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

The effects of long-term cilazapril therapy on glucose tolerance and serum lipid profiles were investigated in 19 hypertensive patients: seven with normal glucose tolerance and 12 with glucose intolerance (including three patients with noninsulin-dependent diabetes). Cilazapril was administered once daily for a mean duration of 6.4 months. A 75-g oral glucose tolerance test was performed before and during long-term therapy with cilazapril. Cilazapril produced satisfactory control of blood pressure in both patient groups during long-term therapy. It was well tolerated by all patients. Neither fasting nor postglucose-load venous plasma glucose levels were altered in either group of patients, and no patients with normal glucose tolerance developed diabetes mellitus during the study. There were no significant changes in the insulinogenic index (delta IRI/delta BS at 30 min postglucoseload) in patients with normal or impaired glucose tolerance. No significant changes in fasting levels of serum cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides were observed in either group. These results suggest that effective long-term cilazapril therapy does not compromise glucose or lipid metabolism in hypertensive patients. Cilazapril may have a clinical advantage in that it can be given to hypertensive patients without concern that it might alter their serum lipid concentrations or impair glucose tolerance.
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PMID:Glucose and lipid metabolism during long-term treatment with cilazapril in hypertensive patients with or without impaired glucose metabolism. 169 16

Contrasting information has been reported concerning the course of renal function in NIDDM with hypertension alone or in association with renal damage. The aim of the present study was to elucidate the course of the glomerular filtration rate (GFR) in hypertensive NIDDM patients during antihypertensive therapy. Furthermore, we compared the effects of ACE inhibitors (cilazapril, Inibace, Roche, Milan, Italy) and Ca(2+)-channel blockers (amlodipine, Norvasc, Pfizer, Rome, Italy). Of the hypertensive NIDDM patients attending the outpatient's clinic of the internal medicine departments of the University of Padova and Sassari, 44 participated in the present study. Of these patients, 26 were normoalbuminuric and 18 microalbuminuric. They were randomly treated with either cilazapril or amlodipine. The target of antihypertensive treatment was a value < 140 mmHg for systolic and 85 mmHg for diastolic blood pressure (BP). Microalbuminuria was defined as an albumin excretion rate (AER) between 20 and 200 micrograms/min. GFR was measured by plasma clearance of 51Cr-labeled EDTA at baseline and every 6-12 months during a 3-year follow-up interval. A significant decrease was observed in the values of GFR, AER, and systolic and diastolic BP in normoalbuminuric and microalbuminuric patients during antihypertensive therapy. The GFR fall in the overall population of NIDDM patients was significantly and inversely related to the decrease of mean BP (diastolic + 1/3 pulse pressure) (r = -0.80, P < 0.0001) but not to that of HbA1c, triglycerides, and BMI. The GFR decline (mean +/- SE) per year in the normoalbuminuric patient was 2.03 +/- 0.66 ml.min-1 x 1.73 m-2 (95% CI 0.92-3.17) during cilazapril and 2.01 +/- 0.71 ml.min-1 x 1.73 m-2 (95% CI 0.82-3.11) during amlodipine therapy. The GFR decline per year in the microalbuminuric patient was 2.15 +/- 0.69 ml.min-1 x 1.73 m-2 (95% CI 0.86-3.89) during cilazapril and 2.33 +/- 0.83 ml.min-1 x 1.73 m-2 per year (95% CI 1.03-3.67) during amlodipine therapy. Cilazapril and amlodipine lowered AER to a similar extent in normoalbuminuric and microalbuminuric patients. No significant changes were observed concerning other clinical and biochemical features between the two antihypertensive therapies and particularly HbA1c, BMI, triglycerides, and cholesterol plasma values. These results support the tenet that arterial hypertension plays a pivotal role in contributing to renal damage in NIDDM, even when AER is normal. However, the degree of BP control, with both cilazapril and amlodipine, can successfully delay the slope of GFR decline in hypertensive NIDDM patients with or without incipient nephropathy.
Diabetes 1996 Feb
PMID:Effects of cilazapril and amlodipine on kidney function in hypertensive NIDDM patients. 854 68

