Microalbuminuric Group Research Articles

Increased Ambulatory Arterial Stiffness Index and Pulse Pressure in Microalbuminuric Patients With Type 1 Diabetes

Ambulatory arterial stiffness index (AASI) has been proposed as an indirect measure of arterial stiffness. The aims of this study were (i) to analyze AASI and pulse pressure (PP) in micro- and normoalbuminuric type 1 diabetes mellitus (T1DM) patients and healthy controls and (ii) to explore the relation between nocturnal blood pressure (BP) reduction, BP variability, and AASI. Ambulatory BP monitoring was performed in 34 micro- and 34 normoalbuminuric T1DM patients matched for gender, age, and diabetes duration and in 34 nondiabetic controls matched for gender and age. AASI and PP were calculated based on 24-h, day, and night BP recordings. AASI increased from the control group (0.30 +/- 0.14) to the normo- (0.35 +/- 0.15) and microalbuminuric group (0.41 +/- 0.19; P < 0.05). After adjustment for nightly systolic BP reduction and systolic daytime BP variability (s.d.) in multivariate analysis, the association weakened and became nonsignificant (P = 0.078). No significant intergroup differences were found when AASI was calculated separately from day and night BP data. There was no significant difference between day and night AASI. The 24-h PP increased from the control group (48 +/- 7 mm Hg) to the normo- (50 +/- 6 mm Hg) and microalbuminuric group (54 +/- 9 mm Hg; P < 0.01). The association remained in the multivariate analysis. Day and night PPs were higher in microalbuminuric patients compared to healthy controls. AASI and PP are higher in microalbuminuric T1DM patients compared to healthy controls. The nocturnal BP reduction and systolic daytime BP variability are determinants of AASI. We propose these associations to reflect biological characteristics of arterial stiffness.

Is Serum Cystatin C an Accurate Endogenous Marker of Glomerular Filteration Rate for Detection of Early Renal Impairment in Patients with Type 2 Diabetes Mellitus?

Background. Researches have recently reported that serum cystatin C is a more sensitive marker of changes in glomerular filtration rate (GFR) than serum creatinine. We conducted this study to evaluate the significance of serum cystatin C as a more sensitive marker of GFR for early detection of renal impairment in special groups of patients with type 2 diabetes mellitus (DM). Methods. The present study included 40 patients with type 2 DM divided into four equal groups based on their urinary albumin excretion and renal function: group 1 was normoalbuminuric, group 2 was microalbuminuric, group 3 was macroalbuminuric, and group 4 was macroalbuminuric with renal dysfunction. All patients underwent a thorough history, full clinical examination, fasting, and renal function tests. Post-prandial blood glucose levels, glycosylated hemoglobin A1c (HbA1c), proteins, albumin in 24 hr urine, and serum cystatin C were collected. Results. Serum cystatin C and creatinine were significantly higher in macrolbuminuric type 2 diabetic patients with renal dysfunction (group 4: 2.26 ± 1.28, 4.21 ± 2.38 mg/dl, respectively; p < 0.001) than macrolbuminuric type 2 diabetic patients with normal renal function (group 3: 1.04 ± 0.24, 0.96 ± 0.20 mg/dl, respectively), the microalbuminuric group (0.87 ± 0.28, 0.71 ± 0.12 mg/dl, respectively), as well as the normoalbuminuric group (0.55 ± 0.41, 0.60 ± 0.18 mg/dl, respectively). ROC plots demonstrated that area under the curve (AUC) of cystatin C (0.74) was greater than that for creatinine clearance (cr.cl) (0.67) and serum creatinine (s‐cr) (0.74); therefore, the sensitivity and diagnostic accuracy of cystatin c was better than cr. cl., and both were better than s-cr. Serum cystatin C showed significant correlation in groups 2–4 with s-cr, cr.cl, and 24 hr urine albumin, but no correlation was found in group 1. Conclusion. Serum cystatin C is a reliable and easily performed marker for GFR to detect renal impairment in patients with type 2 DM.

