Long-term effects of angiotensin-converting enzyme inhibition and metabolic control in hypertensive type 2 diabetic patients

Abstract

in the nifedipine group (N ϭ 13). In the macroalbuminuric Long-term effects of angiotensin-converting enzyme inhibition patients, enalapril treatment (N ϭ 11) was associated with and metabolic control in hypertensive type 2 diabetic patients. stabilization compared with a decline in renal function in the Background. In hypertensive type 2 diabetic patients, treatnifedipine group, as shown by the ␤-1/Cr (0.65 Ϯ 4.29 vs. ment with angiotensin-converting enzyme (ACE) inhibitors is Ϫ1.93 Ϯ 2.35 1/mol ϫ 10 Ϫ3 , P Ͻ 0.05) after adjustment for associated with a lower incidence of cardiovascular events than those treated with calcium channel-blocking agents. However, baseline values. Compared with the normoalbuminuric and the long-term renal effects of ACE inhibitors in these patients microalbuminuric patients, those with macroalbuminuria had remain inconclusive. In 1989, we commenced a placebo-conthe lowest mean C Cr (75.5 Ϯ 24.1 vs. 63.5 Ϯ 21.3 vs. 41.9 Ϯ trolled, double-blind, randomized study to examine the anti-18.5 mL/min, P Ͻ 0.001) and the highest frequency of clinical albuminuric effects of enalapril versus nifedipine (slow release) events (4.7 vs. 5.9 vs. 52%, P Ͻ 0.001). On multivariate analysis, in 102 hypertensive, type 2 diabetic patients. These patients ␤-1/Cr (R 2 ϭ 0.195, P Ͻ 0.001) was independently associated have been followed up for a mean trial duration of 5.5 Ϯ 2.2 with baseline HbA 1c (␤ ϭ Ϫ0.285, P ϭ 0.004), whereas clinical years. We examined the determinants, including the effect of outcomes (R 2 ϭ 0.176, P Ͻ 0.001) were independently related ACE inhibition on clinical outcomes in these patients. to the mean low-density lipoprotein cholesterol (␤ ϭ 2.426, P ϭ Methods. After a six-week placebo-controlled, run-in pe-0.018), high-density lipoprotein cholesterol (␤ ϭ Ϫ8.797, P ϭ riod, 52 patients were randomized double-blind to receive 0.03), baseline UAE (␤ ϭ 0.002, P ϭ 0.04), and mean C Cr nifedipine (slow release) and 50 patients to receive enalapril. during treatment (␤ ϭ Ϫ0.211, P ϭ 0.006). After the one-year analysis, which confirmed the superior anti-Conclusion. In this prospective cohort analysis involving 102 albuminuric effects of enalapril (Ϫ54%) over nifedipine hypertensive, type 2 diabetic patients with varying degrees of (ϩ11%), all patients were continued on their previously asalbuminuria followed up for a mean duration of five years, we signed treatment with informed consent. They were subdivided observed the importance of good metabolic and blood pressure into normoalbuminuric (N ϭ 43), microalbuminuric (N ϭ 34), control on the progression of albuminuria and renal function. and macroalbuminuric (N ϭ 25) groups based on two of three Treatment with enalapril was associated with a greater reduc-24-hour urinary albumin excretion (UAE) measurements tion in albuminuria than with nifedipine in the entire patient during the run-in period. Renal function was shown by the group, and especially in those with microalbuminuria. In the 24-hour UAE, creatinine clearance (C Cr), and the regression...

Microalbuminuria and hypertension with focus on type 1 and type 2 diabetes*

“…Chan et al . [132] compared nifedipine with enalapril, and reported that enalapril had a better effect on microalbuminuria and renal function. Lacourcière et al .…”

The Effects of Enalapril and Irbesartan in Experimental Diabetic Nephropathy

“…In a similar way, in experimentally DN formed rats, we did not observe any increase in lipid peroxidation products with low doses of those two drugs. On this occasion, partial improvements in renal functions and histopathologic alterations with treatment in our experimental rats, result from decrease of local metabolic changes and lipid peroxidation owing to the suppressor effects of ACEi and ARB on AT1 receptors (2,7). Decrease of glomerular collagen accumulation with both drugs is consequentially related with decrease in production of mesangiocellular TGF-β1 and free oxygen radicals that play major role in stimulation of mesangial cells (24).…”

“…However, angiotensin T 1 (AT 1 ) receptors speed up deterioration of organs by their proliferative, vasoconstrictor, Na + retaining effects, by increasing blood pressure and by stimulating ROP production (17,18). It has been reported that ACEi which decreases Ang II production (7,18), and recently ARB, which suppresses AT 1 receptor (5, 13), slow down progress to DN. Ang II T 1 receptors speed up progress to DN by hemodynamic and local metabolic alterations via their Na retaining effects from proximal tubules.…”

“…When compared to HC group there was signifi cant type IV collagen accumulation in PC group, however, accumulation was lesser in the treatment groups (23).There was no signifi cant difference in the comparison of treatment groups with PAS stained specimens however, type IV collagen accumulation in the EN group was lesser than the IR group. Decrease in the collagen accumulation may result from its effect on glycemia, which is the major cause of progress to DN (6,7). When basement membrane thicknesses of all groups were compared by electron microscopic examination, it was noted that, basement membranes were fairly thick in DN and the average width of the basement membranes was lesser in EN group than IR group ( Table 2).…”

Review: The practical aspects of combination therapy with angiotensin receptor blockers and angiotensin-converting enzyme inhibitors

“…51 This traditional pathway for production of Ang II is incompletely suppressed even by high-dose ACE-I therapy. 44,53 If Ang II escape with ACE-I is ever to be of relevance to clinical practice, it will not be on the basis of loss of BP control, an easily measured and treated parameter; rather, it is likely to be as a consequence of 'suboptimal tissue protection'. 44,53 If Ang II escape with ACE-I is ever to be of relevance to clinical practice, it will not be on the basis of loss of BP control, an easily measured and treated parameter; rather, it is likely to be as a consequence of 'suboptimal tissue protection'.…”