Microalbuminuria,insulin sensitivity and haemostatic factors in non-diabetic treated hypertensive men

Abstract. Objective . To examine whether microalbuminuria in non-diabetic, treated hypertensive men is associated with insulin resistance and measures of endothelial function, thrombogenesis and fibrinolysis. Design . Cross-sectional study. Setting . Outpatient clinic in city hospital. Patients . Ninety-two treated hypertensive men, aged 57–77 years, either with a serum cholesterol of ≥ 6.5 mmol L^?1 or smokers, or both. Patients with diabetes mellitus or overnight urinary albumin excretion of > 100 mg 12 h^?1 were excluded. Main outcome measures . Overnight urinary albumin excretion, insulin-mediated glucose disposal (hyper-insulinaemic euglycaemic clamp), blood glucose and plasma insulin during oral glucose tolerance test, fibrinogen, von Willebrand factor and plasminogen activator inhibitor activity. Results . Microalbuminuric patients had increased blood glucose concentrations during the oral glucose tolerance test and higher plasma fibrinogen levels compared with the normoalbuminuric patients. In a randomly selected subgroup (n = 36), insulin-mediated glucose disposal was lower in microalbuminuric than in normoalbuminuric patients, and an inverse relationship between insulin sensitivity and albuminuria (r = –0.37; P = 0.028) was found. This relationship was not significant after adjustment for body-mass index (P = 0.098). In the univariate analyses including all patients, albuminuria was associated with blood glucose, serum creatinine, body-mass index, systolic blood pressure, fibrinogen, von Willebrand factor and cholesterol (negatively). In a multiple regression analysis, only the body-mass index was independently related to urinary albumin excretion. Conclusions . Microalbuminuria was associated with insulin resistance but obesity was a confounding factor. Relationships between microalbuminuria and fibrinogen as well as von Willebrand factor were found, but only in univariate analysis.     

Characteristic of Ambulatory Blood Pressure in Normotensive Subjects With Type 2 Diabetes Mellitus

INTRODUCTIONAmbulatory blood pressure monitoring (ABPM) isa wide-used method for BP measurement and known asmore effective than clinic readings, especially inevaluation of circadian variation and identification ofthe so-called "white-coat hypertension". Reduction inthe nocturnal BP fall in ABPM may be associated withan increased risk of end-organ damage including renaland cardiovascular complications in patients withessential hypertension. In diabetic patients,microalbuminuria is a ke…     

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.     

Prothrombin Fragment 1 + 2 and Antithrombin III-Thrombin Complex in Microalbuminuric Type 2 Diabetic Patients

In microalbuminuria there is an increased cardiovascular risk not fully explained by the excess of conventional risk factors. To investigate whether or not microalbuminuria is associated with haemostatic abnormalities in Type 2 diabetic patients, we measured the prothrombin fragment 1 + 2, a marker of thrombin generation, and the thrombin-antithrombin complex, a marker of thrombin neutralization. Plasma levels of prothrombin fragment 1 + 2 and thrombin-antithrombin complex were assayed in 17 microalbuminuric patients (albumin excretion rate, AER 20–200 μg min^?1) and in 17 comparable normoalbuminuric (AER < 20 μg min^?1) Type 2 diabetic patients. Plasma prothrombin fragment 1 + 2 was significantly higher in microalbuminuric than in normoalbuminuric patients (1.09 ± 0.06 vs 0.86 ± 0.04 nM, p = 0.003). Individual values of F1 + 2 were above the upper limit of the normal range in 8/17 microalbuminuric and in none of the normoalbuminuric Type 2 diabetic patients. Plasma thrombin-antithrombin complex values were not significantly different in the two groups and were not correlated with AER. These results suggest that microalbuminuria is associated with a prethrombotic state and a relatively defective thrombin neutralization. Coagulation abnormalities might be part of the cardiovascular risk in microalbuminuric patients.     

