Retinal changes and alterations in blood pressure and albumin excretion rate (AER) during exercise in type 1 diabetes

The association of retinal changes with exercise microalbuminuria and with changes in systolic and diastolic blood pressure (BP) were evaluated in 162 young subjects with insulin-dependent (type 1) diabetes mellitus. Higher systolic and diastolic BPs at rest or after 10 or 20 min of exercise were significantly associated with more severe retinal changes in the subjects with diabetes compared to controls (P less than 0.02; global ANOVA). The mean (+/- SEM) exercise albumin excretion rate (AER) was 17.6 +/- 3.1 if there was no evidence of retinopathy compared to 81.5 +/- 23.5 when only microaneurysms were detected and 467.1 +/- 133.3 when more severe retinopathy was present. The percentage of subjects with abnormal AERs for these three retinal groups was 13, 30 and 60, respectively. (P less than 0.0001, chi-square test). It is clear that retinal changes relate to early renal changes, as monitored by exercise AERs and changes in resting and exercise BPs. It is concluded that the renal and retinal microvascular changes occur concurrently in young subjects with type 1 diabetes.     

Relationship between albumin excretion rate and aortic stiffness in untreated essential hypertensive patients

OBJECTIVES: To evaluate, in a group of nondiabetic essential hypertensive patients with normal renal function, the relationship between albumin excretion rate (AER) and carotid-femoral pulse wave velocity (PWV), as an index of aortic stiffness. DESIGN: Cross-sectional study. SETTING: Outpatient hypertension clinic. SUBJECTS: Seventy patients with mild-to-moderate essential hypertension, aged 42 +/- 8 years, never pharmacologically treated. All subjects underwent routine laboratory tests, 24-h ambulatory blood pressure (BP) monitoring, measurement of carotid-femoral PWV, by means of a computerized method, and AER. RESULTS: Microalbuminuric patients (AER > or = 20 microg min(-1); n = 19), when compared with normoalbuminuric subjects, showed more elevated 24-h BP (136/88 +/- 10/10 vs. 128/83 +/- 7/6 mmHg; P < 0.001 and P = 0.013, for systolic and diastolic BP respectively) and higher values of carotid-femoral PWV (10.4 +/- 2 m s(-1) vs. 9.2 +/- 1.3; P = 0.006). This latter difference remained statistically significant, even after correction by ancova for 24-h systolic and diastolic BP, and body mass index (BMI, P = 0.016). Univariate regression analysis disclosed a tight correlation between AER and carotid-femoral PWV (r = 0.42; P = 0.0003). This association was confirmed in a multiple regression model (beta = 0.35; P = 0.009) in which, as independent variables, besides PWV, 24-h BP, age, serum glucose values, smoking status, gender and BMI, were added. CONCLUSIONS: Our results seem to confirm that microalbuminuria may represent the early renal manifestation of a widespread vascular dysfunction, and therefore it is an integrated marker of cardiovascular risk.     

Comparison of microalbuminuria in 2 blood pressure categories of prehypertensive subjects.

BACKGROUND: Subjects with high normal blood pressure (BP: systolic, 130-139 mmHg or diastolic, 85-89 mmHg) have higher cardiovascular risks compared with individuals with normal BP (systolic BP, 120-129 mmHg or diastolic BP, 80-84 mmHg). In the present study the prevalence of microalbuminuria and cardiovascular risk factors, as well as factors that influence microalbuminuria, were assessed in 2 groups of subjects with prehypertension. METHODS AND RESULTS: Of 2,678 prehypertensive subjects (1,689 men, 989 women), none had a history of diabetes or hypertension. Urine albumin excretion was measured by an immunoradiometric assay in a morning urine sample. The prevalence of microalbuminuria in the high normal BP group was higher than in the normal BP group (4.9% vs 2.8%, p=0.009). Subjects with high normal BP were older, and had higher prevalence of males and metabolic syndrome; larger waist circumference and body mass index, higher levels of triglycerides, fasting blood glucose, uric acid and ferritin, and lower levels of high-density lipoprotein-cholesterol were more common in subjects with high normal BP than in those with normal BP. Multiple logistic regression analysis showed that the high normal BP category had an independently significant association with microalbuminuria (odds ratio=1.692, 95% confidence interval 1.097-2.611). CONCLUSIONS: Subjects with high normal BP have greater risk factors for cardiovascular disease, including microalbuminuria, than those with normal BP. Further investigations are needed to ascertain whether more positive treatment strategies for the early prevention of cardiovascular disease might be needed for individuals with high normal BP.     

