Microalbuminuric Group Research Articles

Endothelial dysfunction in Type 2 diabetic subjects with and without microalbuminuria.

The primary aim of this study was to determine whether microalbuminuria is associated with endothelial dysfunction in Type 1 diabetes mellitus. The secondary aim was to determine whether any reported biochemical markers of cardiovascular risk are associated with endothelial dysfunction in this group. Measurements were made of the vasodilatory responses of the brachial artery to post-ischaemic hyperaemia and to sublingual glyceryl trinitrate (GTN) (causing endothelium-dependent and endothelium-independent dilation, respectively) using a high-resolution ultrasound technique in 18 Type 1 diabetic patients with microalbuminuria, 18 age and sex-matched normoalbuminuric Type 1 diabetic patients and 18 non-diabetic control subjects. There was a significant reduction in flow-mediated dilation (FMD) in microalbuminuric and normoalbuminuric diabetic patients compared with control subjects (2.4% (95% confidence interval (CI) 1.0-3.8%) and 2.3% (95% CI 0.7-3.9%) respectively vs. 6.3% (95% CI 5.1-7.5%), P<0.0001) but no difference in GTN-mediated dilation (14.7% (95% CI 10.7-18.7%) and 15.2% (95% CI 11.2-19.2%) vs. 18.7% (95% CI 16.1-21.3%), P = 0.09). There was no significant difference in FMD, however, between the microalbuminuric group and normoalbuminuric group (P=0.45). FMD was not significantly associated with urinary albumin-creatinine ratio, glycosylated haemoglobin, plasma glucose, lipid or lipoprotein concentrations in diabetic patients. There was a positive correlation between active transforming growth factor (TGF)-beta concentration, a novel biochemical marker of macrovascular disease, and FMD in diabetic patients (r=0.36, P<0.05). GTN-mediated dilation was positively associated with HDL-cholesterol concentration (r = 0.49, P = 0.002) but not with other biochemical variables (including active TGF-beta concentration). Active TGF-beta concentration was not associated with degree of microalbuminuria or other biochemical parameters. These data suggest that endothelial dysfunction occurs in Type 1 diabetic patients regardless of urine albumin status. Endothelial dysfunction appears therefore to predate the development of microalbuminuria as a marker for the development of coronary artery disease. It is also concluded that low plasma levels of active TGF-beta are associated with an impaired endothelial response and this may provide a useful tool for identifying Type 1 diabetic patients at a greater risk of coronary artery disease.

Autonomic nerve function in adolescents with Type 1 diabetes mellitus: relationship to microalbuminuria.

Thirty adolescent patients with Type 1 diabetes mellitus and microalbuminuria were studied for evidence of early autonomic neuropathy. Using tests involving cardiovascular and pupillary reflexes, the adolescents were compared with a normoalbuminuric group of patients with diabetes, who were matched for age, sex, puberty and duration of diabetes. There was an increased prevalence of autonomic nerve dysfunction in the patients with microalbuminuria. These patients had higher resting heart rates (86 beats/min in the microalbuminuric group vs. 77 beats/min in normoalbuminuric controls, P = 0.002), and impaired pupillary dilatation in darkness (pupillary diameter % 56.5% vs. 62.5%, P = 0.003). Patients with microalbuminuria also had poorer long term glycaemic control (mean HbA1C 8.7% vs. 7.8%, P = 0.002) and higher blood pressures (systolic 125 vs. 116 mmHg, P = 0.001; diastolic 69 vs. 62 mmHg, P = 0.0001; mean arterial pressure 90 vs. 83 mmHg, P = 0.002) than those with normal urinary albumin excretion. Microalbuminuria and autonomic nerve dysfunction co-exist in patients with Type 1 DM. Longitudinal studies will determine whether these findings have implications for the identification of patients at higher risk of progression of early renal complications.

Increased left ventricular systolic function in insulin dependent diabetic patients with normal albumin excretion.

