Microalbuminuric Diabetic Patients Research Articles

Association Between Monocyte-to-High-Density Lipoprotein (HDL) Cholesterol Ratio and Proteinuria in Patients With Type 2 Diabetes Mellitus: A Prospective Observational Study.

Background Diabetes mellitus (DM) refers to a group of metabolic disorders that share the phenotype of hyperglycemia. "Diabetic nephropathy (DN)" is a microvascular complication of DM, and it is the leading cause of end-stage renal failure. Increased urinary albumin excretion (UAE) and a decrease in glomerular filtration rate (GFR) are associated with DN along with elevated blood pressure and end-stage renal disease (ESRD). The purpose of this study is to analyze the prognostic significance of the monocyte-to-high-density lipoprotein (HDL) cholesterol ratio (MHR) in DN patients. Materials and methods This prospective observational study was carried out over a period of 1.5 years, with patients being followed up for three months. One hundred twenty participants were enrolled and allotted into groups based on the measure of urine albumin-to-creatinine ratio (UACR). The participants were categorized into healthy individuals, normoalbuminuric diabetic patients, microalbuminuric diabetic patients, and macroalbuminuric diabetic patients group. The MHR, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were estimated and compared between the baseline measurements. Conclusion The MHR, NLR, and PLR showed a positive correlation with UACR levels which could serve as an inflammatory marker and be used as an inexpensive and accessible prognostic marker in DN patients.

Evaluation of serum cystatin C level as an early biomarker of nephropathy in children with type 1 diabetes mellitus attending Suez Canal University Hospital

Background Diabetic nephropathy is a syndrome characterized by a secondary renal disease in patients with diabetes mellitus (DM). It is a serious complication of DM and is the most common cause of the end-stage renal disease. Aim To evaluate the diagnostic value of serum cystatin C level as an early biomarker of nephropathy in children with type 1 diabetes mellitus (T1DM) attending Suez Canal University Hospital. Patients and methods This was a descriptive cross-sectional study that included 49 children with T1DM attending the pediatric endocrinology outpatient clinic of at Suez Canal University Hospital, Ismailia, Egypt, and 49 matched healthy controls during the period from 1/12/2020 to 1/3/2021. The target population was children with T1DM aged between 6 and 18 years of both sexes who were attending the pediatric endocrinology outpatient clinic of Suez Canal University Hospital, Ismailia, Egypt. All studied patients and healthy controls were subjected to history taking and general and systemic examination. The following investigations were done: fasting blood sugar, serum creatinine, estimated glomerular filtration rate, albumin/creatinine ratio (ACR), urine analysis, hemoglobin A1C, and serum cystatin C level). Results ACR and cystatin C levels were significantly higher in albuminuric than nonalbuminuric diabetic patients. There was a significant positive correlation between serum cystatin C and duration of diabetes, hemoglobin A1C, and ACR. For serum cystatin C, regarding detection of microalbuminuria, the sensitivity was 66.7%, specificity was 75%, the positive predictive value was 49%, and the negative predictive value was 0.52%, with the best cut-off value of 0.98 (mg/l). Conclusion Microalbuminuric diabetic patients showed an increased serum cystatin C levels, whereas their creatinine levels were still within normal. Serum cystatin C levels well reflect the severity of renal damage caused by DM. The serum cystatin C measurement might become a useful, practical, noninvasive, and accurate tool for early detection of microalbuminuria and renal insufficiency in T1DM.

