Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A prospective open clinical trial was carried out with 23 hypertensive type I diabetics (13 men, ten women, mean age 49 +/- 9.1 years, duration of diabetes 18 +/- 9.1 years) with early nephropathy. Glomerular and tubular renal function and metabolic parameters were monitored during 8 months' treatment with the angiotensin converting enzyme (ACE) inhibitor, captopril, in addition to previous antihypertensive treatment with one or more drugs. Blood pressure control tended to improve on captopril (systolic pressures 152 +/- 13 vs 140 +/- 13 mm Hg, P < 0.05; diastolic pressures 89 +/- 10 vs 87 +/- 10 mm Hg, not significant). Proteinuria (> 0.5 g/24 hours) fell into the microalbuminuria range (albumin excretion 2-20 mg/mmol creatinine) in four out of 13 patients, and microalbuminuria disappeared in four out of ten patients. Urinary levels of the brush border enzyme N-acetyl-beta-D-glucosaminidase (NAG), a marker of tubular dysfunction, were initially raised and fell significantly after 8 months' treatment with captopril (20.3 +/- 14.4 vs 8.8 +/- 8.1 U/g creatinine; P < 0.01). Captopril did not affect metabolic control (HbA1, total, HDL and LDL cholesterol, triglycerides, apolipoproteins A1 and B) or the insulin dosage. These results show that long-term treatment with captopril may favourably influence both albumin excretion and NAG activity, a marker of tubular dysfunction, in type I diabetics with nephropathy.
 ...
PMID:[The effect of blood pressure-reducing therapy with captopril on tubular marker excretion in type-1 diabetics with nephropathy]. 820 41

The present study was conducted to evaluate whether captopril prevents the organomegaly and accumulation of matrix proteins that normally accompanies the diabetic state. The following groups of rats were studied: normal rats, normal rats treated with captopril (30 mg/kg/d orally), streptozotocin diabetic rats, and diabetic rats treated with captopril. All rats were killed at 10 weeks for histologic and morphometric evaluation of tissues. Compared with the normal rats, the diabetic rats demonstrated significant hepatomegaly, nephromegaly, and cardiomegaly, and the increase in organ size was directly related to increasing levels of protein glycosylation. The development of organomegaly was partially prevented by captopril. We determined by morphometry that the hepatomegaly seen in the diabetic rats was due to an increase in cell size and number, while the nephromegaly seen in the diabetic rats was due to an increase in tubular and glomerular cell size and is associated with glomerular hypertrophy. Captopril prevented the development of hepatic and renal cell hypertrophy and glomerular hypertrophy. These effects of captopril were not associated with detectable changes in body weight or levels of glucose, protein glycosylation, glycosuria, or renal histologic changes secondary to glycosuria. The diabetic rats demonstrated significant glomerular mesangial matrix expansion, and captopril treatment partially prevented that expansion. In conclusion, captopril prevents, in part, the development of organomegaly in diabetic rats, and this effect is due mainly to the prevention of the development of cellular hypertrophy. The present findings are most consistent with a direct effect of captopril on cell metabolism during diabetes mellitus.
 ...
PMID:Angiotensin-converting enzyme inhibition partially prevents diabetic organomegaly. 828 84

Captopril's short-term effects on clinical and biochemical parameters were studied in 21 diabetic nephropathic patients. Their mean age was 57.50 +/- 2.28 years; 16 of them were women and 5 were men. Eleven patients had been regulated with insulin and 10 of them had been regulated with oral antidiabetics. Fifteen patients were microalbuminuric (200 mg/daily and below albuminuria) and their mean diabetes mellitus history was 14.86 +/- 1.44 years. Six patients had advanced diabetic nephropathy (400 mg/daily and above albuminuria). Their mean diabetes mellitus history was 4.50 +/- 2.87 years. Captopril in a low dose (37.5 mg/daily p.o., three separated doses) was given during 20 days. In the microalbuminuria group there were insignificant alterations in renal function, blood glucose levels, and systolic blood pressure. Diastolic blood pressure decreased significantly in this group (p < .05). Microalbuminuria increased significantly after the therapy in this group (p < .05). In the advanced diabetic nephropathy group, blood glucose and systemic blood pressure levels did not change significantly (p > .05), while serum BUN and creatinine levels increased significantly (p < .05), and GFR decreased significantly in this group (p < .05). Albuminuria decreased after the therapy in this group (p < .05). In all study groups, serum potassium levels increased significantly while serum total protein and albumin levels did not change significantly.We concluded that in the microalbuminuria group, increasing microalbuminuria may be related to a captopril-induced increase in renal plasma flow rate and single nephron glomerular filtration rate. This increase in microalbuminuria cannot be related with blood glucose levels, renal functions, and systemic blood pressure alterations.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The effects of angiotensin-converting enzyme inhibitors on the clinical and biochemical parameters in diabetic nephropathy. 829 Jul 8

