Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report here the alterations of serum angiotensin-converting enzyme activity (S-ACE) and of active renin plasma concentrations (ARPC) in 41 insulin-dependent diabetes mellitus (IDDM) patients compared with those of 26 control subjects. The IDDM patients had S-ACE activity (54 +/- 16 I.E.) in the upper normal range (controls, 39 +/- 7). When the patients were subclassified according to their diabetic complications, a significant increase of S-ACE within the IDDM group compared to the controls was observed in patients with nephropathy (68 +/- 13, P less than 0.001) with persistent proteinuria and with retinopathy (63 +/- 14, P less than 0.001). A significant correlation was found between proteinuria and S-ACE (r = 0.98, P less than 0.001) and between retinopathy and S-ACE levels (r = 64, P less than 0.001). No correlation between blood pressure and S-ACE or between blood glucose and S-ACE was observed. The ARPC were within the normal range in the IDDM (21 +/- 9 ng/l) and in control (19 +/- 3) groups. No correlations between ARPC and blood pressure or blood glucose or the degree of diabetic complications were registered. These data show that S-ACE activity is elevated in IDDM patients with nephropathy-proteinuria and/or with retinopathy and the circulating renin may not represent the renal renin-angiotensin vascular system.
Diabetes Res Clin Pract 1992 Jun
PMID:Serum angiotensin-converting enzyme activity and active renin plasma concentrations in insulin-dependent diabetes mellitus. 133 Apr 63

Spontaneously hypertensive rats (SHR) were injected with streptozotocin (STZ-SHR) to induce diabetes. The effect of DP-1904, a thromboxane A2 synthetase inhibitor, on diabetic nephropathy was then studied by administering it for 5 months (1 or 10 mg/kg). DP-1904 did not affect renal 6-keto prostaglandin (PG)F1 alpha production in STZ-SHR, but markedly inhibited renal thromboxane (TX) B2 production, so that the 6-keto PGF1 alpha/TXB2 ratio was significantly increased (P less than 0.05). STZ-SHR showed significant uraemia and proteinuria, plus increases in urinary gamma-glutamyl-transpeptidase and urinary N-acetyl-beta-glucosaminidase. DP-1904 significantly decreased (P less than 0.01) the urinary changes. STZ-SHR also showed an increase in mesangial periodic acid-Schiff-positive substance and in relative renal weight, both of which were significantly inhibited by DP-1904 (P less than 0.05). Thus, DP-1904 inhibited both TXB2 production and the progression of renal damage in STZ-SHR.
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PMID:A thromboxane A2 synthetase inhibitor retards hypertensive rat diabetic nephropathy. 135 Sep 91

To investigate plasma renin and prorenin levels in non-insulin-dependent diabetes mellitus (NIDDM) and their relation with autonomic nervous function and renal impairment, we measured plasma renin and prorenin levels in 39 NIDDM patients. The patients included 21 males and 18 females, aged 56.3 +/- 6.2. Thirty-four normal age-matched subjects served as controls. Autonomic nervous function was evaluated in 23 patients by the performance of cardiovascular reflex tests. The plasma renin concentration was measured by angiotensin I generation after the addition of an exogenous substrate. Plasma prorenin was activated by trypsin. The results showed that the plasma renin concentration was similar between NIDDM patients and normal subjects, while plasma prorenin was higher in NIDDM patients. No correlation existed between the plasma renin or prorenin levels and autonomic nervous function. The patients with abnormally high levels of prorenin also had a similarly high plasma renin level but not a high creatinine clearance (Ccr) or daily proteinuria. The plasma renin level was correlated inversely with daily proteinuria but not with Ccr. These results suggest that the high plasma prorenin levels in some diabetic patients cannot be explained by renal impairment, poor prorenin conversion or autonomic dysfunction. The hyporeninemia in some patients may be related to microvascular involvement of the kidney.
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PMID:Plasma prorenin and renin levels in non-insulin-dependent diabetes mellitus. 136 16

