Preventing diabetic nephropathy: an audit.

In type 1 diabetic patients with microalbuminuria not receiving antihypertensive treatment, an increase in urinary albumin excretion rate (AER) of 6% to 14%/year and a risk for the development of diabetic nephropathy of 3% to 30%/year have previously been reported. The aim of the present study was to audit the effect of angiotensin converting enzyme (ACE) inhibition on the progression of microalbuminuria and development of diabetic nephropathy. We consecutively identified 227 type 1 diabetic patients with persistent microalbuminuria (urinary AER between 30 and 300mg/24h, ELISA).

Remission of nephrotic-range albuminuria in type 1 diabetic patients.

Objective: To evaluate the cumulative incidence of nephrotic-range albuminuria (NRA), the frequency of remission, and the impact on progression, we analyzed data from a prospective cohort study of type 1 diabetic patients with diabetic nephropathy.

Research Design And Methods: All of the albuminuric type 1 diabetic patients (n = 321, 121 women), who had at least yearly measurements of glomerular filtration rate (GFR) with a (51)Cr-EDTA plasma clearance technique and were followed for at least 3 years, were evaluated. NRA, defined as persistent albuminuria >2,500 mg/24 h, occurred in 126 patients (35 women) aged (mean +/- SD) 34 +/- 8 years, with duration of diabetes 22 +/- 8 years and follow-up time from onset of NRA (median [range]) 8.

Diabetic microvascular complications are not associated with two polymorphisms in the GLUT-1 and PC-1 genes regulating glucose metabolism in Caucasian type 1 diabetic patients.

Background: An XbaI polymorphism in the gene encoding the glucose transporter, GLUT-1, is associated with development of diabetic nephropathy in Chinese type 2 diabetic patients. In addition, an amino acid variant (K121Q) in the gene encoding the glycoprotein plasma cell differentiating antigen (PC-1), a specific inhibitor of insulin receptor signalling, has been reported to predict a faster progression of nephropathy in Italian and British type 1 diabetic patients.

Methods: The XbaI and K121Q polymorphisms were determined by PCR-RFLP in Danish type 1 diabetic patients with nephropathy (122 men/77 women, age 40.

Remission and regression in the nephropathy of type 1 diabetes when blood pressure is controlled aggressively.

Background: Diabetic nephropathy is a chronic, progressive kidney disease with a mean rate of decline of in glomerular filtration rate (GFR) of 10 to 12 mL/min/year (natural history). The introduction of aggressive antihypertensive treatment has improved the renal prognosis during the last decades. To examine whether remission and regression of diabetic nephropathy are possible in type 1 diabetic patients, we analyzed data from a prospective observational cohort study that was started in 1983.

Polymorphism screening of four genes encoding advanced glycation end-product putative receptors. Association study with nephropathy in type 1 diabetic patients.

Advanced glycation end-products (AGEs) may play an important role in the pathogenesis and progression of cardiovascular and renal complications of diabetes. Four putative AGE receptors (RAGEs), AGE-R1, AGE-R2, and AGE-R3 have been described. In this study, we scanned the sequence of the genes encoding these AGE receptors in 48 patients with type 1 diabetes and investigated the identified polymorphisms (n = 19) in 199 type 1 diabetic patients with nephropathy and 193 type 1 diabetic patients without nephropathy.

Progression of diabetic nephropathy.

Background: Diabetic nephropathy is a major cause of renal failure. The decline in glomerular filtration rate (GFR) is highly variable, ranging from 2 to 20, with a median of 12 mL/min/year. The risk factors of losing filtration power (progression promoters) have not been clearly identified.

Long-term renoprotective effect of nisoldipine and lisinopril in type 1 diabetic patients with diabetic nephropathy.

Objective: To compare the long-term effect on kidney function of a long-acting calcium antagonist (nisoldipine) versus a long-acting ACE inhibitor (lisinopril) in hypertensive type 1 diabetic patients with diabetic nephropathy.

Research Design And Methods: We performed a 4-year prospective, randomized, double-dummy controlled study comparing nisoldipine (20-40 mg once a day) with lisinopril (10-20 mg once a day). The study was double-blinded for the first year and single-blinded thereafter.

Lack of synergism between long-term poor glycaemic control and three gene polymorphisms of the renin angiotensin system on risk of developing diabetic nephropathy in type I diabetic patients.

