Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Points of agreement: (1) In IDDM, hypertension occurs in patients who have already developed nephropathy, probably in the microalbuminuric phase. (2) Hypertension is an important accelerator of the development of diabetic nephropathy. (3) Hypertension, obesity and NIDDM are often associated, and insulin resistance is commonly observed in all three states. (4) Antihypertensive therapy retards the development of diabetic nephropathy in IDDM and reduces proteinuria in NIDDM. (5) The choice of antihypertensive agent in the diabetic patient must be based upon the efficacy of the drug as well as avoidance of side effects including deleterious influence on glucose, insulin and lipid levels and renoprotection. (6) Carefully conducted long-term comparative trials between different classes of antihypertensive drugs in microalbuminuric IDDM and NIDDM patients are essential. Points of major controversy: (1) Detection of IDDM patients prone to the development of diabetic nephropathy can be performed by measuring specific parameters such as erythrocyte Na(+)-Li+ countertransport activity. (2) Insulin resistance is a pathogenic mechanism rather than purely an association with hypertension and obesity. (3) A certain class of antihypertensive agents--ACE inhibitors--confers a specific renoprotective effect in diabetic nephropathy, in addition to its effects upon systemic blood pressure. (4) Reduction of blood pressure should be considered in the normotensive microalbuminuric diabetic patient. (5) Microalbuminuria is a sufficient 'surrogate endpoint' for the progression of renal failure.
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PMID:Meeting report of the International Society of Hypertension Conference on Hypertension and Diabetes. 131 6

The pathogenetic determinants of sodium retention in IDDM are not fully understood. The aim of this study was to elucidate the action of ANP in 11 IDDM patients with high GFR (greater than or equal to 135 ml.min-1 x 1.73 m-2), referred to here as HF patients; in 10 IDDM patients with normal GFR (greater than 90 and less than 135 ml.min-1 x 1.73 m-2), referred to here as NF patients; and 12 control subjects, here called C subjects, at baseline and during saline infusion administered on the basis of either body weight (2 mmol.kg-1 x 60 min-1; Saline 1) or of ECV (12 mM.ECVL-1 x 90 min-1; Saline 2) during euglycemic insulin-glucose clamp. C subjects and both HF and NF IDDM patients received a second Saline 1 infusion accompanied by ANP infusion (0.02 microgram.kg-1.min-1) at euglycemic levels. HF and NF patients were studied again after 3 mo of treatment with (10 mg/day). Quinapril (CI 906, Malesci, Florence, Italy), an ACE inhibitor without sulfhydryl group. At baseline, both HF and NF IDDM patients had higher plasma ANP concentrations than C subjects (HF, 36 +/- 4, P less than 0.01 and NF, 34 +/- 3, P less than 0.01 vs. C, 19 +/- 3 pg/ml). Plasma ANP and natriuretic response to isotonic volume expansion was impaired both in HF (44 +/- 8 pg/ml, NS vs. base) and NF (40 +/- 7 pg/ml, NS vs. base) compared with C (41 +/- 4 pg/ml, P less than 0.01 vs. base) during Saline 1. On the contrary, plasma ANP response to Saline 2 was similar in HF and NF patients and C subjects, but IDDM patients had still lower urinary sodium excretion rates. The simultaneous administration of ANP and Saline 1 resulted in comparable plasma ANP plateaus in C subjects and HF and NF patients. However, urinary sodium excretion rate was significantly lower in HF and NF patients than in C subjects: HF, 267 +/- 64, P less than 0.01 and NF, 281 +/- 42, P less than 0.01 vs. C, 424 +/- 39 mumol.min-1 x 1.73 m-2. During simultaneous administration of ANP and Saline 1, GFR and FF increased in C subjects, but not in HF and NF patients. HF and NF patients had higher urinary vasodilatory prostanoid excretion rates than C subjects at baseline. Saline infusion did not change urinary excretion rate of prostanoids either in C subjects or IDDM patients (both NF and HF).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of atrial natriuretic peptide in the pathogenesis of sodium retention in IDDM with and without glomerular hyperfiltration. 138 91

Diabetic renal disease is a clinical syndrome in which proteinuria is followed by the development of renal failure, and is commonly associated with the concomitant development of hypertension. In insulin-dependent diabetic (IDDM) patients, hypertension often first appears in the microalbuminuric phase of diabetic nephropathy whereas in non-insulin-dependent diabetic (NIDDM) patients, hypertension often antecedes nephropathy and may precede the diagnosis of diabetes. Antihypertensive regimens including diuretics, vasodilators such as hydralazine, beta-blockers and ACE inhibitors reduce proteinuria and delay the decline in renal function in IDDM patients with established nephropathy. No such data are as yet available for calcium antagonists. In microalbuminuric diabetic patients with hypertension, conventional antihypertensive agents, ACE inhibitors and calcium antagonists have been shown to decrease urinary albumin excretion. In the diabetic patient with normal blood pressure and microalbuminuria, there is much less information. It appears likely that ACE inhibitors reduce or retard the rate of increase in albuminuria in these patients. The effect on ultimately delaying or preventing renal failure remains unknown although the preliminary evidence is encouraging. Data on calcium antagonists remain inconclusive with some reports suggesting an increase in proteinuria with the dihydropyridine calcium antagonists. However, a recent longer term study suggested that nifedipine may prevent the rise in albuminuria which is generally observed in the untreated normotensive microalbuminuric subject.
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PMID:The management of diabetic proteinuria. Which antihypertensive agent? 150 44