The effects of long-term cilazapril treatment on glucose and lipid metabolism were assessed in 25 hypertensive patients with non-insulin-dependent diabetes mellitus (NIDDM). Patients were treated with 0.5 to 1 mg of cilazapril once daily or a combination of cilazapril and other antihypertensive drugs once daily for 48 weeks. Both systolic and diastolic blood pressures were significantly reduced (P < 0.001) throughout the study with no significant changes in heart rate and no adverse effects such as cough. There were no significant changes in body mass index or serum levels of glycated hemoglobin A1c, fructosamine, total cholesterol, triglycerides, lipoproteins (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and very-low-density lipoprotein cholesterol), or apolipoproteins (apo A-I, apo C-II, apo C-III, apo B, and apo E). Cilazapril caused a significant increase (P < 0.05) in levels of apo A-II and a significant decrease (P < 0.05) in the apo B:apo A-I ratio, an index of arteriosclerosis. These results suggest that cilazapril has favorable effects on glucose and lipid metabolism and that it may be useful as the first or second choice of antihypertensive drugs in hypertensive patients with NIDDM.
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PMID:Effects of long-term cilazapril treatment on glucose and lipid metabolism in hypertensive patients with non-insulin-dependent diabetes mellitus. 856 36

The effects of long-term monotherapy with cilazapril, an angiotensin-converting enzyme inhibitor, on blood pressure, glucose tolerance, and serum lipid profiles were prospectively investigated in 66 patients with hypertension: 23 with normal glucose tolerance and 43 with glucose intolerance (including 9 patients with non-insulin-dependent diabetes mellitus). The levels of plasma glucose, serum insulin, serum lipids, glycated hemoglobin A(lc) (Hb A(lc)), and fructosamine were determined before and during long-term (mean +/- SD, 26.2 +/- 1.2 weeks) therapy with cilazapril. A 75-g oral glucose tolerance test was performed before and during treatment. Significant reductions in both systolic and diastolic blood pressures in both patient groups were maintained during the study. Neither fasting nor post-glucose load venous plasma glucose levels were altered in either group of patients, and no patient with normal glucose tolerance developed diabetes mellitus during the study. There was no significant change in the insulinogenic index (delta serum insulin/delta venous plasma glucose at 30 minutes post-glucose load) in either group, and glucose intolerance was slightly improved with significant reductions (P < 0.01) in Hb A(lc) and fructosamine in the patient group with impaired glucose tolerance. Serum total cholesterol (TC), low-density lipoprotein cholesterol, and triglyceride levels were significantly (P < 0.01) decreased and high-density lipoprotein cholesterol levels increased in patients with hypercholesterolemia (TC levels > or = 5.69 mmol/L). These results suggest that long-term cilazapril therapy may improve glucose and lipid metabolism in hypertensive patients with impaired glucose tolerance. Cilazapril also appears to be useful as an antihypertensive agent for hypertensive patients with either impaired glucose tolerance or hypercholesterolemia.
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PMID:Effect of cilazapril therapy on glucose and lipid metabolism in patients with hypertension. 875 Apr 4

Using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a new model of human non-insulin-dependent diabetes mellitus (NIDDM), we examined the role of local angiotensin II in cardiovascular and renal complications of NIDDM. OLETF rats were orally given cilazapril (an angiotensin-converting enzyme inhibitor, 1 or 10 mg/kg), E4177 (an angiotensin AT1 receptor antagonist, 10 mg/kg), or vehicle for 26 or 40 weeks (from the age of 20 to 46 or 60 weeks). Cardiac mRNAs were measured by Northern blot analysis, and the thickening of the coronary arterial wall and the degree of perivascular fibrosis were determined by an image analyzer. Cilazapril or E4177 did not significantly affect body weight or plasma glucose and insulin levels of OLETF rats, indicating the minor effects on diabetes itself. However, both drugs significantly and similarly prevented coronary microvascular remodeling (the increase in wall thickening and perivascular fibrosis in coronary arterioles and small coronary arteries) in OLETF rats, and they were associated with the suppression of cardiac transforming growth factor-beta1 expression. Both drugs suppressed not only the increase in left ventricular weight but also the downregulation of cardiac alpha-myosin heavy chain expression in OLETF rats. Glomerulosclerosis and glomerular hypertrophy in OLETF rats were improved by cilazapril and E4177 to a comparable extent. These results, taken together with the fact that OLETF rats show normal plasma renin levels, support that the AT1 receptor is involved in the pathogenesis of cardiac and renal complications in NIDDM.
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PMID:Angiotensin blockade improves cardiac and renal complications of type II diabetic rats. 936 55

