lisinopril and Diabetes-Mellitus--Type-1

The pathogenesis and medical management of diabetic retinopathy is reviewed. The importance of good control of blood glucose and blood pressure remain key elements in the prevention and treatment of diabetic retinopathy, and a number of specific metabolic pathways have been identified that may be useful additional targets for therapeutic intervention. Trial data, however, aimed specifically to answer the questions of optimum medical management are limited, so the DIRECT study of renin-angiotensin blockade using oral candesartan 32 mg daily is a welcome addition to our knowledge. This arose from the promising improvement of retinopathy outcomes in the EUCLID study of lisinopril in type I diabetes. In DIRECT, 5 years of candesartan treatment in type I diabetes reduced the incidence of retinopathy by two or more steps (EDTRS) in severity by 18% (P=0.0508) and, in a post hoc analysis, reduced the incidence of retinopathy by three-step progression by 35% (P=0.034). In type I diabetes patients there was no effect on progression of established retinopathy. In contrast, in type II diabetes, 5 years of candesartan treatment resulted in 34% regression of retinopathy (P=0.009). Importantly, an overall significant change towards less-severe retinopathy was noted in both type I and II diabetes (P

Topics: Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Humans; Incidence; Lisinopril; Tetrazoles

Retinopathy is the most common complication of diabetes, and a leading cause of blindness in people of working age. Optimal blood pressure and metabolic control can reduce the risk of diabetic retinopathy, but are difficult to achieve in clinical practice. In the EUCLID Study, the angiotensin converting enzyme (ACE) inhibitor lisinopril reduced the risk of progression of retinopathy by approximately 50%, and also significantly reduced the risk of progression to proliferative retinopathy. These findings are consistent with extensive evidence that the renin-angiotensin system is expressed in the eye, and that adverse effects of angiotensin II on retinal angiogenesis and function can be inhibited by ACE inhibitors or angiotensin II-receptor blockers. However, in the EUCLID Study retinopathy was not a primary end-point and the study was not sufficiently powered for the eye-related outcomes. Hence, the Diabetic Retinopathy Candesartan Trials (DIRECT) programme has been established to determine whether AT(1)-receptor blockade with candesartan can prevent the incidence and progression of diabetic retinopathy. This programme comprises three studies, involving a total of 4500 patients recruited from about 300 centres worldwide. The patients are normotensive or treated hypertensive individuals, and so the DIRECT programme should assess the potential of an AT(1)-receptor blocker to protect against the pathological changes in the eye following diabetes.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Humans; Hypertension; Lisinopril; Randomized Controlled Trials as Topic; Renin-Angiotensin System; Retina; Tetrazoles

Topics: Angiotensin-Converting Enzyme Inhibitors; Diabetes Mellitus, Type 1; Exercise; Humans; Hypertension; Lisinopril; Male; Obesity; Ramipril; Risk Factors; Weight Loss

Lisinopril, like other ACE inhibitors, lowers blood pressure and preserves renal function in hypertensive patients with non-insulin-dependent or insulin-dependent diabetes mellitus (NIDDM or IDDM) and early or overt nephropathy, without adversely affecting glycaemic control or lipid profiles. On available evidence, renoprotective effects appear to be greater with lisinopril than with comparator calcium channel blockers, diuretics and beta-blockers, despite similar antihypertensive efficacy. As shown by the EUCLID (EUrodiab Controlled trial of Lisinopril in Insulin-Dependent Diabetes) trial, lisinopril is also renoprotective in normotensive patients with IDDM and microalbuminuria. The effect in normotensive patients with normoalbuminuria was smaller than in those with microalbuminuria, and no conclusions can yet be made about its use in patients with normoalbuminuria. In complications other than nephropathy, lisinopril has shown some benefit. Progression to retinopathy was slowed during 2 years' lisinopril therapy in the EUCLID study. Although not yet fully published, these results provide the most convincing evidence to date for an effect of an ACE inhibitor in retinopathy. The drug may also improve neurological function, but this finding is preliminary. Lastly, post hoc analysis of the GISSI-3 trial indicates that lisinopril reduces 6-week mortality rates in diabetic patients when begun as early treatment after an acute myocardial infarction. The tolerability profile of lisinopril is typical of ACE inhibitors and appears to be similar in diabetic and nondiabetic individuals. Hypoglycaemia has occurred at a similar frequency with lisinopril and placebo, as shown in the EUCLID trial. In addition, the GISSI-3 study indicates that the incidence of persistent hypotension and renal dysfunction is increased with lisinopril in general, but the presence of diabetes does not appear to confer additional risk of these events in diabetic patients with acute myocardial infarction receiving lisinopril. In summary, lisinopril lowers blood pressure and produces a renoprotective effect in patients with IDDM and NIDDM without detriment to glycaemic control or lipid profiles. Like other ACE inhibitors, lisinopril should thus be viewed as a first-line agent for reducing blood pressure and preventing or attenuating nephropathy in hypertensive diabetic patients with IDDM or NIDDM and microalbuminuria or overt renal disease. The EUCLID study, using lisinopril, provides new data

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Interactions; Drug Tolerance; Humans; Hypoglycemic Agents; Lisinopril

Diabetic retinopathy is characterized by morphological changes in the retina secondary to disturbances in retinal blood flow. It has been shown that antihypertensive treatment has a protective effect on the development of diabetic retinopathy, and evidence suggests that inhibitors of the renin-angiotensin system have a protective effect beyond the antihypertensive effect. The background for this additional effect is unknown but might be related to an effect on retinal autoregulation.. In a double-blinded, two-way cross-over study, 25 normotensive patients with type 1 diabetes (T1D) aged 20.6-33.9 (mean 27.9) with mild retinopathy were randomized to receive either 5 mg of the calcium channel blocker (CCB) amlodipine for 14 days followed by a washout period and treatment with 10 mg of the angiotensin converting enzyme (ACE) inhibitor lisinopril for another 14 days or the two treatments in the reverse order. Using a Dynamic Vessel Analyzer (DVA), the diameter response of retinal arterioles during an acute increase in the blood pressure induced by isometric exercise, during flicker stimulation and during both stimulus conditions simultaneously was studied before and during the two treatments periods.. Amlodipine and lisinopril induced a similar non-significant decrease in the arterial blood pressure. At baseline, the arterial diameter decreased by 2.4 ± 0.9% (p = 0.004) during isometric exercise, increased by 2.2 ± 0.9% (p = 0.019) during flicker stimulation and increased by 1.8 ± 0.9% (p = 0.03) during the combined stimulus conditions. Neither of the antihypertensive drugs amlodipine (p = 0.76) or lisinopril (p = 0.11) changed the diameter response of retinal vessels significantly; however, the two treatments induced a different response in the veins during combined exercise and flicker (p = 0.021).. Short-term treatment with amlodipine and lisinopril had no significant effect on retinal autoregulation in young normotensive patients with T1D and mild retinopathy, and this lack of effect was similar for the two drugs. A possible normalizing effect of antihypertensive treatment on retinal autoregulation was not observed; however, it might take longer time to improve autoregulation than to reduce the arterial blood pressure.