Levels of glycated albumin at different stages of diabetic nephropathy in India

Aims: Glycated haemoglobin (HbA1c) which is an index of long term glycaemic control in diabetic patients is measured in majority of patients worldwide. Glycated albumin (GA) is useful for the evaluation of short term glycaemic control (2 weeks) in patients with diabetes. The aim of this study was to assess the GA levels at different stages of diabetic nephropathy in Indian population. Materials and Methods: A total of 147 subjects (M:F; 95:52) were selected for this study and were divided into three groups based on their renal function and compared with a non diabetic control group (n = 50, M:F; 14:36). The groups were as follows; group1 (control) n = 50, group2 (normoalbuminuria) n = 42, group 3 (microalbuminuria) n = 55, group 4 (proteinuria) n = 50. GA was measured by enzymatic procedure using the Lucica GA – L kit (Asahi Kasei Pharma Corp, Japan). Results: The normal cutoff value for GA was derived using control group and it was found to be 15% (range 7-17%). GA was significantly higher in diabetic patients at different stages of diabetic nephropathy compared to non diabetic control group [cont: 12.9 ± 1.8, normo: 20.8 ± 5.8, micro: 26.1 ± 8.6, macro: 23.5 ± 8.3). Microalbuminuric patients had significantly higher GA levels than normoalbuminuric patients (p< 0.05). Proteinuric subjects had slightly lower GA levels compared to microalbuminuric group but it was not statistically significant. Conclusion: GA was found to be a better marker for evaluating short term glycaemic status among diabetic patients with different degree of renal impairment prior to ESRD.

Modification of Coronary artery disease (Macroangiopathy) in Type II DM patient by intervening microalbuminuria

Cardiovascular disease are major burden in patients with T2DM causing work unfitness, disability and premature death. In order to establish, microalbuminuria as a modifiable risk factor for these conditions. The present study was conducted by intervening with ACE inhibitor, antioxidant, antithrombotic as modifiable agents of microabluminuria in T2DM Patients.The study was randomized control trial. We selected 1605 T2DM Patients of 40-50 years by pre-determined criteria from OPD of BIRDEM. By estimating microalbuminuria we included 368 as study group (&gt; 300mg/day) and 682 as control group (&lt; 300mg/day). The following parameters were the key variables, duration of diabetes, FBG, Total cholesterol, HDL, blood pressure and ECG at entry and after 18 Months.The mean SD age duration of diabetes in microabuminuric and nonmicroalbuminuric subject were 45.67 3.98, 3.78 3.14 and 45.45 3.98, 72 3.04 respectively. The microalbuminuric group showed statistically significant difference (p&lt; 0.005) in the following parameters FBG, HBA1C, SBP, DBP, T- cholesterol in comparison to nonmicroalbuminuric group. Nonmicroalbuminuric subjects showed the deterioration in HDLc, LDLc and a conversion rate of 21.7% from nonmicroalbuminuric to microalbuminuric.ACE inhibitor, Antioxidant and Antithrombotic are advantageous to conventional therapy for T2DM patients with in IHD as evident by this intervent ion. The achieving improvement were 68.50% for those conditions.University Heart Journal Vol.4(1) January 2008

Antiproteinuric effects of antihypertensive agents in non-diabetic hypertensive population

Abstract Arterial hypertension and proteinuria are important factors associated with the progression of both diabetic and nondiabetic chronic kidney disease. The objective of the present study was to determine the influence of different antihypertensive drug groups on urinary albumin excretion (UAE) as related to blood pressure in non-diabetic population. Subjects (n=39) with chronic renal disease accompanied by mild to moderate hypertension and varying degrees of proteinuria were divided into 3 groups based on UAE values and placed on nonpharmacological and/or treatment with an antihypertensive drug regimen (consisting of one or more antihypertensive drugs [beta blocker, ACE inhibitor or calcium-channel blocker]) to achieve a target blood pressure ≤ 130/85 mmHg. Periodic UAE measurements were performed. A reduction was observed over time in most patients, however, it reached statistical significance only in the microalbuminuric group (P&lt;0.01). Patients were further stratified into 5 groups depending on assigned therapy: 0, nonpharmacological treatment; 1-drug group 1; 12-drug groups 1 and 2; 13-drug groups 1 and 3; 123-all 3 drug groups (1-ACE inhibitors, 2-beta blockers, 3-calcium channel blockers). A statistically significant change in mean UAE values at the start and end of the study period in patients assigned to drug groups 12, 13, and 123 was achieved (P &lt; 0.05). Also, there was a statistically significant difference in the average reduction of proteinuria under varying antihypertensive drug regimens (P &lt; 0.05). In conclusion, in patients with hypertension, changes in UAE depend on initial UAE values and administered antihypertensive treatment. ACE inhibitors combined with calcium channel blockers resulted in a higher UAE reduction than other drug groups.

