Hydroxy-methylglutaryl-coenzyme A reductase inhibition improves endothelial dysfunction in type-1 diabetes.
OBJECTIVE
We hypothesize that treatment with Pravastatin, a HMG CoA reductase inhibitor would improve flow-mediated dilation (FMD), a nitric oxide dependent phenomenon and the earliest detectable marker of endothelial dysfunction, in asymptomatic patients with type-1 diabetes.


METHODS
FMD of the brachial artery in response to reactive hyperaemia was measured using high-resolution ultrasonography. Young male patients with type-1 diabetes (n=9) were compared with age matched non-diabetic controls (n=8).


RESULTS
The FMD response in the control group was a median increase in diameter of 7.9 (range 3.8-12.6)%. In the diabetic group the FMD response was impaired when compared with controls with a median increase only of 4.4 (range 3.7-5.8)% (p<0.01). Following Pravastatin, 40 mg per day for one month in the diabetic group, there was a significant diameter change in response to reactive hyperaemia with a median of 8.4 (range 6.9-12.6)% (p<0.01).


CONCLUSIONS
These data confirm the presence of endothelial dysfunction in young patients with type-1 diabetes. We have shown that 1-month of Pravastatin treatment normalizes FMD. This suggests that HMG CoA reductase inhibitors may have a role in the management of diabetes mellitus, even in the presence of normal serum cholesterol levels.
Joyce
M
M
Department of Surgery, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.
Moore
K
K
Thompson
C
C
Fitzgerald
P
P
Fennessy
F
F
Kelly
C J
CJ
Bouchier-Hayes
D J
DJ
D000293:Adolescent; D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D019001:Nitric Oxide Synthase / Q000502:physiology; D052250:Nitric Oxide Synthase Type III; D010865:Pilot Projects; D017035:Pravastatin / Q000494:pharmacology* / Q000627:therapeutic use; D015854:Up-Regulation
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D017035:Pravastatin