Aims/hypothesis: Reports on a putative synergism between poor glycaemic control and carriage of the angiotensin II type 1 receptor (AGTR1) C1166-allele and risk of diabetic nephropathy have been conflicting. Therefore, we investigated the interaction between long-term glycaemic control and three polymorphisms in the genes coding for AGTR1 (A1166-->C), angiotensin converting enzyme (ACE/ID) and angiotensinogen (M235T) on risk of developing diabetic nephropathy. Furthermore, we investigated the relation between a random measurement and long-term measurements of haemoglobin A1c (HbA1c).

Genetic polymorphisms of the renin-angiotensin system and complications of insulin-dependent diabetes mellitus.

Objective: Patients with insulin-dependent diabetes mellitus (IDDM) have a high risk of developing diabetic nephropathy, retinopathy and cardiovascular diseases. The contribution of gene polymorphisms of the renin angiotensin system to these complications is controversial and may differ among populations.

Methods: In 257 Dutch IDDM patients (188 with urinary albumin excretion (UAE) <30 mg/24 h), logistic regression analysis was used to study the relationships among, on the one hand, the insertion/deletion gene polymorphism of the angiotensin-converting enzyme gene (ACE-ID), the M235T gene polymorphism of the angiotensinogen gene (AGT-M235T), and the A1166C gene polymorphism of the angiotensin type 1 receptor gene (AT1-A1166C), and, on the other hand, UAE, retinopathy, hypertension, and coronary heart disease.

Cardiovascular morbidity and early mortality cluster in parents of type 1 diabetic patients with diabetic nephropathy.

Objective: A familial predisposition was proposed to be a determinant of the increased morbidity and mortality from cardiovascular disease in type 1 diabetic patients with diabetic nephropathy. The insertion allele of an insertion/deletion polymorphism in the ACE (ACE/ID) gene seems to protect against coronary heart disease in nondiabetic and diabetic subjects. The aim of the present study was to evaluate these hypotheses in parents of a large group of type 1 diabetic patients with and without diabetic nephropathy.

Elevated vascular endothelial growth factor in type 1 diabetic patients with diabetic nephropathy.

Background: Growth factors have been suggested to play a role in the development and progression of diabetic nephropathy. Vascular endothelial growth factor (VEGF) is a potent cytokine family that induces angiogenesis and markedly increases endothelial permeability. The aim of the present study was to investigate plasma levels of VEGF in a large cohort of type 1 diabetic patients with diabetic nephropathy and in long-standing type 1 diabetic patients with persistent normoalbuminuria, and to evaluate VEGF as a predictor of nephropathy progression.

Plasminogen activator inhibitor-1 and apolipoprotein E gene polymorphisms and diabetic angiopathy.

Background: A point mutation in the plasminogen activator inhibitor-1 (PAI-1) gene and a three-allelic variation in the apolipoprotein-E (ApoE) gene have been suggested as risk factors for the development of diabetic micro- and macrovascular complications.

Methods: We studied 198 type 1 diabetic patients with diabetic nephropathy [121 men, age (mean+/-SD) 41+/-10 years, diabetes duration 28+/-8 years] and 192 patients with persistent normoalbuminuria (118 men, age 43+/-10 years, diabetes duration 27+/-9 years).

Results: Male patients with nephropathy had elevated plasma PAI-1 levels [geometric mean (95% CI)], 70 (62-79) ng/ml, compared with normoalbuminuric men, 43 (38-47) ng/ml, P<0.

Renoprotective effects of angiotensin II receptor blockade in type 1 diabetic patients with diabetic nephropathy.

Background: Angiotensin I-converting enzyme (ACE) inhibitors reduce angiotensin II formation and induce bradykinin accumulation. Animal studies suggest that bradykinin may play a role for the effects of ACE inhibition on blood pressure and kidney function. Therefore, we compared the renal and hemodynamic effects of specific intervention in the renin-angiotensin system by blockade of the angiotensin II subtype-1 receptor to the effect of ACE inhibition.

Amadori albumin in type 1 diabetic patients: correlation with markers of endothelial function, association with diabetic nephropathy, and localization in retinal capillaries.

Nonenzymatic glycation is increased in diabetes. Most studies so far have focused on the role of advanced glycation end products (AGEs) in vascular complications, whereas the role of early glycation Amadori-modified proteins, which is the predominant form of glycated proteins, has not been systemically investigated in humans. We developed an antiserum against glycated human serum albumin (HSA) and used this to study the role of early glycation products in vascular complications in type 1 diabetic patients.