SUMO4 M55V Variant Is Associated With Diabetic Nephropathy in Type 2 Diabetes

OBJECTIVE-SUMO4 mRNA was recently found to be mainly expressed in the kidney, and the methionine-to-valine substitution at codon 55 (M55V) variant of SUMO4 may induce higher nuclear factor-kappaB (NF-kappaB) activity. Because NF-kappaB is known to mediate the development of diabetic nephropathy, we examined the association between the SUMO4 M55V variant and the severity of diabetic nephropathy. RESEARCH DESIGN AND METHODS-We recruited a total of 430 patients with type 2 diabetes. The M55V (rs237025, 163A-->G) polymorphism of SUMO4 was genotyped by real-time PCR, and urine albumin concentration was measured by radioimmunoassay. RESULTS-The frequencies of SUMO4 AA, GA, and GG were 52.6, 40.7, and 6.7%, respectively, in the normoalbuminuric group; 45.5, 47.3, and 7.1% in the microalbuminuric group; and 36.9, 46.2, and 16.9% in the macroalbuminuric group. We detected a significant linear trend for SUMO4 genotype between the macroalbuminuric and normoalbuminuric groups. The mean urine albumin-to-creatinine ratio (42.3 +/- 108.82 mg/mmol) in the GG group was significantly higher than in the AA (14.9 +/- 51.49 mg/mmol) and GA (17.0 +/- 43.74 mg/mmol) groups. Multivariate logistic regression analysis showed the SUMO4 M55V variant to be independently associated with the severity of diabetic nephropathy. CONCLUSIONS-This study indicates that the SUMO4 gene M55V variant is associated with severity of diabetic nephropathy in patients with type 2 diabetes.

Radionuclide Staging of Renal Function in Type 1 Diabetes Mellitus

Aim. The aim of this study was to assess renal function in different stages of type 1 diabetes mellitus by radionuclide methods. Additionally, glomerular and tubular functions were correlated with urinary albumin (UAER) and N-acetyl-β-D-glucosaminidase (NAGA) excretion rates. Patients and methods. Fifty-three patients with diabetes mellitus were classified into four groups: normoalbuminuric (NA, 18 patients), microalbuminuric (MiA, 12 patients), macroalbuminuric (MaA, 13 patients), and chronic renal failure group (CRF, 10 patients). Glomerular filtration rate (GFR) was estimated by diethylenetriamine pentaacetic acid-technetium 99m (99mTc-DTPA) clearance rate while tubular function was calculated as a percentage of net injected activity fixed in both kidneys, 4 h after intravenous injection of dimercaptosuccinate acid-technetium 99m (99mTc-DMSA). Additionally, 99mTc-DTPA clearance was correlated with estimated GFR (eGFR) by using modified Modification of Diet in Renal Disease (MDRD) Study Group formula. Results. 99mTc-DTPA clearance and 99mTc-DMSA fixation were found significantly higher in normoalbuminuric group (p < 0.05 and p < 0.02, respectively), unchanged in microalbuminuric group (p > 0.05, p > 0.05), and decreased in both macroalbuminuric (p < 0.0001, p < 0.00001) and chronic renal failure group (p < 0.0001, p < 0.00001). Renal function was denoted as normal, increased (hyperfunction), or decreased (hypofunction). It was found normal in a high percentage of patients with normalbuminuria (filtration 44.4%, fixation 72.2% pts) and microalbuminuria (66.7% and 66.7%). Renal hyperfunction was not only found frequent in normalbuminuric group (55.6% and 27.8%), but was also recorded in microalbuminuric group (8.3% and 8.3%). Renal hypofunction was present in all macroalbuminuric patients and in one-quarter of those with microalbuminuria as well. Such distribution of renal function conditions indicated normalbuminuric and microalbuminiric groups functionally heterogeneous. Regression analysis showed a significant correlation between 99mTc-DTPA clearance and eGFR in MaA and CRF groups only. Although urinary NAGA excretion rate was shown as a less sensitive staging parameter, being significantly increased when compared to control group only in MaA and CRF groups (p < 0.05), it significantly correlated with 99mTc-DTPA clearance rate (r = −0.485, p = 0.0004) and 99mTc-DMSA tubular fixation (r = −0.526, p = 0.0002). Conclusions. The results of this study favor the performance of radionuclide studies together with the determination of urinary albumin excretion rate in patients with type 1 diabetes mellitus in order to achieve more reliable staging of diabetic kidney disease. The demonstration of glomerular hyperfiltration and tubular hyperfunction by radiopharmaceuticals contributes to the early detection of diabetic kidney disease, while the quantification of renal function enables the follow-up of the progressive function loss in the later course of the disease.