Apolipoprotein H is increased in type 2 diabetic patients with microalbuminuria

BACKGROUND AND AIM: Serum apolipoprotein H (Apo H) levels are increased in hyperlipidemic subjects and type 2 diabetics, but unknown in microalbuminuria, another disorder with an increased cardiovascular risk. We looked to see whether increased Apo H levels are associated with microalbuminuria in type 2 diabetes. METHODS AND RESULTS: Serum Apo H was calculated in 20 normoalbuminuric and 17 microalbuminuric type 2 diabetics matched for age, sex, body mass index (BMI), glycosylated haemoglobin, plasma lipids and duration of diabetes, and also compared with 20 non-diabetic controls matched for age, sex, BMI and plasma lipids. Mean serum Apo H was significantly higher in the microalbuminuric patients (31.12 +/- 1.58 SEM vs 25.25 +/- 1.52 and 24.72 +/- 0.99 mg/dL, p = 0.003). CONCLUSION: Serum apo H levels are increased in type 2 diabetics with microalbuminuria.     

Plasma angiotensin II, renin activity and serum angiotensin-converting enzyme activity in non-insulin dependent diabetes mellitus patients with diabetic nephropathy

The renin-angiotensin system (RAS) has been unequivocally implicated as a mediator of diabetic complications. The present study was designed to evaluate the RAS in non-insulin dependent diabetic patients with diabetic nephropathy. Plasma renin activity, plasma angiotensin II and serum angiotensin-converting enzyme (ACE) activity were measured in 45 non-insulin dependent diabetes mellitus (NIDDM) patients and 15 healthy non-diabetic controls. Diabetics were subdivided into 15 normoalbuminuric NIDDM subjects, 15 NIDDM patients with microalbuminuria and 15 diabetics with macroalbuminuria. Mean plasma renin activity for macroalbuminuric diabetics (0.65+/-0.10 ng/ml/hr) was significantly reduced than the controls (1.28+/-0.37 ng/ml/hr) (P<0.001), the diabetic group with microalbuminuria (1.08+/-0.48 ng/ml/hr) (P<0.05) and normoalbuminuric patients (1.56+/-0.82 ng/ml/hr) (P<0.001). A significant negative correlation was obtained between serum creatinine and plasma renin activity (r=-0.842, p<0.001) in macroalbuminuric NIDDM patients. Plasma angiotensin II was significantly decreased in non-complicated diabetics compared to healthy controls (4.36+/-1.49 pg/ml vs 14.87+/-3.48 pg/ml respectively, p<0.001). Non-insulin dependent diabetic patients with nephropathy had significantly higher plasma angiotensin II levels (28.99+/-5.88 pg/ml) than non-complicated diabetics (p<0.001). Serum ACE activity was increased in 53.3% of NIDDM patients. All diabetic groups showed increased serum ACE activity (normoalbuminuric NIDDM 114.9+/-28.3 nmol/min/ml, microalbuminuric NIDDM 127.9+/-31.2 nmol/min/ml and macroalbuminuric NIDDM 127.0+/-29.3 nmol/min/ml) when compared to the normal control group (76.3+/-16.5 nmol/min/ml) (p<0.001). No significant difference in serum ACE activity was obtained between normoalbuminuric and nephropathic diabetics or between diabetics with and without retinopathy. No significant correlation was obtained between serum ACE activity and blood pressure, blood glucose level and duration of diabetes. Thus plasma renin activity is decreased in diabetic nephropathy and negatively correlates with serum creatinine. Plasma angiotensin II is decreased in normoalbuminuric diabetics and elevated in diabetic nephropathy. Serum ACE activity is raised in NIDDM patients with no relation to albumin excretion rate. The role of increased ACE activity in NIDDM remains to be established.     

Circulating vascular endothelial growth factor in the normo- and/or microalbuminuric patients with type 2 diabetes mellitus

Relationship between serum vascular endothelial growth factor (VEGF) level and parameters of endothelial injury and/or dysfunction in patients with diabetes mellitus type 2 with or without microalbuminuria was investigated. Eighty-four diabetic patients were divided in two subgroups (42 each): normoalbuminuric (NAU) and microalbuminuric (MAU). Forty-two blood donors were in control group. Serum VEGF and plasma von Willebrand factor, soluble thrombomodulin, plasminogen activator inhibitor 1, thrombin-activatable fibrinolysis inhibitor (TAFI) and tissue plasminogen activator (t-PA) were measured using enzyme-linked immunosorbent assay in all subjects. VEGF was significantly higher in NAU compared to controls. The difference between MAU and controls was not statistically significant, but there was a trend toward significance. Only TAFI correlated with VEGF in MAU. An observed significant increase of serum VEGF level already in NAU suggests that serum VEGF could be a sensitive predictor of endothelial dysfunction in type 2 diabetes.     