Topics: Adult; Amlodipine; Antihypertensive Agents; Blood Flow Velocity; Blood Pressure; Cross-Over Studies; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Double-Blind Method; Exercise; Female; Homeostasis; Humans; Intraocular Pressure; Lisinopril; Male; Retinal Artery; Tonometry, Ocular; Young Adult

Our aim was to evaluate the markers of tubulointerstitial damage, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule1 (KIM1) in Type 1 diabetic patients with different levels of albuminuria and in control subjects. In addition, the effect of renoprotective treatment on urinary NGAL was evaluated in diabetic nephropathy.. This was a cross-sectional study in 58 normoalbuminuric (u-albumin <30 mg/24 h), 45 microalbuminuric (30-300 mg/24 h) and 45 macroalbuminuric (>300 mg/24 h) Type 1 diabetic patients and 55 non-diabetic control subjects. Furthermore, in a second study, urine-NGAL was measured in a randomized cross-over study of 56 Type 1 diabetic patients with diabetic nephropathy treated with lisinopril 20, 40 and 60 mg daily..   Urine-NGAL levels were [geometric mean (95% CI)]: control subjects 74 (52-104) (pg/mmol creatinine), normoalbuminuric 146 (97-221), microalbuminuric 222 (158-312) and macroalbuminuric group 261 (175-390). Urine-NGAL increased significantly from the normo- to the micro- and further to the macroalbuminuric group (P<0.05). Urine-NGAL was higher in normoalbuminuric vs. control subjects (P<0.01). Plasma-NGAL was significantly higher in the normoalbuminuric and macroalbuminuric groups than in the control group. Urine-KIM1 was higher in all diabetic groups than in the control group (P<0.001), with no difference between diabetic groups. During lisinopril treatment, urine-NGAL was reduced (95% CI) 17% (11-50) (not significant).. Urine-NGAL and urine-KIM1 (u-KIM1) are elevated in Type1 diabetic patients, with or without albuminuria, indicating tubular damage at an early stage. Urine-NGAL increases significantly with increasing albuminuria. The ACE inhibitor lisinopril reduced urine-NGAL, but this was not statistically significant.

Topics: Acute-Phase Proteins; Albuminuria; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Hepatitis A Virus Cellular Receptor 1; Humans; Lipocalin-2; Lipocalins; Lisinopril; Male; Membrane Glycoproteins; Middle Aged; Proto-Oncogene Proteins; Receptors, Virus

The purpose of this study was to evaluate the optimal renoprotective effect of ultrahigh doses of lisinopril, as reflected by short-term changes in urinary albumin excretion rate (UAER), in type 1 diabetic patients with diabetic nephropathy.. At the Steno Diabetes Center, 49 type 1 diabetic patients with diabetic nephropathy completed this double-masked randomised crossover trial consisting of an initial washout period followed by three treatment periods each lasting 2 months, where all patients received lisinopril 20, 40 and 60 mg once daily in randomised order in addition to slow-release furosemide. Allocation was concealed by sequentially numbered opaque sealed envelopes. UAER, 24 h ambulatory blood pressure (ABP) and estimated GFR were determined at baseline and after each treatment period.. All 49 patients completed all three treatment periods. Baseline values were: UAER (geometric mean [95% CI]) 362 (240-545) mg/24 h, 24 h ABP (mean [SD]) 142 (14)/74 (8) mmHg and estimated GFR 75 (29) ml min(-1) 1.73 m(-2). Reductions in UAER from baseline were 63%, 71% and 70%, respectively, with the increasing doses of lisinopril (p < 0.001). Compared with lisinopril 20 mg there was a further reduction in UAER of 23% with lisinopril 40 mg and 19% with 60 mg, p < 0.05. ABP was reduced from baseline by 10/5, 13/7 and 12/7 mmHg (p < 0.001 vs baseline, p < 0.05 for diastolic ABP 20 vs 40 mg, otherwise NS between doses). The difference in UAER between 20 and 40 mg lisinopril was significant after adjustment for changes in ABP (p < 0.01). Two patients were excluded from the study because of an increase in plasma creatinine and one because of high BP; otherwise the study medication was well tolerated with few, mild, dose-independent adverse effects.. Lisinopril 40 mg once daily is generally safe and offers additional reductions in BP and UAER in comparison with the currently recommended dose of 20 mg. Lisinopril 60 mg offers no further beneficial effect.. ClinicalTrials.gov NCT00118976.

Topics: Adult; Albuminuria; Antihypertensive Agents; Cross-Over Studies; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Nephropathies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Glomerular Filtration Rate; Humans; Lisinopril; Male; Middle Aged; Protective Agents

To assess and compare the long-term effects of the combination of candesartan and lisinopril with high-dose lisinopril on systolic blood pressure in patients with hypertension and diabetes.. This was a prospective, randomized, parallel-group, double-blind, double-dummy study with a 12-month follow-up. Drug therapy was either lisinopril 40 mg once daily or dual-blockade treatment with candesartan 16 mg once daily and lisinopril 20 mg once daily. The study comprised 75 type 1 and type 2 diabetic patients aged 35-74 years. The main outcome measures were seated and 24-h ambulatory systolic blood pressure.. Reduction in systolic blood pressure (24-h systolic blood pressure) reduction was obtained in both treatment arms (mean reduction at final follow-up: dual blockade 6 mmHg vs. lisinopril 2 mmHg), but no significant difference was found between dual-blockade and lisinopril 40 mg once daily (P = 0.10). Both treatments were generally well tolerated, and similar low rates of side effects were found in the two groups.. There was no statistically significant difference between lisinopril 40 mg once daily and lisinopril 20 mg in combination with candesartan 16 mg once daily in reducing systolic blood pressure in hypertensive patients with diabetes.