Alterations in cardiovascular function may be an aetiological factor for the development of microalbuminuria in patients with insulin-dependent diabetes mellitus. We studied cardiac function with echocardiography in relation to the degree of albuminuria in 27 insulin-dependent diabetes mellitus patients and 13 healthy subjects. Patients were grouped according to urinary albumin excretion: <20 microg x min(-1) (normoalbuminuric), and 20 to 200 microg x min(-1) (microalbuminuric). None were or had been treated with cardiovascular drugs. The normoalbuminuric patients had a higher heart rate, mean velocity of circumferential shortening, stroke velocity index (a measure of contractility), and aortic peak velocity than controls. No difference in diastolic function was present. In the microalbuminuric group, the stroke velocity index was comparable to values observed in healthy subjects. The increased systolic performance (heart rate and contractility) may contribute to the renal hyperperfusion and glomerular hyperfiltration observed in insulin-dependent diabetes mellitus patients before the development of micro- and in turn macroalbuminuria. The possible cause effect mechanisms should be further studied, as preventive medical treatment of the hypercontractile heart is possible. In conclusion, cardiac contractility is increased in insulin-dependent diabetes mellitus patients with normoalbuminuria and returns to levels observed in healthy subjects when microalbuminuria develops.

Diurnal blood pressure variation and albuminuria in normotensive patients with insulin-dependent diabetes mellitus.

Abnormalities of the systemic blood pressure are closely associated with the development of diabetic nephropathy. Our aim was to examine the relationship between diurnal blood pressure pattern and albuminuria in insulin-dependent normotensive diabetic patients before the development of overt nephropathy. Urinary albumin excretion rates were determined by radioimmunoassay, and 24-h ambulatory blood pressure monitoring was performed. Means and diurnal index was calculated for systolic, diastolic and mean arterial blood pressure, for day-time, night-time, and the whole day. The results of the normoalbuminuric (n = 39) and microalbuminuric (n = 29) groups are compared, and correlation of the blood pressure parameters with albuminuria is analysed. Twenty-four hours and night-time mean blood pressures were significantly higher, diurnal indices characterizing the night-time blood pressure drop were smaller in the microalbuminuric group. With multiple regression analysis a significant positive correlation was found between albumin excretion rates and 24-h mean systolic blood pressure and a significant negative correlation between albumin excretion rates and the diurnal index of mean arterial pressure (r2= 0.40, P<0.0001). In the normoalbuminuric group 1 (2.6%) patient, in the microalbuminuric group 7 (24.1%/) were 'non-dippers'. We conclude that in normotensive insulin-dependent diabetic patients the night-time decrease of blood pressure is smaller if microalbuminuria is present. Higher nocturnal blood pressure load is associated with the increase of albuminuria, even before the onset of overt diabetic nephropathy or hypertension.

Increased night:day blood pressure ratio in microalbuminuric normotensive NIDDM subjects

Objective: 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). Research design and methods: 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 ≥15 μg/min), respectively. Results: 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. Conclusions: 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.

Follow-up study on urinary type IV collagen in patients with early stage diabetic nephropathy.

Type IV collagen is a major component released from the glomerular and tubular basement membranes. To investigate the alteration of renal type IV collagen turnover in early stage diabetic nephropathy, urinary type IV collagen was measured by a highly sensitive one-step sandwich enzyme immunoassay (EIA). Urinary samples were obtained from 94 diabetic patients without overt proteinuria. Among those patients, 61 were normoalbuminuric and 33 patients were in the microalbuminuric group. Levels of urinary type IV collagen were serially examined at the start of this study and again one year later. The levels of urinary type IV collagen in patients in the microalbuminuric group were significantly higher than those in the normoalbuminuric group (P < 0.01). There was a significant correlation between the concentration of urinary albumin and urinary type IV collagen in both groups (P < 0.05). Twenty-eight patients (45.3%) in the normoalbuminuric group who showed an abnormal elevation of urinary type IV collagen in comparison to the reference range of normal healthy adults (normal range; less than 3.5 microg/g x Cr). Seven (25%) out of these 28 normoalbuminuric patients with increased urinary type IV collagen progressed to the microalbuminuric group one year later. The levels of urinary type IV collagen in such patients were significantly increased. In the 21 patients who stayed within the normoalbuminuric group, the urinary type IV collagen levels were significantly decreased one year later. It appears that the levels of urinary type IV collagen might reflect ongoing alteration of the extracellular matrix (ECM) turnover and might define more specifically the early stage diabetic nephropathy than the detection of microalbuminuria. It is concluded that the serial measurement of urinary type IV collagen can be a useful marker for detecting renal injury in diabetes.

