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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The long-term effects of different antihypertensive regimens were studied in uninephrectomized beagles with alloxan-induced diabetes mellitus. Mean arterial pressure (MAP) was elevated (P < 0.05) in untreated diabetic dogs. Treatment of diabetic dogs with an angiotensin converting enzyme inhibitor (ACEI; lisinopril), a calcium antagonist (CA;TA-3090), or both lowered MAP. At one year, the RBF, GFR, and SNGFR were similarly elevated (P < 0.05) in all groups of diabetic dogs. The increase in SNGFR present in untreated diabetic dogs was primarily attributable to an increased (P < 0.05) glomerular capillary pressure (PGC). Treatment with lisinopril lowered the PGC to a mean value that was indistinguishable from that for nondiabetic dogs. In contrast, diabetic dogs treated with TA-3090 had an elevated PGC. While untreated diabetic dogs exhibited marked increases in glomerular volume (P < 0.05 vs. nondiabetic dogs), treatment with lisinopril and TA-3090, either alone or in combination, blunted the extent of glomerular hypertrophy observed in diabetic dogs (P < 0.05 vs. untreated diabetic dogs). Proteinuria was similarly reduced (P < 0.05 vs. untreated diabetic dogs) in dogs treated with lisinopril and TA-3090. Combination therapy of diabetic dogs produced a further significant (P < 0.05) decrement in proteinuria. We conclude that although treatment of diabetic dogs with either lisinopril or TA-3090 results in differential effects on PGC; each produces a similar decrement in proteinuria. Further, combination therapy has a greater effect on proteinuria than either agent alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term effects of antihypertensive regimens on renal hemodynamics and proteinuria. 839 Oct 95

In the Prague register of all adult diabetics by April 1, 1992 data on 1443 patients above 18 years with type 1 DM were recorded. In 42.2% of diabetics diabetic retinopathy was observed which is manifested most frequently after 11 to 15 years' persistence of diabetes. Proteinuria, the first sign of diabetic nephropathy, was found in 13.8% of the group, 5.4% of the diabetics are in the stage of renal insufficiency. Nephropathy is 3 to 4 times more frequent in diabetics with retinopathy. Peripheral neuropathy is found in 32.8% type 1 diabetics.
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PMID:[The Prague Diabetes Registry. 3. Retinopathies, nephropathies and neuropathies in type 1 diabetics. The Prague Diabetes Collective]. 840 14

We investigated the incidence and significance of proteinuria in recipients of liver transplants. The overall incidence of proteinuria was 59.72%. The peak incidence of proteinuria was at 3 months and at the end of 1 yr posttransplant. Proteinuria was higher in those patients who developed posttransplant diabetes mellitus, and those who developed both posttransplant diabetes and posttransplant hyperlipidemia. Patients who received higher total dosage of steroids and CsA had significantly greater proteinuria. Patients who had a Cr Cl greater than 50 ml/min had greater proteinuria posttransplant for the first 6 months, but the trend was reversed later. We did not find any association of proteinuria with age, weight, rejection episodes, or with the etiology of liver failure. Hypertension was a common occurrence in our patients, and therefore its significance in the causation of proteinuria could not be defined.
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PMID:Proteinuria in recipients of liver transplants. 865 96