Retinal Microcirculation Alterations in Microalbuminuric Diabetic Patients With and Without Retinopathy

ABSTRACT Purpose To investigate the effect of microalbuminuria (MA) on superficial vessel density (SVD), deep vessel density (DVD), and choriocapillaris vessel density (CVD) in type-2 diabetic patients. Methods Twenty patients without diabetic retinopathy (DR) and MA (group 1), 20 patients without DR but with MA (group 2) and 30 patients with mild DR and MA (group 3) were enrolled in this prospective and cross-sectional study. SVD, DVD, and CVD of all patients were screened with optical coherence tomography angiography (OCTA). The relationships between these values and age, diabetes duration and metabolic parameters were also evaluated. Results The whole macular SVD value was 50.15 ± 4.52 in group 1 and 47.81 ± 4.12 in group 2 (p = .04). The whole macular DVD value was 47.66 ± 2.76 in group 1, 44.37 ± 3.39 in group 3 (p = .02). Parafoveal DVD value was 52.58 ± 3.47 in group 1, 51.84 ± 2.23 in group 2, and 49.23 ± 3.38 in group 3 (p G1&3 = .001, p G2&3 = .02). Perifoveal DVD value was 47.92 ± 3.30 in group 1, 43.96 ± 4.19 in group 2, and 42.85 ± 2.98 in group 3 (p G1&2 = .02 and p G1&3 < .001). There were inverse correlations between diabetes duration, urea, creatinine, albumin, urinary sodium and some DVD values (p < .05, for all). Also, there were inverse correlations between parafoveal and perifoveal DVD values and MA (p = .002 and p = .031). Additionally, inverse correlations were determined between diabetes duration, creatinine, urea, serum Na and some CVD values (p < .05 for all). Conclusion: Decreased SVD and DVD values measured by OCTA in type-2 diabetic patients, whether they have mild DR or not, may be associated with MA causing early retinal microvascular changes.

Association of Retinol Binding Protein-4 and Microalbuminuria and Blood Glucose Regulation in Type 2 Diabetic Iraqi Patients

Retinol binding protein 4 (RBP-4) has long been known as the carriers for vitamin A, in the plasma it is banded to transthyretin to form too large complex for glomerulus filtration. Discovered as adipokine involved in the pathogenesis of type 2 diabetes induced insulin resistant and linked to obesity. Diabetic nephropathy one of serious microvascular complication that impact large numbers of the patient however, association with RBP-4 is not fully known. The present study tested this hypothesis by measuring serum RBP4 in samples of Iraqi type 2 diabetic (n=120) with normal albumin excretion (n=57) and microalbuminuria (n=63) of either sex. and Also apparently health subjects (n=30) were involved to serve as control. Concentrations of the RBP4 were significantly elevated in serum of microalbuminuric diabetic patients as compare with normoalbuminuric patients, (p=0.000&lt;0.05). also glycemic index parameters significantly higher (for all p&lt;0.05). In conclusion, the study suggested that serum level of RBP4 are affected by microalbuminuria and the assessment of RBP-4 as controller for insulin resistant in type 2 diabetic in further studies must take into consideration other renal problems.

Liver-type fatty acid-binding protein as an early biomarker of nephropathy in type-2 diabetes

Objective The aim of this study was to evaluate serum liver-type fatty acid-binding protein (L-FABP) level as an early biomarker of diabetic nephropathy (DN) in type-2 diabetic patients. Background Tubular hypoxia upregulates the expression of the L-FABP gene in the kidney and increases the urinary excretion of L-FABP from the proximal tubules. Thus, in early stage DN, it is possible that chronic hypoxia could have induced an increase in urinary excretion of L-FABP. Patients and methods This was a case–control study that included ninety patients with type-2 diabetes mellitus selected from Military Hospital and Menoufia University Hospital who were divided into three groups: the first group comprised diabetic patients with microalbuminuria, second group comprised diabetic patients with macroalbuminuria, and the third group comprised nondiabetic patients with chronic kidney disease. A fourth group of healthy participants served as the control group. Results We found a significant increase of urinary L-FABP level in microalbuminuric diabetic patients and a significant positive correlation between urinary L-FABP level and the duration of diabetes. By using receiver operating characteristics curve analysis, calcium level at a cutoff point (≤8.3) discriminated patients with microalbuminuria from patients with macroalbuminuria, with excellent accuracy, sensitivity of 95% and specificity of 96%. Conclusion We conclude that the L-FABP level could be a suitable biomarker for early detection with good value to detect DN in patients with type-2 diabetes.