Research on antihypertensive drugs not only provides new information on presently used agents but also leads to the introduction of exciting new compounds. Several important clinical trials involving currently available drugs have been published recently. Angiotensin-converting enzyme inhibitors improved survival in patients with milder degrees of congestive heart failure, which indicates that they have become the cornerstone of treatment for this condition. Angiotensin-converting enzyme inhibitors delayed or prevented the development of diabetic proteinuria (> 200 micrograms/min) in a placebo-controlled randomized trial. Further, enalapril was more effective than metoprolol in reducing the rate of decline in renal function in patients with type I diabetes. Calcium channel blockers protected against acute renal failure in patients after renal transplantation in two separate studies. Calcium channel blockers were shown to promote natriuresis, with negative sodium balance the same as that associated with thiazide diuretics. The voltage-dependent calcium channel has been cloned, and the binding sites of the three classes of calcium channel blockers are now known. beta-Blockers and thiazide diuretics were the drug treatments in the Systolic Hypertension in the Elderly Program trial and in the Swedish Trial in Old Patients with Hypertension study (patients 65 to 85 years). In both investigations, stroke and cardiovascular events were significantly reduced by these conventional inexpensive agents. Clonidine was found to lower blood pressure primarily by its interaction with the imidazole receptor rather than the alpha 2 receptor. Elucidation of the imidazole receptor promises to shed light on physiologic mechanisms as well as lead to the introduction of new agents, such as moxonidine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New classes of antihypertensive drugs and new findings with established agents. 136 36

Hypertension and diabetes mellitus are strongly associated conditions from epidemiologic, genetic, and pathophysiologic points of view. The prevalence of hypertension is high in patients with diabetes, and, conversely, many patients with essential hypertension are glucose intolerant. Proteinuria appears in 40-50% of patients with insulin-dependent diabetes mellitus and 20-30% of patients with non-insulin-dependent diabetes mellitus. Progressive renal failure occurs in 30-40 and 3-8% of patients, respectively, hypertension being a leading factor in its rate of progression. In various animal experiments, ACE inhibitors are able to prevent proteinuria and glomerular sclerosis, presumably by lowering transglomerular capillary pressure. In the diabetic human, ACE inhibitors are powerful antihypertensive drugs, devoid of metabolic side effects. Clinical studies indicate that ACE inhibitors reduce proteinuria and possibly slow the rate of decline in renal function. Such an effect is not observed with beta-blockers. Large-scale studies are needed to confirm this very important hypothesis.
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PMID:Angiotensin-converting enzyme inhibition and diabetic nephropathy. 138 63

A cross-sectional study was performed to investigate the distribution, methods of detection, and potential risk factors for peripheral vascular disease in a diabetic population with comparison to an age and sex matched non-diabetic group. The population came from a geographically defined area consisting of 10 general practices (total list size 97,034) and covered rural and urban districts of East Dorset. Peripheral vascular disease was defined as an ankle/brachial Doppler pressure ratio of 0.9 or less. Of the diabetic subjects reviewed, 864 were classified as having Type 2 diabetes and 213 Type 1 diabetes. The prevalence of peripheral vascular disease in Type 1 diabetes was 8.7% (95% CI 4.9-12.5) and in Type 2 diabetes 23.5% (95% CI 20.5-26.5), which after adjusting for age was not significantly different (odds ratio 1.5, 95% CI 0.8-2.7, p = 0.18). There was no difference in the frequency of symptomatic peripheral vascular disease or the site of occlusion between diabetic and non-diabetic subjects with peripheral vascular disease. Age, cerebrovascular disease, coronary artery disease, glucose, body mass index, and cholesterol in Type 2 diabetes and age and proteinuria in Type 1 diabetes were significant predictors of peripheral vascular disease. In the non-diabetic group, age and cigarettes smoked were significant variables. These findings suggest that clinical features of peripheral vascular disease in diabetic and non-diabetic subjects are similar but risk determinants may be different.
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PMID:The prevalence, detection, and epidemiological correlates of peripheral vascular disease: a comparison of diabetic and non-diabetic subjects in an English community. 139 62

It is clearly recognized that patients with NIDDM have an increased risk for CHD. Recent data indicate that persons with glucose concentrations in the nondiabetic range also may be at higher risk for CHD. These associations may not represent cause and effect, however. Emerging data suggest that hyperglycemia and CHD may both arise from hyperinsulinemia/insulin resistance. In support of this hypothesis are studies showing that NIDDM and CHD have many risk factors in common, including age, elevated blood pressure, dyslipidemia, adiposity, and a central pattern of fat distribution. Moreover, these risk factors are frequent concomitants of hyperinsulinemia, itself a risk factor for CHD and perhaps for NIDDM. Although the duration of NIDDM has been infrequently related to risk of CHD, the authors hypothesize that duration of hyperinsulinemia/insulin resistance would be a more sensitive marker for risk of CHD. The relation of IDDM to CHD is a different situation. The etiological process leading to IDDM, namely the destruction of beta-cells in genetically predisposed persons, is not related to cardiovascular risk. However, IDDM patients still have an excess of CVD, the risk factors for which may vary according to the location of the diseases (e.g., LEAD vs. CHD). There is a strong relationship between proteinuria and CVD, which has led to a general theory of vascular complications in IDDM based on defective heparan sulfate metabolism (Steno hypothesis). Recent evidence challenges parts of this hypothesis, and the possibility is raised that a higher case-fatality rate in a subgroup of patients with both renal and CVD explains part of the renal connection, as does the general worsening of CVD risk factors.
Diabetes Care 1992 Sep
PMID:Diabetes mellitus and macrovascular complications. An epidemiological perspective. 139 12