Topics: Aged; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hypertension; Lisinopril; Male; Middle Aged; Tetrazoles

Amadori-albumin, a major glycated protein, is involved in experimental hyperglycaemia-induced microvascular complications, and is associated with advanced nephropathy in Type I diabetic patients in humans. Our aim was to assess the association of Amadori-albumin with early nephropathy and with retinopathy in Type I diabetic patients and the involvement of chronic low-degree inflammation therein.. Amadori-albumin, the Amadori product of haemoglobin (HbA1c), C-reactive protein, and fibrinogen levels were measured in the EUCLID study, a 2-year randomised, double-blind, placebo-controlled trial of lisinopril in 447 Type I diabetic patients. Retinal photographs were taken in 341 patients at baseline and 294 at follow up.. Amadori-albumin was positively associated with albumin the excretion rate and retinopathy status (P = 0.0001 and P = 0.02 for trend, respectively) and with the progression from normoalbuminuria to (micro)albuminuria (38.6 U mL(-1) in nonprogressors, 44.3 U mL-1 in progressors; P = 0.02), but not with the development or progression of retinopathy during a 2-year follow up. Amadori-albumin levels at baseline were associated with C-reactive protein and fibrinogen (P = 0.0007 and P = 0.0001, respectively). C-reactive protein and fibrinogen were also associated with albumin excretion rates (P = 0.03 and P = 0.01, respectively) and retinopathy status (P = 0.02 and P = 0.0006, respectively). Adjustment for these inflammatory markers did not markedly attenuate the association between Amadori-albumin and the albumin excretion rate, while adjustment for fibrinogen, but not C-reactive protein, abolished the association between Amadori-albumin and retinopathy. Lisinopril had no impact on the association between the levels of Amadori-albumin and albumin excretion rates or retinopathy.. Amadori-albumin was associated with early nephropathy and with retinopathy in Type I diabetic patients and preceded an increase in albumin excretion rate, but not retinopathy. A chronic low-degree inflammation does not appear to be involved in Amadori-albumin-associated microvascular complications in Type I diabetes.

Topics: Adult; Albumins; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Diabetic Retinopathy; Double-Blind Method; Female; Humans; Lisinopril; Male; Middle Aged; Regression Analysis

Antihypertensive treatment is presently recommended in most type 1 diabetic patients with microalbuminuria. The long-term effect of angiotensin converting enzymes (ACE) inhibitor (ACE-i) treatment on exercise urinary albumin excretion (E-UAE) and exercise blood pressure (E-BP) in type 1 diabetic patients with low grade microalbuminuria is not well documented. In addition, the possible predictive effect of baseline E-UAE on the progression of overnight UAE remains to be clarified.. In a randomized placebo controlled double blind study the effects of 2 years treatment with either lisinopril (20 mg o.d.) or placebo was evaluated in 21 normotensive type 1 diabetic patients with overnight UAE between 20 and 70 microg min-1. Determinations of E-UAE and E-BP were performed after exercise on an ergometercycle with a load of 70% of estimated maximal VO2 for 20 min. Patients in the placebo and lisinopril groups were similar with regard to age (35.8 +/- 11.3 vs. 29.3 +/- 8.6 years), duration of diabetes (19.4 +/- 8.2 vs. 16.8 +/- 5.3 years), and HbA1c (9.0 +/- 1.0 vs. 9.4 +/- 1.7%).. At baseline, E-UAE was similar in the two groups (placebo: 150.1 x or divide 3.7, lisinopril: 96.8 x or divide 1.8 microg min-1 (geometric mean x or divide tolerance factor)). After 2 years treatment E-UAE had increased in the placebo group, whereas E-UAE was reduced in the lisinopril treated patients (placebo: 213.6 x or divide 6.9, lisinopril: 48.3 x or divide 3.1 microg min-1, P = 0.04). The relative increase in E-UAE (E-UAE/Pre-exercise UAE) was similar at baseline in both groups (3.7 x or divide 2.3 vs. 2.8 x or divide 2.0) but significantly higher in the placebo group after 2 years (4.4 x or divide 2.4 compared with 1.6 x or divide 1.7 in the lisinopril group, P < 0.01) These changes over two years in relative increase in E-UAE were significantly different (P = 0.03). Exercise blood pressure was similar in both groups at baseline and over 2 years increased in the placebo group (from 166.5 +/- 15.1-179.9 +/- 35.6 mmHg), in contrast to the lisinopril group where E-BP was slightly reduced (from 168.5 +/- 20.6-165.1 +/- 16.6 mmHg) but the difference in blood pressure over the 2 years did not reach statistical significance. Exercise urinary albumin excretion and E-BP were closely associated (correlation for year 2: r = 0.734, P < 0.001), and also changes over the 2 years in E-UAE and E-BP were positively correlated (r = 0.53, P = 0.01). At year 2, overnight UAE, pre-exercise UAE (pre-E-UAE), E-UAE and E-BP were all closely linked (r-values between 0.6 and 0.9, P-values < 0.01). In the prediction of changes in overnight UAE over 2 years, neither baseline E-UAE nor baseline E-BP conveyed explanatory information in comparison with baseline overnight UAE and HbA1c.. In type 1 diabetic patients with low-grade microalbuminuria, 2 years of ACE-i treatment with lisinopril significantly reduced E-UAE. Strong correlations were found between E-UAE and E-BP and also changes over 2 years in these parameters were significantly associated.

Topics: Adult; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Diabetes Mellitus, Type 1; Exercise Test; Humans; Lisinopril

To study the effects of ACE-i in type 1 diabetic patients with early microalbuminuria with regard to: i) UAE, ii) 24 h AMBP, including the effect on diurnal BP variation, and iii) renal haemodynamics.. 58 patients with urinary albumin excretion (UAE) between 20-70 microg/min were treated for two years with either the ACE inhibitor (ACE-i) lisinopril (20 mg od) or placebo in two randomised placebo controlled double blind studies. In a subgroup of patients (n=22) we performed 24 h ambulatory blood pressure measurements (AMBP) and renal function tests (constant infusion technique).. i) Changes in UAE over the two years were significantly different (p<0.01) in the two groups with final UAE in the lisinopril group of 19.1 microg/min x/divide 2.5 (geometric mean x/divide tolerance factor) and 44.1 microg/min x/divide 2.8 in the placebo group. In the lisinopril group 20 patients (60.6%) reversed to normoalbuminuria compared to 6 patients (24%) in the placebo group (p<0.02). ii) Clinical BP measurements revealed no differences between groups, but by AMBP significant reductions were detectable in the lisinopril group, primarily in night AMBP (systolic/diastolic: - 6.9 +/- 8.6/- 6.0 +/- 5.3 mmHg, p<0.01) as opposed to increases in the placebo group (3.1 +/- 9.3/1.9 +/- 7.3 mmHg). iii) Changes in UAE and changes in filtration fraction (FF) were positively correlated in the intervention group (r=0.9, p<0.01), i.e. the patients who showed the greatest fall in UAE were the ones with the greatest fall in FF.. ACE-i treatment in patients with low-grade microalbuminuria reduces 24 h AMBP without attenuating diurnal blood pressure variation, reduces UAE significantly, with changes in UAE being strongly associated with changes in FF. Furthermore, compared to placebo, ACE-i reverses micro- to normoalbuminuria in a significant fraction of patients.