URINARY EXCRETION OF HUMAN EPIDERMAL GROWTH FACTOR IN THE VARIOUS STAGES OF DIABETIC NEPHROPATHY

Epidermal growth factor (EGF) is a polypeptide mitogen first isolated from mouse submaxillary glands and later from human urine. We have examined the pattern of urinary excretion of human EGF (hEGF) in normal subjects and in diabetic patients with varying degrees of nephropathy. hEGF was measured by homologous radioimmunoassay and expressed in terms of urinary creatinine excretion. On the basis of their albumin excretion rate, the diabetic patients were divided into those with normoalbuminuria (albumin excretion rate 3.5 (1.4-9.8) micrograms/min; mean (range)), microalbuminuria (albumin excretion rate 75 (30-128) micrograms/min) and macroalbuminuria (289 (169-879) micrograms/min). The albumin excretion rate for the normal subjects was 3.7 (1.6-9.7) micrograms/min. The mean (range) hEGF excretion (nmol hEGF/mmol creatinine) was 0.69 (0.47-1.29) for 19 healthy subjects, 0.60 (0.16-1.36) for the normoalbuminuric group (n = 18; NS), 0.47 (0.10-0.83) for the microalbuminuric patients (n = 19; P less than 0.001 vs controls and normoalbuminuric diabetics) and 0.38 (0.10-0.63) for the macroalbuminuric group (n = 18; P less than 0.001 vs controls and normoalbuminuric diabetics). There was an inverse correlation between albumin excretion rate and hEGF: creatinine ratio (r = -0.49; P = 0.02). These results show a progressive decline in hEGF excretion in diabetic patients with varying degrees of nephropathy and do not support the hypothesis that increased kidney size seen in early nephropathy is due to excessive amounts of EGF in the urine.     

Serum and urinary nitric oxide in Type 2 diabetes with or without microalbuminuria: relation to glomerular hyperfiltration

BACKGROUND: Glomerular hyperfiltration is considered as one of the pathophysiological mechanisms for the development of diabetic nephropathy. Oxidative stress is enhanced in patients with diabetes mellitus. Reportedly, nitric oxide (NO) might be involved in the pathogenesis of hyperfiltration. We investigated the relationship between hyperfiltration and NO system, and malondialdehyde (MDA) levels in Type 2 diabetics with/without microalbuminuria. METHODS: In 39 microalbuminuric, 29 normoalbuminuric Type 2 diabetic patients and 32 healthy controls, serum creatinine, nitrite, nitrate, urinary microalbumin, nitrite, nitrate, plasma MDA and estimated glomerular filtration rate (EGFR) values, calculated according to the Cockcroft and Gault formula, were recorded. RESULTS: Serum and urine NO levels were higher in both microalbuminurics and normoalbuminurics than controls. There were no significant differences in EGFR between groups. However, hyperfiltration was determined in 31% of normoalbuminurics and 20% of microalbuminurics. Serum and urine NO levels were higher in patients with hyperfiltration. Plasma MDA levels were significantly elevated in both microalbuminurics and normoalbuminurics when compared with controls. Serum glucose and microalbuminuria were positively correlated in microalbuminuric diabetics. Serum NO levels were also positively correlated with EGFR in both normoalbuminurics and microalbuminurics. HbA1c levels were positively correlated with both urinary albumin excretion and plasma MDA levels in normoalbuminuric diabetics. CONCLUSIONS: Hyperglycemia is associated with an increased NO biosynthesis and lipid peroxidation. Increased oxidative stress may contribute to the high NO levels in Type 2 diabetes. Furthermore, the high NO levels may lead to hyperfiltration and hyperperfusion, which in turn leads to an increase in urinary albumin excretion and thus causes progression of nephropathy in early Type 2 diabetes.     

