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Rosiglitazone Treatment Increases Subcutaneous Adipose Tissue Glucose Uptake in Parallel with Perfusion in Patients with Type 2 Diabetes: A Double-Blind, Randomized Study with Metformin

Positron Emission Tomography Centre (A.P.M.V., K.A.V., M.J.J., K.H., P.N.), Departments of Radiology (R.P.) and Medicine (T.R.), Turku University Central Hospital, FIN-20520 Turku, Finland; Karolinska Institutet (F.L.), Stockholm, SE-17177 Sweden; and Department of Internal Medicine and Consiglio Nazionale delle Ricerche Institute of Clinical Physiology (P.I., E.F.), 56126 Pisa, Italy

Address all correspondence and requests for reprints to: Pirjo Nuutila, M.D., Ph.D., Turku PET Centre, Kiinamyllynkatu 4-8, FIN-20520, Turku, Finland. E-mail: pirjo.nuutila{at}utu.fi.

Context: We have shown that rosiglitazone increases whole-body and adipose tissue insulin sensitivity in humans.

Objective: The aim of this study was to further examine whether possible changes in adipose perfusion could explain increased adipose tissue glucose uptake (GU).

Patients: Thirty-seven patients with newly diagnosed type 2 diabetes were included.

Intervention: Patients were randomized into treatment with rosiglitazone, metformin, or placebo for 26 wk in a double-blinded trial.

Design: Femoral adipose flow and GU were measured with [¹⁵O]H₂O, [¹⁸F]fluorodeoxyglucose and positron emission tomography during euglycemic hyperinsulinemia. Adipose masses were measured using magnetic resonance imaging.

Results: Metformin and rosiglitazone treatment improved glycemic control, but only rosiglitazone increased whole-body insulin sensitivity. Rosiglitazone treatment increased flow by 72% (P < 0.01) and GU by 23% (P < 0.05) and thereby decreased adipose tissue glucose extraction by 18% (P < 0.05); no changes were observed in the metformin or placebo-treated groups. When the adipose masses were taken into account, rosiglitazone treatment increased flow by 73% (P < 0.01) and GU by 24% (P < 0.05). During hyperinsulinemia, flow correlated with GU (r = 0.63; P < 0.01).

Conclusions: In conclusion, sc GU is associated with flow in patients with type 2 diabetes. Rosiglitazone treatment enhances GU and flow but decreases glucose extraction, suggesting that perfusion may contribute to adipose tissue insulin sensitization by rosiglitazone.

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