Usefulness of Microalbuminuria in Predicting Cardiovascular Mortality in Treated Hypertensive Men With and Without Diabetes Mellitus

In the present study we report on the predictive power of microalbuminuria for total and cardiovascular mortality in a prospective study (mean follow up 6.3 years) of treated hypertensive men, aged 50 to 72 years, with (n = 94) and without (n = 345) maturity onset diabetes mellitus. Thirty-three (35.1%) of the hypertensive patients with diabetes mellitus died during the follow-up period compared with 57 patients (16.5%) in the hypertensive group without diabetes mellitus (p <0.0002). In those with diabetes mellitus and hypertension, a log-rank test revealed a lower cardiovascular mortality in the normoalbuminuric group compared with both the microalbuminuric (p = 0.035) and the macroalbuminuric group (p = 0.002). The logarithm of urinary albumin excretion was a predictor of both total (p = 0.009) and cardiovascular (p = 0.001) mortality during the follow-up period using Cox regression analysis. This relation remained significant even after adjustment for other risk factors. HbA1c was also an independent predictor of total and cardiovascular mortality. In patients without diabetes mellitus, the small group of patients with macroalbuminuria had a markedly increased cardiovascular mortality compared with both the microalbuminuric (p <0.0001) and the normoalbuminuric groups (p <0.0001). No difference was observed between the normoalbuminuric and the microalbuminuric groups. Smoking at entry and concomitant cardiovascular disease at entry were independent predictors of cardiovascular mortality in these patients. We conclude that microalbuminuria was an independent predictor for cardiovascular mortality in treated hypertensive men with maturity onset diabetes mellitus. Macroalbuminuria, but not microalbuminuria, predicted cardiovascular mortality in nondiabetic treated hypertensive men.

Microalbuminuria in Patients with Non-Insulin-dependent Diabetes Mellitus Relates to Nocturnal Systolic Blood Pressure

PURPOSE: Microalbuminuria predicts early mortality in non-insulin-dependent-diabetes mellitus patients (NIDDM). Our objective in the present study was to compare and assess the relationship between 24-hour, day and nocturnal ambulatory blood pressure (BP) and urinary albumin excretion rate (UAE) in microalbuminuric and normoalbuminuric NIDDM and in normal control subjects.PATIENTS AND METHODS: In the present cross-sectional study, 24 hour ambulatory BP (daytime BP and nocturnal BP) and HbA1c were compared in microalbuminuric (n = 10) and nonmicroalbuminuric NIDDM patients (n = 10) and in nondiabetic controls (n = 9). None of the patients were taking antihypertensive agents.RESULTS: In the microalbuminuric group, whereas 24 hour and daytime systolic BP differed significantly from control values (P <0.025 and P <0.05 respectively), there was no difference between diabetic groups. However, nocturnal systolic BP in the microalbuminuric group was significantly higher than in the normoalbuminuric diabetic patients (139 vs. 125) (P <0.05) and a significant difference was also found between the NIDDM patients and the control group (139, 125 vs. 114) (P <0.025). In multiple regression analysis, only nocturnal systolic BP showed a significant relationship with UAE (P <0.05).CONCLUSIONS: We suggest that the higher nocturnal systolic blood pressure seen in our microalbuminuric NIDDM patients may contribute to the increased morbidity in this group.

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

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

Relationships between beta-cell function and diabetic duration and albuminuria in type 2 diabetes mellitus.

To clarify whether beta-cell function deteriorates with increasing albuminuria and duration of diabetes, we investigated the insulin and c-peptide response to oral glucose tolerance test in 47 healthy subjects and 75 normoalbuminuric (group 1), 30 microalbuminuric (group 2), and 35 macroalbuminuric (group 3) Type 2 diabetes mellitus patients. The total area under the insulin curve (AUCI) values of groups 1, 2, and 3 were 245 +/- 16, 193 +/- 17, and 88 +/- 8 pmol/L.h, respectively, significantly lower than that (624 +/- 34 pmol/L.h) of the healthy group. The mean total area under the c-peptide curve (AUCC-P) values of groups 1, 2, and 3, respectively, were 2.50 +/- 0.11, 2.05 +/- 0.15, and 1.73 +/- 0.07 nmol/L.h, respectively, significantly lower than that (5.47 +/- 0.19 nmol/L.h) of the healthy controls. The mean AUCI and AUCC-P values of group 3 were significantly reduced compared to those of group 1. The mean AUCI and AUCC-P values of patients with 0-5, 5-10, 10-15, and > 15 years' duration were significantly decreased compared to those of healthy subjects. The mean AUCI and AUCC-P values of patients with > 15 years' duration were significantly lower than those of patients with 0-5 years' duration. The mean hemoglobin Alc values of the three diabetic groups were not significantly different. These data suggest that beta-cell function deterioration was associated with increasing albuminuria and diabetic duration in Type 2 diabetic patients.