Correlation between Increased Serum sFas Levels and Microalbuminuria in Type 1 Diabetic Patients

Objective: The aim of this study was to elucidate if apoptosis dysregulation is present in type 1 diabetic patients with microalbuminuria. Subjects and Methods: The following variables were determined in 29 type 1 diabetic patients: the duration of diabetes, soluble Fas (sFas), Bcl-2, hemoglobin A_1c levels, glomerular filtration rate (GFR) and microalbuminuria, using the urine albumin to urine creatinine ratio (ACR). Age and gender were assessed and patients were categorized into two groups, according to their ACR: the microalbuminuric (MA) group with an ACR ≧30 mg/g, and the normoalbuminuric (NA) group with an ACR <30 mg/g. Results: The differences between the two groups regarding sFas, Bcl-2 and GFR were not statistically significant. However, in the MA group, a significant positive relationship between sFas and ACR was observed (r = 0.736, p = 0.015). Dividing patients into two subgroups – mild versus severe (ACR ≧150 mg/g) microalbuminuric patients – significant differences in sFas (60.4 vs. 87.2 pg/ml; p = 0.047) and GFR (113 vs. 69.5 ml min^–1 1.73 m^–2; p = 0.021) were observed, whereas in Bcl-2, the difference was not significant (77.96 vs. 71.13 ng/ml). Conclusions: At the early stages of diabetic nephropathy in type 1 diabetic patients, there seems to be a dysregulation of apoptosis, as expressed by enhanced sFas levels, leading to the speculation that the prevalence of antiapoptotic mechanisms (sFas) may promote mesangial proliferation.

High postprandial triglyceridemia in patients with type 2 diabetes and microalbuminuria

Microalbuminuria (MA) is an independent risk factor for atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Postprandial lipemia is also associated with excess cardiovascular risk. However, the association between MA and postprandial lipemia in diabetes has not been investigated. A total of 64 patients with T2DM, 30 with and 34 without MA, were examined. Plasma total triglycerides (TGs), triglycerides contained in chylomicrons (CM-TG), and TGs in CM-deficient plasma were measured at baseline and every 2 h for 6 h after a mixed meal. Postheparin LPL and HL activities were also determined. Plasma levels of apolipoprotein A-V (apoA-V), apoC-II, and apoC-III were measured in the fasting state and 2 h postprandially. Patients with MA had higher postprandial total TG levels than those without MA (P < 0.001); this increase been attributed mainly to CM-TG. LPL activity and fasting concentrations of the measured apolipoproteins were not different between the studied groups, whereas HL activity was higher in the patients with MA. ApoC-II and apoC-III levels did not change postprandially in either study group, whereas apoA-V increased more in the patients with MA. These data demonstrate for the first time that MA is characterized by increased postprandial lipemia in patients with T2DM and may explain in part the excess cardiovascular risk in these patients.

Endothelial dysfunction in geriatric diabetic patients: the role of microalbuminuria in elderly type 2 diabetic patients? A randomized controlled study

Microalbuminuria is considered a marker of extensive endothelial dysfunction and is associated with excess of other cardiovascular risk factors. Our aim is to assess the importance of the presence of microalbuminuria in elderly diabetic patients. A total of 40 normotensive elderly type 2 diabetic patients of both genders with mean age >65 years were randomly included and were further subdivided according to the presence of persistent microalbuminuria into microalbuminuric and normoalbuminuric groups. All patients in both groups were subjected to thorough clinical and laboratory investigations including the assay of serum thrombomodulin (TM) and glycosylated hemoglobin level. Early-morning midstream urine samples were evaluated for levels of beta 2 microglobulin, alpha 1 microglobulin, TM, and N-acetyl-beta-D-glucosaminidase (NAG). There was no significant difference between both groups regarding the clinical demographic characteristics. There were statistically significant higher values for glycosylated hemoglobin percentage, serum triglycerides and serum TM and urinary B2 microglobulin, urinary alpha 1 microglobulin, urinary NAG and urinary thrombomodulin in microalbuminuric group in comparison to normoalbuminuric group (P < 0.05). Microalbuminuria is associated with markers of endothelial dysfunction in elderly normotensive type 2 diabetic patients. We recommend incorporation of periodic testing for microalbuminuria in this sector of patients.

Alterations of blood pressure in type 1 diabetic children and adolescents

The aim of this study was to assess the association between metabolic control, microalbuminuria, and diabetic nephropathy with ambulatory blood pressure monitoring (ABPM) in normotensive individuals with type 1 diabetes mellitus (DM). ABPM was undertaken in 68 normotensive type 1 diabetic patients with a mean age of 14.4+/-4.2 years. Microalbuminuria was diagnosed on the basis of a urinary albumin excretion rate grater than 20 microg/min in two of the three 24-h urine collections. Hypertension (HT) frequency was greater in the microalbuminuric patients than normoalbuminuric patients (54 vs 17.54%, p=0.05) with ABPM. Microalbuminuric patients had a higher diastolic pressure burden than normoalbuminuric patients. There were no differences in systolic and diastolic dips between the two groups. Diastolic pressure loads in all periods showed a significant correlation with duration of diabetes, mean HbA1c from the onset of diabetes, and level of microalbuminuria. Nocturnal dipping was reduced in 41.2% of the patients. In the normoalbuminuric group 41.1% and in the microalbuminuric group 63.6% were nondippers. Our data demonstrate higher 24-h and daytime diastolic blood pressure load and loss of nocturnal dip in type 1 diabetic adolescents and children. High diastolic blood pressure burden in diabetic patients could represent a risk for nephropathy.

