime and nighttime SBP and DBP were higher in group B compared to group A (p < 0.01). Nighttime decrease in SBP and DBP correlated with nighttime decrease in UAE in group B (p < 0.05, p < 0.001), but not in group A. There was no correlation between BP and actual glycemic control in either group. We found higher daytime and nighttime URBP in group B compared to group A (p < 0.05). We conclude that, in microalbuminuric and low-proteinuric patients, daytime and nighttime BP was elevated but still in the normal or borderline range, and nighttime decrease in BP correlated with nighttime decrease in UAE but not with actual glycemic control. Increased URBP in these patients suggests slightly impaired proximal tubular function in early stages of diabetic nephropathy.

We studied a circadian blood pressure variation in relation to the progression of diabetic nephropathy in patients with non-insulin-dependent diabetes mellitus (NIDDM). Age, duration of diabetes, body mass index and glycemic control did not differ among the groups of patients with normo-, micro- and macroalbuminuria. None of the patients received antihypertensive drugs. There were no differences in renal and autonomic functions between normo- and microalbuminuric groups, but these functions were impaired in the macroalbuminuric group. The rise in blood pressure was more apparent in 24-h ambulatory blood pressure (AMBP), especially during night-time, as compared with casual blood pressure. Such blood pressure rise was in accordance with the progression of nephropathy. However, pulse rate did not differ among the three groups. The nocturnal fall in blood pressure was blunted in the micro- and macroalbuminuria groups, but evident in the normoalbuminuric group. In the latter, daytime systolic blood pressure (SBP) was significantly higher than night-time SBP (123 +/- 5 mmHg vs. 113 +/- 3 mmHg, P = 0.002). In contrast, in the former two groups of patients, there were no significant differences in SBP between daytime and night-time (134 +/- 9 mmHg vs. 134 +/- 9 mmHg, ns, for microalbuminuria and 159 +/- 8 mmHg vs. 165 +/- 7 mmHg, ns, for macroalbuminuria). Urinary albumin excretion was significantly correlated with night-time SBP (r = 0.48, P = 0.015), but not with daytime SBP (r = 0.30, ns).(ABSTRACT TRUNCATED AT 250 WORDS)

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.