The pregnancy complication characterized by proteinuric hypertension is called preeclampsia. Preeclampsia, an important cause of maternal and perinatal death, has an onset and progression impossible to predict. Termination of pregnancy is the only cure of preeclampsia. It is indicated when the fetus can survive outside the uterus or when the maternal condition deteriorates to such a condition that continuation would bring greater harm to the mother. The etiology of preeclampsia is unknown. Preeclampsia appears to be linked to abnormal trophoblastic implantation. In normal pregnancies, implantation effects changes in the spiral arteries that supply the intervillous space and fibrin-containing trophoblast, and amorphous matrix replace the endothelium and the internal elastic lamina. These changes do not occur or are limited in pre-eclamptic women. There appears to be a familial tendency to preeclampsia. Impaired formation of blocking antibodies to antigenic sites on the placenta increases the risk of pre-eclampsia. Risk factors are primigravidity, short duration of sexual cohabitation before conception, abundance of trophoblastic tissue (e.g., multifetal and molar pregnancies), and underlying vascular disease as in diabetes. Poor placental perfusion may account for the increase in maternal blood pressure. Preeclampsia can lead to eclampsia, cerebral hemorrhage, coagulopathy, and death. Poor utero-placental circulation retards fetal growth and causes fetal distress and maybe even perinatal death. When the diastolic blood pressure is higher than 110 mmHg, pre-eclamptic women should be administered antihypertensive drugs (e.g., methyldopa, beta-blockers, calcium channel blockers, hydralazine, labetatol, or diazoxide) to prevent maternal complications, but these drugs do not improve utero-placental blood flow nor do they prevent proteinuria. Diuretics should not be administered. Proteinuria indicates that the kidneys have been affected. A large randomized trial shows that aspirin does not effectively prevent preeclampsia. Routine calcium supplementation does appear to prevent it and preterm delivery.
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PMID:Pre-eclampsia. 875 7

1. Treatment with angiotensin converting enzyme (ACE) inhibitors ameliorates human and experimental diabetic nephropathy, possibly as a result of changes in angiotensin II (AngII) and/or bradykinin concentrations. However, ACE is an indiscriminate enzyme, which hydrolyses numerous vasoactive peptides at two catalytic sites that are thought to be substrate specific. AngI is cleaved at the C-terminal site, bradykinin at both the C- and N-terminal sites, while other substrates may be preferentially cleaved at the N-terminal site. Of the various ACE inhibitors, some (e.g. perindopril) bind preferentially to the C-terminal site while others (e.g. enalapril) bind to both. We compared the efficacy of perindopril and enalapril in the diabetic SHR to determine whether all the benefits of ACE inhibition derive from changes in the concentrations of C-terminal related substrates. 2. Diabetes was induced by tail vein injection of streptozotocin (60 mg/kg) in 14 week old SHR. Blood glucose was maintained at 4-8 mmol/L by daily ultralente insulin injection and rats were randomized to control, enalapril (10 mg/kg per day) or perindopril (4 mg/kg per day) groups. Blood pressure, creatinine clearance and urinary protein excretion were monitored for 3 months. 3. Blood pressure in both treatment groups was lower than in control (perindopril P < 0.0001; enalapril P < 0.0001). Levels were marginally higher in the perindopril group than the enalapril group, although this difference was significant only in the second month (P < 0.025). Creatinine clearance was significantly lower in the perindopril group (0.44 +/- 0.05 mL/min) than in either the control rats (0.85 +/- 0.11 mL/min; P < 0.001) or the enalapril-treated group (0.66 +/- 0.05 mL/min; P < 0.005). Proteinuria was also lower in this group (4.3 +/- 0.9 mg/24h) than in the enalapril-treated (11.3 +/- 5.8 mg/24h; P < 0.05) or control groups (32.1 +/- 4.5 mg/24h; P < 0.0005). 4. The difference in efficacy between perindopril and enalapril that we have observed suggests that the benefits of ACE inhibition derive from changes in the concentrations of peptides catalysed by the C-terminal rather than the N-terminal site.
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PMID:Differential efficacy of perindopril and enalapril in experimental diabetic nephropathy. 880 Jun