Clinical significance of microalbuminuria in Japanese subjects with non-insulin-dependent diabetes

In order to elucidate the clinical significance of microalbuminuria in non-insulin-dependent diabetes mellitus (NIDDM), 62 Japanese subjects with NIDDM and without proteinuria were followed for three years. After the three-year follow up, four (19%) of 21 microalbuminuric patients—albumin excretion rates (AER) greater than 15 μg/min—developed overt proteinuria, while none of the 42 normoalbuminuric patients did. Among these normoalbuminuric patients, eight patients (19.5%) developed microalbuminuria. The microalbuminuric patients who developed overt proteinuria had higher AER at the beginning of the study than the patients who stayed microalbuminuric. The patients who developed microalbuminuria showed a significantly higher systolic blood pressure in the final year than the patients who stayed normoalbuminuric. These results indicate that microalbuminuria precedes overt proteinuria in Japanese NIDDM, and progression of diabetic nephropathy is rapid and associated with a rise in blood pressure.     

Prior long term glycaemic control and insulin therapy in insulin-dependent diabetic adolescents with microalbuminuria

Adolescence seems to be a period of increased risk for the initiation of diabetic renal disease in insulin-dependent diabetic children. Poor glycaemic control is a risk factor for diabetic nephropathy. We have therefore evaluated prior long-term glycaemic control in 23 diabetic adolescents with microalbuminuria (albumin excretion rate (AER) 20-200 micrograms/min, median 39.0 micrograms/min) and in 23 matched diabetic controls with AER less than 20 micrograms/min (median 9.3 micrograms/min). Glycaemic control was assessed by mean HbA1 and clinic blood glucose levels over a period ranging from 12 to 84 months (median 48 months). Mean HbA1 was 13.6 +/- 2.0% in the microalbuminuric subjects, compared to 11.5 +/- 2.2% in the controls (P less than 0.002); mean blood glucose levels were 13.5 +/- 3.0 and 11.4 +/- 3.0 mmol/l, respectively (P less than 0.02). There appeared to be a 'threshold effect' (mean HbA1 greater than 12.0%), above which the development of microalbuminuria was more likely. More patients with microalbuminuria than controls had been treated with a single rather than twice-daily insulin injections (P less than 0.001), and glycaemic control was significantly worse in patients treated with one injection. We conclude that poor long term glycaemic control is a risk factor for microalbuminuria, and that improving control during childhood is likely to reduce the prevalence of later microalbuminuria. Two insulin injections, of combined intermediate and short-acting preparations, are more likely to provide better control than a single daily insulin dose.     

A screening test for microalbuminuria in type 1 (insulin-dependent) diabetes

In this study we evaluated the acceptability of using the first morning urine albumin concentration (FMAC) and the first morning urine albumin/creatinine (FMA/C) ratio as an indirect estimation of timed albumin excretion in order to screen for microalbuminuria in a large diabetic population. Urinary albumin excretion rate (AER) was determined in samples from 4-h urine collection in 99 type 1 diabetic patients aged 30 +/- 10 years with a mean duration of diabetes of 15 +/- 8 years. The results of timed albumin excretion were successively compared with single-void first morning samples. On the basis of AER, 46 patients were normoalbuminuric (AER less than 20 micrograms/min), 28 microalbuminuric (AER 20-200 micrograms/min), and 25 proteinuric (AER greater than 200 micrograms/min). The relationship of 4-h AER to FMAC and FMA/C ratio was highly significant (r = 0.96 and r = 0.98 respectively). High sensitivity and specificity were found when cut-offs of 20 micrograms/ml and 2.5 mg/mmol were selected for albumin concentration and albumin/creatinine ratio respectively to discriminate between normal and elevated albuminuria. It is concluded that the measurements of albumin concentration and albumin/creatinine ratio in first morning urine samples are highly representative of 4-h timed albumin excretion. Because of their sensitivity, specificity and simplicity to perform, the tests proposed might be used in routine diabetic care and as a screening test for microalbuminuria in type 1 (insulin-dependent) diabetic patients. The not negligible day-to-day variability in albumin excretion confirms the need of several measurements to establish the presence of abnormal levels of albuminuria above all in patients with borderline values and/or clinically unstable metabolic control.     

