Rosiglitazone produces a greater reduction in circulating platelet activity compared with gliclazide in patients with type 2 diabetes mellitus--an effect probably mediated by direct platelet PPARgamma activation.

AIMS: Type 2 diabetes mellitus (T2DM) is associated with enhanced platelet activation. We conducted a randomised double-blind study to compare the effects of combination metformin and rosiglitazone or metformin and gliclazide therapy on platelet function in persons with T2DM. METHODS: Fifty subjects on metformin monotherapy received either rosiglitazone 4 mg or gliclazide 80 mg. HbA1c, HOMA-R, markers of platelet activation, inflammation, endothelial activation and oxidative stress were measured at baseline and after 24 weeks of treatment. Separate in vitro platelet function studies were conducted on platelets pre-incubated with rosiglitazone and gliclazide. RESULTS: A significantly greater reduction in platelet aggregation was observed in the rosiglitazone treated group compared to gliclazide. HbA1c and markers of endothelial activation were reduced to a similar extent in both groups. A significant reduction in HOMA-R, markers of inflammation and oxidative stress was only observed with rosiglitazone. Reduction in platelet aggregation with rosiglitazone correlated with reduction in oxidative stress. In the in vitro study, rosiglitazone produced significantly greater reduction in platelet aggregation compared with gliclazide. CONCLUSION: Greater reduction in platelet activity observed with rosiglitazone may be related to reduced oxidative stress and a possible direct PPARgamma mediated effect on platelet function.

Subclinical hypothyroidism: an audit of management.

BACKGROUND: Subclinical hypothyroidism (SH) is a marker for overt hypothyroidism and vascular disease. Treatment guidelines are not universally followed. Thyroxine is recommended if serum thyroid-stimulating hormone (TSH) concentration is 10 mU/L or more, or if serum TSH is 5-9.9 mU/L (mild SH) with other risk factors, such as thyroid peroxidase antibodies (TPOAb). METHODS: We examined the management of mild SH in a retrospective case note audit of 150 consecutive subjects. Twenty-seven subjects with a serum TSH concentration above 10 mU/L were excluded from analysis. Of the group with mild SH, 27 were also excluded because of previous thyroid disease or amiodarone therapy. RESULTS: The prevalence of previous thyroid disease was similar in subjects with TSH 10 mU/L or more, compared to those with mild SH. Overall, both TPOAb and goitre status were determined in only 39% of subjects with mild SH, but in more by endocrinologists compared with general physicians (63% versus 22% for TPOAb; 47% versus 17% for goitre) (P = 0.001). Endocrinologists treated a greater number of subjects with mild SH who were eligible for thyroxine therapy compared to nonendocrine colleagues (96% versus 67%) (P = 0.024). Both groups treated subjects in whom TPOAb status was not determined (endocrinologists 21% versus general physicians 40%) (P = 0.21). CONCLUSION: In subjects with mild SH, evaluation is incomplete, a large percentage who were TPOAb positive were on appropriate therapy, thyroxine was prescribed when TPOAb status was unknown and, on the whole, endocrinologists performed better than general physicians.