Evaluation of Netrin-1 Levels and Albuminuria in Patients With Diabetes.

Netrin-1 is a diagnostic biomarker that has been identified recently for chronic renal failure (CRF) in animal experiments. Netrin-1 levels in urine have been shown to have increased significantly at the acute kidney damage. Human studies on the relation between the CRF and plasma netrin-1 levels have not been found in the literature. This study aimed to investigate whether plasma netrin-1 levels increased in the early stages of the CRF in diabetic patients. Plasma samples from healthy volunteers and diabetic patients with and without microalbuminuria were collected after receiving consent. Netrin-1 in plasma was quantified by enzyme-linked immunosorbent assay and the data were analyzed to determine whether plasma netrin-1 correlates significantly with disease progression. Plasma netrin-1 level in microalbuminuric diabetic patients was significantly higher than in normoalbuminuric diabetic patients and the control group. However, no significant difference between normoalbuminuric patients and control group was determined. Plasma netrin-1 level was significantly associated with albuminuria and estimated glomerular filtration rate, independently of age and sex. This study supports that plasma netrin-1 level increases significantly when glomerular damage occurs in diabetic nephropathy.

Study of ambulatory blood pressure in diabetic children: prediction of early renal insult.

BackgroundHypertension is a highly prevalent risk factor for cardiovascular disease in patients with type 1 diabetes mellitus. Elevated blood pressure (BP) promotes the development and progression of microvascular complications, eg, nephropathy and retinopathy. The purpose of this study was to identify and detect early BP changes in diabetic children and adolescents, aiming for the early prediction of future renal and cardiovascular disease risk during childhood.Methods and materialsAmbulatory BP monitoring was undertaken for 40 normotensive type 1 diabetic children with mean age of 11.56±2.82 years, and 24 healthy children as control group with matched age and sex. Albumin/creatinine ratio and glycated hemoglobin were tested. BP indices and standard deviation scores were calculated using reference standards. The data were analyzed by SPSS software version 20 using mean and standard deviations for descriptive data. Correlation and regression analysis tests were used to study relations between BP indices and diabetic parameters.ResultsAll parameters of BP z-scores were highly significantly increased in diabetic patients compared with controlled group (P<0.0001). The frequency of non-dipping was greater and highly significant in microalbuminuric diabetic patients (P<0.0001). Regression analysis revealed that BP parameters were significantly related to albumin/creatinine ratio, glycated hemoglobin, insulin dose, and body mass index.ConclusionOur observation revealed a clear link between the nocturnal BP and microalbuminuria which mandates BP follow-up via ambulatory BP monitoring with therapeutic intervention to prevent renal and cardiovascular diabetic complications in adulthood.

Urinary monocyte chemoattractant protein-1 and vitamin D-binding protein as biomarkers for early detection of diabetic nephropathy in type 2 diabetes mellitus.

Diabetic nephropathy is a serious complication of both type 1 and type 2 diabetes and, unless arrested, leads to end-stage renal disease. Therefore, early prediction and detection of DN would greatly benefit the disease management and delay its progression. The aim of this study is to evaluate the levels of urinary monocyte chemoattractant protein-1 (uMCP-1) and urinary vitamin D-binding protein (uVDBP) in type 2 diabetic patients with different degrees of diabetic nephropathy (DN) and to assess the value of uMCP-1 and uVDBP in the early detection of DN. Seventy-five type 2 diabetic patients with normoalbuminuria (n = 25), microalbuminuria (n = 25), macroalbuminuria (n = 25), and 25 healthy controls were included in this study. Urinary MCP-1 and VDBP levels were evaluated by enzyme-linked immunosorbent assay. A significant elevation in the uMCP-1 and uVDBP levels was found in macroalbuminuric (p < 0.001) and microalbuminuric (p < 0.01) diabetic patients compared to that in normoalbuminuric diabetic patients and control subjects (p < 0.001). Correlation study revealed that both uMCP-1 and uVDBP were significantly positively correlated to urinary albumin/creatinine ratio (r = 0.968, p < 0.001 and r = 0.973, p < 0.001, respectively), serum urea (r = 0.461, p = 0.001 and r = 0.456, p = 0.002, respectively), and serum creatinine (r = 0.475, p = 0.001 and r = 0.448, p = 0.004, respectively) and significantly inversely correlated to glomerular filtration rate (r = -0.983, p < 0.001 and r = -0.988, p < 0.001, respectively). Receiver operating characteristic (ROC) curve analysis of uMCP-1 and uVDBP levels for early diagnosis and detection of DN revealed that the cut-off value of uMCP-1 was 110 pg/mg with 92% sensitivity and 100% specificity; whereas, the cut-off value of uVDBP was 550 ng/mg with 96% sensitivity and 84% specificity. The findings of the present study suggest that uMCP-1 and uVDBP may be considered as novel potential diagnostic biomarkers for the early detection of diabetic nephropathy.