Topics: Adult; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Circadian Rhythm; Diabetes Mellitus, Type 1; Double-Blind Method; Female; Follow-Up Studies; Glomerular Filtration Rate; Glycated Hemoglobin; Hemodynamics; Humans; Lisinopril; Male; Placebos; Time Factors

To determine whether circulating plasma vascular endothelial growth factor (VEGF) is elevated in the presence of diabetic microvascular complications, and whether the impact of angiotensin-converting enzyme (ACE) inhibitors on these complications can be accounted for by changes in circulating VEGF.. Samples (299/354 of those with retinal photographs) from the EUCLID placebo-controlled clinical trial of the ACE inhibitor lisinopril in mainly normoalbuminuric non-hypertensive Type 1 diabetic patients were used. Albumin excretion rate (AER) was measured 6 monthly. Geometric mean VEGF levels by baseline retinopathy status, change in retinopathy over 2 years, and by treatment with lisinopril were calculated.. No significant correlation was observed between VEGF at baseline and age, diabetes duration, glycaemic control, blood pressure, smoking, fibrinogen and von Willebrand factor. Mean VEGF concentration at baseline was 11.5 (95% confidence interval 6.0--27.9) pg/ml in those without retinopathy, 12.9 (6.0--38.9) pg/ml in those with non-proliferative retinopathy, and 16.1 (8.1--33.5) pg/ml in those with proliferative retinopathy (P = 0.06 for trend). Baseline VEGF was 15.2 pg/ml in those who progressed by at least one level of retinopathy by 2 years compared to 11.8 pg/ml in those who did not (P = 0.3). VEGF levels were not altered by lisinopril treatment. Results were similar for AER.. Circulating plasma VEGF concentration is not strongly correlated with risk factor status or microvascular disease in Type 1 diabetes, nor is it affected by ACE inhibition. Changes in circulating VEGF cannot account for the beneficial effect of ACE inhibition on retinopathy.

Topics: Adult; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Retinopathy; Endothelial Growth Factors; Fibrinogen; Glycated Hemoglobin; Humans; Lisinopril; Lymphokines; Middle Aged; Placebos; Smoking; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; von Willebrand Factor

To compare the long-term effect on kidney function of a long-acting calcium antagonist (nisoldipine) versus a long-acting ACE inhibitor (lisinopril) in hypertensive type 1 diabetic patients with diabetic nephropathy.. We performed a 4-year prospective, randomized, double-dummy controlled study comparing nisoldipine (20-40 mg once a day) with lisinopril (10-20 mg once a day). The study was double-blinded for the first year and single-blinded thereafter. The study included 51 hypertensive type 1 diabetic patients with diabetic nephropathy. Three patients dropped out during the first month; results for the remaining 48 patients are presented.. At baseline, the two groups were comparable: glomerular filtration rate (GFR) was 85 +/- 5 and 85 +/- 6 ml x min(-1) x [1.73 m](-2); mean 24-h ambulatory blood pressure was 108 +/- 3 and 105 +/- 2 mmHg, and albuminuria was 1,554 mg/24 h (95% CI 980-2,465) and 1,033 mg/24 h (760-1,406) in the lisinopril and nisoldipine groups, respectively. Mean 24-h arterial blood pressure during the study did not differ between the lisinopril and nisoldipine groups (100 +/- 2 and 103 +/- 1 mmHg, respectively). The time-course of albuminuria differed between groups (P < 0.001). Whereas initiation of treatment with lisinopril resulted in a reduction from baseline albuminuria by 52% (95% CI 14-73), albuminuria in the nisoldipine group did not change throughout the study GFR declined in a biphasic manner with an initial (0-6 months) reduction of 1.3 +/- 0.3 ml x min(-1) x month(-1) in the lisinopril group compared with 0.2 +/- 0.4 ml x min(-1) x month(-1) in the nisoldipine group (P < 0.01). The subsequent sustained decline (6 to 48 months or the end of treatment) was identical in the two groups: 0.5 +/- 0.1 ml min(-1) x month(-1) (NS). Two patients in the lisinopril group and three patients in the nisoldipine group entered therapy for end-stage renal failure.. Long-term treatment with lisinopril or nisoldipine has similar beneficial effects on progression of diabetic nephropathy in hypertensive type 1 diabetic patients.

Topics: Adult; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Double-Blind Method; Female; Glomerular Filtration Rate; Humans; Kinetics; Lisinopril; Male; Nisoldipine; Placebos; Prospective Studies; Treatment Outcome

To compare the effects of the calcium channel blocker, nisoldipine, and the ACE inhibitor, lisinopril, on left ventricular mass (LVM) and systolic function in type 1 diabetic patients with diabetic nephropathy.. M-mode echocardiography was performed in 50 hypertensive type 1 diabetic patients with diabetic nephropathy enrolled in a 1-year, randomized, double-blind, parallel study of antihypertensive treatment with nisoldipine CC (20-40 mg/day) or lisinopril (10-20 mg/day). Ambulatory 24-h blood pressure was measured with the Takeda TM 2420 device (A & D, Tokyo, Japan) every 3 months. Three patients dropped out and seven patients were excluded due to technical difficulties.. The 24-h diastolic blood pressure was reduced from 83 to 80 mmHg in the nisoldipine group (P = 0.06) and from 85 to 80 mmHg in the lisinopril group (P = 0.02). The decline in systolic blood pressure was not significant with any of the two treatments, and no difference in reduction of blood pressure was seen between groups. LVM corrected for body surface area (LVMI) was comparable between groups at baseline and increased from 96 +/- 5 to 107 +/- 6 g/m2 (mean +/- SEM; P = 0.007) in the nisoldipine group and from 95 +/- 4 to 103 +/- 5 g/m2 (P = 0.03) in the lisinopril group. The mean difference between the change in LVMI in the two groups was 2.9 (95% CI 6.8 to 12.7) g/m2. The prevalence of left ventricular hypertrophy rose from 18 (95% CI 6-30) to 30% (16-44) during the study period. A multiple linear regression analysis revealed that after 1 year of treatment, LVMI increased with higher systolic blood pressure level and declining glomerular filtration rate (R2 = 0.25). Fractional shortening was within normal range at baseline, 42 +/- 1 vs. 41 +/- 1% with nisoldipine and lisinopril, respectively, and did not change during follow-up.. Antihypertensive treatment with nisoldipine or lisinopril to bring diastolic blood pressure level within the normal target range does not hinder a rise in LVMI in type 1 diabetic patients with diabetic nephropathy.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Calcium Channel Blockers; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Diastole; Double-Blind Method; Echocardiography; Female; Humans; Lisinopril; Male; Middle Aged; Nisoldipine; Ventricular Function, Left

