Circulating endothelin-1 levels in lean non-insulin-dependent diabetic patients. Influence of ACE inhibition.
To evaluate the effect of captopril on plasma endothelin-1 (ET-1) levels and insulin sensitivity, 15 lean normotensive men (51.6 +/- 3.8 years) affected by non-insulin-dependent diabetes mellitus (NIDDM) underwent 2-h euglycemic hyperinsulinemic clamp. Each patient was then assigned to receive either captopril (25 mg twice daily for 1 week) or placebo, in a double-blind randomized fashion, before repeating clamp. At baseline, plasma ET-1 levels were 0.77 +/- 0.25 pg/mL in captopril (n = 10) and 0.83 +/- 0.3 pg/mL in placebo patients (n = 5). A twofold increase in plasma ET-1 levels occurred during the 2-h insulin infusion in both groups (P < .05 after 60 and 120 min), with a rapid return to baseline after 30 min from insulin withdrawal. After 1 week of therapy, total glucose uptake significantly increased in captopril (from 3.71 +/- 1.70 mg/kg/min to 4.24 +/- 1.72 mg/kg/min, P < .03) but not in placebo patients. Plasma ET-1 levels significantly decreased after captopril therapy (0.48 +/- 0.25 pg/mL at time 0, P < .03 v pretreatment levels), but were unaffected by placebo. Moreover, captopril slightly reduced the magnitude of ET-1 increment during insulin infusion (0.65 +/- 0.28 pg/mL and 0.88 +/- 0.48 pg/mL at 60 and 120 min, respectively, P < .05 v time 0). As a consequence, during the second insulin infusion circulating ET-1 levels were significantly lower in captopril- than in placebo-treated patients at time 0 (P < .02), 60 (P < .002), 120 (P < .004), and 150 min (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)
Ferri
C
C
University La Sapienza, Institute of I Clinica Medica, Andrea Cesalpino Foundation, Rome, Italy.
Laurenti
O
O
Bellini
C
C
Faldetta
M R
MR
Properzi
G
G
Santucci
A
A
De Mattia
G
G
D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D002216:Captopril / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D004311:Double-Blind Method; D016232:Endothelins / Q000097:blood* / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity
D001786:Blood Glucose; D016232:Endothelins; D007328:Insulin; D002216:Captopril