Although complications of diabetes are common among Southwest American Indians, little is known about diabetes and associated risk factors for nephropathy and cardiovascular disease in other genetically distinct tribes. We conducted a retrospective analysis of 665 diabetic patients at two Chippewa Indian reservations in northern Minnesota to evaluate the prevalence of risk factors for diabetic nephropathy and cardiovascular disease. In 79 patients, a more detailed study was carried out, including an assessment of renal function and urinary albumin excretion (UAE). The overall prevalences of proteinuria and hypertension were 47.9% and 62.6%, respectively. Proteinuria was observed more often in hypertensive than in non-hypertensive patients (55.2% vs 44.4%, p < 0.05), and in patients with diabetes for longer than 10 years (57% vs 40% for diabetes less than 10 years, p < 0.05). Although hypercholesterolemia (total cholesterol > or = 200 mg/dl) was observed in 54% of patients, there was no relationship between hypercholesterolemia and proteinuria. In the 79 patients studied in more detail, UAE was greater in hypertensive patients compared to non-hypertensive patients (606 +/- 15600 mg/24h vs 101 +/- 157 mg/24 h, p < 0.05), and in patients with diabetes for 10 years or longer compared to patients in the first decade of disease (748 +/- 1732 mg/24 h vs 96 +/- 171 mg/24 h, p < 0.05). Hypercholesterolemia and elevated LDL-cholesterol (> 130 mg/dl) were observed in 56% and 49% of patients, respectively, but were not associated with increased UAE. In contrast, hypertriglyceridemia (> 250 mg/dl) was associated with an elevated UAE (932 +/- 2150 mg/24 h vs 245 +/- 735 mg/24h, p < 0.05). Increased lipoprotein(a) was found in patients with overt albuminuria. In summary, the prevalence of risk factors for diabetic nephropathy and associated cardiovascular disease is high in Chippewa American Indians in northern Minnesota. Although detecting abnormal UAE may be useful in identifying high-risk patients who may benefit from early intervention, traditional risk factors such as hypercholesterolemia may not explain the risk associated with increased UAE.
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PMID:Risk factors for nephropathy and cardiovascular disease in diabetic Northern Minnesota American Indians. 886 85

Diabetic nephropathy is the major cause of illness and premature death in people with diabetes, largely through accompanying cardiovascular disease and end-stage renal failure. Diabetic patients are several times as prone to kidney disease as nondiabetic people and the accumulative risk of diabetic nephropathy in insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) is about 30%-50% after 25 years of disease. Diabetic nephropathy is a progressive disease that takes several years to develop, ending in chronic renal insufficiency. Proteinuria heralds the onset of diabetic nephropathy, and the worsening of proteinuria parallels the progression of renal disease. The main risk factors for the frequency, severity, and progression of diabetic nephropathy are the degree of hyperglycemia and associated metabolic disturbances, hypertension, protein overload, cigarette smoking, as well as the duration of diabetes. Interventional strategies for primary, secondary, and tertiary prevention of diabetic nephropathy therefore include meticulous glycemic control, appropriate treatment of associated lipid abnormalities, rigorous control of the blood pressure, reduction in dietary protein intake, in particular animal protein, and of fat intake, and stopping cigarette smoking. Randomized clinical trials indicate that antihypertensive therapy is beneficial in preventing and slowing down the progression of diabetic nephropathy. There is now increasing evidence that angiotensin-converting enzyme inhibitors and certain calcium antagonists produce a more beneficial effect on diabetic nephropathy in terms of reducing proteinuria and slowing the progression to diabetic renal failure. These drugs are attributed nephroprotective capacity beyond their blood pressure lowering capacity and initial clinical trials with combinations have revealed even additive protective effects on end organs.
J Diabetes Complications
PMID:Prevention and slowing down the progression of the diabetic nephropathy through antihypertensive therapy. 910 97

Diabetic nephropathy is a major cause of illness and premature death in diabetic patients, largely through accompanying cardiovascular disease and end-stage renal failure. Proteinuria heralds the clinical nephropathy, and the worsening of proteinuria parallels the progression of renal disease towards chronic renal failure. A large body of evidence has accumulated that emphasizes the role of elevated blood pressure in the progression of renal disease, as well as the clear benefit of antihypertensive treatment. However, the choice of antihypertensive drug to protect renal function was less clear in the past. In earlier studies, a reduction in the rate of progressive renal failure in hypertensive subjects has been shown with diuretics, beta-blockers, and vasodilators. However, there is now increasing evidence that angiotensin converting enzyme (ACE) inhibitors and some calcium antagonists produce a more beneficial effect on nephropathy in terms of reducing proteinuria and slowing progression to renal failure. These drugs are attributed nephroprotective capacity beyond their systemic blood pressure lowering effects, and initial clinical trials with combinations have revealed additive nephroprotective effects. Finally, ACE-inhibitors and calcium antagonists have no adverse effects on glycemic control or lipid levels and may even improve insulin sensitivity. This further promotes these antihypertensives to first-line drugs when treating subjects at risk of metabolic disorders or people with diabetes.
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PMID:Protecting the residual renal function: which drugs of choice? 923 93