Retinopathy commonly occurs in people with type 1 diabetes. Strict glycaemic control can decrease development and progression of retinopathy only partially. Blood pressure is also a risk factor for microvascular complications. Antihypertensive therapy, especially with inhibitors of angiotensin-converting enzyme (ACE), can slow progression of nephropathy, but the effects on retinopathy have not been established. We investigated the effect of lisinopril on retinopathy in type 1 diabetes.. As part of a 2-year randomised double-blind placebo-controlled trial, we took retinal photographs at baseline and follow-up (24 months) in patients aged 20-59 in 15 European centres. Patients were not hypertensive, and were normoalbuminuric (85%) or microalbuminuric. Retinopathy was classified from photographs on a five-level scale (none to proliferative).. The proportion of patients with retinopathy at baseline was 65% (117) in the placebo group and 59% (103) in the lisinopril group (p = 0.2). Patients on lisinopril had significantly lower HbA1c at baseline than those on placebo (6.9% vs 7.3 p = 0.05). Retinopathy progressed by at least one level in 21 (13.2%) of 159 patients on lisinopril and 39 (23.4%) of 166 patients on placebo (odds ratio 0.50 [95% CI 0.28-0.89], p = 0.02). This 50% reduction was the same when adjusted for centre and glycaemic control (0.55 [0.30-1.03], p = 0.06). Lisinopril also decreased progression by two or more grades (0.27 [0.07-1.00], p = 0.05), and progression to proliferative retinopathy (0.18 [0.04-0.82], p = 0.03). Progression was not associated with albuminuric status at baseline. Treatment reduced retinopathy incidence (0.69 [0.30-1.59], p = 0.4).. Lisinopril may decrease retinopathy progression in non-hypertensive patients who have type 1 diabetes with little or no nephropathy. These findings need to be confirmed before changes to clinical practice can be advocated.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Disease Progression; Double-Blind Method; Female; Follow-Up Studies; Humans; Lisinopril; Logistic Models; Male; Risk Factors; Time Factors

Intervention trials on renal function in IDDM patients with microalbuminuria (MA) should adopt the rate of decline of glomerular filtration rate (GFR) as an outcome measure. However, normotensive IDDM patients with MA show no change in GFR over a follow-up period of 10 years. Thus, in the present study, we used the cumulative incidence of progression to albuminuria (albumin excretion rate [AER] > 200 micrograms/min) from MA as the primary endpoint and the yearly increase in AER at a rate of 50% above baseline as the secondary end-point of renal function.. Ninety-two normotensive IDDM patients underwent double-blind, double-dummy treatment with either lisinopril or slow-release nifedipine in comparison with placebo. Ten patients discontinued the study during the 3-year follow-up period.. During the 3-year follow-up period, 7 of 34 placebo-treated (20.6%), 2 of 32 lisinopril-treated (6.3%), and 2 of 26 nifedipine-treated (7.7%) patients progressed to clinical albuminuria (Fisher's exact test, P < 0.03). Time-to-event analysis indicated a reduction in the risk of progression to macroalbuminuria of 58.1% (95% CI 27.8-68.4%) in the 32 patients on lisinopril (P < 0.02) and of 62.5% (95% CI 32.5-73.4%) in the 26 patients on nifedipine (P < 0.02) after adjustment for mean blood pressure, glycated hemoglobin, and baseline AER in comparison with the 34 patients on placebo. Baseline AER was 71 micrograms/min (range: 20.7-187.3) in progressors and 73 micrograms/min (range: 20.2-174.1) in nonprogressors (NS). The percentage of patients who showed a > 50% yearly increase of AER above baseline values was significantly lower in the lisinopril group (13 of 32, 40.6%, P < 0.02), but not in the nifedipine group (15 of 26, 57.7%), than in the placebo group (23 of 34, 67.6%). The lisinopril group had significantly lower blood pressure values during follow-up than either the nifedipine (P < 0.05) or the placebo (P < 0.01) group.. Our data show that both lisinopril and nifedipine are effective in delaying the occurrence of macroalbuminuria in normotensive IDDM patients with MA. As overt proteinuria strongly predicts end-stage renal failure, both treatments appear capable of preventing such a complication in normotensive IDDM patients with MA. However, lisinopril appears more powerful in slowing the course of nephropathy.

Topics: Adult; Aged; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Creatinine; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Disease Progression; Double-Blind Method; Electrocardiography; Female; Glomerular Filtration Rate; Glycated Hemoglobin; Humans; Italy; Lisinopril; Male; Middle Aged; Nifedipine; Potassium; Smoking; Time Factors; Vasodilator Agents

To study the effect of lisinopril on the exercise-induced urinary albumin excretion rate.. A total of 26 IDDM patients with normoalbuminuria were randomized into two groups, with one group receiving placebo (n = 13, age 36 +/- 3 years, BMI 24.5 +/- 1.1 kg/m2) and the other group receiving an average of 15 mg lisinopril daily (n = 13, age 34 +/- 2 years, BMI 24.4 +/- 0.9 kg/m2). Overnight and exercise-induced urinary albumin excretion rate was measured at baseline and after 1 and 2 years of treatment. Two patients in the placebo group and none in the lisinopril group developed microalbuminuria.. In the lisinopril group, the exercise-induced urinary albumin excretion rate diminished 46% after the 1st year (P = 0.059) and 66% (P < 0.01) after the 2nd year. However, it remained unchanged in the control group. Systolic blood pressure (sBP) and diastolic blood pressure (dBP) were similar at baseline and after 1 year, but at 2 years, sBP was 13 mmHg lower (P = 0.03) and dBP was 9 mmHg lower (P = 0.052) in the lisinopril group as compared with the control group. The dBP decreased significantly at 1 and 2 years in the lisinopril group, while there was no significant change in the sBP. In the whole group at baseline, the overnight albumin excretion rate correlated with HbA1c (r = 0.50, P < 0.01) and the duration of diabetes (r = 0.39, P < 0.05), and sBP correlated with both the overnight (r = 0.42, P < 0.05) and the exercise-induced (r = 0.48, P < 0.05) albumin excretion rate.. Glycemic control and blood pressure are directly related to the overnight albumin excretion rate also in normotensive normoalbuminuric IDDM patients. Lisinopril treatment reduces the exercise-induced urinary albumin excretion rate in such patients. These data suggest a protective effect of lisinopril against the development of microalbuminuria.

