Microvascular endothelial function in subjects with Type 2 diabetes and the effect of lipid-lowering therapy.
OBJECTIVE
Abnormalities of microvascular and endothelial function are present in subjects with Type 2 diabetes. Although statin therapy improves cardiovascular risk in diabetes, dyslipidaemia in diabetes may be more responsive to combined statin and fibrate therapy. We examined the effect of cerivastatin and fenofibrate on microvascular function in subjects with Type 2 diabetes with no clinical evidence of cardiovascular disease and near normal lipid levels.


METHODS
Age-, sex-, lipid- and blood pressure-matched subjects with Type 2 diabetes were randomized in double-blind fashion to one of four treatment groups: group 1 placebo/placebo (n=12), group 2 fenofibrate/placebo (n=10), group 3 cerivastatin/placebo (n=20) and group 4 cerivastatin/fenofibrate (n=11). The subjects were recruited from the Lipid in Diabetes Study. Microvascular function was assessed by skin blood flow response to iontophoresis of acetylcholine and sodium nitroprusside and by skin maximum hyperaemia to local heating. Measurements were carried out at baseline and 3 months later.


RESULTS
Although all lipid parameters improved in groups 2-4 after 3 months' therapy, no difference was detected in skin blood flow to iontophoresis or maximum hyperaemia in any of the groups. Highly sensitive c-reactive protein (Hs-CRP) did not change with therapy.


CONCLUSIONS
In conclusion, we were unable to demonstrate any improvement in microvascular endothelial function in non-hyperlipidaemic Type 2 diabetic subjects treated with single or combination lipid-lowering therapy.
Fegan
P G
PG
Clinical Microvascular Research, Peninsula Medical School, Exeter, UK. gerryfegan@hotmail.com
Shore
A C
AC
Mawson
D
D
Tooke
J E
JE
MacLeod
K M
KM
D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D011345:Fenofibrate / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D008875:Middle Aged; D011725:Pyridines / Q000008:administration & dosage*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D011725:Pyridines; D002097:C-Reactive Protein; C086276:cerivastatin; D011345:Fenofibrate