Angiotensin converting enzyme inhibitors (CEI) are logically proposed for the treatment of hypertension and heart failure because of their effect on reducing arteriol resistance. When administered early after myocardial infarction, CEI reduce mortality, particularly patients with severely deteriorated myocardium. Up to 74 lives can be saved for every 1000 patients treated. This beneficial effect is additive with that resulting from aspirin, beta-blockers and fibrinolysis. The effect occurs within the first month of treatment if initiated within the first 24 hours following the infarction, and persists even if treatment is discontinued. Tolerance is generally good, but dosage must be adapted in case of hypotension or temporary renal failure. Macroproteinuric nephropathy in insulin-dependent-diabetes is another indication for CEI. Captopril and enalapril have been shown to slow progression of renal failure and decrease the risk of death and of chronic dialysis. Further studies are being conducted to determine the effect of CEI in non-insulin-dependent diabetes. Finally, experimental arguments suggest that atherosclerosis is partly dependent on the renin/angiotensin system and that CEI might inhibit its development. Most clinical trials evaluating the action of CEI on atheromatosis have studied the effect in the carotid and coronary arteries.
 ...
PMID:[Enzyme converting inhibitors. Current knowledge and perspectives]. 854 40

In insulin-dependent diabetes mellitus (IDDM), microalbuminuria predicts renal and cardiovascular disease. We report a combined analysis of 235 normotensive IDDM patients with microalbuminuria who participated in two 24-month double-blind, randomised, placebo-controlled trials to assess the effects of captopril 50 mg twice daily on the progression to overt clinical albuminuria. Of the 225 patients who were evaluable on an intent to treat basis, 25 of 114 placebo-treated patients (21.9%) and 8 or 111 captopril-treated patients (7.2%) progressed to persistent clinical albuminuria. The risk of progression over 24 months was significantly reduced by captopril (p = 0.004) with a risk reduction of 69.2% (95% confidence interval (CI):31.7 to 86.1%). This degree of risk reduction remained at the same level (62.9% [16.1-83.6%], p = 0.017) after adjustment for differences in time-varying mean arterial blood pressure. Albumin excretion rate increased by an average of 14.2% [3.1-26.5%] per year in the placebo-treated group compared with a reduction of 9.6% [-18.6-0.4%] per year in the captopril-treated group (p = 0.002). The rate of fall of creatinine clearance tended to be faster in the placebo-treated group than in the captopril-treated group (-6.4 [-10.2- -2.5] vs -1.4 [-5.3-2.6] ml.min-1.1.73m-2, p = 0.07). Baseline albumin excretion rate (p < 0.0001) and glycated haemoglobin (p = 0.03) were independent predictors of progression to clinical albuminuria and changes in mean arterial blood pressure (p = 0.02) and serum cholesterol level (p = 0.003) were significantly associated with percentage changes in albumin excretion rate. Captopril reduces the risk of progression to overt nephropathy in IDDM patients with microalbuminuria, an effect partly independent of its blood pressure-lowering effects.
 ...
PMID:Captopril reduces the risk of nephropathy in IDDM patients with microalbuminuria. The Microalbuminuria Captopril Study Group. 873 19