Topics: Adult; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Blood Glucose; Blood Pressure; Body Mass Index; Diabetes Mellitus, Type 1; Diastole; Exercise; Exercise Test; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Lisinopril; Placebos; Systole; Time Factors

We examined whether the ACE gene insertion/deletion (I/D) polymorphism modulates renal disease progression in IDDM and how ACE inhibitors influence this relationship. The EURODIAB Controlled Trial of Lisinopril in IDDM is a multicenter randomized placebo-controlled trial in 530 nonhypertensive, mainly normoalbuminuric IDDM patients aged 20-59 years. Albumin excretion rate (AER) was measured every 6 months for 2 years. Genotype distribution was 15% II, 58% ID, and 27% DD. Between genotypes, there were no differences in baseline characteristics or in changes in blood pressure and glycemic control throughout the trial. There was a significant interaction between the II and DD genotype groups and treatment on change in AER (P = 0.05). Patients with the II genotype showed the fastest rate of AER progression on placebo but had an enhanced response to lisinopril. AER at 2 years (adjusted for baseline AER) was 51.3% lower on lisinopril than placebo in the II genotype patients (95% CI, 15.7 to 71.8; P = 0.01), 14.8% in the ID group (-7.8 to 32.7; P = 0.2), and 7.7% in the DD group (-36.6 to 37.6; P = 0.7). Absolute differences in AER between placebo and lisinopril at 2 years were 8.1, 1.7, and 0.8 microg/min in the II, ID, and DD groups, respectively. The significant beneficial effect of lisinopril on AER in the II group persisted when adjusted for center, blood pressure, and glycemic control, and also for diastolic blood pressure at 1 month into the study. Progression from normoalbuminuria to microalbuminuria (lisinopril versus placebo) was 0.27 (0.03-2.26; P = 0.2) in the II group, and 1.30 (0.33-5.17; P = 0.7) in the DD group (P = 0.6 for interaction). Knowledge of ACE genotype may be of value in determining the likely impact of ACE inhibitor treatment.

Topics: Adult; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Disease Progression; Follow-Up Studies; Genotype; Humans; Lisinopril; Middle Aged; Peptidyl-Dipeptidase A; Placebos; Polymorphism, Genetic; Time Factors

1. Our objective was to compare the effect of a long-acting calcium antagonist (nisoldipine) compared with an angiotensin-converting enzyme inhibitor (lisinopril) on the non-neurogenic regulation of the microvascular blood flow in hypertensive Type I diabetes patients with diabetic nephropathy.2. We performed a 1-year double-blind, double-dummy randomized controlled study comparing nisoldipine (20-40 mg once daily) with lisinopril (10-20 mg once daily) in 48 hypertensive Type I diabetes patients with diabetic nephropathy. For comparison, 22 age-matched normotensive healthy control subjects were included. Measurements were performed at baseline and after 1 year of antihypertensive treatment. The minimal vascular resistance and distensibility (stiffness) of resistance vessels in skin and skeletal muscle were measured using the local isotope washout method.3. Mean arterial pressure was reduced to the same extent in both groups: nisoldipine, 113+/-2.1 to 105+/-1.6 mmHg (P<0.001); lisinopril, 110+/-2.7 to 101+/-2.1 mmHg (P<0.002) (controls, 88+/-2.2 mmHg; P<0.0001 compared with diabetic patients). Nisoldipine improved the skin vascular distensibility from 28+/-3.3 to 43+/-3.8% (P<0.005) and decreased skin minimal vascular resistance from 16.9+/-1.0 to 13.6+/-0.8 mmHg.ml-1.min.100 g (P<0. 02). Lisinopril had no significant effect on skin vascular distensibility (40+/-4.0% and 41+/-4.4%), but minimal vascular resistance tended to diminish (18.1+/-0.9 to 15.8+/-1.3 mmHg.ml-1. min.100 g (P=0.09). Nisoldipine significantly increased the skin distensibility (P=0.05) after 1 year of antihypertensive treatment compared with lisinopril.4. The control group had a skin vascular distensibility of 54+/-3.2% and a minimal vascular resistance of 10. 8+/-0.7 mmHg.ml-1.min.100 g, both significantly different from the values in the diabetic groups (P<0.0001 for all). Skeletal muscle vascular distensibility was unaltered after 1 year of treatment with both nisoldipine (22+/-3.3% and 19+/-2.7%) and lisinopril (19+/-2.1% and 24+/-2.5%), but was reduced compared with a control value of 43+/-3.7% (P<0.0001 for diabetes patients versus controls). However, neither nisoldipine nor lisinopril had any effect on the increased minimal vascular resistance or the reduced skeletal muscle distensibility.5. Enhanced thickening of the basement membranes of the terminal arteriolar wall was found in skin biopsy specimens in 91% of diabetic patients and 38% only in control subjects (P<0. 000001 bot

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Calcium Channel Blockers; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Double-Blind Method; Female; Humans; Lisinopril; Male; Middle Aged; Nisoldipine; Regional Blood Flow; Skin; Time Factors; Vascular Resistance; Vasodilation

Our objective was to compare the effect of a long-acting calcium antagonist (nisoldipine) versus an ACE inhibitor (lisinopril) on albuminuria, arterial blood pressure, and glomerular filtration rate (GFR) in hypertensive IDDM patients with diabetic nephropathy. We performed a 1-year, double-blind, double-dummy, randomized, controlled study comparing nisoldipine (20-40 mg once daily) with lisinopril (10-20 mg once daily) in 52 hypertensive IDDM subjects with diabetic nephropathy. Three patients dropped out, and results for the remaining 49 (25 nisoldipine, 24 lisinopril) are presented. Diuretics were required in 10 nisoldipine- and 8 lisinopril-treated patients. Every 3 months, 24-h ambulatory blood pressure (TM2420, A&D, Tokyo, Japan) and albuminuria in three 24-h samples (enzyme immunoassay) were measured; GFR (51Cr-EDTA plasma clearance) was recorded every 6 months. Mean arterial blood pressure (24 h) was reduced from (mean +/- SE) 108 +/- 3 mmHg at baseline to 101 +/- 2 in average during treatment in the lisinopril group and from 105 +/- 2 to 103 +/- 2 in the nisoldipine group (P = 0.06 comparing changes in the two groups). Albuminuria was reduced 47% (95% CI 21-65) in the lisinopril group versus an increase of 11% (-3 to 27) in the nisoldipine group (P = 0.001). Fractional albumin clearance was reduced 37% (95% CI 4-59%) in the lisinopril versus an increase of 35% (8-69%) in the nisoldipine group (P < 0.01). GFR decreased from 85 +/- 5 ml x min(-1) x 1.73 m(-2) to 73 +/- 5 in the lisinopril group and from 84 +/- 6 to 80 +/- 7 in the nisoldipine group (P < 0.05). The effect of study medication on albuminuria and GFR was independent of changes in systemic blood pressure and baseline variables in multiple regression analyses. In summary, lisinopril reduced albuminuria, but also GFR, to a greater extent than did nisoldipine in hypertensive IDDM patients with diabetic nephropathy during the 1st year of treatment. Longer follow-up is required to clarify whether these drugs have different renoprotective effects.