Although post exercise proteinuria has long been known, its exact pathophysiology is unclear. Our objective was to determine whether long-term angiotensin converting enzyme (ACE) inhibition by different ACE inhibitors had an influence on post exercise proteinuria. We studied 14 patients who also had mild, chronic proteinuria caused by diabetes mellitus or chronic glomerulonephritis. We compared changes both in chronic (baseline) and post exercise proteinuria, during and after treatment with three different ACE inhibitors, with appropriate washout periods for the three drugs to all 14 patients. Proteinuria (mg/24 hours +/- SD), prior to the treatment was 682 +/- 92. Proteinuria after treatment for 30 days with benazepril was 464.4 +/- 82.6 (p < 0.001), with enalapril: 477.1 +/- 105.5 (p < 0.001), and captopril: 504.7 +/- 100.1 (p < 0.001). Proteinuria three days after discontinuing the treatment with benazepril was 532.4 +/- 113.5, (p < 0.01), with enalapril: 561.3 +/- 128.5, (p < 0.01), and with captopril: 620.8 +/- 101.8, p = n.s. Post exercise proteinuria prior to treatment (mg/min. +/- SD) was: 1.38 +/- 0.32, vs. after a 30-day treatment period with benazepril: 0.81 +/- 0.19 (p < 0.001), enalapril: 0.95 +/- 0.24, (p < 0.001), captopril: 1.09 +/- 0.27 (p < 0.02). Post exercise proteinuria three days after discontinuing the treatment was (blood pressure already back to baseline): in case of benazepril: 1.26 +/- 0.36 (p = n.s.), of enalapril: 1.17 +/- 0.46 (p = n.s.), and of captopril: 1.34 +/- 0.41 (p = n.s.). We conclude that the renin-angiotensin system plays a significant role in the pathogenesis of post exercise proteinuria; the antiproteinuric effect of ACE inhibition in exercise-induced proteinuria seems to be associated chiefly with the hemodynamic changes due to these drugs, whereas in chronic proteinuria the antiproteinuric and antihypertensive effects are, at least partially, dissociated.
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PMID:Effect of ACE inhibition by benazepril, enalapril and captopril on chronic and post exercise proteinuria. 932 8

Proteinuria has been shown to be strongly associated with the prevalence and incidence of cardiovascular disease. It has been difficult to determine if the link is causal and independent. The mortality follow-up for the Multiple Risk Factor Intervention Trial (MRFIT) randomized cohort provides an opportunity to examine these relationships. Between 1973 and 1975, 361,662 men, ages 35 to 57, were screened for blood pressure, serum cholesterol, and cigarette smoking. Patients receiving medication for diabetes were excluded. Men in the upper 10 to 15% of coronary heart disease (CHD) risk (12,866) were randomized into the MRFIT trial. Standard casual urine dipstick determinations (Labstix) for protein were done at baseline and annually for six years. Post-trial cause-specific mortality was ascertained using the National Death Index. During the trial, 2326 (18.1%) of participants had + or higher proteinuria, and 593 (4.6%) had +2 or higher proteinuria. The presence of proteinuria during the six years of follow-up was consistently associated with higher all cause, cardiovascular disease (CVD) and CHD mortality, even after adjusting for other risk factors. The higher and more persistent the proteinuria, the greater the risk. In this data set, proteinuria is a strong and independent risk factor for CVD mortality.
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PMID:Proteinuria is a risk factor for mortality over 10 years of follow-up. MRFIT Research Group. Multiple Risk Factor Intervention Trial. 940 12


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