Relationships between Heart Rate Variability and Urinary Albumin Excretion in Patients with Type 2 Diabetes

Although in type 1 diabetes the close association between heart rate variability and urinary albumin excretion (UAE) is recognized even in patients with normoalbuminuria, this association has not yet been fully established in patients with type 2 diabetes. Therefore, we investigated the association in patients with type 2 diabetes. All the hospital's 185 inpatients with type 2 diabetes were prospectively enrolled. Heart rate variability was evaluated by coefficients of variance of RR intervals (CVRR). The mean age, duration of diabetes, and hemoglobin A1C of the patients were 59.7+/-9.9 years, 10.4+/-7.8 years, and 9.7+/-2.3%, respectively. An analysis of the patients showed a significant negative correlation between CVRR and log10-transformed (log) UAE (R=-0.3340, P <0.0001). CVRR showed a significant negative correlation with age, duration of diabetes, hemoglobin AIC, systolic blood pressure, diastolic blood pressure, and triglyceride level. Log UAE showed a significant positive correlation with body mass index, hemoglobin A1C, systolic blood pressure, diastolic blood pressure, total cholesterol, and triglyceride level. In the macroalbuminuric group (UAE above 300 mg/g creatinine; n=57), although CVRR showed a significant negative correlation with log UAE (R=-0.3571, P= 0.0064), but in normoalbuminuric (UAE below 30 mg/g Cr; n=79) and in microalbuminuric groups (30 to 300 mg/g Cr; n = 49), CVRR and log UAE showed no correlation. Our data suggest that in type 2 diabetes, the association between CVRR and UAE is significant only in patients with macroalbuminuria.

Altered Transcapillary Escape of Albumin and Microalbuminuria Reflects Two Different Pathogenetic Mechanisms

We studied the following in normo- and microalbuminuric hypertensive type 2 diabetic patients: 1) transcapillary escape rate of albumin (TERalb) and 2) expression of mRNA slit diaphragm and podocyte proteins in renal biopsies. Normoalbuminuric subjects had renal cancer, and kidney biopsy was performed during surgery. TERalb was evaluated by clearance of (125)I-albumin. Real-time PCR of mRNA slit diaphragm was measured in kidney specimens. Albumin excretion rate (AER) was by definition lower in normoalbuminuric subjects than in microalbuminuric subjects with typical diabetic glomerulopathy (group 1), in microalbuminuric subjects with normal or near-normal glomerular structure (group 2), and in microalbuminuric subjects with atypical diabetic nephropathy (group 3). This classification was based on light microscopy analysis of renal tissue. TERalb (%/h) was similar in normoalbuminuric and microalbuminuric group 1, 2, and 3 diabetic patients (medians: 14.1 vs. 14.4 vs. 15.7 vs. 14.9, respectively) (ANOVA, NS). mRNA expression of slit diaphragm proteins CD2AP, FAT, Actn 4, NPHS1, and NPHS2 was higher in normoalbuminuric patients than in microalbuminuric patients (groups 1, 2, and 3) (ANOVA, P < 0.001). All diabetic patients had greater carotid artery intimal thickness than normal control subjects using ultrasound technique (ANOVA, P < 0.01). In conclusion, the present study suggests that microalbuminuria identifies a subgroup of hypertensive type 2 diabetic patients who have altered mRNA expression of slit diaphragm and podocyte proteins, even before glomerular structure shows abnormalities using light microscopy analysis. On the contrary, altered TERalb and increased carotid artery intimal thickness are shown by all hypertensive type 2 diabetic patients, both with normal and altered patterns of AER.

Effect of angiotensin-converting enzyme inhibition on survival in 3773 Chinese type 2 diabetic patients.