Comparison of 3 methods of measurement of blood pressure in insulin-dependent diabetic patients with or without incipient diabetic nephropathy]

Incipient diabetic nephropathy is characterized by a urinary albumin excretion (UAE) between 30-300 mg/24 h and a slightly elevated blood pressure. We measured blood pressure in 14 insulin-dependent diabetic subjects (IDDs) with persistent microalbuminuria (group A) and 50 IDDs with persistent normoalbuminuria (group B) using 3 different methods: 1) Sphygmomanometer, by a nurse, on supine position since 10 min, on the third day of hospitalization; 2) automatic device (Dinamap), on supine position, every 5 min, during 30 min; 3) ambulatory blood pressure (Spacelab 90202 every 15 min between 8 a.m. and 8 p.m.; values obtained with this last method were compared to the mean values of healthy subjects of same age. Recorded UAE was the median value of 3 twenty-four-hours urines. Blood pressure was not different among the two groups with any of the three methods: 1) SBP/DBP A: 136 +/- 14/81 +/- 9 vs B: 131 +/- 13/78 +/- 8 mmHg; ns; 2) SBP/MBP/DBP A: 134 +/- 17/96 +/- 12/79 +/- 10 vs B: 127 +/- 13/90 +/- 10/74 +/- 10 mmHg; ns; 3) A: 132 +/- 12/97 +/- 11/84 +/- 9 vs B: 127 +/- 11/91 +/- 9/82 +/- 12 mmHg; ns. There were no concordance between microalbuminuria/normoalbuminuria and systolic or diastolic blood pressure higher/lower than the mean of the healthy subjects (X2 = 1.6; ns). However, UAE was significantly related to MBP measured with 1): r = 0.29; p = 0.027, but not with 2): r = 0.24; ns, nor with 3): r = 0.26; ns. These results suggest that: 1-blood pressure of IDDs should be measured in standardized conditions; 2-diurnal ambulatory blood pressure recording does not predict incipient nephropathy in these subjects.     

Correlation of urinary albumin and beta-2-microglobulin and growth hormone excretion in patients with diabetes mellitus and short stature

We examined the correlation between urinary GH, urinary albumin, and beta-2-microglobulin excretion to determine how the excretion of GH relates to markers of renal glomerular and tubular function. Urinary albumin and GH excretion was determined in timed daytime and nighttime urine collections obtained from both subjects with diabetes mellitus and subjects with short stature. For subjects with diabetes, urinary GH excretion rate correlated highly with urinary albumin concentration and excretion rate in both the range of 0 to 1.6 g/L (r = 0.75), P less than 0.001) and in the microalbuminuria range, 0 to 0.4 g/L (r = 0.53, P less than 0.001). Changes in GH and albumin excretion occurred in parallel in 71% of the subjects with diabetes and elevated albumin excretion. The mean GH excretion rate was higher in the group with elevated albumin excretion rate (AER) during both day and night compared to the group with microalbuminuria during the day and normal AER at night. For subjects with short stature, the mean albumin excretion rate was 0.7 +/- 1.3 micrograms/min (range 0.05-8.3 micrograms/min) using a sensitive enzyme-linked immunosorbent assay to measure albumin concentration. The correlation of GH and albumin excretion rates for the subjects with short stature was not statistically significant (r = 0.14, P less than 0.5). About half of the subjects with diabetes and elevated AER (greater than 10 micrograms/min) had a GH excretion rate within the range observed in subjects with short stature. The GH and albumin excretion rate were not correlated in this group. There was a positive correlation of both albumin and GH excretion rate with age in the subjects with diabetes. Urinary GH and beta-2-microglobulin excretion rates were determined in a larger group of subjects with diabetes and a separate group with short stature. Urinary GH and beta-2-microglobulin excretion were correlated both in subjects with diabetes (r = 0.46, P less than 0.001) and with short stature (r = 0.64, P less than 0.001). The association was present in urine collected either during the day or night. The mean GH excretion rate of the group with diabetes was greater than the group with short stature. In conclusion, there was an association of urinary GH and albumin excretion rate in subjects with abnormal glomerular function as indicated by elevated albumin excretion rate. An association of urinary GH and beta-2-microglobulin excretion was observed in subjects with normal tubular function.(ABSTRACT TRUNCATED AT 400 WORDS)     

High blood pressure is a risk factor for the development of microalbuminuria in Japanese subjects with non-insulin-dependent diabetes mellitus.