NIDDM and hypertension are both characterized by insulin resistance and/or hyperinsulinemia. In IDDM, factors associated with nephropathy produce hypertension. To avoid exacerbation of the metabolic condition, and to prevent further deterioration in glycemic control, treatment of hypertension in the diabetic patient should include the administration of medication with the fewest adverse effects on glucose homeostasis. If diuretics are to be used, it appears that loop diuretics may be preferable to the thiazides or potassium-sparing compounds. Among the remaining classes of antihypertensive drugs, ACE inhibitors may be the agents of choice because of their potential positive effects on insulin sensitivity and renal function, and their lack of severe adverse side-effects.
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PMID:Insulin sensitivity and blood lipids during antihypertensive treatment with special reference to ACE inhibition. 197 44

Hyperfiltration is a very characteristic feature in insulin-dependent diabetes. Hyperfiltration is to some extent associated with long-term glycemic control but the correlation is not very strong. Long-term hyperfiltration may play a role in the genesis of late diabetic nephropathy, but it is difficult to distinguish effects of hyperfiltration per se from effects of poor metabolic control. Long-term hyperfiltration without diabetes does not produce nephropathy. It is hypothesized that IDDM patients who do not show considerable hyperfiltration in spite of poor metabolic control may be those who are to some extent protected against late diabetic nephropathy, but other mechanisms may also be involved in the renal protection of these patients, who survive long-term diabetes without nephropathy. On the other hand, those with poor metabolic control combined with hyperfiltration are likely to develop nephropathy. In addition, it is suggested that the metabolic aberrations in diabetes, with the subsequent changes in the biochemistry of the glomerular wall, are permissive and absolutely required for the development of diabetic nephropathy. Of note, diabetic glomerulopathy in NIDDM occurs without significant hyperfiltration and extreme hyperfiltration in the one-kidney-model (without diabetes) does not produce nephropathy. Nonglycemic modalities of intervention, resulting in reduced hyperfiltration, e.g., low-protein diet or administration of somatostatin analogues, deserves interest as new potential ways of preventing or postponing diabetic nephropathy. Also intervention with aldose-reductase inhibitors may be an important therapeutic modality for those patients in whom good metabolic control is not obtainable. It is now well-established that antihypertensive treatment, including ACE-inhibition, reduces rate of decline in GFR in patients with already established nephropathy. In addition, protein excretion is diminished in IDDM patients with incipient diabetic nephropathy by antihypertensive treatment where GFR is well-preserved during treatment. No data are available for NIDDM.
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PMID:Comparative renal pathophysiology relevant to IDDM and NIDDM patients. 306 56

Management has changed dramatically: There is no doubt now that strict glycemic control protects against nephropathy, neuropathy, and retinopathy. Direct evidence comes from study of intensive insulin therapy in IDDM. The implication is that similar protection can be gained in NIDDM. Microalbuminuria mandates ACE inhibition and dietary protein restriction. Proliferative retinopathy can be arrested with laser photocoagulation.
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PMID:Taking control of diabetes. 759 89

Initiation of antihypertensive treatment (AHT) in hypertensive insulin-dependent diabetic (IDDM) patients with diabetic nephropathy (DN) induces a faster initial (0 to 6 months) and a slower subsequent (6 months to end of observation) decline in GFR [delta GFR (ml/min/month) approximately 1.5 vs. 0.35]. Whether this initial phenomenon is reversible (hemodynamic) or irreversible (structural damage) after prolonged AHT is not known. To elucidate these mechanisms we investigated 42 hypertensive IDDM patients (16F/26M, age 40 +/- 7 years, mean +/- SD) with DN receiving AHT (angiotensin converting enzyme inhibition, N = 30) for 6 (2 to 15) years [median (range)]. GFR (ml/min/1.73 m2), arterial blood pressure (BP, mm Hg) and albuminuria (mg/24 hr) were measured the last day on AHT and one month after withdrawal of AHT. The measured variables were all significantly elevated after withdrawal of AHT: GFR [mean(SEM)] from 76(4) to 81(4) (P < 0.0001), BP [mean(SEM)] from 140/82 (2/1) to 151/89 (2/1) (P < 0.0005) and albuminuria [geometric mean (antilog SEM)] from 704 (1.2) to 1122 (1.2) (P < 0.0001). A correlation between relative rise in systolic blood pressure (delta Sys%) and relative change in GFR (delta GFR%) was found (r = 0.44, P < 0.005). Our results render some support of the hypothesis that the faster initial decline in GFR is due to a functional (hemodynamic) effect of AHT, which does not attenuate over time, while the subsequent slower decline reflects the beneficial effect on progression of diabetic nephropathy.
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PMID:Increased glomerular filtration rate after withdrawal of long-term antihypertensive treatment in diabetic nephropathy. 764 42