Alterations in l-arginine and inflammatory markers in type 2 diabetic patients with and without microalbuminuria

Low-grade inflammation is closely involved in the pathogenesis of type 2 diabetes and associated micro- and macrovascular complications. The nitric oxide (NO) precursor l-arginine, is relevant to diverse pathological conditions including type 2 diabetes and its complications. High sensitive-CRP (hs-CRP), neopterin and arginine levels were measured in 46 normoalbuminuric, 45 microalbuminuric type 2 diabetics and in 32 healthy controls in order to assess the relationship between markers of inflammation and l-arginine. Hs-CRP concentrations were higher in microalbuminuric diabetic patients compared to normoalbuminuric patients and controls. Diabetics had higher serum and urine neopterin levels than controls. Urine neopterin and l-arginine levels differed significantly among diabetic patients with and without microalbuminuria. There were significant positive correlations between hs-CRP and BMI in healthy controls and diabetics with and without microalbuminuria. In microalbuminuric diabetics, hs-CRP correlated with microalbuminuria (MAU). Significant predictors for the development of microalbuminuria were higher postprandial glucose levels, lower creatinine clearance and lower serum l-arginine levels. Assessment of early markers of inflammation and endothelial function, such as neopterin and NO precursor l-arginine, may help to predict incipient nephropathy more accurately in type 2 diabetic patients.     

Activity of the unstimulated renin-angiotensin-aldosterone system in type 1 diabetic patients with and without proteinuria

There have been conflicting reports of the activity of the renin-angiotensin-aldosterone system in diabetes. We studied the activity of the unstimulated renin-angiotensin-aldosterone system in 73 consecutive Type 1 diabetic patients with varying degrees of albuminuria. Patients with elevated albumin excretion rates had elevated median plasma renin activity (macroalbuminuric 2.2, range 0.5-8.2, p less than 0.05; microalbuminuric 2.3, 0.7-7.1, p less than 0.001; vs normoalbuminuric 1.0, 0.2-4.5 nmol l-1 h-1) and higher systolic blood pressure (macroalbuminuric 141 +/- 27 vs normoalbuminuric 116 +/- 13 mmHg, mean +/- SD, p less than 0.01) compared with those with normal albumin excretion rates. Aldosterone secretion and function were normal in all patients studied.     

Erythrocyte Na+/H+ exchange and preclinical abnormalities of the left ventricular diastolic function in normotensive type 1 (insulin-dependent) diabetic patients

We assessed the relationship between erythrocyte Na⁺/H⁺ antiport activity and myocardial anatomical-functional parameters (by Doppler echocardiography) in normotensive IDDM patients, with and without microalbuminuria. We studied 33 normotensive IDDM subjects and 14 matched healthy controls (group 4). Based on urinary albumin excretion rate (UAER), 23 diabetics were normoalbuminuric, 10 microalbuminuric (group 3). Normoalbuminurics were divided up for normal (group 1, n = 13) or high (group 2, n = 10) antiport activity. We evaluated fasting glycaemia and 24-h urine glucose output, HbA1c, plasma lipids, urea, creatinine and electrolyte clearances, UAER, erythrocyte Na⁺/H⁺ countertransport, M-Mode and 2D echocardiograms with Doppler analysis. Antiport, which was higher in diabetics than controls, was significantly overactive in groups 2 and 3 vs group 4, independently from UAER. Diabetics showed left ventricular volume, cardiac mass and systolic function within the control range. In left ventricular diastolic filling, while peak E was similar in diabetic and healthy people, the late peak transmitral flow velocity (peak A) was significantly higher in diabetics than controls, and this was also true in groups 2 and 3 vs group 4. Antiport activity was positively related to peak A (p<0.03). These observations suggest that (a) the Na⁺/H⁺ antiport may be overactive in diabetes, apart from microalbuminuria; (b) increased Na⁺/H⁺ antiport activity, in normotensive IDDM people, may be associated with preclinical diastolic myocardial dysfunction (``incipient diabetic cardiomyopathy''?).     

Microalbuminuria and transcapillary albumin leakage in essential hypertension.