The mechanism of decreased albuminuria caused by an inhibitor of angiotensin converting enzyme (ACE) was investigated in patients with early diabetic nephropathy. The subjects were 10 patients with non-insulin-dependent diabetes mellitus without azotemia but with albuminuria (less than 650 mg/day). First, a two-week study was done: one week with a diet with ordinary sodium levels and one week with a sodium-restricted diet, in random order. The systemic blood pressure and urinary excretion of sodium and albumin were measured daily. Intrarenal hemodynamics, in terms of the resistance of afferent and efferent arterioles (RA and RE) and glomerular capillary pressure (PGC), were calculated from renal clearance, the plasma total protein concentration, and the pressure-natriuresis relationship. Results obtained before and two weeks after starting the ACE inhibitor cilazapril (2 mg/day) were compared. Urinary excretion of albumin was decreased by cilazapril in 8 of the 10 patients. Cilazapril decreased the RE [6830 (3680, 14,750) to 4660 (1750, 10,790) dynes.sec.cm-5, P < 0.05, mean (minimum, maximum)] and PGC (53 +/- 5 to 43 +/- 9 mm Hg, P < 0.02, mean +/- SD) in these 8 patients, but not in the two other patients. The RA was not significantly changed in any patient. The percent change caused by cilazapril in the urinary excretion of albumin was significantly correlated with the change in PGC (N = 10, r = 0.875, P < 0.01), but not with changes in the systemic blood pressure. In conclusion, the mechanism by which an ACE inhibitor caused a short-term decrease in albuminuria in early diabetic nephropathy involved a glomerular hemodynamic change, namely, a decrease in PGC.
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PMID:Mechanism of decreased albuminuria caused by angiotensin converting enzyme inhibitor in early diabetic nephropathy. 940 58

alpha-Adrenergic blockers are potential alternative antihypertensive agents for diabetic patients. Data on their relative efficacy and their effect on kidney function and albuminuria are very limited however. 76 patients with diabetes type 2, hypertension (>/=140/90 mm Hg) and albuminuria (>/=30 mg/24 h) were randomized into three groups to receive cilazapril (2.5-10 mg), doxazosin (2-8 mg) or both. Patients of the first and second groups received a single agent for 4 months, the agents were then crossed for an additional period of 4 months followed by the addition of hydrochlorothiazide (25 mg) for a third 4-month period. Blood pressure was monitored monthly, creatinine clearance and HbA1c were measured before and at the end of each treatment period. Patients of the third group received reduced doses of cilazapril and doxazosin for 4 months. Hydrochlorothiazide was then added for the subsequent 4 months. There was a significant decline in blood pressure values during the first period in all groups. Cilazapril: systolic blood pressure (SBP) 160 +/- 6 to 149 +/- 5 mm Hg; diastolic blood pressure (DBP): 101 +/- 3 to 94 +/- 3 mm Hg (p = 0.001). Albuminuria declined from 350 +/- 105 to 205 +/- 96 mg/24 h (p = 0.001), creatinine clearance (CrCl) was unchanged. Doxazosin: SBP: 160 +/- 7 to 151 +/- 6 mm Hg; DBP: 97 +/- 4 to 90 +/- 4 mm Hg (p = 0.001). Albuminuria 373 +/- 121 to 322 +/- 107 mg/24 h (p = 0.065) and CrCl 87 +/- 7 to 91 +/- 6 ml/min. The combination of both agents at half doses was equipotent or superior to either drug alone. Cross-over of cilazapril and doxazosin reproduced the hypotensive effect and reversed the antialbuminuric effect. The addition of hydrochlorothiazide resulted in a further decline of 6-14 mm Hg in SBP and 3-11 mm Hg in DPB.
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PMID:Effect of an alpha-adrenergic blocker, and ACE inhibitor and hydrochlorothiazide on blood pressure and on renal function in type 2 diabetic patients with hypertension and albuminuria. A randomized cross-over study. 973 16

