Effects of rosiglitazone on lipids, adipokines, and inflammatory markers in nondiabetic patients with low high-density lipoprotein cholesterol and metabolic syndrome.
BACKGROUND
PPAR-gamma agonists improve insulin sensitivity and glycemic control in type 2 diabetes and may reduce atherosclerosis progression. Thus, PPAR-gamma agonists may be an effective therapy for metabolic syndrome. However, the full spectrum of potentially antiatherogenic mechanisms of PPAR-gamma agonists have not been fully tested in nondiabetic patients with metabolic syndrome.


RESULTS
We performed a prospective, double-blinded, placebo-controlled study of 60 nondiabetic subjects with low high-density lipoprotein cholesterol (HDL-C) level and metabolic syndrome to rosiglitazone 8 mg daily or placebo for 12 weeks. We found no significant effect of rosiglitazone on HDL-C (+5.5% versus +5.8%, P=0.89), and an increase in total cholesterol (+8% versus -1%; P=0.03). Nevertheless, rosiglitazone significantly increased adiponectin (+168% versus +25%; P<0.001), and lowered resistin (-6% versus +4%; P=0.009), C-reactive protein (-32% versus +36%, P=0.002), interleukin (IL)-6 (-22% versus +4%, P<0.001), and soluble tumor-necrosis factor-alpha receptor-2 (-5% versus +7%, P<0.001).


CONCLUSIONS
These findings suggest that rosiglitazone, presumably through its PPAR-gamma agonist properties, has direct effects on inflammatory markers and adipokines in the absence of favorable lipid effects. These findings may help explain the mechanism underlying the possible antiatherosclerotic effects of rosiglitazone.
Samaha
Frederick F
FF
Cardiovascular Division, Department of Medicine, Cardiovascular Institute, University of Pennsylvania Medical Center, Philadelphia, PA, USA. rick.samaha@med.va.gov
Szapary
Philippe O
PO
Iqbal
Nayyar
N
Williams
Monica M
MM
Bloedon
LeAnne T
LT
Kochar
Arshneel
A
Wolfe
Megan L
ML
Rader
Daniel J
DJ
D052242:Adiponectin / Q000097:blood; D000293:Adolescent; D000328:Adult; D000368:Aged; D001055:Apolipoproteins B / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D008875:Middle Aged; D047495:PPAR gamma / Q000819:agonists; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D052243:Resistin / Q000097:blood; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000009:adverse effects
D052242:Adiponectin; D001055:Apolipoproteins B; D015415:Biomarkers; D008076:Cholesterol, HDL; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D015850:Interleukin-6; D047495:PPAR gamma; C499624:RETN protein, human; D047889:Receptors, Tumor Necrosis Factor, Type II; D052243:Resistin; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D002097:C-Reactive Protein