Topics: Adult; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Chi-Square Distribution; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Nephropathies; Double-Blind Method; Female; Glomerular Filtration Rate; Humans; Hypertension; Lisinopril; Male; Nisoldipine; Patient Compliance; Renin; Time Factors

Renal disease in people with insulin-dependent diabetes (IDDM) continues to pose a major health threat. Inhibitors of angiotensin-converting enzyme (ACE) slow the decline of renal function in advanced renal disease, but their effects at earlier stages are unclear, and the degree of albuminuria at which treatment should start is not known.. We carried out a randomised, double-blind, placebo-controlled trial of the ACE inhibitor lisinopril in 530 men and women with IDDM aged 20-59 years with normoalbuminuria or microalbuminuria. Patients were recruited from 18 European centres, and were not on medication for hypertension. Resting blood pressure at entry was at least 75 and no more than 90 mm Hg diastolic, and no more than 155 mm Hg systolic. Urinary albumin excretion rate (AER) was centrally assessed by means of two overnight urine collections at baseline, 6, 12, 18, and 24 months.. There were no difference in baseline characteristics by treatment group; mean AER was 8.0 micrograms/min in both groups; and prevalence of microalbuminuria was 13% and 17% in the placebo and lisinopril groups, respectively. On intention-to-treat analysis at 2 years, AER was 2.2 micrograms/min lower in the lisinopril than in the placebo group, a percentage difference of 18.8% (95% CI 2.0-32.7, p = 0.03), adjusted for baseline AER and centre, absolute difference 2.2 micrograms/min. In people with normoalbuminuria, the treatment difference was 1.0 microgram/min (12.7% [-2.9 to 26.0], p = 0.1). In those with microalbuminuria, however, the treatment difference was 34.2 micrograms/min (49.7% [-14.5 to 77.9], p = 0.1; for interaction, p = 0.04). For patients who completed 24 months on the trial, the final treatment difference in AER was 38.5 micrograms/min in those with microalbuminuria at baseline (p = 0.001), and 0.23 microgram/min in those with normoalbuminuria at baseline (p = 0.6). There was no treatment difference in hypoglycaemic events or in metabolic control as assessed by glycated haemoglobin.. Lisinopril slows the progression of renal disease in normotensive IDDM patients with little or no albuminuria, though greatest effect was in those with microalbuminuria (AER > or = 20 micrograms/min). Our results show that lisinopril does not increase the risk of hypoglycaemic events in IDDM.

Topics: Adult; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Double-Blind Method; Female; Humans; Lisinopril; Male; Middle Aged

Thirteen diabetic patients with hypertension (mean diastolic blood pressure 96.2 +/- 1.1 mmHg) were included in a study to assess the effects of lisinopril (20 mg day-1) on measures of nerve function. Patients had nerve conduction velocity (NCV), temperature discrimination threshold (TDT), and vibration perception threshold (VPT) measurements. At the end of 12 weeks of treatment with lisinopril, there was a significant improvement in median motor NCV (mean change +/- SEM 2.7 +/- 0.6 m s-1, p < 0.0001), median sensory NCV (2.1 +/- 0.9 m s-1, p = 0.03), peroneal motor NCV (1.0 +/- 0.4 m s-1, p = 0.03), and sural sensory NCV (1.9 +/- 0.7 m s-1, p = 0.01) values. There were also significant improvements in warm TDT and VPT. Diastolic BP decreased significantly, but there was no significant change in HbA1. Double blind controlled studies are now needed to confirm the effect of lisinopril on measures of nerve function.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Discrimination, Psychological; Double-Blind Method; Humans; Hypertension; Lisinopril; Median Nerve; Middle Aged; Motor Neurons; Neural Conduction; Neurons, Afferent; Peroneal Nerve; Sensory Thresholds; Sural Nerve; Temperature; Vibration

An open, randomized, cross-over study was undertaken to assess the effects of lisinopril and nifedipine on albumin excretion, renal haemodynamics and segmental tubular reabsorption in overt diabetic nephropathy. The study consisted of a 4-week run-in period, a 3-week active treatment period, a 4-week wash-out period and a second 3-week active treatment period. Twelve patients with type 1 diabetes with albuminuria, mild to moderate hypertension and a serum creatinine level of less than 200 mumol l-1 were included. Lisinopril reduced albumin excretion from 1343 +/- 337 micrograms min-1 to 879 +/- 299 micrograms min-1 (P less than 0.01), whereas nifedipine was without effect, 1436 +/- 336 micrograms min-1 vs. 1319 +/- 342 micrograms min-1. Glomerular filtration rate (GFR) was unchanged by either drug. Both drugs increased effective renal plasma flow (ERPF) by about 20%. No differences between the drugs were observed with regard to their effect on renal haemodynamic parameters. By contrast, nifedipine exerted an inhibitory effect on several proximal tubular transport markers, whereas lisinopril was without effect. The different actions on tubular transport mechanisms exerted by lisinopril and nifedipine may contribute to the observed effect on albumin excretion.

Topics: Adult; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Biological Transport; Blood Pressure; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Enalapril; Female; Glomerular Filtration Rate; Hemodynamics; Humans; Kidney; Kidney Tubules; Lisinopril; Lithium; Male; Nifedipine; Sodium

Diabetes, hypertension, and aging are major contributors to cardiovascular and chronic kidney disease (CKD). Sodium/glucose cotransporter 2 (SGLT2) inhibitors have become a preferred treatment for type II diabetic patients since they have cardiorenal protective effects. However, most elderly diabetic patients also have hypertension, and the effects of SGLT2 inhibitors have not been studied in hypertensive diabetic patients or animal models. The present study examined if controlling hyperglycemia with empagliflozin, or given in combination with lisinopril, slows the progression of renal injury in hypertensive diabetic rats. Studies were performed using hypertensive streptozotocin-induced type 1 diabetic Dahl salt-sensitive (STZ-SS) rats and in deoxycorticosterone-salt hypertensive type 2 diabetic nephropathy (T2DN) rats. Administration of empagliflozin alone or in combination with lisinopril reduced blood glucose, proteinuria, glomerular injury, and renal fibrosis in STZ-SS rats without altering renal blood flow (RBF) or glomerular filtration rate (GFR). Blood pressure and renal hypertrophy were also reduced in rats treated with empagliflozin and lisinopril. Administration of empagliflozin alone or in combination with lisinopril lowered blood glucose, glomerulosclerosis, and renal fibrosis but had no effect on blood pressure, kidney weight, or proteinuria in hypertensive T2DN rats. RBF was not altered in any of the treatment groups, and GFR was elevated in empagliflozin-treated hypertensive T2DN rats. These results indicate that empagliflozin is highly effective in controlling blood glucose levels and slows the progression of renal injury in both hypertensive type 1 and type 2 diabetic rats, especially when given in combination with lisinopril to lower blood pressure.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Fibrosis; Hypertension; Lisinopril; Proteinuria; Rats; Rats, Inbred Dahl