Should We Sweat the Small (Micro) Things?

Thirty years ago, a physician whose patient had diabetes and was urine protein dipstick–positive could only say, “You will most likely progress to end-stage renal disease in 10 years and need dialysis or a kidney transplant, and there is not much we can do about it.” Following the landmark microalbuminuria study of Mogensen and Christensen in 1984 (1), clinicians could say to patients with diabetes and microalbuminuria, “The good news is, we can now tell you 20 years ahead of time that you will likely progress to end-stage renal disease, but the bad news is that we still cannot do anything about it.” However, by the early 1990s, it was shown that treatment of microalbuminuric diabetic patients with ACE inhibitors to control blood pressure, diet modification, and intensive glucose control could slow or prevent progression to end-stage renal disease (ESRD)3 (2). Microalbumin quickly became a textbook example of a new laboratory test with profound impact on treatment and long-term outcomes of patients with a chronic disease. Since then, the term microalbumin has been abandoned in favor of urine albumin because there is nothing “small” or “low molecular weight” about the albumin measured in urine. Urine albumin assays are simply immunoassays capable of measuring albumin concentrations that are more than 3 orders of magnitude lower than those encountered in serum, which are measured by dye-binding methods. Since its first use in patients with diabetes, urine albumin concentration has shown to predict progression to all-cause chronic kidney disease (CKD) and be an independent risk factor for cardiovascular disease (3). Today, numerous clinical practice guidelines exist for the use of urine albumin to predict progression to CKD and cardiovascular risk (4). Two of the most cited are the Kidney Disease Improving Global Outcomes (KDIGO) and the American Diabetes Association (ADA) Standards of …

Significance of estimating the glomerular filtration rate for the management of hypertension in type 2 diabetes with microalbuminuria

The Home Blood Pressure for Diabetic Nephropathy (HBP-DN) study is a prospective cohort study to determine the optimal home blood pressure (HBP) required to improve the prognosis of type 2 diabetic patients with microalbuminuria. The glomerular filtration rate (GFR) is heterogeneous in microalbuminuric diabetic patients. The first step of the HBP-DN study explored the significance of estimating GFR for the identification of patients for whom HBP measurement would be more helpful. The patients were divided into two groups based on their estimated GFR (eGFR): a low eGFR group (eGFR <60 ml min(-1) per 1.73 m(2), N=75) and a preserved eGFR group (eGFR 60 ml min(-1) per 1.73 m(2), N=193). HBP, variability of HBP and a previous history of vascular complications were compared between the two groups. The number of antihypertensive drugs used for the patients and the s.d. of home systolic blood pressure (HSBP) in the low eGFR group were significantly higher than those in the preserved eGFR group. A stepwise multiple linear regression analysis also revealed that the low eGFR group was independently correlated with the s.d. of HSBP. A multiple logistic regression analysis revealed that a low eGFR was an independent risk factor for coronary heart disease and advanced retinopathy. Estimating the GFR is important to identify patients with elevated blood pressure variability, as well as those with a high risk of vascular complications. Measuring HBP would be more helpful for the effective and safe treatment of hypertension in patients with a low eGFR than in those with a preserved eGFR.