A prospective self-controlled evaluation of renal function in non-insulin-dependent diabetic patients with early nephropathy, mild to moderate hypertension, and retinopathy was undertaken over a 1-year period. Thereafter, the effects of treatment with captopril on blood pressure, albumin excretion, and renal function were assessed. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and systolic and diastolic blood pressures remained stable during the pretreatment period; 24-h urinary protein excretion increased progressively from 0.79 +/- 0.13 to 1.23 +/- 0.18 g/24 h (p < 0.05) (mean +/- standard error). Captopril (25 mg b.i.d.) for 3 months reduced systolic and diastolic blood pressures significantly (p < 0.01). Simultaneously, 24-h urinary protein excretion declined by 41 +/- 2.4%, to 0.70 +/- 0.12 g/24 h (p < 0.05) while GFR, ERPF, and fractional filtration demonstrated small but insignificant changes. Subsequently, increase in captopril to 50 mg b.i.d. for the remaining 6 months did not produce further significant changes in renal hemodynamics, blood pressure, or urinary protein excretion (0.48 +/- 0.10 g/24 h at the termination of the study). Non-insulin-dependent diabetic patients with early nephropathy and mild to moderate hypertension demonstrate a progressive increase in urinary protein excretion. Administration of captopril resulted in prompt control of hypertension and reversal of the increase in urinary protein excretion.
J Diabetes Complications
PMID:Longitudinal evaluation of renal function in non-insulin-dependent diabetic patients with early nephropathy: effects of angiotensin-converting enzyme inhibition. 877 36

We designed a prospective, double-blind controlled trial to determine predictors of loss of renal function in patients with insulin dependent diabetes and established nephropathy. A total of 409 insulin-dependent diabetic patients with established nephropathy enrolled in a trial on the effect of Captopril on the rate of progression of renal disease. Baseline demographic, clinical (history and physical) and laboratory parameters were analyzed as risk factors for time to progression. Dichotomous characteristics were compared by Fisher's exact test and continuous characteristics with the Wilcoxon rank-sum test. Univariate proportional hazards regression analysis was used to estimate relative risk of nephropathy progression, and bivariate proportional hazard regression to identify interactions with the treatment group assignment. Multivariate proportional hazard regression was employed to determine which characteristics were independent risk factors. We found that a number of demographic and clinical characteristics were significantly associated with nephropathy progression even after adjustment for treatment group. However, after multivariate analysis, the risk factors that independently predicted progression were onset of IDDM later in life, parental diagnosis of IDDM, the presence of edema, increased mean arterial pressure, and an abnormal electrocardiogram. Likewise, a number of laboratory characteristics were also predictive of nephropathy progression. A low hematocrit, high blood sugar, and higher protein excretion predicted nephropathy progression as did a higher serum creatinine, particularly in the face of a normal serum albumin. In conclusion, this study identifies a number of clinical and laboratory risk factors that can predict which patients with insulin-dependent diabetes with established nephropathy are more likely to sustain a clinically important decrease in renal function over a median follow-up of three years.
 ...
PMID:Predictors of the progression of renal insufficiency in patients with insulin-dependent diabetes and overt diabetic nephropathy. The Collaborative Study Group. 891 32

Treatment with beta-blockers and diuretics has been associated with an increased risk of developing diabetes mellitus in three prospective cohort studies. Prospective, randomized studies with antihypertensive drugs have demonstrated differences between different classes of drugs regarding effects on insulin sensitivity. Thus, treatment with beta-blockers or diuretics is associated with impairment in insulin sensitivity, whereas most modern calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors are neutral. However, there are exceptions within the different classes. Captopril seems to differ from the other ACE inhibitors and results in improvement of insulin sensitivity. The most pronounced improvements have been obtained with alpha 1-blockers. In populations at high risk for diabetes mellitus, it may be justified to select drugs that improve insulin sensitivity when treating hypertension in insulin resistant individuals.
 ...
PMID:Hyperinsulinemia, insulin resistance, and the treatment of hypertension. 893 47

