Low-dose rosiglitazone exerts an antiinflammatory effect with an increase in adiponectin independently of free fatty acid fall and insulin sensitization in obese type 2 diabetics.
BACKGROUND
We have previously demonstrated an early and potent antiinflammatory effect of troglitazone and rosiglitazone.


OBJECTIVE
Because inflammatory mediators interfere with insulin signal transduction, we have now hypothesized that rosiglitazone exerts an initial antiinflammatory effect independently of its metabolic actions including the suppression of the plasma concentration of free fatty acids (FFAs), insulin, and glucose after which insulin sensitization occurs.


METHODS
Fourteen patients with type 2 diabetes were included in the study. Eight patients were given 2 mg daily of rosiglitazone for 6 wk, whereas the other six patients were given a placebo for the same period.


RESULTS
After a 2-mg dose of rosiglitazone, plasma FFAs, insulin, and glucose concentrations and homeostasis model assessment of insulin resistance did not change. Plasma C-reactive protein, serum amyloid A, and matrix metalloproteinase concentrations fell significantly at wk 1 and continued to be significantly lower than the baseline levels by 25, 29, and 24%, respectively, at wk 6. Leukocyte count was significantly lower at wk 6 after rosiglitazone, whereas there was no change in the control group. Plasma adiponectin concentrations increased significantly at wk 2 and continued to increase during the treatment period with rosiglitazone. Resistin concentrations fell significantly by 10% at wk 6 only. There were no changes in any of these indices in the placebo group.


CONCLUSIONS
A low dose of rosiglitazone exerts an early and potent antiinflammatory effect with an increase in adiponectin and a fall in resistin concentrations without causing any metabolic changes (fall in plasma glucose, FFAs, and insulin concentrations) over a 6-wk period. The increase in adiponectin and the decrease in resistin after rosiglitazone are thus related primarily to its antiinflammatory effects rather than its metabolic actions. These observations have implications in relation to the mode of action of this drug as an insulin-sensitizing agent and also its use as a potential antiinflammatory and antiatherogenic drug in the future.
Ghanim
Husam
H
Diabetes-Endocrinology Center of Western New York, 3 Gates Circle, Buffalo, New York 14209, USA.
Dhindsa
Sandeep
S
Aljada
Ahmad
A
Chaudhuri
Ajay
A
Viswanathan
Prabhakar
P
Dandona
Paresh
P
D052242:Adiponectin / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D007958:Leukocyte Count; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000188:drug therapy*; D052243:Resistin / Q000097:blood; D000077154:Rosiglitazone; D000685:Serum Amyloid A Protein / Q000378:metabolism; D045162:Thiazolidinediones / Q000008:administration & dosage*
D052242:Adiponectin; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D052243:Resistin; D000685:Serum Amyloid A Protein; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D002097:C-Reactive Protein; D020780:Matrix Metalloproteinase 9