Microalbuminuria is not associated with cardiovascular death in Japanese NIDDM

To evaluate whether the presence of microalbuminuria can predict cardiovascular death in Japanese subjects with non-insulin-dependent diabetes mellitus (NIDDM), we investigated 297 Japanese NIDDM patients with Albustix-negative urine. Patients were divided into two groups, normoalbuminuric ( n = 201) and microalbuminuric ( n = 96), and followed until death or the end of 1994 (the mean follow-up period was 6.4 years). During the follow-up period, 28 deaths (14 normoalbuminuric and 14 microalbuminuric patients) were confirmed and only 10 deaths were attributed to cardiovascular disease (6 normoalbuminuric and 4 microalbuminuric patients). Although the age- and sex-adjusted mortality rate from all-causes in the microalbuminuric group was significantly higher than that in the normoalbuminuric group (13.5 vs. 8.2 per 1000 person-years: P < 0.05), the mortality rate from cardiovascular disease was not significantly different between two groups (3.4 vs. 3.3 per 1000 person-years). On age-adjusted Cox proportional hazards analysis, HbA1c and triglyceride were independent risk factors in mortality from cardiovascular disease, while microalbuminuria was not associated with cardiovascular death. These results indicate that, unlike Caucasians, the presence of microalbuminuria can not predict cardiovascular death in Japanese subjects with NIDDM.

Hyperinsulinemia as a determinant of microalbuminuria in essential hypertension.

To analyze the relationship between insulinemia and urinary albumin excretion in a group of nonobese, young adult hypertensive patients, who had never been treated with antihypertensive drugs. Forty-nine patients who fulfilled the inclusion criteria were included. Twenty-four-hour ambulatory blood pressure monitorings, urinary albumin excretion (UAE) measurements, and an oral glucose-tolerance test measuring glucose and insulin, were performed, and left ventricular mass was measured by echocardiography. Hypertensive patients were classified as normoalbuminuric when their UAE was < 30 mg/24 h (40 patients; mean UAE 13.4 +/- 7.0 mg/24 h), and as microalbuminuric when their UAE was 30-300 mg/24 h (nine patients; mean UAE 90.5 +/- 86.6 mg/24 h). In comparison with that of the normoalbuminuric group, the fasting plasma glucose concentration for the microalbuminuric group was only slightly higher (100 +/- 9 versus 95 +/- 8 mg/dl, NS). In contrast, the fasting insulin concentration in the microalbuminuric group was significantly higher than that observed in the normoalbuminuric group (25.2 +/- 6.7 versus 16.6 +/- 5.2 microU/ml, P<0.0001). During the oral glucose-tolerance test, the area under the curve (AUC) for glucose (317 +/- 41 versus 253 +/- 53 mg/dl x 2/h, P<0.001) and the AUC for insulin (253 +/- 171 versus 124 +/- 43 microU/ml x 2/h, P<0.001) were significantly higher in the microalbuminuric group than were those AUC observed in the normoalbuminuric group. After adjustments for age, sex, body mass index and average 24 h ambulatory mean blood pressure were made, the fasting insulin level was associated independently with an increase in UAE in a multiple regression model with base 10 logarithm of the UAE as the dependent variable. Variations in fasting insulin level alone accounted for 33% of the UAE variance. In contrast, the 24 h ambulatory mean blood pressure, rather than the insulin level, was the strongest predictor of the left ventricular mass index. Mild hypertensive patients with microalbuminuria were hyperinsulinemic in the absence of obesity, and their insulin level was the main determinant of microalbuminuria in these patients. Microalbuminuria in essential hypertension seems to identify patients with a cluster of cardiovascular risk factors and a bad risk profile. Thus, assessment of microalbuminuria may be useful in the stratification of risk in essential hypertension.