Diabetes mellitus has become the leading cause of ESRF in the United States. Patients with diabetic nephropathy suffer high cardiovascular morbidity and mortality. Because only 40% of diabetic patients eventually develop diabetic kidney disease, it may be possible to devise primary prevention measures targeted at the subset of patients at risk. Recently, a predisposition to hypertension, a family history of diabetic nephropathy, and a family history of CVD disease each have been associated independently with the development of diabetic renal complication in IDDM. Risk factors for macrovascular damage, including raised arterial BP, dyslipidemia, and insulin resistance, can be detected early in the course of progression to diabetic nephropathy. These risk indicators recently have been shown to be already present at the stage of normoalbuminuria in those patients who eventually will progress to microalbuminuria. Treatment of established renal disease can only delay the onset of ESRF, and lowering of microalbuminuria has been shown to retard the onset of persistent proteinuria. However, no study to date has demonstrated prevention of renal disease in these patients. The ultimate aim should, therefore, be the prevention of the transition from normoalbuminuria to microalbuminuria in individuals who are at higher risk of diabetic renal disease and CVD.
Diabetes Care 1992 Sep
PMID:Diabetic nephropathy. Future avenue. 139 18

Pentosidine is an advanced glycosylation end product and protein cross-link that results from the reaction of pentoses with proteins. Recent data indicate that long-term glycation of proteins with glucose also leads to pentosidine formation through sugar fragmentation. In this study, the relationship between the severity of diabetic complications and pentosidine formation was investigated in collagen from skin-punch biopsies from 25 nondiabetic control subjects and 41 IDDM patients with diabetes duration greater than 17 yr. Pentosidine was significantly elevated in all IDDM patients versus control subjects (P less than 0.0001). It correlated strongly with age (P less than 0.0001) and weakly with duration (P less than 0.082). Age-adjusted pentosidine levels were highest in grade 2 (severe) versus grade 1 and 0 complication in all four parameters tested (retinopathy, proteinuria, arterial stiffness, and joint stiffness). Significant differences were found for retinopathy (P less than 0.014) and joint stiffness (P less than 0.041). The highest degree of association was with the cumulative grade of individual complication (P less than 0.005), determined by summing indexes of all four parameters. Pentosidine also was significantly elevated in the serum of IDDM patients compared with control subjects (P less than 0.0001), but levels were not significantly correlated with age, diabetes duration, complication, or skin collagen pentosidine (P greater than 0.05). A high correlation between pentosidine levels and long-wave collagen-linked fluorescence also was observed, suggesting that pentosidine is a generalized marker of accelerated tissue modification by the advanced glycosylation/Maillard reaction, which is enhanced in IDDM patients with severe complications.
Diabetes 1992 Oct
PMID:Pentosidine formation in skin correlates with severity of complications in individuals with long-standing IDDM. 139 2

In patients with diabetes mellitus, metabolic control, hypertension and kidney function are important prognostic factors. In this respect ACE inhibitors exhibit, according to previous publications, a potentially beneficial effect on diabetic patients. To further clarify this effect of ACE inhibitors, a meta-analysis of 21 studies of type I and II diabetics under therapy with ACE inhibitors was performed. Altogether 325 cases were analyzed. The duration of diabetes varied between 2.5 and 22 years. Therapy with ACE inhibitors under long-term treatment (up to 12 months) reduced diastolic blood pressure (-25%) and, both for type I and II diabetics, fasting blood sugar (-14%) and HbA1 (-9%). Microalbuminuria/proteinuria was reduced by 33% under short-term treatment with ACE inhibitors (up to 3 months) and by 66% under long-term treatment. Analysis of the subgroups with microalbuminuria (30-300 mg/day, n = 48) or clinical proteinuria (greater than 300-1500 mg/day, n = 9) showed similar results. The outcome of this meta-analysis shows that the treatment of diabetic patients with ACE inhibitors not only effectively reduces high blood pressure but also reduces microalbuminuria/proteinuria and, in addition, exhibits an anti-hyperglycemic effect by improving blood sugar levels.
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PMID:[Improved glucose regulation and microalbuminuria/proteinuria in diabetic patients treated with ACE inhibitors. A meta-analysis of published studies of 1985-1990]. 141 95


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