Diabetes is a metabolic disorder affecting a large percentage of the population worldwide. The chronic hyperglycemic condition leads to the generation of advanced glycation end products, reactive oxygen species and inflammatory cytokines, which worsen the functioning of the kidney. Clinical management of diabetic nephropathy is difficult as it requires a multi-focused approach. Hence, a combination of lisinopril a drug used in clinical practice for nephropathy, and naringenin, a flavonoid reported to have a significant effect in nephropathy, may show additive or synergistic effect with less side effects.. The objective of the present study was to evaluate the effect of a combination of lisinopril with naringenin in diabetic nephropathy.. Diabetes was induced in male Sprague Dawley rats by streptozotocin (55 mg/kg, i.p.). After four weeks of diabetes induction animals were treated with naringenin alone and a combination of Lisinopril and naringenin for the next four weeks. At the end of the study, various urine and biochemical parameters were evaluated. Oxidative stress parameters like malondialdehyde, reduced glutathione; catalase and superoxide dismutase for kidney tissues were estimated and histopathology studies of kidneys were carried out.. The combination of lisinopril (10 mg/kg) and naringenin (25 and 50 mg/kg) treatment showed significant improvement in the biochemical and urine parameters. Combination treatment also attenuated renal oxidative stress and renal damage as observed in histopathological studies.. Treatment with a combination of lisinopril and naringenin showed a promising effect on diabetic nephropathy in rats.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Drug Therapy, Combination; Flavanones; Kidney; Lisinopril; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Streptozocin

Progress in research and developing therapeutics to prevent diabetic kidney disease (DKD) is limited by a lack of animal models exhibiting progressive kidney disease. Chronic hypertension, a driving factor of disease progression in human patients, is lacking in most available models of diabetes. We hypothesized that superimposition of hypertension on diabetic mouse models would accelerate DKD. To test this possibility, we induced persistent hypertension in three mouse models of type 1 diabetes and two models of type 2 diabetes by adeno-associated virus delivery of renin (ReninAAV). Compared with LacZAAV-treated counterparts, ReninAAV-treated type 1 diabetic Akita/129 mice exhibited a substantial increase in albumin-to-creatinine ratio (ACR) and serum creatinine level and more severe renal lesions. In type 2 models of diabetes (C57BKLS

Topics: Animals; Antihypertensive Agents; Creatinine; Dependovirus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Models, Animal; Disease Progression; Female; Genetic Vectors; Hypertension; Hypoglycemic Agents; Janus Kinases; Lac Operon; Lisinopril; Male; Mice; Nephrectomy; Nitric Oxide Synthase Type III; Renin; Rosiglitazone; Serum Albumin; Severity of Illness Index; Signal Transduction; STAT Transcription Factors

Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Nephropathies; Glomerular Filtration Rate; Humans; Lisinopril; Renin-Angiotensin System

We studied tubular and glomerular damage in type 1 diabetic patients by measuring urinary-liver fatty acid binding protein (U-LFABP) and albuminuria. Subsequently, we evaluated the effect of ACE inhibition on U-LFABP in patients with diabetic nephropathy.. We studied Caucasians with type 1 diabetes: 58 with normoalbuminuria (urinary albumin <30 mg/24 h), 45 with persistent microalbuminuria (30-300 mg/24 h), and 45 with persistent macroalbuminuria (> or =300 mg/24 h). A control group consisted of 57 healthy individuals. The groups were matched by sex and duration of diabetes. In addition, U-LFABP was measured in 48 type 1 diabetic patients with diabetic nephropathy in a randomized crossover trial consisting of 2 months of treatment with 20, 40, and 60 mg lisinopril once daily in random order.. In the cross-sectional study, levels of U-LFABP were significantly higher in normoalbuminuric patients versus those in the control group (median 2.6 [interquartile range 1.3-4.1] vs. 19 [0.8-3.0] microg/g creatinine, P = 0.02) and increased with increasing levels of albuminuria (microalbuminuric group 4.2 [1.8-8.3] microg/g creatinine and nephropathy group 71.2 [8.1-123.4], P < 0.05 for all comparisons). U-LFABP correlates with the urinary albumin-to-creatinine ratio (R(2) = 0.54, P < 0.001). In the intervention study, all doses of lisinopril significantly reduced urinary albumin excretion rate and U-LFABP from baseline. The reductions in U-LFABP were 43, 46, and 40% with increasing doses of lisinopril (NS).. An early and progressive increase in tubulointerstitial damage as reflected by increased U-LFABP levels occurs in type 1 diabetic patients and is associated with albuminuria. Furthermore, ACE inhibition reduces the tubular and glomerular damage and dysfunction.

Topics: Adult; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Case-Control Studies; Creatinine; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Fatty Acid-Binding Proteins; Female; Humans; Lisinopril; Male; Middle Aged

Although recurrent diabetic nephropathy is common in patients with type I diabetes after kidney transplantation, the development of focal segmental glomerulosclerosis (FGS) is rare, and its development generally takes several years. We report here a case of type I diabetes mellitus with secondary FGS accompanied by proteinuria 10 months following kidney transplantation. Episode biopsy showed secondary FGS, evidenced by glomerular capillary collapse and large epithelial cells with ballooning degeneration. Exudative dense deposition of IgM in a diffuse global mesangial pattern and enlarged glomerular diameters were observed, suggestive of glomerular hyperfiltration which can lead to secondary FGS. An imbalance in body size between donor and recipient and/or uncontrolled diabetes are potential causes of glomerular hyperfiltration. We administered angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker to reduce hyperfiltration-induced renal damage; the combination therapy reduced proteinuria from 2346 to 258 mg/d. Secondary FGS should be a consideration after kidney transplantation in patients with type I diabetes mellitus.

Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Biphenyl Compounds; Diabetes Mellitus, Type 1; Glomerulosclerosis, Focal Segmental; Humans; Kidney Transplantation; Lisinopril; Male; Proteinuria; Tetrazoles

Topics: Antihypertensive Agents; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Energy Metabolism; Fatty Liver; Female; Gastric Bypass; Humans; Hypertension; Lisinopril; Liver; Middle Aged; Nutritional Status; Obesity; Obesity, Morbid; Sciatica; Sleep Apnea Syndromes

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Beverages; Diabetes Mellitus, Type 1; Humans; Hyperkalemia; Kidney Failure, Chronic; Lisinopril; Male; Rosales

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Humans; Lisinopril; Nisoldipine

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Glycated Hemoglobin; Humans; Lisinopril; Research Design

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Endothelial Growth Factors; Humans; Lisinopril; Lymphokines; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Disease Progression; Humans; Kidney; Lisinopril

Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Humans; Lisinopril; Research Design

Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Disease Progression; Humans; Lisinopril

Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Humans; Lisinopril

Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Glomerular Filtration Rate; Humans; Hypertension; Lisinopril; Ramipril