Controlled study of the effect of angiotensin converting enzyme inhibitionversus calcium-entry blockade on insulin sensitivity in overweight hypertensive patients: Trandolapril Italian study (TRIS)

Objective The aim of this study was to evaluate the effect of trandolapril, an angiotensin converting enzyme inhibitor, on blood pressure, forearm blo od flow and insulin sensitivity in comparison with nifedipine gastrointesti nal therapeutic system. Patients and methods This is a multicentre, two-way parallel-group, open-la bel comparative study in 90 overweight hypertensive patients, who were rand omly assigned to treatment for 8 weeks with either trandolapril or nifedipi ne. At baseline and after treatment, all patients underwent an oral glucose tolerance test, an evaluation of their metabolic profiles and a euglycaemi c hyperinsulinaemic clamp test In a subgroup of 18 patients, a forearm stud y was carried out. Results Blood pressure fell by the second week of treatment and remained si gnificantly reduced compared with baseline in both treatment groups. Plasma triglyceride levels were also significantly reduced after trandolapril the rapy, but no significant changes occurred in the other metabolic parameters during treatment with either drug. During the euglycaemic hyperinsulinaemi c clamp, whole-body glucose use was similar in the two treatment groups at baseline, and a moderate but statistically significant increase in insulin sensitivity was observed after trandolapril treatment (trandolapril: 5.0 +/ - 0.2 versus 4.5 +/- 0.2 mg/kg per min; nifedipine: 4.1 +/- 0.3 versus 4.2 +/- 0.3 mg/kg per min; P < 0.05, versus baseline and trandolapril versus ni fedipine treatment). Skeletal muscle glucose uptake was significantly highe r after trandolapril than after nifedipine therapy (5.0 +/- 0.7 and 3.0 +/- 0.4 mg/min, respectively; P < 0.01). As forearm blood flow was similar in the two treatment groups at baseline and was unchanged after 8 weeks of the rapy, skeletal muscle glucose extraction was significantly greater in the A CE inhibitor treated-group than in the nifedipine comparative group (trando lapril: baseline 21 +/- 2, treatment 24 +/- 3 mg/dl; nifedipine: baseline 1 8 +/- 3, treatment 16 +/- 2 mg/dl; P < 0.05, trandolapril versus nifedipine treatment). Conclusions During short-term treatment, ACE inhibition with trandolapril w as able to moderately improve insulin sensitivity, in comparison with calci um blockade, and this effect appeared to be independent of the haemodynamic action of the drug. J Hypertens 1999, 17:439-445 (C) Lippincott Williams & Wilkins.