Vascular effects of improving metabolic control with metformin or rosiglitazone in type 2 diabetes.
OBJECTIVE
The aim of this study was to test whether vascular reactivity is modified by improving metabolic control and peripheral insulin resistance in type 2 diabetes.


METHODS
In a randomized, double-blind design, we assigned 74 type 2 diabetic patients to rosiglitazone (8 mg/day), metformin (1,500 mg/day), or placebo treatment for 16 weeks and measured insulin sensitivity (euglycemic insulin clamp), ambulatory blood pressure, and forearm blood flow response to 1) intra-arterial acetylcholine (ACh), 2) intra-arterial nitroprusside, 3) the clamp, and 4) blockade of nitric oxide (NO) synthase.


RESULTS
Compared with 25 nondiabetic subjects, patients had reduced insulin sensitivity (30 +/- 1 vs. 41 +/- 3 micromol. min(-1). kg fat-free mass(-1); P < 0.001) and reduced maximal response to ACh (586 +/- 42 vs. 883 +/- 81%; P < 0.001). Relative to placebo, 16 weeks of rosiglitazone and metformin similarly reduced fasting glucose (-2.3 +/- 0.5 and -2.3 +/- 0.5 mmol/l) and HbA(1c) (-1.2 +/- 0.3 and -1.6 +/- 0.3%). Insulin sensitivity increased with rosiglitazone (+6 +/- 3 micromol. min(-1). kg fat-free mass(-1); P < 0.01) but not with metformin or placebo. Ambulatory diastolic blood pressure fell consistently (-2 +/- 1 mmHg; P < 0.05) only in the rosiglitazone group. Nitroprusside dose response, clamp-induced vasodilatation, and NO blockade were not affected by either treatment. In contrast, the slope of the ACh dose response improved with rosiglitazone (+40% versus baseline, P < 0.05, +70% versus placebo, P < 0.005) but did not change with either metformin or placebo. This improvement in endothelium-dependent vasodilatation was accompanied by decrements in circulating levels of free fatty acids and tumor necrosis factor-alpha.


CONCLUSIONS
At equivalent glycemic control, rosiglitazone, but not metformin, improves endothelium dependent vasodilatation and insulin sensitivity in type 2 diabetes.
Natali
Andrea
A
Department of Internal Medicine, CNR Institute of Clinical Physiology, University of Pisa, Via Roma 67, 56100 Pisa, Italy. anatali@ifc.cnr.it
Baldeweg
Stephanie
S
Toschi
Elena
E
Capaldo
Brunella
B
Barbaro
Daniele
D
Gastaldelli
Amalia
A
Yudkin
John S
JS
Ferrannini
Ele
E
D000109:Acetylcholine / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005542:Forearm / Q000098:blood supply; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*
D000109:Acetylcholine; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D009599:Nitroprusside; D000077154:Rosiglitazone; D045162:Thiazolidinediones