High circulating levels of RBP4 and mRNA levels of aP2, PGC-1alpha and UCP-2 predict improvement in insulin sensitivity following pioglitazone treatment of drug-naïve type 2 diabetic subjects.
BACKGROUND
High levels of circulating retinol-binding protein 4 (RBP4) and baseline expression of adipogenic genes correlate with subsequent improvement in insulin sensitivity following Thiazolidinedione (TZD) treatment.


OBJECTIVE
The aim was to identify baseline characteristics and early changes related to TZD treatment that could predict a good treatment response.


METHODS
Subjects were examined with oral glucose tolerance test, intravenous glucose tolerance test, hyperinsulinaemic euglycaemic clamp, body composition and standard blood sampling at baseline and after 4 and 12 weeks treatment. Subcutaneous adipose tissue biopsies were taken from the abdominal region at baseline, after 3 days and 4 weeks treatment to examine the gene expression profile.


METHODS
Research laboratory in a University hospital.


METHODS
Ten newly diagnosed and previously untreated type 2 diabetic subjects were treated with pioglitazone for 3 months.


METHODS
Baseline characteristics and early changes related to TZD treatment that could predict the response after 3 months.


RESULTS
Pioglitazone improved insulin sensitivity after 4 weeks combined with lower glucose and insulin levels without any change in BMI. It was accompanied by lower circulating resistin and plasminogen activator inhibitor-1 levels rapidly increased levels of circulating total and high molecular weight adiponectin as well as adiponectin and adipocyte fatty acid-binding protein (aP2) mRNA expression in the adipose tissue. High levels of circulating RBP4 at baseline and adipose tissue expression of aP2, proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1alpha) and uncoupling protein 2 (UCP-2) predicted a good treatment response measured as improvement in insulin-stimulated whole-body glucose uptake after 3 months.


CONCLUSIONS
Circulating levels of RBP4 as an index of insulin sensitivity and mRNA levels of adipogenic genes correlate with the subsequent improvement in insulin sensitivity following TZD treatment.
Hammarstedt
A
A
The Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine/Diabetes, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden. ann.hammarstedt@medic.gu.se
Pihlajamäki
J
J
Graham
T E
TE
Kainulainen
S
S
Kahn
B B
BB
Laakso
M
M
Smith
U
U
D000273:Adipose Tissue / Q000378:metabolism; D001823:Body Composition; D002352:Carrier Proteins / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance / Q000502:physiology; D007473:Ion Channels / Q000097:blood*; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000097:blood*; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000097:blood; D016601:RNA-Binding Proteins; D054839:Retinol-Binding Proteins, Plasma / Q000378:metabolism*; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome; D000071246:Uncoupling Protein 2
D002352:Carrier Proteins; D007004:Hypoglycemic Agents; D007473:Ion Channels; D024101:Mitochondrial Proteins; C455622:PPARGC1B protein, human; C101326:RBP4 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D054839:Retinol-Binding Proteins, Plasma; D045162:Thiazolidinediones; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2; D000077205:Pioglitazone