Effects of metformin and rosiglitazone monotherapy on insulin-mediated hepatic glucose uptake and their relation to visceral fat in type 2 diabetes.
OBJECTIVE
Impaired insulin-mediated hepatic glucose uptake (HGU) has been implicated in the hyperglycemia of type 2 diabetes. We examined the effects of metformin (2 g/day) and rosiglitazone (8 mg/day) monotherapy on HGU and its relation to subcutaneous fat, visceral fat (VF), and whole-body insulin-mediated glucose metabolism in type 2 diabetic patients.


METHODS
Glucose uptake was measured before and after 26 weeks of treatment using positron emission tomography with [(18)F]2-fluoro-2-deoxyglucose during euglycemic hyperinsulinemia; fat depots were quantified by magnetic resonance imaging.


RESULTS
Fasting plasma glucose levels were significantly decreased after either rosiglitazone (-0.9 +/- 0.5 mmol/l) or metformin treatment (-1.1 +/- 0.5 mmol/l) in comparison with placebo; only metformin was associated with weight loss (P < 0.02 vs. placebo). When controlling for the latter, the placebo-subtracted change in whole-body glucose uptake averaged -1 +/- 4 micromol x min(-1) x kg(-1) in metformin-treated patients (NS) and +9 +/- 3 micromol x min(-1) x kg(-1) in rosiglitazone-treated patients (P = 0.01). Both rosiglitazone and metformin treatment were associated with an increase in HGU; versus placebo, the change reached statistical significance when controlling for sex (placebo-subtracted values = +0.008 +/- 0.004 micromol x min(-1) x kg(-1) x pmol/l(-1), P < 0.03, for metformin; and +0.007 +/- 0.004, P < 0.07, for rosiglitazone). After treatment with either drug, insulin-mediated VF glucose uptake (VFGU) was higher than with placebo. In the whole dataset, changes in HGU were negatively related to changes in HbA(1c) (r = 0.43, P = 0.01) and positively associated with changes in VFGU (r = 0.48, P < 0.01).


CONCLUSIONS
We conclude that both metformin and rosiglitazone monotherapy increase HGU in type 2 diabetes; direct drug actions, better glycemic control, and enhanced VF insulin sensitivity are likely determinants of this phenomenon.
Iozzo
Patricia
P
Turku PET Centre, Department of Nuclear Medicine, University of Turku, Turku, Finland. patricia.iozzo@ifc.cnr
Hallsten
Kirsti
K
Oikonen
Vesa
V
Virtanen
Kirsi A
KA
Parkkola
Riitta
R
Kemppainen
Jukka
J
Solin
Olof
O
Lonnqvist
Fredrik
F
Ferrannini
Ele
E
Knuuti
Juhani
J
Nuutila
Pirjo
P
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010919:Placebos; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012044:Regression Analysis; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014055:Tomography, Emission-Computed
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D008055:Lipids; D010919:Placebos; D019275:Radiopharmaceuticals; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D019788:Fluorodeoxyglucose F18; D008687:Metformin; D005947:Glucose