Microalbuminuria (an increased urinary albumin excretion that is not detectable by the usual dipstick methods for macroproteinuria) predicts cardiovascular events in essential hypertensive patients. A possible reason for this behavior is that albumin leaks through exaggeratedly permeant glomeruli exposed to the damaging impact of subclinical atherogenesis. To evaluate this possibility, the transcapillary escape rate of albumin (TER(alb), the 1-hour decline rate of intravenous (125)I-albumin), a parameter that estimates the integrity of systemic capillary permeability, albuminuria, blood pressure, echocardiographic left ventricular mass, lipids, and body mass index were measured in 73 uncomplicated, glucose-tolerant men with essential hypertension and normal renal function; 53 were normoalbuminuric, and 20 were microalbuminuric. Twenty-one normotensive age-matched male subjects were the controls. TER(alb) was higher in hypertensives, a behavior explained in part by a positive correlation with blood pressure values, although body mass index, lipids, and left ventricular mass showed no association. Transcapillary albumin leakage values did not differ between normoalbuminuric and microalbuminuric patients and were unrelated to albuminuria. Blood pressure, particularly systolic, and cardiac mass were higher in microalbuminuric patients in whom albuminuria correlated with both cardiovascular variables and indicated the influence of the hemodynamic load on urinary albumin levels. Thus, TER(alb), a parameter influenced by the permeability surface area product for macromolecules and the filtration power across the vascular wall, is altered in essential hypertensives. However, this abnormality is dissociated from the amount of albuminuria, which is contrary to the hypothesis that a higher albumin excretion reflects a greater degree of systemic microvascular damage in essential hypertension.     

Abnormal increases in urinary albumin excretion during pregnancy in IDDM women with pre-existing microalbuminuria

Summary We compared urinary albumin excretion during and after pregnancy in 30 insulin-dependent diabetic (IDDM) women with normoalbuminuria and in 12 IDDM women with microalbuminuria (>15 g·min^–1) prior to conception. There was a 6.7-fold increase in the urinary albumin excretion up until the third trimester in the women with pre-existing microalbuminuria, compared with a 3.8-fold increase in the normoalbuminuric women. In both groups of patients the urinary albumin excretion reached a peak during the third trimester with 492±404 g·min^–1 in the microalbuminuric women vs 43±36g·min^–1 in the normoalbuminuric women (p<0.0005). Two women from each of the groups developed eclampsia with diastolic blood pressure over 90 mm Hg, mild or moderate oedema and macroproteinuria. Four of the pregnant women with pre-existing microalbuminuria showed a transient nephrotic syndrome (33.3%) with protein excretion over 3 g in 24-h urine samples during the third trimester. In contrast, this was not observed in any of the normoalbuminuric women (p<0.05). Within 12 weeks after delivery the urinary albumin excretion rates dropped to the pre-conception values in both patient groups. Renal function remained normal during pregnancy in both of the groups, with a physiological increase in creatinine clearance up until the third trimester (26% increase in the normoalbuminuric women vs 22% in the microalbuminuric women). In conclusion, the effect of pregnancy on the urinary albumin excretion in diabetic women with preexisting microalbuminuria is an exaggeration of the increase of albuminuria in diabetic women with normoalbuminuria; normalization occurs within 12 weeks after delivery in all cases. This enhancement of the albumin excretion in the microalbuminuric women cannot be explained by a larger increase in the hyperfiltration during pregnancy.Abbreviations IDDM Insulin-dependent diabetes mellitus - NIDDM non-insulin-dependent diabetes mellitus     

Impaired flow-mediated vasodilatation and insulin resistance in type 2 diabetic patients with albuminuria