In this study, 52 nonproteinuric Japanese patients with non-insulin-dependent diabetes (NIDDM) were followed from 1985 to 1990 to investigate the rate of development and progression of microalbuminuria and the factors which influence it. In 1985, 34 patients were normoalbuminuric, and 18 patients were microalbuminuric. Five years later, 11 of 34 initially normoalbuminuric patients (32.4%) developed microalbuminuria, and 6 of 18 initially microalbuminuric patients (33.3%) developed overt proteinuria. At the beginning of the study, hypertension existed more frequently in the patients who later developed microalbuminuria (8 of 11, 72.7%) than in the patients who stayed normoalbuminuric (4 of 23, 17.4%). Age-adjusted values of mean blood pressure (+/- SEM) at the beginning of the study in the patients who developed microalbuminuria (98.2 +/- 3.4 mm Hg, n = 11) were significantly higher than those in the patients who stayed normoalbuminuric (87.3 +/- 2.4 mm Hg, n = 23). In six patients who developed overt proteinuria, initial urinary albumin excretion rates (AER) were higher than those in the patients who stayed microalbuminuric, and four patients who presented with initial AER greater than 100 micrograms/min all developed overt proteinuria. These results indicate that, in Japanese patients with NIDDM, the rate of development of microalbuminuria is faster than that reported in Caucasian IDDM, and preexisting hypertension with relatively poor control of blood pressure may be a risk factor for the development of microalbuminuria.     

Acute and long-term renal effects of angiotensin converting enzyme inhibition in normotensive, normoalbuminuric insulin-dependent diabetic patients

Glomerular filtration rate (GFR) (thalamate clearance), renal plasma flow (RPF) (hippuran clearance), and urinary albumin excretion rate (AER) were measured in 10 normoalbuminuric, normotensive insulin-dependent diabetic patients and 8 normal subjects before and during acute angiotensin converting enzyme (ACE) inhibition by means of enalapril (10 mg IV). The effect of placebo versus enalapril (30 mg day-1) was also studied for 3-month treatment periods in the insulin-dependent diabetic patients. Acute ACE-inhibition caused a decline in filtration fraction (FF) from 0.259 +/- 0.011 (+/- SE) to 0.237 +/- 0.013 (2p less than 0.01) in the diabetic patients, and from 0.210 +/- 0.010 to 0.188 +/- 0.006 (2p less than 0.02) in the normal subjects. Mean arterial blood pressure was lowered from 90 +/- 1 to 84 +/- 2 mmHg (2p less than 0.01) and from 91 +/- 1 to 86 +/- 2 mmHg (2p less than 0.05). No significant change in blood glucose, AER or fractional albumin excretion (theta Alb) was seen in either group. After 3 months of enalapril treatment FF was decreased from 0.253 +/- 0.011 to 0.235 +/- 0.011 (2p less than 0.05), AER from 5.6 x/ divided by 1.7 to 4.3 x/divided by 1.6 micrograms min-1 (2p less than 0.01) and theta Alb from 1.22 +/- 0.22 x 10(-6) to 0.92 +/- 0.12 x 10(-6) (2p less than 0.02). The decline in total renal resistance was not significant (0.175 +/- 0.013 to 0.165 +/- 0.012 mmHg ml-1 min-1) and significant changes in GFR, RPF, mean arterial pressure or HbA1c were not observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of combination therapy of angiotensin-converting enzyme inhibitor plus calcium channel blocker on urinary albumin excretion in hypertensive microalbuminuric patients with type II diabetes.