Plasma renin and prorenin and renin gene variation in patients with insulin-dependent diabetes mellitus and nephropathy.

Background: The most striking abnormality in the renin angiotensin system in diabetic nephropathy (DN) is increased plasma prorenin. Renin is thought to be low or normal in DN. In spite of altered (pro)renin regulation the renin gene has not been studied for contribution to the development of DN.

Progression of diabetic nephropathy in normotensive type 1 diabetic patients.

Background: The first aim of our long-term study was to describe the natural history of diabetic nephropathy in 59 normotensive type 1 diabetic patients. Secondly, we evaluated genetic and nongenetic progression promoters.

Methods: The following progression promoters were determined: the insertion/deletion polymorphism in the angiotensin converting enzyme (ACE) gene, blood pressure, albuminuria, hemoglobin A1c, cholesterol, smoking, height, and gender.

The Trp64Arg amino acid polymorphism of the beta3-adrenergic receptor gene does not contribute to the genetic susceptibility of diabetic microvascular complications in Caucasian type 1 diabetic patients.

Objective: The beta3-adrenergic receptor is involved in regulation of microvascular blood flow. A missense mutation (Trp64Arg) in the beta3-adrenergic receptor gene has been suggested as a risk factor for proliferative retinopathy in Japanese type 2 diabetic patients. The aim of the present study was to evaluate the contribution of this polymorphism to the development of microangiopathic complications in Caucasian type 1 diabetic patients.

Effects of nisoldipine and lisinopril on left ventricular mass and function in diabetic nephropathy.

Objective: To compare the effects of the calcium channel blocker, nisoldipine, and the ACE inhibitor, lisinopril, on left ventricular mass (LVM) and systolic function in type 1 diabetic patients with diabetic nephropathy.

Research Design And Methods: M-mode echocardiography was performed in 50 hypertensive type 1 diabetic patients with diabetic nephropathy enrolled in a 1-year, randomized, double-blind, parallel study of antihypertensive treatment with nisoldipine CC (20-40 mg/day) or lisinopril (10-20 mg/day). Ambulatory 24-h blood pressure was measured with the Takeda TM 2420 device (A & D, Tokyo, Japan) every 3 months.

Cyclosporine nephrotoxicity in type 1 diabetic patients. A 7-year follow-up study.

Objective: To evaluate kidney function 7 years after the end of treatment with cyclosporine A (CsA) (initial dosage of 9.3 tapered off to 7.0 mg.

Prevalence of left ventricular hypertrophy in Type I diabetic patients with diabetic nephropathy.

The increased mortality of patients with diabetic nephropathy is mainly due to cardiovascular disease and end stage renal failure. Left ventricular hypertrophy is an independent risk factor for myocardial ischaemia and sudden death. The aim of our cross-sectional study was to evaluate left ventricular structure and function in Type I (insulin-dependent) diabetic patients with diabetic nephropathy.

Effects of nisoldipine and lisinopril on microvascular dysfunction in hypertensive Type I diabetes patients with nephropathy.

1. Our objective was to compare the effect of a long-acting calcium antagonist (nisoldipine) compared with an angiotensin-converting enzyme inhibitor (lisinopril) on the non-neurogenic regulation of the microvascular blood flow in hypertensive Type I diabetes patients with diabetic nephropathy.2.

[The significance of deletion polymorphism in the ACE gene for progression of diabetic nephropathies treated with ACE inhibitors].

The aim of the study was to evaluate the effect of an insertion/deletion polymorphism of the angiotensin converting enzyme (ACE) gene on progression of diabetic nephropathy. We performed an observational follow-up study of 35 patients with insulin-dependent diabetes and diabetic nephropathy. Patients were investigated during captopril treatment for a median of seven (range three to nine) years.

Increased left ventricular mass in normotensive type 1 diabetic patients with diabetic nephropathy.

Objective: Diabetic nephropathy increases the risk of premature cardiovascular disease and sudden death, particularly in type 1 diabetic patients. One possible mechanism for this risk may be left ventricular hypertrophy. In our study, we aimed to evaluate left ventricular structure and function in normotensive type 1 diabetic patients with and without nephropathy.