An elevated urinary albumin excretion is associated with an increased risk of cardiovascular disease due to atherosclerosis, but the pathophysiological mechanism underlying this association is poorly understood. We studied 217 diabetic patients, that is, 121 normoalbuminuric patients, 71 microalbuminuric patients, and 25 macroalbuminuric patients. We evaluated flow-mediated dilatation of brachial artery (%FMD, one endothelial function marker associated with endogenous NO production), von Willebrand factor (vWF, endothelial activation marker), high-sensitive CRP (hsCRP, a low-grade inflammation marker), asymmetric dimethyl arginine (ADMA, an endogenous inhibitor of NO synthesis), and insulin sensitivity by steady-state plasma glucose method. %FMD was apparently decreased in microalbuminuric and macroalbuminuric patients compared with normoalbuminuric patients (p<0.001). Moreover, %FMD was significantly correlated with the degree of albuminuria (r=-0.38, p<0.05). On the other hand, vWF and hsCRP did not show significant difference between normoalbuminuric patients and microalbuminuric patients. In diabetic patients with macroalbuminuria, ADMA was significantly elevated compared to those with normoalbuminuria. Insulin sensitivity was significantly associated with urinary albumin excretion rate. These results suggested that endothelial dysfunction which may be due to impaired NO production and insulin resistance underlie the association between diabetic nephropathy and atherosclerosis in diabetic patients.     

QT dispersion in type 2 diabetic patients with altered diurnal blood pressure rhythm

BACKGROUND: QT dispersion (QTd) is a good prognostic marker in type 2 diabetic patients without previous cardiovascular disease. Diabetic patients with an attenuated decline in nocturnal blood pressure (non-dippers) have been shown to have increased risk of diabetic complications, vascular events and mortality. AIM: The aim of this study was to evaluate the relationship between diurnal blood pressure rhythm, QTd and microvascular complications in type 2 diabetic patients. METHODS: Cardiovascular autonomic function tests, 24-h ambulatory blood pressure monitoring and urinary albumin excretion measurements were performed in healthy controls (n = 25), normoalbuminuric (n = 34) and microalbuminuric (n = 23) type 2 diabetic patients. QTd was assessed manually from 12-lead surface electrocardiograms. RESULTS: Compared with the controls, both normoalbuminuric and microalbuminuric diabetic patients had increased QTd (59.11 +/- 15.86; 60.27 +/- 17.95 vs. 40.48 +/- 10.92, p < 0.001 and p < 0.001, respectively). Similarly, diabetic patients had increased QTd regardless of the presence of autonomic neuropathy. On the other hand, non-dipper diabetic patients had increased QTd compared with the controls and dipper diabetic patients (69.73 +/- 14.50 vs. 40.48 +/- 10.92; 47.84 +/- 9.62 ms, p < 0.001). There was a negative correlation between QTd and diurnal diastolic blood pressure change (r = -0.48, p < 0.0005). CONCLUSION: Patients with type 2 diabetes mellitus were found to have increased QT dispersion irrespective of the presence of diabetic autonomic neuropathy. However, QT dispersion in dipper diabetic patients was similar to the controls. This finding might point out that attenuated decline of nocturnal blood pressure could be a more sensitive marker for autonomic neuropathy.     

Normoalbuminuria ensures no reduction of renal function in type 1 (insulin-dependent) diabetic patients.

Recent reports have suggested that impaired renal function in type 1 diabetic patients may be present despite normal urinary albumin excretion (UAE). We have studied kidney function by means of a constant-infusion technique in normoalbuminuric type 1 diabetic patients without antihypertensive medication (UAE less than 20 micrograms min-1, n = 134), in microalbuminuric patients (20 greater than or equal to UAE less than 200 micrograms min-1, n = 50) and in 27 non-diabetic control subjects. Mean UAE was 4.5 micrograms min-1 (range 1.0-19.3 micrograms min-1) in normoalbuminuric patients, 53.1 micrograms min-1 (range 20.8-147.5 micrograms min-1) in microalbuminuric patients, and 4.0 micrograms min-1 (range 2.1-17.9 micrograms min-1) in controls. Glycosylated haemoglobin A1c was significantly higher in microalbuminuric patients (8.9%, range 5.9-12.6%) than in normoalbuminuric patients (7.9%, range 5.5-11.5%) (P less than 0.0001). Glomerular filtration rate in normoalbuminuric patients (135 ml min-1, range 97-198 ml min-1) was significantly higher than in controls (118 ml min-1, range 94-139 ml min-1) (P less than 1 x 10(-6), and significantly lower than in microalbuminuric patients (142 ml min-1, range 100-186 ml min-1) (P less than 0.05). Mean arterial blood pressure was lower in normoalbuminuric patients (91 mmHg, range 78-108 mmHg) than in microalbuminuric patients (98 mmHg, range 82-131 mmHg) (P less than 1 x 10(-6), but not significantly different from that of controls (89 mmHg, range 73-103 mmHg). We conclude that normal UAE is a reliable indicator of well-preserved renal function. Glomerular hyperfiltration, elevated blood pressure and poor metabolic control are characteristic features of microalbuminuric patients.     