We assessed the effects of angiotensin-converting enzyme (ACE) inhibition on survival and cardiorenal outcomes in a consecutive cohort of Chinese type 2 diabetic patients with varying degree of albuminuria, ranging from normoalbuminuria to macroalbuminuria. A total of 3773 consecutive Chinese type 2 diabetic patients were followed prospectively for a mean period of 35.8 months. Clinical end points included all-cause mortality, with cardiovascular end point defined as first hospitalization because of ischemic heart disease, congestive heart failure, revascularization procedures, or cerebrovascular accident as well as renal end point defined as dialysis, doubling of baseline plasma creatinine, or plasma creatinine > or =500 micromol/L. The use of ACE inhibitor was 26.3% in normoalbuminuric (NA), 70.1% in microalbuminuric (MI), and 82.6% in macroalbuminuric (MA) groups. Albuminuria was a major predictor for all-cause mortality with 4-fold difference between NA and MA patients. The 7-year cumulative mortality rate was 7.1%, 10.8%, and 21.7% in the NA, MI, and MA groups, respectively. The use of ACE inhibition was associated with significant reduction of mortality (hazard ratio 0.41 and 95% confidence interval, 0.29, 0.58) in the entire group and was most evident in high-risk patients who had cardiorenal complications or retinopathy at baseline for all albuminuric groups (NA 0.76 [0.31,1.87]; MI 0.32 [0.16, 0.65]; and MA 0.20 [0.13, 0.33]). The prognostic value of albuminuria for death in type 2 diabetes and the beneficial effects of ACE inhibitors in Chinese type 2 diabetic patients with micro- or macroalbuminuria has been confirmed. The effects of ACE inhibitors in type 2 diabetic patients with normoalbuminuria require further evaluation.

QT prolongation in patients with Type 2 diabetes and microalbuminuria.

The link between microalbuminuria and premature death in Type 2 diabetes is not fully explained by conventional cardiovascular risk factors. We aimed to determine if QT prolongation and/or dispersion are linked to microalbuminuria in patients with Type 2 diabetes and to investigate their associations with other risk factors. We have studied asymptomatic patients with Type 2 diabetes with no clinical evidence of coronary disease (43 with microalbuminuria matched with 43 normoalbuminuric patients). Rate-corrected maximum QT interval (QT(c) max) was greater in the microalbuminuric group [mean (SD): 450 (23) vs 440 (20) ms(1/2), p = 0.046] as was the proportion of patients with QT(c) max > 440 ms (67 % vs 38 %, p = 0.01). Rate-corrected QT dispersion (QT(cd)) was similar in the two groups [57 (21) vs 53 (23) ms(1/2), p = 0.41]. Linear regression analysis showed that QT(c) max and/or QT(cd) were not strongly linked to albumin excretion rate but more strongly to factors associated with microalbuminuria such as blood pressure and factor XIIa. Our findings support the hypothesis that QT prolongation and microalbuminuria have common determinants in Type 2 diabetes. QT prolongation may contribute to the increased mortality observed in microalbuminuric subjects with Type 2 diabetes.

Relationship between transforming growth factor beta1 and progression of hypertensive renal disease.

In this study the role of circulating transforming growth factor beta1 (TGFbeta1) on progression of renal hypertensive disease has been investigated. Fifty consecutive outpatients with essential hypertension were enrolled and divided into three groups, according to their urinary albumin excretion (UAE). Group A comprised 10 hypertensives with UAE <or=20 mg/24 h (normoalbuminuric group); Group B included 21 hypertensives with UAE > 20 < 300 mg/24 h (microalbuminuric group); Group C encompassed 19 hypertensives with UAE >or= 300 mg/24 h (proteinuric group). In all patients UAE by immunonephelometric assay, circulating TGFbeta1 by a solid phase specific sandwich ELISA technique, BUN and creatinine by routine laboratory methods were determined. In addition, left ventricular telediastolic internal diameter, interventricular septum diastolic (IVSTd), posterior wall thickness, total and normalised to height(2.7) left ventricular mass, relative wall thickness and left ventricular ejection fraction by M-B Mode echocardiography were calculated. Our results indicated that TGFbeta1 levels were significantly (P < 0.05) higher in Group B and C than Group A and in Group C than Group B. In addition IVSTd values were significantly (P < 0.05) higher in both Group B and C than Group A. An evident, but not significant, higher prevalence of subjects with left ventricular hypertrophy were observed in Group C as compared with other groups. In all hypertensive subjects TGFbeta1 correlated directly with UAE (P < 0.0001) but not with BMI, LVM/h(2.7) and mean blood pressure. Our data indicated that TGFbeta1 might be considered a useful marker to evaluate the severity and progression of hypertensive renal disease. Additional long-term clinical data are needed to evaluate whether inhibition of TGFbeta1 system may prolong the time to the ESRD in hypertensive patients.

The spectrum of circadian blood pressure changes in type I diabetic patients.