Using Otsuka Long Evans Tokushima Fatty (OLETF) rats, a model of human non-insulin-dependent diabetes mellitus (NIDDM) that exhibits hypertension, obesity, hyperglycemia and hyperlipidemia, the role of local angiotensin II in cardiovascular complications at early stages of NIDDM was characterized. OLETF rats were given an angiotensin converting enzyme (ACE) inhibitor, cilazapril (10 mg/kg/day) or vehicle from the age of 5 weeks to 20 weeks. Arteriolar, intermediate and venular capillary proportions were determined by the double-staining method and levels of collagen and non-collagenous proteins were determined by the selective dye-binding method in heart tissues. In OLETF rats at 20 weeks of age, capillary network remodeling (i.e., an increase in arteriolar portions and a decrease in venular portions) and an increase in collagen content were detected. Cilazapril not only exerted favorable effects on markers of diabetes, but also prevented capillary network remodeling and ameliorated the increase in collagen content. These results suggest that 1) capillary network remodeling and increase in extracellular matrix protein levels precede the onset of overt NIDDM in OLETF rats, and 2) angiotensin II may be involved in the pathogenesis of cardiac complications in the early stages of NIDDM.
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PMID:Coronary capillary remodeling in non-insulin-dependent diabetic rats: amelioration by inhibition of angiotensin converting enzyme and its potential clinical implications. 1121 33

The long-term effects of the angiotensin-converting enzyme (ACE) inhibitor cilazapril on retinal and choroidal circulation in rats with spontaneous diabetes type 2 were assessed by corrosion casts, scanning electron microscopy (SEM) and transmission electron microscopy. One group of 20 male Otsuka Long-Evans Tokushima Fatty (OLETF) rats was treated with 10 mg/kg/day of cilazapril from 4 to 64 weeks of age, and 20 other OLETF rats received no treatment. A third group, 20 male Long-Evans Tokushima Otsuka (LETO) rats, served as age-matched controls. At regular intervals, the rats were weighed, and their blood glucose was measured. Before the experiment, their systolic blood pressure and total cholesterol level were determined. At 64 weeks of age, the OLETF rats weighed significantly less than the cilazapril-treated OLETF and the LETO rats (p < 0.0001). At the same age, 100% of the untreated OLETF rats had bilateral cataracts, while the lens was clear and no fundus abnormality was detected in the cilazapril-treated OLETF rats and the LETO rats. Cilazapril lowered systolic blood pressure to a nearly normal level, significantly prevented the increase in blood sugar and inhibited the increase in serum cholesterol in the OLETF rats throughout the treatment. In the 64-week-old OLETF rats without treatment, corrosion cast and SEM revealed diabetic retinal and choroidal vascular changes: tortuosity of the vessels, variations in caliber, narrowing of arteries, arterio-arteriolar anastomoses and hairpin loop formation in precapillary arterioles, sparse collecting venules in the choroid and marked capillary changes such as caliber irregularity, narrowing, tortuosity, loop formation and decreased capillaries, outpouching and microaneurysms. In the cilazapril-treated OLETF rats, these changes were markedly decreased to the level seen in the LETO rats, in which the retinal and choroidal blood vessels had a definite and fairly constant pattern and the capillaries were more regularly and densely arranged and had a remarkably uniform caliber. Our results show that the long-term administration of cilazapril before or from the initial onset significantly prevented the increase in blood sugar and inhibited the increases in serum cholesterol in OLETF rats throughout the treatment, lowered systolic arterial pressure to a nearly normal level and prevented diabetic ocular complications. The effects of cilazapril on the diabetic retinal and choroidal vasculature are described for the first time. SEM of corrosion casts is a valuable and easy technique for showing precisely and three-dimensionally the effects of some drugs on the vasculature.
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PMID:Retinal and choroidal vasculature in rats with spontaneous diabetes type 2 treated with the angiotensin-converting enzyme inhibitor cilazapril: corrosion cast and electron-microscopic study. 1229 95