Urinary excretion of apolipoprotein(a) fragments in type 1 diabetes mellitus patients

High levels of plasma lipoprotein(a) [Lp(a)] represent an independent risk factor for cardiovascular morbidity; however, Lp(a) has not yet been identified as a risk factor for type 1 diabetic patients. Results from the limited number of available studies on plasma Lp(a) levels in relation to renal function in type 1 diabetes mellitus are inconclusive. We hypothesized that only type 1 diabetes mellitus patients with impaired renal function show increased plasma Lp(a) levels, due to decreased urinary apolipoprotein(a) [apo(a)] excretion. We therefore measured urinary apo(a) levels in 52 type 1 diabetes mellitus patients and 52 matched controls, and related the urinary apo(a) concentration to the plasma Lp(a) level, kidney function, and metabolic control. Our findings indicate that patients with incipient diabetic nephropathy as evidenced by microalbuminuria (20 to 200 microg/min) exhibit significantly higher plasma Lp(a) levels (median, 15.6 mg/dL) in comparison to normoalbuminuric patients (median, 10.3 mg/dL) and healthy controls (median, 12.0 mg/dL). Urinary apo(a) normalized to creatinine excretion was significantly elevated in both normoalbuminuric (median, 22.3 microg/dL) and microalbuminuric type 1 diabetic patients (median, 29.1 microg/dL) compared with healthy subjects (median, 16.0 microg/dL) and correlated significantly with Lp(a) plasma levels in both patient and control groups (P < .003). No correlation existed between the Lp(a) plasma level or urinary apo(a) concentration and metabolic control in type 1 diabetes mellitus patients. From these studies, we conclude that urinary apo(a) excretion is significantly increased in type 1 diabetic patients and correlates with plasma Lp(a) levels, and only type 1 diabetic patients with microalbuminuria have higher plasma levels of Lp(a) compared with patients with normoalbuminuria and healthy controls.     

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

AIMS: Thirty adolescent patients with Type 1 diabetes mellitus and microalbuminuria were studied for evidence of early autonomic neuropathy. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Elevated serum leptin concentrations in type 2 diabetic patients with microalbuminuria and macroalbuminuria.

Leptin levels are elevated in end-stage renal disease, suggesting an impairment of renal leptin degradation. The present study aimed to determine whether leptin levels are also elevated in patients with earlier stages of renal disease, ie, microalbuminuric and macroalbuminuric nephropathy. A total of 60 subjects were assigned to two study groups. Group A contained 10 type 2 diabetics with macroalbuminuria, 10 type 2 diabetics with normoalbuminuria, and 10 healthy control subjects. Group B contained 10 type 2 diabetics with microalbuminuria, 10 type 2 diabetics with normoalbuminuria, and 10 healthy controls. The subgroups of both study groups were matched for sex and body fatness. In group A, macroalbuminuric diabetic patients had higher serum leptin levels than the normoalbuminuric diabetics (11.90 +/- 2.98 v 4.13 +/- 0.92 ng/mL, P < .002) and control subjects (4.78 +/- 1.37 ng/mL, P < .006). In group B, microalbuminuric diabetics had higher serum leptin levels than the normoalbuminuric diabetics (21.16 +/- 5.80 v8.74 +/- 1.89 ng/mL, P < .04) and control subjects (10.06 + 3.00 ng/mL, P < .06). In both groups A and B, creatinine clearance was inversely correlated with the serum leptin level after adjusting for body fat. In conclusion, serum leptin levels are elevated in type 2 diabetic patients with microalbuminuria and macroalbuminuria, suggesting that renal leptin degradation is already impaired in the early stages of renal disease.