The objective of the present study was to characterize the spectrum of circadian blood pressure changes in type I diabetes at different stages of nephropathy by using two monitorings in each patient in order to avoid intra-individual variability. A total of 80 type I diabetic subjects and the same number of age, sex and awake mean blood pressure (BP)-matched controls were included. According to urinary albumin excretion, there were 57 normoalbuminurics, 15 persistent microalbuminurics and eight proteinurics. Two 24 h ambulatory blood pressure monitorings were performed at the same urinary albumin excretion stage in absence of antihypertensive treatment for each diabetic subject and for their respective control. Blood pressure and heart rate averages during 24 h, awake, sleep, and day: night ratio were calculated. Seven of the eight proteinuric subjects were hypertensives, whereas hypertension was absent in the normoalbuminuric and microalbuminuric groups. The intraindividual reproducibility in diabetics showed repeatability coefficients for the 24 h systolic and diastolic pressure of 33 and 42%, respectively. This reproducibility for the day: night ratio was generally worse, 57% for systolic and 59% for diastolic. A progressive increment in the mean ambulatory BP was observed across the three groups of diabetics and the differences in BP observed were most evident during the night-time period. Though no differences in the 24 h circadian pattern were present between the normoalbuminurics and their controls, nocturnal differences were observed, not only in microalbuminurics for systolic BP (P < 0.05), but also in proteinurics for both systolic BP (P < 0.01) as well as diastolic BP (P < 0.05). No differences were observed in heart rate among the diabetic groups. The non-dipping pattern in the two monitorings was observed in 80, 58, 18 and 10% of the proteinurics, microalbuminurics, normoalbuminurics and control groups, respectively. Persistent abnormal circadian variability seems to be an early and frequent characteristic of type I diabetics with an increased urinary albumin excretion. Although present in some normalbuminuric subjects, the frequency of this abnormality increases as the incipient nephropathy progresses. By the time proteinuria is established, nearly all subjects present the abnormal pattern.

Insulin action and skeletal muscle blood flow in patients with Type 1 diabetes and microalbuminuria

Our objective was to determine whether Type 1 diabetic patients with microalbuminuria are less sensitive to the effects of insulin on glucose metabolism and skeletal muscle blood flow, compared to those with normal albumin excretion, after careful matching for confounding variables. We recruited 10 normotensive Type 1 diabetic patients with microalbuminuria and 11 with normoalbuminuria matched for age, sex, body mass index, duration of diabetes and HbA 1c. Peripheral and hepatic insulin action was assessed using a two-step euglycaemic hyperinsulinaemic clamp (2 h at 0.4 mU kg −1 min −1, 2 h at 2.0 mU kg −1 min −1) combined with isotope dilution methodology. Skeletal muscle blood flow was determined by venous occlusion plethysmography. During the clamps, glucose infusion rates required to maintain euglycaemia were similar in the microalbuminuric subjects and controls (step 1, 8.2±1.4 (SE) vs 9.2±1.3 μmol kg −1 min −1: step 2, 30.9±2.7 vs 32.0±3.8 μmol kg −1 min −1), as was hepatic glucose production basally and at steady state in step 1. In step 2, hepatic glucose production was lower in the microalbuminuric group (2.9±0.9 vs 6.4±0.7 μmol kg −1 min −1, P=0.005). During step 2, skeletal muscle blood flow increased significantly above baseline in the normoalbuminuric group (4.1±0.5 vs 3.2±0.4 ml 100-ml −1 min −1, P=0.01) but not in the microalbuminuric group (2.4±0.3 vs 2.3±0.4 ml 100-ml −1 min −1). In conclusion, microalbuminuria in Type 1 diabetes was found to be associated with impairment of insulin-mediated skeletal muscle blood flow, but not with insulin resistance.

Association between albumin:creatinine ratio and 24-hour ambulatory blood pressure in essential hypertension

