Honisett S1,2*, Stojanovska L1, Sudhir K2, Kingwell BA2, Komesaroff PA21

Department of Life Sciences and Technology, Victoria University, Melbourne, Victoria2 Baker Medical Research Institute, Melbourne, Victoria

Diabetes and menopause are associated with impaired endothelial function and altered arterial mechanical properties.Rosiglitazone, a thiazolidinedione insulin sensitising agent, improves glycaemic control. However, its effects on vascularfunction, either alone or in combination with postmenopausal hormonal therapy (HT), are unknown. To assess theseeffects we conducted a double-blind placebo-controlled study of the effects of 12 weeks of treatment with rosiglitazone4 mg daily (n=15) or matching placebo (n=8) on glycaemic control, lipids, blood pressure (BP), flow mediated dilation ofthe brachial artery (FMD) and systemic arterial compliance (SAC).

Rosiglitazone reduced glucose (9.15±1.2 (SEM) mM/L to7.5±1.0 mM/L; p=0.013), insulin (11.7±2.0 to 8.8±1.6 mU/L; p=0.026), HbA1c (8.0±0.6 to 6.9±0.4 %; p=0.001), triglycerides(2.3±0.4 to 1.8±0.2 mM/L; p=0.009), systolic BP (130±11 to 117±10 mm Hg; p=0.02), diastolic BP (72±5 to 67±3 mm Hg;p=0.02) and mean arterial pressure (94±7 to 86±4 mm Hg; p=0.001) and increased FMD (7.9±2.3 to 15±4.0 %; p=0.019)and SAC (0.09±0.02 to 0.12±0.03 ACU, p=0.015). Placebo had no effect on any variables measured. To assess whether HT(transdermal oestradiol 50ug and micronised progesterone 100mg/daily) offered further vascular benefits, 12 womenreceiving rosiglitazone were randomly assigned to receive HT or placebo for an additional 12 weeks in a double blindcrossover design. FMD was significantly reduced (15.3 + 3.8 to 6.6 + 1.6 %, p<0.05) after HT, with no changes in lipids,BP or SAC, or in any of the variables following placebo. We conclude that rosiglitazone improves glycaemic control andindependently improves vascular function in postmenopausal women with Type 2 diabetes mellitus but that HT given inaddition to rosiglitazone attenuates these beneficial effects.