Apolipoprotein (a) levels and phenotypes in NIDDM patients with microalbuminuria and albuminuria.

This study was conducted to determine whether circulating levels of lipoprotein (a), an independent risk factor of macrovascular disease, are increased in non-insulin-dependent diabetes mellitus (NIDDM) patients with microalbuminuria who have an increased risk of cardiovascular mortality. Apolipoprotein (a) [apo(a)] levels and phenotypes, and other circulating lipid levels were determined in 227 Chinese NIDDM patients with varying stages of diabetic nephropathy. None was on lipid-lowering therapy. Apo(a) levels in normoalbuminuric (geometric mean 166 U/L; 95% confidence intervals 137, 200; n = 105) and microalbuminuric patients (162; 132, 209; n = 77) were similar to values in controls (166; 143, 193, n = 168). Albuminuric patients, however, had higher apo(a) levels than both normoalbuminuric patients and controls (242; 184, 317; n = 45; P < 0.05). The overall size range of the apo(a) phenotypes and the frequency of having at least one small isoform, i.e. < 700 kDa, were similar among the four groups of subjects. A positive correlation was found between log apo(a) and log plasma creatinine levels (P < 0.01). Compared to normoalbuminuric patients, both microalbuminuric and albuminuric patients were older (P < 0.01) and had higher HbA1c (P < 0.01), greater BMI (P < 0.05) and longer disease duration (P < 0.05) compared to normoalbuminuric patients. Nevertheless, using multiple linear regression analysis, it was found that the presence of nephropathy conferred an independent influence on increasing total cholesterol (P < 0.001), triglyceride (P < 0.001) and apoB (P < 0.01), and decreasing HDL cholesterol (P < 0.05) levels even when only the normoalbuminuric and microalbuminuric groups were analysed. The prevalence of macrovascular disease was significantly increased in microalbuminuric and albuminuric patients (45.1 and 48.7% respectively vs 20.2% in normoalbuminuric patients, P < 0.01). It is concluded that circulating apo(a) levels were not increased in Chinese NIDDM patients with microalbuminuria. However, atherogenic changes in other lipid and lipoprotein levels may contribute to an increased risk of macrovascular disease in these patients.

Prevalence and Clinical Correlates of Microalbuminuria in Stage I Hypertension: Results From the Hypertension and Ambulatory Recording Venetia Study (HARVEST Study)

The objective of the present study was to examine the association between albumin excretion rate (AER) and office and ambulatory blood pressures (BP), and other recognized cardiovascular risk factors in stage I hypertension. The study was carried out in 870 never-treated 18- to 45-year-old hypertensives (628 men, 242 women). Office and ambulatory BP, 24-h urinary collection for AER assessment, and echocardiographic left ventricular mass (n = 587) were obtained. AER was similar in men and women (12.3 v 12.5 mg/24 h) and was unrelated to age and body mass index. In 85.2% of the subjects, AER was < 16 mg/24 h, in 8.3% it was between 16 and 29 mg/24 h (borderline microalbuminuria), and in 6.1% it was >or= 30 mg/24 h (overt microalbuminuria). Office systolic BP was not different in the three groups, whereas 24-h systolic BP was higher in the subjects with microalbuminuria than in those with normal AER (P < .0001) and was similar in the two microalbuminuric groups. Office and 24-h diastolic BPs were higher in the subjects with overt microalbuminuria than in those with normal AER. Left ventricular mass was correlated to systolic (P < .0001) and diastolic (P = .01) 24-h BP, but was unrelated to AER. Family history for hypertension, smoking, coffee and alcohol intake, and physical activity habits did not influence AER. In a logistic regression analysis, 24-h systolic BP emerged as the only determinant of microalbuminuria (P < .0001). In conclusion, these results indicate that borderline levels of microalbuminuria may also be clinically relevant in stage I hypertension. Overweight and lifestyle factors do not appear to influence AER in these patients. Finally, the lack of correlation between AER and left ventricular mass suggests that renal and cardiac involvement do not occur in a parallel fashion in the initial phase of hypertension.

Is microalbuminuria progressive?