Predictive value of serum NT-proBNP levels in type 2 diabetic people with diabetic nephropathy

ObjectiveThe serum N-terminal fragment of pro brain natriuretic peptide (NT-proBNP) level in type 2 diabetic subjects with or without diabetic nephropathy (DN) is still unclear. We aimed to evaluate the relationship between serum NT-proBNP levels and different stages of diabetic nephropathy, and identify probable factors predicting serum NT-proBNP level. Subjects and methodsThis cross-sectional study included 20 normoalbuminuric (Group-I), 28 microalbuminuric (Group-II), 20 macroalbuminuric type 2 diabetic patients (Group-III), and 20 healthy volunteers (Group-IV). Serum NT-proBNP levels were measured with highly sensitive and specific immunoassay. ResultsMean NT-proBNP levels were 32±55, 91±95, 331±297, 42±34pg/ml for Groups I–IV, respectively. When patients with LVH were excluded, mean logNT-proBNP was still significantly higher in Group-III than all other groups. The three diabetic groups were similar in age, BMI, HbA1c, fasting serum glucose, and GFR. In a multivariate linear regression model, adjusting for factors significantly correlated with NT-proBNP levels, the patient group, presence of LVH, and hemoglobin remained as an independent predictor of serum NT-proBNP. These variables explained 68% of the variability of NT-proBNP (adjusted R2=0.683). ConclusionsMean serum NT-proBNP level of macroalbuminuric diabetic patients was higher than normoalbuminuric and microalbuminuric diabetic patients, and healthy control subjects even after exclusion of LVH. NT-proBNP may be a useful and predictive marker of diabetic nephropathy.

Non-invasive investigation of kidney disease in type 1 diabetes by magnetic resonance imaging

Pathophysiological abnormalities in early diabetic nephropathy are poorly understood. We employed MRI to characterise renal perfusion, tissue oxygenation and kidney size in non-diabetic volunteers and type 1 diabetic patients without and with early renal disease. We studied ten control participants (C; age 40.0 [range 31-54] years), nine longstanding normotensive type 1 diabetic patients (T1Normo; age 40.1 [31-50] years, estimated glomerular filtration rate [eGFR] 83.4 ± 10.6 ml min(-1) 1.73 m(-2)) and eight microalbuminuric type 1 diabetic patients (T1Micro; age 42.4 [33-52] years, eGFR 71.6 ± 13.7 ml min(-1) 1.73 m(-2)). Six microalbuminuric patients were restudied after 4 weeks without renin-angiotensin-aldosterone system inhibitors. Phase contrast angiography and kidney blood oxygen level dependent (BOLD) (R(2)(*)) MRI were performed, before and during water diuresis. Contrast-enhanced MRI was performed at baseline urine flow rate. Renal artery flow, renal vascular resistance (RVR), cortical and medullary volumes, and R(2)(*) were determined. Renal cortical and medullary volumes were similar in all groups (cortex: C 108 ± 16, T1Normo 112 ± 21, T1Micro 111 ± 10 cm(3)/1.73 m(2); medulla: C 35 ± 14, T1Normo 29 ± 10, 33 ± 6 cm(3)/1.73 m(2)). RVR increased from control to normoalbuminuric to microalbuminuric type 1 diabetic patients (C 0.061 ± 0.018, T1Normo 0.077 ± 0.014, T1Micro 0.093 ± 0.024 mmHg ml(-1) min(-1) 1.73 m(-2), ANOVA p = 0.012). RVR correlated inversely with eGFR in normoalbuminuric, but not in microalbuminuric diabetic patients. Renal artery flow was lower in the whole diabetes cohort (control 740 ± 205 vs diabetes 591 ± 128 ml min(-1) 1.73 m(-2), p = 0.035). Cortical and medullary volumes remain normal in early diabetic nephropathy. Decreased renal flow in longstanding normoalbuminuric type 1 diabetic patients may reflect intrarenal vascular stiffening, whereas in the microalbuminuric patients it may also reflect increased intraglomerular pressure.