It has been demonstrated that antihypertensive treatment of hypertensive diabetic patients is quite effective in preventing macrovascular and microvascular complications and improving prognosis. Nevertheless, the target blood pressure level of antihypertensive treatment in hypertensive diabetic patients with microalbuminuria (i.e., with early diabetic nephropathy) remains to be established. In this study, we evaluated the effect of intensive blood pressure control (diastolic blood pressure <80 mmHg) on urinary albumin excretion in hypertensive, type II diabetic patients with microalbuminuria. We examined the effects of a combination therapy using an angiotensin-converting enzyme (ACE) inhibitor plus a long-acting calcium channel blocker (amlodipine), and compared them with the effect of an ACE inhibitor alone. Thirty hypertensive, type II diabetic patients with microalbuminuria were treated with either an ACE inhibitor alone (group I, n=17) or an ACE inhibitor plus amlodipine (group II, n=13) for 32 weeks. With treatment, blood pressures in both groups were significantly reduced, and diastolic blood pressure was lowered to a much greater extent in group II (76 +/- 2 mmHg) than in group I (83 +/- 2 mmHg, p < 0.05). Although the urinary albumin excretion rate was decreased in both groups, the decrease attained statistical significance only in group II (from 141 +/- 25 mg/day to 69 +/- 18 mg/day, p < 0.05); the extent of reduction in microalbuminuria during antihypertensive treatment was significantly greater in group II (50 +/- 10%) than in group I (14 +/- 13%, p < 0.05). In conclusion, this study showed that in hypertensive microalbuminuric type II diabetic patients, the combination of an ACE inhibitor plus amlodipine resulted in a more pronounced decreased in blood pressure (diastolic blood pressure <80 mmHg) and a greater reduction in urinary albumin excretion than did use of an ACE inhibitor alone. This combination strategy should thus be a more effective tool for obtaining optimal blood pressure control in patients with diabetic nephropathy.     

Low prevalence of microalbuminuria in normotensive patients with insulin-dependent diabetes mellitus

We studied the prevalence of microalbuminuria (urinary albumin excretion rate [UAER] greater than 20 micrograms/min less than or equal to 200 micrograms/min) as determined in a single, timed, overnight urine collection in 156 normotensive (BP less than 140/90), Albustix negative subjects with type 1 diabetes and its association with arterial blood pressure, the duration of diabetes, levels of glycosylated hemoglobin, body mass index, daily insulin dose and serum cholesterol. Nineteen subjects (12.2%) had a UAER in the microalbuminuric range. The microalbuminuric patients had a significantly longer duration of diabetes, 21 +/- 2 vs 15 +/- 1 years (P less than 0.01), higher diastolic blood pressure, 80 +/- 2 vs 76 +/- 1 mmHg (P less than 0.05) and serum cholesterol concentration, 206 +/- 11 vs 186 +/- 3 mg/dl (P less than 0.05) than did the normoalbuminuric subjects. There were no differences between the normoalbuminuric and microalbuminuric subjects in terms of age, systolic blood pressure, body mass index, daily insulin dose or glycosylated hemoglobin levels. These data indicate that the prevalence of microalbuminuria in type 1 diabetes has probably been overestimated in previous studies due to the inclusion of patients with hypertension. Thus, microalbuminuria, rather than being a predictor of the development of diabetic renal disease, may indicate the presence of diabetic nephropathy with rising blood pressure levels. Further investigation is needed to clarify the relationship between microalbuminuria and coronary risk factors such as serum cholesterol and diastolic blood pressure levels.     

Predictors of the development of microalbuminuria in patients with Type 1 diabetes mellitus: a seven-year prospective study

Aims To determine risk factors for the development of persistent microalbuminuria (albumin excretion rate (AER) ≥ 30 μg/min) in Type 1 diabetes mellitus. Methods One hundred and forty-eight initially normotensive Type 1 diabetic patients with normal albumin excretion (< 30 μg/min) were followed prospectively in hospital diabetes outpatient clinics for a median of 7 years. Main outcome measures were: progression to persistent microalbuminuria (albumin excretion rate ≥ 30 μg/min on at least two consecutive occasions); rate of change of albumin excretion rate; development of arterial hypertension (systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 95 mmHg or commencement of antihypertensive therapy). Results In a median follow-up period of 7 years (range 6 months to 8 years), 14 patients progressed to persistent microalbuminuria, a cumulative incidence of 11% (95% confidence interval 6.36–16.94). AER remained persistently < 30 μg/min in 109 subjects and 25 developed intermittent microalbuminuria. In those who developed persistent microalbuminuria, baseline AER (16.2 (13.9–19.1) vs. 5.2 (3.8–9.2) μg/min, P < 0.01), blood pressure (136 (123–148)/80 (74–85) vs. 121 (118–124)/72 (70–73) mmHg, P < 0.05), and HbA₁ (10.2 (9.1–11.4) vs. 9.0 (8.7–9.4)%, P < 0.05) were higher than in those who continued to have persistent normoalbuminuria, retinopathy was more severe and height (1.64 (1.57–1.71) vs. 1.70 (1.69–1.72) m, P < 0.05) less. In multivariate analysis, baseline AER was the strongest predictor of the development of persistent microalbuminuria (P < 0.0001), followed by mean arterial pressure (P = 0.02) and HbA₁ (P = 0.05). Conclusions The level of AER, raised blood pressure and poor glycaemic control are the most important predictors of the development of microalbuminuria in Type 1 diabetes.     

