Controlled study of the effect of angiotensin converting enzyme inhibition versus 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 blood flow and insulin sensitivity in comparison with nifedipine gastrointestinal therapeutic system.


METHODS
This is a multicentre, two-way parallel-group, open-label comparative study in 90 overweight hypertensive patients, who were randomly assigned to treatment for 8 weeks with either trandolapril or nifedipine. At baseline and after treatment, all patients underwent an oral glucose tolerance test, an evaluation of their metabolic profiles and a euglycaemic hyperinsulinaemic clamp test. In a subgroup of 18 patients, a forearm study was carried out.


RESULTS
Blood pressure fell by the second week of treatment and remained significantly reduced compared with baseline in both treatment groups. Plasma triglyceride levels were also significantly reduced after trandolapril therapy, but no significant changes occurred in the other metabolic parameters during treatment with either drug. During the euglycaemic hyperinsulinaemic 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 nifedipine treatment). Skeletal muscle glucose uptake was significantly higher 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 therapy, skeletal muscle glucose extraction was significantly greater in the ACE inhibitor treated-group than in the nifedipine comparative group (trandolapril: baseline 21 +/- 2, treatment 24 +/- 3 mg/dl; nifedipine: baseline 18 +/- 3, treatment 16 +/- 2 mg/dl; P < 0.05, trandolapril versus nifedipine treatment).


CONCLUSIONS
During short-term treatment, ACE inhibition with trandolapril was able to moderately improve insulin sensitivity, in comparison with calcium blockade, and this effect appeared to be independent of the haemodynamic action of the drug.
Galletti
F
F
Department of Clinical and Experimental Medicine, Federico II University of Naples, Italy. galletti@unina.it
Strazzullo
P
P
Capaldo
B
B
Carretta
R
R
Fabris
F
F
Ferrara
L A
LA
Glorioso
N
N
Semplicini
A
A
Mancini
M
M
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000097:blood; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005542:Forearm / Q000098:blood supply; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D007211:Indoles / Q000627:therapeutic use*; D007333:Insulin Resistance / Q000502:physiology*; D007558:Italy; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism; D009543:Nifedipine / Q000627:therapeutic use; D009765:Obesity / Q000150:complications* / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000097:blood* / Q000187:drug effects; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D007211:Indoles; C052035:trandolapril; D007703:Peptidyl-Dipeptidase A; D009543:Nifedipine; D005947:Glucose; D002118:Calcium