The presence of albumin antibodies was neither related to the presence of diabetic late complications, islet cell antibodies, HLA-status nor duration of diabetes.
We now report that a single administration of the p277 peptide conjugated to carrier molecules such as bovine serum albumin or ovalbumin can induce diabetes in C57BL/6 mice and in other strains not genetically prone to develop diabetes.
The observation suggests that changes in transglomerular albumin traffic are demonstrable prior to the onset of diabetes and diabetic nephropathy in subjects with a potential genetic predisposition to these conditions.
We identified 75 patients with an albumin excretion rate > or =15 microg/min in more than two overnight urinary samples and compared them in a nested case-control study with three normoalbuminuric control subjects per patient from the same cohort, matched for diabetes duration.
We found that in patients with type 2 diabetes the methylenetetrahydrofolate reductase VV genotype was associated with a low urinary albumin excretion but not with coronary artery disease or diabetes per se.
In a multiple linear regression model, independent correlates of albumin excretion (P < 0.05) included: fasting blood sugar, treated diabetes, treated hypertension, higher systolic blood pressure, lower diastolic blood pressure, abnormal electrocardiogram, a history of stroke, the degree of American Indian heritage, and lower household income.
We addressed the role of hyperglycemia in leukocyte-endothelium interaction under flow conditions by exposing human umbilical vein endothelial cells for 24 h to normal (5 mM), high concentration of glucose (30 mM), advanced glycosylation end product-albumin (100 microg/ml), or hyperglycemic (174-316 mg/dl) sera from patients with diabetes and abnormal hemoglobin A1c (8.1+/-1.4%).
Thus, in a large ethnically homogeneous cohort of diabetic subjects, our data show: (1) a significant association of C708/T polymorphism with microalbuminuria in long-term diabetes and with both lower plasma ANP levels and widespread albumin leakage; and (2) a strong association between ScaI polymorphism and both diabetic nephropathy and plasma ANP concentrations.
Applying more stringent criteria, only 12 ASPs (sib with diabetes >10 years, diabetic retinopathy, and nephrotic proteinuria) and 9 DSPs (sib with diabetes >10 years and normal urine albumin excretion) were identified.
Patients were divided into three groups based on their urinary albumin excretion rate (AER) and the stage of diabetic retinopathy as follows: uncomplicated group (U), normal albuminuria (AER <20 microg/min) without proliferative retinopathy and with the duration of diabetes more than 20 years (N = 32); microalbuminuria group (M), 20 < or = AER < 200 microg/min (N = 155); overt nephropathy group (O), AER > or = 200 microg/min (N = 63).
The correlations between uric acid levels and triglycerides, BMI, systolic blood pressure, albumin excretion rate, C-peptide, creatinine clearance, HDL-cholesterol and HbA1c remained significant in a multiple regression analysis after adjustment for age, sex and duration of diabetes.
In a two-by-two factorial study of urinary albumin in non-diabetic Polynesians, 90 people with a first degree relative (FDR) with end-stage renal failure (ESRF) and diabetes (group 1) were compared with 90 people with a FDR with non-diabetic ESRF (group 2), with 90 people with a FDR with diabetes but no known nephropathy (group 3) and 90 people with no known relatives with either diabetes or nephropathy (group 4).
Genomic DNA was obtained from 659 patients: 307 with normal urinary albumin excretion despite diabetes duration of >15 years (control subjects) and 352 with advanced diabetic nephropathy, of whom 200 had persistent proteinuria and 152 had end-stage renal disease (ESRD).
The independent predictors of death in the multivariate survival analysis were age [relative risk (RR) = 1.03, p = 0.23], diabetes (RR = 3.00, p = 0.03), diastolic blood pressure < or = 70 mmHg (RR = 2.94, p = 0.03), serum albumin (RR = 0.87, p < 0.01), and Lp(a) level (RR = 1.004, p < 0.01).
The peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala polymorphism has been associated with a decreased risk of type 2 diabetes and a lower albumin excretion rate (AER) in patients with established diabetes.
This study indicates that the alteration in nephrin expression is an early event in proteinuric patients with diabetes and suggests that glycated albumin and angiotensin II contribute to nephrin downregulation.
To test this hypothesis we searched for association between the A-->G (-3862) variant in UCP1, the insertion/deletion (I/D) polymorphism in exon 8 in UCP2, and the C-->T (-55) polymorphism in UCP3 and diabetic nephropathy in 218 diabetic patients with normal urinary albumin excretion rate (AER), 216 with micro- or macroalbuminuria, and in 106 control subjects without a family history of diabetes.
They were all Korean and type 2 diabetic patients who had normal renal function, history of diabetes longer than 10 years and the data of urine albumin excretion rate at 10th year diabetes duration.
We constructed a recombinant adenoviral vector (rAd-BTC) containing the cytomegalovirus promoter/enhancer, beta-globin chimeric intron, and albumin leader sequence to facilitate secretion, followed by BTC (1-80) complementary DNA (cDNA) encoding mature BTC.A single intravenous (i.v.) administration of rAd-BTC resulted in complete remission of streptozotocin (STZ)-induced diabetes within 2 weeks in mice.
A total of 441 cases with diabetic nephropathy (albumin excretion > or =300 mg/24 h) and 314 controls with persistent normoalbuminuria (<30 mg/24 h), despite diabetes of duration > or =20 years, were identified.
A total of 458 cases with diabetic nephropathy (albumin excretion >300 mg/24h) and 319 controls with persistent normoalbuminuria (<30 mg/24h), despite > or =20 years of diabetes duration at follow-up were identified.
We studied three adiponectin polymorphisms (-11391G > A, +45T > G and +276G > T) in 3086 subjects with type 2 diabetes and high levels of albumin excretion from the diabetes, hypertension, microalbuminuria or proteinuria, cardiovascular events and ramipril (DIABHYCAR) trial.
The biological impact of glycated albumin on cell physiology is also discussed, specifically the role of the protein as a biological marker of diabetes.