Urine Proteome Analysis May Allow Noninvasive Differential Diagnosis of Diabetic Nephropathy

OBJECTIVEChronic renal insufficiency and/or proteinuria in type 2 diabetes may stem from chronic renal diseases (CKD) other than classic diabetic nephropathy in more than one-third of patients. We interrogated urine proteomic profiles generated by surface-enhanced laser desorption/ionization-time of flight/mass spectrometry with the aim of isolating a set of biomarkers able to reliably identify biopsy-proven diabetic nephropathy and to establish a stringent correlation with the different patterns of renal injury.RESEARCH DESIGN AND METHODSTen micrograms of urine proteins from 190 subjects (20 healthy subjects, 20 normoalbuminuric, and 18 microalbuminuric diabetic patients and 132 patients with biopsy-proven nephropathy: 65 diabetic nephropathy, 10 diabetic with nondiabetic CKD [nd-CKD], and 57 nondiabetic with CKD) were run using a CM10 ProteinChip array and analyzed by supervised learning methods (Classification and Regression Tree analysis).RESULTSThe classification model correctly identified 75% of patients with normoalbuminuria, 87.5% of those with microalbuminuria, and 87.5% of those with diabetic nephropathy when applied to a blinded testing set. Most importantly, it was able to reliably differentiate diabetic nephropathy from nd-CKD in both diabetic and nondiabetic patients. Among the best predictors of the classification model, we identified and validated two proteins, ubiquitin and β2-microglobulin.CONCLUSIONSOur data suggest the presence of a specific urine proteomic signature able to reliably identify type 2 diabetic patients with diabetic glomerulosclerosis.

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.

Addition of Manidipine Improves the Antiproteinuric Effect of Candesartan in Hypertensive Patients With Type II Diabetes and Microalbuminuria

We sought to compare the effect of manidipine versus hydrochlorothiazide (HCTZ) in addition to candesartan on the urinary albumin excretion rate (UAER) in hypertensive patients with type II diabetes and microalbuminuria. After a 2-week washout and run-in period, and 8-week monotherapy with candesartan 16 mg every day, 174 microalbuminuric diabetic hypertensive patients with uncontrolled blood pressure (BP) (>130/80 mm Hg) were randomized to addition of manidipine 10 mg every day (n = 87) or HCTZ 12.5 mg every day (n = 87) for 24 weeks, with a titration after 4 weeks (manidipine or HCTZ dose-doubling) in nonresponder patients. Blood pressure, UAER, creatinine clearance, serum electrolytes, fasting plasma glycemia, and glycosylated hemoglobin were evaluated at baseline (end of run-in period), after candesartan monotherapy, and at the end of the combination treatment period. Both combinations produced greater systolic BP/diastolic BP reduction than candesartan monotherapy (-28/21 mm Hg versus -16/11 mm Hg and -28/20 mm Hg versus -15/11 mm Hg, respectively; all P < .05 versus monotherapy), with no significant difference between the two combinations. The addition of manidipine produced a greater reduction in UAER than candesartan monotherapy (-55.4 mg/24 h v -36.1 mg/24 h, P < .05), whereas the addition of HCTZ did not significantly modify UAER; the difference between the two combinations was statistically significant (P < .05). Similarly, the percentage of patients moving to a normoalbuminuric state (UAER <30 mg/24 h) was increased by the addition of manidipine to candesartan (from 35% to 64%, P < .05), but not by the addition of HCTZ (from 34% to 39%, NS), with a statistical difference between the two combinations (P < .05). These findings show that, despite equivalent reduction in BP, the addition of manidipine to candesartan further reduced the UAER, whereas the addition of HCTZ did not modify the UAER. This suggests that the antiproteinuric effect of manidipine is partially independent of BP reduction, and is attributable to mechanisms different from those mediated by angiotensin receptor blockade.