In 1990, 81 children and adolescents with insulin dependent diabetes were studied for early signs of diabetic nephropathy. Nine patients were identified as having microalbuminuria (incipient nephropathy). These subjects were re-examined three years later. In five of these cases, the second examination revealed normal albumin excretion; in three of the four cases in whom microalbuminuria persisted, the rate of albumin excretion had decreased. The general improvement in albumin excretion rates in the initially microalbuminuric group could not be explained by improved glycaemic control nor interventional drug treatment. The lack of progression in this microalbuminuric group from the original prevalence study suggests that this method of identifying early nephropathy in childhood may not be valid or that the progression of incipient nephropathy in childhood is more irregular or slower than in later life.

Microalbuminuria cannot predict cardiovascular death in Japanese subjects with non-insulin-dependent diabetes mellitus

In order to examine whether the existence of microalbuminuria can predict the development of overt proteinuria and cardiovascular death in Japanese subjects with non-insulin-dependent diabetes mellitus (NIDDM), we investigated 47 patients for a 10-year follow-up period. Patients were divided into two groups by the initial values of urinary albumin excretion rates. The percentage of patients who developed overt proteinuria during the follow-up period was significantly higher in patients who were initially classified as microalbuminuric group (63.6%) than in normoalbuminuric group (17.4%). During the follow-up period, one of the patients with normoalbuminuria had died of congestive heart failure, while four of those with microalbuminuria had died; one of stroke and three from noncardiovascular diseases. These results indicate that the existence of microalbuminuria had the predictive power for the development of overt proteinuria, but not for cardiovascular death in Japanese subjects with NIDDM.

Aspects of haemostatic function in healthy subjects with microalbuminuria — A potential atherosclerotic risk factor

Microalbuminuria, i.e., slightly elevated urinary albumin excretion rate (UAER), notifies increased risk for atherosclerotic disease and may reflect an early generalized vascular abnormality in healthy subjects. This study was designed in order to examine whether such abnormality is associated with a shift of the haemostatic balance in prothrombotic direction. The following haemostatic factors were measured in two representative groups of clinically healthy subjects, 28 with microalbuminuria (UAER of 6.6–150 μg/min) and 60 age- and sex-matched controls with normoalbuminuria (UAER < 6.6 μg/min): Coagulation factors: blood platelet count and mean volume, plasma Factor VII antigen concentration and coagulant activity, and plasma concentrations of prothrombin fragment 1+2, thrombin-antithrombin III complexes, fibrinogen, and fibrinopeptide A; fibrinolytic and endothelial factors: plasma concentrations of tissue plasminogen activator antigen and plasminogen activator inhibitor type 1 antigen; and endothelial factor: plasma von Willebrand factor antigen concentration. The fibrinolytic and endothelial factors were measured both before and after 10 minutes of venous occlusion of the arm. None of the haemostatic factors were significantly altered in the microalbuminuric group. Plasma fibrinogen concentration tended to be elevated but not statistically significant ((mean (95% C.I.) 7.8 (7.2–8.3) vs. 7.2 (6.9–7.5) μmol/l; p<0.1). Neither did any of the haemostatic factors correlate with UAER in regression analyses. It is concluded that the haemostatic balance is unaltered in healthy subjects with microalbuminuria. It is unlikely that a prothrombotic state is present as an intermedial factor early in a causal chain between microalbuminuria and atherosclerotic vascular disease.

Atherosclerotic risk factors are increased in clinically healthy subjects with microalbuminuria

Increased morbidity and mortality from atherosclerotic vascular disease were observed in subjects with slightly elevated urinary albumin excretion rate (UAER), known as microalbuminuria. Therefore, the association between microalbuminuria and established atherogenic risk factors was studied in clinically healthy subjects. All healthy 40–65 year-old participants with microalbuminuria, examined within the first 21 months of The Copenhagen City Heart Study, were invited, and 28 were studied. An age- and sex-matched group of 60 randomly chosen subjects with normoalbuminuria served as control. Microalbuminuria was defined as a UAER of 6.6–150 μg/min, and normoalbuminuria as a UAER ≤6.6 μg/min. In the microalbuminuric group, systolic and diastolic blood pressures were both elevated (mean (95% C.I.) 128 (123–134) vs. 119 (116–122) mmHg; P = 0.005, and 75 (71–78) vs. 69 (67–71) mmHg; P = 0.008, respectively), and serum apolipoprotein (apo) A-1 concentration was lower (1.30 (1.20–1.37) vs. 1.42 (1.36–1.47) g/l; P = 0.02) in comparison with the normoalbuminuric group. Furthermore, serum HDL-cholesterol concentration tended to be lower, whereas body weight, body mass index and fasting serum insulin concentration were slightly elevated in the microalbuminuric group but not statistically significant. It is concluded that microalbuminuria in clinically healthy subjects is associated with increased levels of atherogenic risk factors. This may contribute to the increased vascular morbidity and mortality observed in these individuals.