A nation-wide cross-sectional study of urinary albumin excretion rate, arterial blood pressure and blood glucose control in Danish children with type 1 diabetes mellitus. Danish Study Group of Diabetes in Childhood

Nation-wide screening for microalbuminuria in Denmark was performed in 22 paediatric departments treating children with Type 1 diabetes. Over a period of 6 months 1020 children (less than or equal to 12 years) and adolescents (greater than 12 to 19 years) were screened (81% of total). Of these, 957 (94%) performed at least two timed overnight urine collections. In 209 non-diabetic subjects the upper 95% limit for normal albumin excretion rate (AER) was 20 micrograms min-1. Mean overnight AER was significantly (p less than 0.001) elevated in diabetic (3.0 x/divided by 2.3 (SD tolerance factor) micrograms min-1) and in non-diabetic (2.5 x/divided by 2.2 micrograms min-1) adolescents compared with diabetic (1.7 x/divided by 2.1 micrograms min-1) and non-diabetic (1.3 x/divided by 2.2 micrograms min-1) children. In the diabetic patients AER was positively correlated with the body surface area and age. Among the patients with Type 1 diabetes, 4.3% (18 males and 23 females) had AER greater than 20 to 150 micrograms min-1 (persistent microalbuminuria). A further 7 adolescents (0.7%) had overt proteinuria (greater than 150 micrograms min-1). Clinical data for the 41 diabetic patients with AER greater than 20 to 150 micrograms min-1 were compared with those for 569 diabetic adolescents with AER less than or equal to 20 micrograms min-1 and duration of diabetes more than 2 years. The group with AER greater than 20 to 150 micrograms min-1 had significantly higher mean age (16.5 years) than the group with AER less than or equal to 20 micrograms min-1 (15.0 years; p less than 0.001). Females with AER greater than 20 to 150 micrograms min-1 had significantly higher mean HbA1c level (10.8 +/- 1.9%) than those with AER less than or equal to 20 micrograms min-1 (9.8 +/- 1.9%, p less than 0.003); they also had impaired linear growth (standard deviation score -0.25 vs + 0.16; p = 0.003). These associations were not found in males. Mean body mass index (BMI) was significantly increased in both females (22.2 +/- 2.9 kg m-2) and males (20.8 +/- 2.7 kg m-2) with AER greater than 20 to 150 micrograms min-1, compared with diabetic patients with AER less than or equal to 20 micrograms min-1 (females 20.8 +/- 3.0 kg m-2, p = 0.02; males 19.7 +/- 2.4 kg m-2, p less than 0.006).(ABSTRACT TRUNCATED AT 400 WORDS)     

Long term reduction of microalbuminuria after 1 year of angiotensin converting enzyme inhibition by perindopril in hypertensive insulin-treated diabetic patients

We studied the effects of perindopril, an angiotensin converting enzyme (ACE) inhibitor administered during 12 months, on creatinine clearance, albuminuria and glycaemic control in diabetic subjects with mild to moderate hypertension. After 1 month placebo, 40 insulin-treated patients were divided into 3 groups based upon their urinary albumin excretion rate (AER). Group I had a normoalbuminuria (AER less than 15 mg/24 h), group II had a microalbuminuria (AER : 15-150 mg/24 h) and group III had a macroproteinuria (AER greater than 150 mg/24 h and Albustix (+)). They were given perindopril, 4 to 8 mg orally once daily, and received a stable diet. Diastolic blood pressure was normalized within the first 3 months in 80% of the patients. From these, 28 (14.7 and 7 from groups I, II and III respectively) were followed during a total active treatment period of 12 months. They were matched for age, duration of diabetes and hypertension, systolic and diastolic blood pressures, daily insulin dose, postprandial plasma C-peptide and quality of glycaemic control. Mean supine diastolic blood pressure was decreased by 15 and 18% at 1 and 12 months respectively. Heart rate was not significantly modified. At 3 months, plasma ACE activity was nearly totally inhibited while plasma renin activity was markedly increased. In patients of group II, microalbuminuria was reduced from 66 +/- 13 (mean +/- SEM after placebo) to 39 +/- 6 mg/24 h after 1 month perindopril and this effect was maintained at 12 months. In group I, albuminuria remained within the normal range. In group III, macroproteinuria was not consistently modified by perindopril.(ABSTRACT TRUNCATED AT 250 WORDS)     