Metabolism of phytol to phytanic acid in the mouse, and the role of PPARα in its regulation

Phytol, a branched-chain fatty alcohol, is the naturally occurring precursor of phytanic and pristanic acid, branched-chain fatty acids that are both ligands for the nuclear hormone receptor peroxisome proliferator-activated receptor alpha (PPARalpha). To investigate the metabolism of phytol and the role of PPARalpha in its regulation, wild-type and PPARalpha knockout (PPARalpha-/-) mice were fed a phytol-enriched diet or, for comparison, a diet enriched with Wy-14,643, a synthetic PPARalpha agonist. After the phytol-enriched diet, phytol could only be detected in small intestine, the site of uptake, and liver. Upon longer duration of the diet, the level of the (E)-isomer of phytol increased significantly in the liver of PPARalpha-/- mice compared with wild-type mice. Activity measurements of the enzymes involved in phytol metabolism showed that treatment with a PPARalpha agonist resulted in a PPARalpha-dependent induction of at least two steps of the phytol degradation pathway in liver. Furthermore, the enzymes involved showed a higher activity toward the (E)-isomer than the (Z)-isomer of their respective substrates, indicating a stereospecificity toward the metabolism of (E)-phytol. In conclusion, the results described here show that the conversion of phytol to phytanic acid is regulated via PPARalpha and is specific for the breakdown of (E)-phytol.

Plasma homocysteine, oxidative stress and endothelial function in patients with Type 1 diabetes mellitus and microalbuminuria

The purpose of this study was to examine the associations between endothelial function, plasma homocysteine and oxidative stress in patients with Type 1 diabetes mellitus (DM) and microalbuminuria compared with DM patients with normoalbuminuria and non-diabetic control subjects. We wished to test the hypothesis that increased cardiovascular risk in patients with Type 1 diabetes and microalbuminuria may be in part as a result of hyperhomocysteinaemia-mediated oxidative stress leading to impaired endothelial function. We measured forearm blood flow, total plasma homocysteine, total antioxidant status (TAOS) and whole blood glutathione in 31 DM patients, 16 with microalbuminuria and 15 with normoalbuminuria, and 15 non-diabetic control subjects. Plasma homocysteine levels were significantly higher in the microalbuminuric diabetic patients compared with the normoalbuminuric patients and the control subjects. TAOS was significantly lower in the micoalbuminuric and normoalbuminuric diabetic patients compared with the control subjects, although TAOS levels were similar in both groups of diabetic patients. There was no difference in forearm blood flow between the groups and no association between measured endothelial function and antioxidant defence/oxidative stress and homocysteine in each group. There was no association between plasma total homocysteine and TAOS or whole blood glutathione within the groups. We have found mild hyperhomocysteinaemia in microalbuminuric DM patients compared with normoalbuminuric DM patients and non-diabetic subjects and some evidence for reduced antioxidant defence in DM patients. These findings add to our understanding of the increased risk of vascular disease in patients with Type 1 diabetes.

Microalbuminuria en pacientes diabéticos y en pacientes con hipertensión arterial: estudio de una cohorte de 979 pacientes

Microalbuminuria is a known complication of diabetes mellitus but it is also a cardiovascular risk factor commonly present among hypertensive (non diabetic) population. The prevalence of microalbuminuria is variable and it has been never estimated in our region. The aim of this study has been to determine the prevalence of microalbuminuria in hypertensive (non diabetic) and diabetic population in Extremadura (Spain). The study included diabetic patients and non-diabetic hypertensive ones randomly selected. Microalbuminuria was measured in every patient using albumin/creatinin reactive stick in fasting first morning urine. Whenever possible microalbuminuria was confirmed in laboratory by microalbuminuria/creatinina coefficient in first morning urine samples. A total of 979 patients (mean age [SD], 67.9 [10.8] years; 409 men and 570 women, 505 diabetics) were studied. The presence of microalbuminuria was found in 12.4% of hypertensive patients and in 21.4% of diabetic patients (p < 0.001). Hypertensives and normotensive diabetics showed a similar prevalence of microalbuminuria (13.3%, not significant), but it tripled in hypertensive diabetics (33.8; p < 0.01). Glicemic control was not different for microalbuminuric diabetic patients and non microalbuminuric ones. The patients receiving rennin-angiotensin axis blocking drugs do not showed less prevalence of microalbuminuria (hypertensives 10.5%, diabetics 23.5%). Microalbuminuria was confirmed in 65.4% of patients. The prevalence of microalbuminuria in Extremadura seems to be high either in diabetics or non diabetic hypertensive patients. The finding of microalbuminuria in diabetics patients correlates with hypertension but do not with glicemic control. The prevalence of microalbuminuria is high in spite of using rennin-angiotensin axis blocking drugs.