To evaluate the effect of angiotensin-converting enzyme inhibition on spontaneous and insulin-stimulated endothelin-1 (ET-1) secretion in vitro and in vivo, human endothelial cells derived from umbilical cord veins were cultured onto acellular collagen-coated permeable membrane, thus mimicking in vivo conditions with a luminal and abluminal side. Insulin (10(-6,-8,-9) mol/l) significantly stimulated ET-1 secretion by cultured cells (P < 0.05 starting from 2-h incubation). Captopril (10(-7,-8,-9) mol/l) significantly reduced both spontaneous and insulin-stimulated ET-1 secretion, while increasing nitric oxide production. Considering each cell side, captopril significantly inhibited the apical secretion of ET-1, while its effect on the basolateral compartment was modest. In the presence of D-Arg,[Hyp3,Thi5,8,D-Phe7]-bradykinin (10(-6) mol/l), a bradykinin B2 receptor antagonist, captopril had no effects on ET-1 and nitric oxide production and also when insulin was added to the culture media. With regard to in vivo experiments, oral captopril therapy (25 mg twice daily for 1 week) was given to normotensive (n = 5) and hypertensive (n = 6) subjects and significantly decreased plasma ET-1 concentration (normotensive subjects, before: 0.98 +/- 0.09 pg/ml; after: 0.55 +/- 0.08 pg/ml, P < 0.0001; hypertensive subjects, before: 1.05 +/- 0.03 pg/ml; after: 0.56 +/- 0.05 pg/ml, P < 0.0001). Transient hyperinsulinemia was accompanied by a significant rise in plasma ET-1 concentrations in both groups (P < 0.0001 at 180 and 210 min) before but not after captopril treatment. In conclusion, captopril inhibits both spontaneous and insulin-stimulated ET-1 secretion by endothelial cells, acting on angiotensin-converting enzyme bound to the luminal cell side. In vivo, captopril significantly reduces plasma ET-1 levels in both basal and insulin-stimulated conditions.
Diabetes 1997 Jan
PMID:Effects of ACE inhibition on spontaneous and insulin-stimulated endothelin-1 secretion: in vitro and in vivo studies. 897 Oct 86

Culture of mesangial cells (MCs) in 5.6 vs. 30.0 mmol/l glucose for 3 weeks induced a sustained increase in protein kinase C (PKC) activity, transforming growth factor (TGF)-beta1 mRNA, bioactive TGF-beta, and collagen synthesis. Nitric oxide (NO), generated exogenously by the NO donor S-nitroso-N-acetyl, D,L-penicillamine (SNAP) or endogenously after the exposure of MC to interleukin-1beta (IL-1beta), suppressed bioactive TGF-beta in MCs cultured in 5.6 or 30.0 mmol/l glucose and suppressed or abolished increases in TGF-beta1 mRNA and collagen synthesis induced by high concentrations of glucose or phorbol 12,13-dibutyrate without altering values obtained with normal glucose concentrations. SNAP had a transient suppressive effect on PKC activity, which may explain at least in part some of the actions of SNAP. The selective inhibitor of PKC, bisindolylmaleimide (GFX), mimicked NO action. The ability of SNAP and IL-1beta to suppress TGF-beta and collagen synthesis was not mediated by cGMP, since the cGMP analog, 8-Br-PET-cGMP, did not mimic NO action and an antagonist of cGMP-dependent protein kinase, Rp-8-pCPT-cGMPs, did not prevent the inhibitory actions of SNAP. N-omega-L-arginine methyl ester (NMMA) increased TGF-beta in glomerular capillary endothelial cells (GCECs) and stimulated collagen synthesis by MC in a co-culture with GCECs. Captopril inhibited TGF-beta and collagen synthesis and increased cGMP in co-cultures of GCECs and MCs. These effects of captopril were abolished by NMMA, implying mediation by NO. Thus, endogenous NO produced by GCECs may modulate TGF-beta production by both GCECs and MCs and act to suppress matrix protein synthesis by MCs.
Diabetes 1997 Apr
PMID:Nitric oxide inhibition of transforming growth factor-beta and collagen synthesis in mesangial cells. 907 10


<< Previous 1 2 3 4 5 6 7 Next >>