The prevalence of micro-albuminuria and glomerular hyperfiltration in young patients with IDDM

We have assessed the prevalence of two risk factors for diabetic nephropathy, i.e., micro-albuminuria and a raised glomerular filtration rate (GFR), in 127 insulin-dependent diabetic patients aged 13-36 years. Micro-albuminuria (albumin excretion rate (AER) 20-200 micrograms/min) was found in 46 subjects (36%) and GFR was elevated (greater than 135 ml/min/1.73 m2) in 43 (34%). The prevalence of supranormal GFR declined and that of micro-albuminuria rose progressively with the increasing duration of diabetes. While age and sex distribution were similar in subjects with and without raised AER, duration of diabetes was significantly longer, blood pressure (BP) was significantly greater and age of onset was lower in the micro-albuminuria group. Blood pressure was significantly elevated only in the patients with AER of 70-200 micrograms/min; there was a linear trend for BP to rise as AER increased. Stepwise logistic regression analysis indicated that duration of diabetes (P less than 0.0001), age of onset of diabetes (P less than 0.005) and current glycaemic control (HbA1) (P less than 0.01) were risk factors for micro-albuminuria. The association with a rising blood pressure appears to be secondary to the renal involvement. In this cross-sectional study an association of micro-albuminuria with a raised GFR could not be demonstrated.     

Beneficial effect of lisinopril plus telmisartan in patients with type 2 diabetes, microalbuminuria and hypertension

Angiotensin-converting enzyme (ACE) inhibitors have favourable effects on hypertension and diabetic nephropathy, but persistent use may result in incomplete blockade of the renin-angiotensin system. Long-term effects of dual blockade using the ACE inhibitor lisinopril and the long-acting angiotensin II receptor blocker (ARB) telmisartan on blood pressure and albumin excretion rate (AER) were evaluated. Patients with type 2 diabetes mellitus, hypertension (systolic blood pressure [SBP] >or=140 mmHg or diastolic blood pressure [DBP] >or=90 mmHg) and microalbuminuria (AER 30-300 mg/24h) received 20mg of lisinopril or 80 mg of telmisartan once a day for 24 weeks. Patients were then randomised to continuing treatment with the respective monotherapy or with lisinopril plus telmisartan for a further 28 weeks. Significant (P<0.001) declines in SBP (11.1 mmHg versus 10.0 mmHg), DBP (5.6 mmHg versus 5.3 mmHg) and AER (98 mg/24 h versus 80 mg/24 h) were achieved with lisinopril (n=95) or telmisartan (n=97), respectively, after 24 weeks. Subsequent treatment with lisinopril plus telmisartan for 28 weeks resulted in further significant reductions (P<0.001) in SBP, DBP and AER compared with either monotherapy. All treatments were well tolerated. Lisinopril plus telmisartan thus provides superior blood pressure and AER control than either monotherapy. We conclude that use of dual blockade may provide a new approach to prevention of diabetic nephropathy in patients with type 2 diabetes, hypertension and microalbuminuria.     

Diurnal blood pressure pattern may predict the increase of urinary albumin excretion in normotensive normoalbuminuric type 1 diabetes mellitus patients

To characterise the relationship between diurnal blood pressure and the subsequent increase of urinary albumin excretion (UAE) in normotensive normoalbuminuric type 1 diabetic patients, ambulatory blood pressure monitoring (ABPM) was performed in 53 patients, who were then followed for 5 years. Albumin excretion rate changed from 12.4 (8.9-17.2) to 29.3 (15.2-47.0) mg/day. Macroalbuminuria developed in 2 (3.8%), microalbuminuria in 22 (41.5%) patients, 29 (54.7%) remained normoalbuminuric. Night-time diastolic blood pressure was significantly higher (64.3+/-6.5 vs. 60.9+/-5.5 mmHg, P<0.05), diastolic diurnal index significantly lower (15.5+/-9.7 vs. 22.3+/-6.2%, P<0.01) in patients who later progressed to micro- or macroalbuminuria. Diastolic diurnal index (r=-0.40; P<0.01) and nocturnal diastolic pressure (r=0.35; P<0.01) were correlated to the change in albumin excretion. In a multivariate analysis model with the change of albumin excretion as dependent, and means and diurnal indices of systolic and diastolic blood pressure, baseline UAE, cholesterol, triglycerides, HbA1c and retinopathy as independent parameters (r=0.68; P=0.001), diurnal index for diastolic blood pressure (beta=-0.30; r=0.013), baseline HbA1c (beta=0.32; P=0.010) and retinopathy (beta=0.44; P=0.001) were significant independent correlates. We conclude that the relative increase of nocturnal blood pressure is associated with the subsequent increase of albuminuria, which in turn is predictive of overt diabetic nephropathy.     