Circulating erythropoietin in microalbuminuric type 2 diabetic patients with normal renal function: a pilot study

To verify the hypothesis of an early impairment of erythropoietin (Epo) production and to assess the adequacy of its circulating levels in diabetic nephropathy, we investigated Epo values in 18 microalbuminuric type 2 diabetic patients with normal renal function (7 anaemic and 11 nonanaemic), 24 subjects with uncomplicated iron-deficiency anaemia, and 15 healthy controls comparable for sex and age. Mean±S.D. plasma Epo level was 56.4±12.7 mU/mL in iron-deficient patients and 9.3±2.6 mU/mL in controls. In diabetic groups, mean±S.D. Epo level was 11.38±3.65 mU/mL in nonanaemic and 49.12±6.44 mU/mL in anaemic subjects. No significant difference ( P>.05) in Epo values was found between controls and nonanaemic diabetic patients. Anaemic diabetics and iron-deficient subjects had significantly higher values than the nonanaemic groups ( P>.001). An inverse significant relation between Epo levels and Hb concentration resulted in both anaemic diabetics ( r=−.44, P>.05) and iron-deficient patients ( r=−.61, P=.001). Analysis of covariance ( P>.05) and comparison of the two regression lines ( t=0.4, df=29, P>.05) did not show any significant difference between diabetic patients with anaemia and iron-deficient patients. These results suggest that normochromic anaemia observed in microalbuminuric diabetic patients with normal renal function is not due to Epo deficiency, and circulating levels of this hormone are suitably increased with regard to Hb concentration.

Relationship between Reduced BCL-2 Expression in Circulating Mononuclear Cells and Early Nephropathy in Type 1 Diabetes

Microalbuminuria is the earliest clinical evidence of diabetic nephropathy, but the mechanisms linking hyperglycemia and kidney complications are not clear. The aim of this study was to evaluate whether enhanced oxidative stress in patients with microalbuminuria can contribute to diabetic nephropathy development through downregulation of the antiapoptotic gene Bcl-2 that promotes in turn a pro-inflammatory status. We studied 30 patients with type 1 diabetes (15 with and 15 without microalbuminuria) compared to 15 matched healthy controls. Plasma oxidant status, and expression of Bcl-2, activated NF-kB, inducible Nitric Oxide synthase (iNOS), and monocyte chemoattractant protein (MCP)-1 in circulating monocytes were evaluated at baseline and after 8-week oral vitamin E treatment (600 mg b.i.d.). Bcl-2 expression was significantly reduced in microalbuminuric diabetic patients as a consequence of increased oxidant burden secondary to persistent hyperglycemia. Bcl-2 down-regulation was associated with enhanced expression of NF-kB, iNOS and MCP-1, and showed a strong correlation with the albumin excretion rate. Low Bcl-2 expression and high inflammatory status were normalized by vitamin E both in vivo and in vitro. Our study showed that Bcl-2 down-regulation in diabetic patients with poor glycemic control results in the activation of the NF-kB pathway leading to the development of nephropathy. Vitamin E might provide a novel form of therapy for prevention of nephropathy in diabetic patients in which an acceptable glycemic control is difficult to achieve despite insulin therapy.