Microalbuminuria (MAU) is often found in essential hypertension (EH) and represents a sign of renal and cardiovascular damage. In the present study, we aimed to look at the association between ambulatory blood pressure (BP) and urinary albumin excretion (UAE). We studied 140 patients aged 50.1 ± 11.6 years referred for 24-h ambulatory blood pressure monitoring (ABPM) and, separately, 46 untreated subjects with newly diagnosed EH. Urinary albumin excretion was evaluated by determination of the albumin-to-creatinine ratio (ACR) in the first voided morning urine sample taken the same day as the ABPM was started. According to the ACR, patients were categorized as having normoalbuminuria (ACR <1.5 mg/mmol), borderline MAU (1.5 ≤ ACR <3.0 mg/mmol), and overt MAU (ACR ≥3.0 mg/mmol). Mean ACR was significantly higher in hypertensive than normotensive individuals (2.17 ± 2.67 mg/mmol and 1.72 ± 2.97 mg/mmol, respectively, P = .012). Average 24-h, daytime and nighttime systolic BP and diastolic BP were lower in patients with normoalbuminuria than in the other two groups and did not differ among the two microalbuminuric groups. Univariate regression analysis showed a close relationship between ACR and ambulatory BP. Strong correlation between BP and ACR in the normoalbuminuric and borderline microalbuminuric range was also obtained in the group of 46 newly diagnosed hypertensive patients. In conclusion, the threshold level of ACR ≥3.0 mg/mmol currently used to define microalbuminuria may be not applicable to EH. Instead, a threshold level of ACR ≥1. 5 mg/mmol may be more appropriate.

Long-term effects of angiotensin-converting enzyme inhibition and metabolic control in hypertensive type 2 diabetic patients

Long-term effects of angiotensin-converting enzyme inhibition and metabolic control in hypertensive type 2 diabetic patients. In hypertensive type 2 diabetic patients, treatment with angiotensin-converting enzyme (ACE) inhibitors is associated with a lower incidence of cardiovascular events than those treated with calcium channel-blocking agents. However, the long-term renal effects of ACE inhibitors in these patients remain inconclusive. In 1989, we commenced a placebo-controlled, double-blind, randomized study to examine the anti-albuminuric effects of enalapril versus nifedipine (slow release) in 102 hypertensive, type 2 diabetic patients. These patients have been followed up for a mean trial duration of 5.5 +/- 2.2 years. We examined the determinants, including the effect of ACE inhibition on clinical outcomes in these patients. After a six-week placebo-controlled, run-in period, 52 patients were randomized double-blind to receive nifedipine (slow release) and 50 patients to receive enalapril. After the one-year analysis, which confirmed the superior anti-albuminuric effects of enalapril (-54%) over nifedipine (+11%), all patients were continued on their previously assigned treatment with informed consent. They were subdivided into normoalbuminuric (N = 43), microalbuminuric (N = 34), and macroalbuminuric (N = 25) groups based on two of three 24-hour urinary albumin excretion (UAE) measurements during the run-in period. Renal function was shown by the 24-hour UAE, creatinine clearance (CCr), and the regression coefficient of the yearly plasma creatinine reciprocal (beta-1/Cr). Clinical endpoints were defined as death, cardiovascular events, and/or renal events (need for renal replacement therapy or doubling of baseline plasma creatinine). In the whole group, patients treated with enalapril were more likely to revert to being normoalbuminuric (23.8 vs. 15.4%), and fewer of them developed macroalbuminuria (19.1 vs. 30.8%) compared with the nifedipine-treated patients (P < 0.05). In the microalbuminuric group, treatment with enalapril (N = 21) was associated with a 13.0% (P < 0.01) reduction in 24-hour UAE compared with a 17.3% increase in the nifedipine group (N = 13). In the macroalbuminuric patients, enalapril treatment (N = 11) was associated with stabilization compared with a decline in renal function in the nifedipine group, as shown by the beta-1/Cr (0.65 +/- 4.29 vs. -1.93 +/- 2.35 1/micromol x 10-3, P < 0.05) after adjustment for baseline values. Compared with the normoalbuminuric and microalbuminuric patients, those with macroalbuminuria had the lowest mean CCr (75.5 +/- 24.1 vs. 63.5 +/- 21.3 vs. 41.9 +/- 18.5 mL/min, P < 0.001) and the highest frequency of clinical events (4.7 vs. 5.9 vs. 52%, P < 0. 001). On multivariate analysis, beta-1/Cr (R2 = 0.195, P < 0.001) was independently associated with baseline HbA1c (beta = -0.285, P = 0.004), whereas clinical outcomes (R2 = 0.176, P < 0.001) were independently related to the mean low-density lipoprotein cholesterol (beta = 2.426, P = 0.018), high-density lipoprotein cholesterol (beta = -8.797, P = 0.03), baseline UAE (beta = 0.002, P = 0.04), and mean CCr during treatment (beta = -0.211, P = 0.006). In this prospective cohort analysis involving 102 hypertensive, type 2 diabetic patients with varying degrees of albuminuria followed up for a mean duration of five years, we observed the importance of good metabolic and blood pressure control on the progression of albuminuria and renal function. Treatment with enalapril was associated with a greater reduction in albuminuria than with nifedipine in the entire patient group, and especially in those with microalbuminuria. In the macroalbuminuric patients, the rate of deterioration in renal function was also attenuated by treatment with enalapril.