24-h Ambulatory blood pressure in patients with ECG-determined left ventricular hypertrophy: left ventricular geometry and urinary albumin excretion-a LIFE substudy

This study was undertaken to evaluate the relationships among left ventricular (LV) geometric patterns and urinary albumin excretion in patients with hypertension and electrocardiographic (ECG) LV hypertrophy. In 143 patients with stage II-III hypertension, 24-h ambulatory blood pressure (BP) monitoring, single urine albumin determination, and echocardiography were performed after 14 days of placebo treatment. Mean age was 68+/-7 years, 35% were women, body mass index was 28+/-5 kg/m(2), LV mass index (LVMI) was 125+/-26 g/m(2), and 24% had microalbuminuria. The mean office BP was 176+/-15/99+/-8 mmHg and the mean daytime ambulatory BP was 161+/-18/92+/-12 mmHg. Ambulatory BP, but not office BP, was higher among albuminuric compared to normoalbuminuric patients. In patients with established hypertension, daytime pulse pressure and office BP were different in the four patterns of LV geometry, with the highest pressure in those with abnormal geometry. Furthermore, microalbuminuria was more frequent in hypertensive patients with LV hypertrophy than in those with either normal geometry or concentric remodelling. White coat hypertensives (10%) showed lower LVMI and no microalbuminuria compared to patients with established hypertension. There were no differences in the prevalence of nondippers (26%) among the four LV geometric patterns or in microalbuminuria. In conclusion, increased daytime pulse pressure and office BP were associated with increased prevalence of abnormal LV geometry. Microalbuminuria was more frequent in groups with concentric and eccentric LV hypertrophy. Ambulatory BP, but not office BP, was higher in albuminuric than normoalbuminuric patients. With regard to the relationship among BP, LV geometric patterns, and urine albumin excretion in this population, 24-h ambulatory BP did not provide additional information beyond the office BP.     

Comparative effects of angiotensin converting enzyme inhibitors and calcium inhibitors related to baseline ambulatory blood pressure. A French multicenter study]

OBJECTIVE: This multicenter study was aimed at determining whether the baseline ambulatory blood pressure (BP) level does influence the efficacy of angiotensin-converting enzyme inhibitors (CEI) and that of calcium antagonists (CA) to the same degree. METHODS: The BP recordings of 236 patients with mild to moderate hypertension were reviewed: these subjects previously entered clinical trials comprising a mean 2-week placebo period and a mean 6-week active treatment phase (CEI = 115, CA = 121). The 24-hour baseline ambulatory BP was considered as high when greater than 139/87 mmHg, according to Staessen's meta-analysis. RESULTS: In the patients with an high baseline ambulatory BP, CEI and CA have had roughly a similar effect (reduction in systolic = 9.5 +/- 7.8% vs 7.7 +/- 6.3%, NS; reduction in diastolic = 9.8 +/- 8.6% vs 8.3 +/- 5.8%, NS). Conversely, the patients with a baseline ambulatory BP level lower than or equal to 139/87 mmHg experienced a greater reduction in ambulatory BP with CEI than with CA (systolic = 7.9 +/- 7.0% vs 0.6 +/- 6.7%, p = 0.0001; diastolic: 5.0 +/- 7.4% vs 1.9 +/- 7.6%, p = 0.040). Finally, further analysis found the threshold of drug efficacy to be 120/80 and 135/85 mmHg in CEI and CA patients respectively. CONCLUSIONS: 1) CEI are more effective than CA in patients with a low ambulatory BP only. 2) The risk of a visceral hypoperfusion seems however to be limited, since CEI do not reduce diastolic ambulatory BP further, when its baseline level is lower than 80 mmHg.