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.
BACKGROUND
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).


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


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


METHODS
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, s.c. 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.
Viljanen
Antti P M
AP
PET Centre, Turku University Central Hospital, Turku, Finland.
Virtanen
Kirsi A
KA
Järvisalo
Mikko J
MJ
Hällsten
Kirsti
K
Parkkola
Riitta
R
Rönnemaa
Tapani
T
Lönnqvist
Fredrik
F
Iozzo
Patricia
P
Ferrannini
Ele
E
Nuutila
Pirjo
P
D000273:Adipose Tissue / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism*; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010477:Perfusion; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D012039:Regional Blood Flow / Q000187:drug effects; D000077154:Rosiglitazone; D040521:Subcutaneous Tissue / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism*; D045162:Thiazolidinediones / Q000627:therapeutic use*
D007004:Hypoglycemic Agents; D019275:Radiopharmaceuticals; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D019788:Fluorodeoxyglucose F18; D008687:Metformin; D005947:Glucose