The progression of diabetic nephropathy can be positively influenced by maintaining a low blood pressure level. This has been shown in studies with conventional antihypertensive treatment as well as with ACE inhibitors. Whether the latter group of drugs is more effective remains to be proven and was the aim of our study. In a prospective randomized study we compared the effects of ACE inhibition and beta-blockade on retarding progression of renal function in IDDM patients with an early stage of overt diabetic nephropathy. Twenty-nine patients were studied for 2 years, 15 were randomized for treatment with captopril and 14 for atenolol. Every 6 weeks blood pressure and urinary albumin and total protein excretion were measured. GFR was measured every 6 months as 51Cr-EDTA clearance. Baseline values for blood pressure, renal function and albuminuria were identical in the two groups. The effect of both drugs on blood pressure was not significantly different. In the captopril-treated patients MAP before and after 2 years was 110 +/- 3 (SEM) and 100 +/- 2 mm Hg, respectively and in the atenolol-treated patients 105 +/- 2 vs 101 +/- 2 mm Hg. Both drugs reduced albuminuria and total proteinuria to the same extent. With captopril albuminuria decreased from 1549 (989-2399) to 851 (537-1380) mg/24 h and proteinuria from 2.5 (1.6-3.8) to 1.2 (0.8-1.8) g/24 h. With atenolol albuminuria decreased from 933 (603-1445) to 676 (437-1047) mg/24 h and proteinuria from 1.5 (1.0-2.4) to 0.9 (0.6-1.5) g/24 h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Captopril and atenolol are equally effective in retarding progression of diabetic nephropathy. Results of a 2-year prospective, randomized study. 774 19

We now have conclusive proof that intensive treatment reduces the microvascular complications of IDDM. ACE inhibitors appear to slow the progression of established nephropathy. Drug-induced malabsorption has the potential to increase levothyroxine dose requirement.
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PMID:Endocrinology. 818 41

Hyperinsulinemia is very much in the spotlight. Debate rages as to its significance and role in the etiology not only of NIDDM, but also other morphological and metabolic risk factors for atherosclerotic cardiovascular disease, including upper-body obesity, dyslipidemia, hypertension, and hyperuricemia. Epidemiological data support a key role for hyperinsulinemia in these disorders but it is far from conclusive except for the fact that hyperinsulinemia and insulin resistance may be present many years before the onset of impaired glucose tolerance and NIDDM, and clearly play a role in their etiology. The thrifty genotype hypothesis provides a plausible basis for a better understanding of how hyperinsulinemia and insulin resistance could lead to glucose intolerance and atherosclerotic cardiovascular disease, but the detailed biochemical mechanisms remain elusive. A role for increased sympathetic nervous system activity, resulting from hypothalamic stimulation as a primary event causing hyperinsulinemia, cannot be excluded as a cause of hyperinsulinemia. The current focus on hyperinsulinemia also has resulted in closer examination of the therapy of diabetes and hypertension, emphasizing the need to avoid hyperinsulinemia in both IDDM and NIDDM individuals because of the putative risk of atherosclerotic cardiovascular disease and hypertension. There is still a paucity of epidemiological data to support a role for hyperinsulinemia in the etiology of hypertension. However, clinical practice already is being influenced by the fact that ACE inhibitors have been shown to reduce insulin resistance in clinical research studies. The research reviewed here, particularly that relating to hyperinsulinemia, insulin resistance, and cardiovascular disease risk factors, has opened new vistas for the treatment and prevention of NIDDM and atherosclerotic cardiovascular disease. Appropriate exercise clearly is associated with improved insulin sensitivity, modification of CVD risk factors, and lower prevalence of NIDDM. Upper-body obesity, the latest culprit in the field, can also be reduced by exercise. Hyperinsulinemia and insulin resistance can be detected in children, adolescents, and young adults. NIDDM can be prevented, but clearly, intervention needs to commence in childhood, and intensive risk factor intervention in subjects with NIDDM can reduce the risk of atherosclerotic cardiovascular disease. It seems paradoxical that prevention of NIDDM and atherosclerotic cardiovascular disease are now possible even though the biochemical and molecular basis of these disorders is not fully understood.
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PMID:Hyperinsulinemia--how innocent a bystander? 829 79


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