Increased transcapillary escape rate of albumin in microalbuminuric type II diabetic patients.

To evaluate microvascular permeability by the transcapillary escape rate of albumin (TERalb) in type II diabetic patients with normo- and microalbuminuria. The TERalb has been measured following intravenous injection of 125I-labeled human serum albumin in 32 normotensive type II diabetic patients and 9 healthy control subjects matched for sex and age. Type II diabetic subjects were grouped in normoalbuminuric, albumin excretion rate (AER) < 20 micrograms/min (n = 18), and microalbuminuric, AER 20-200 micrograms/min (n = 14) categories. In type II diabetic patients, no differences were noted between normo- and microalbuminuric groups for known diabetes duration (8.3 +/- 5.9 vs. 11.7 +/- 8.0 years), blood pressure (BP) (129/76 +/- 16/8 vs. 131/76 +/- 14/5 mmHg), current metabolic control (HbA1c: 8.0 +/- 1.4 vs. 8.5 +/- 1.6%), and serum lipids. However, previous 2-year mean HbA1c levels were significantly higher in microalbuminuric patients (8.7 +/- 1.45 vs. 7.6 +/- 1.29%; P < 0.05). The TERalb was similar in control subjects and normoalbuminuric patients (5.16 +/- 1.09 vs. 5.71 +/- 1.66 %/h) and significantly higher in the microalbuminuric group (8.98 +/- 1.35 %/h; P < 0.0001). The increased leak of albumin was not explained by differences in diabetes duration, BP, or metabolic control at the time of investigation and was independently related to the presence of microalbuminuria (r = 0.63, percent explained variance approximately 40) and mean "historical" HbA1c (multiple r = 0.705; total explained variance approximately 50%). Type II diabetic patients with microalbuminuria show an increased TERalb, i.e., a widespread microvascular damage that may be important in the pathogenesis of long-term complications. Our findings may contribute to the explanation of why albuminuria seems to be an independent cardiovascular risk factor in type II diabetes.

Prevalence of arterial hypertension in diabetic patients before and after the JNC-V.

To compare the prevalence of arterial hypertension in patients with insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) according to blood pressure (BP) criteria from the World Health Organization (WHO) and The Fifth Report of the Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure (JNC-V). Two cohorts of Caucasian patients attending the outpatient clinic at Hvidöre Hospital were identified: 1) 957 patients with IDDM; 53% men, 40 (18-75) years of age (mean [range]); and 2) 549 patients with NIDDM; 53% men, 60 (20-76) years of age. BP was measured at least yearly, while patients rested in a sitting position, with a standard clinical sphygmomanometer. Patients were classified as hyper- or normotensive based on average BP during a 3-year follow-up period. Patients receiving antihypertensive treatment were classified as hypertensives. In IDDM patients, the prevalence of arterial hypertension rose from 15 to 42% in the normoalbuminuric group, from 26 to 52% in the microalbuminuric group, and from 61 to 79% in the macroalbuminuric group when WHO and JNC-V criteria were compared. The corresponding rises in NIDDM patients were from 51 to 71% (normo-), from 73 to 90% (micro-), and from 82 to 93% (macroalbuminuria). Of the untreated hypertensive patients, 78% of IDDM patients and 50% of NIDDM patients had stage 1 (140-159/90-99 mmHg) hypertension; 20% of IDDM patients and 37% of NIDDM patients had stage 2 (160-179/100-109 mmHg) hypertension. Two out of three untreated hypertensive patients had isolated systolic hypertension. The new JNC-V criteria approved by the American Diabetes Association leads to a considerable increase in the prevalence of arterial hypertension in a population of IDDM and NIDDM patients. Isolated systolic hypertension contributes importantly.