Pharmacodynamic effects of rosiglitazone in nondiabetic patients with metabolic syndrome.
OBJECTIVE
To determine the effects of the thiazolidinedione rosiglitazone on the adipocyte-derived cytokines adiponectin (an antiinflammatory and insulin-sensitizing cytokine; low levels have been associated with metabolic syndrome) and resistin (an inflammation mediator; high levels have been associated with metabolic syndrome) in nondiabetic patients with metabolic syndrome, and to characterize the effects of rosiglitazone on other components of the metabolic syndrome phenotype in this population.


METHODS
Prospective, randomized, double-blind, placebo-controlled study.


METHODS
Outpatient general clinical research center.


METHODS
Thirty-two nondiabetic men and women with a clinical diagnosis of metabolic syndrome (as defined in the American Heart Association-National Heart, Lung, and Blood Institute scientific statement).


METHODS
Patients were randomly assigned to receive either oral rosiglitazone 4 mg/day or matching placebo for 12 weeks.


RESULTS
The primary end point was change in serum adiponectin concentrations from baseline to week 12. Secondary end points were changes in serum resistin concentrations, insulin resistance, fasting glucose level, fasting insulin level, body weight, lipid levels, systolic and diastolic blood pressure, and waist circumference from baseline to week 12. Also, changes from baseline in adiponectin and resistin concentrations and insulin resistance were assessed over time at weeks 2, 4, 8, and 12. Rosiglitazone was associated with a significant increase in serum adiponectin concentration after 12 weeks compared with placebo (45.8% vs 2.6%, p=0.002). The increase in adiponectin concentration occurred quickly, with a significant difference observed after 2 weeks of therapy. Compared with placebo, rosiglitazone was not associated with significant 12-week changes in serum resistin concentrations, insulin resistance, fasting glucose level, fasting insulin level, body weight, lipid levels, systolic or diastolic blood pressure, or waist circumference.


CONCLUSIONS
Rosiglitazone had beneficial effects on adiponectin concentrations without significantly affecting other components of the metabolic syndrome phenotype. Additional studies that further elucidate the time course of thiazolidinedione pharmacodynamic effects, along with their effects on cardiovascular end points, are warranted in nondiabetic patients with metabolic syndrome.
Aquilante
Christina L
CL
Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado, Aurora, Colorado 80045, USA. Christina.aquilante@ucdenver.edu
Kosmiski
Lisa A
LA
Zineh
Issam
I
Rome
Lucille Capo
LC
Knutsen
Shannon D
SD
D052242:Adiponectin / Q000097:blood*; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy*; D008875:Middle Aged; D052243:Resistin / Q000097:blood; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D013997:Time Factors; D055105:Waist Circumference / Q000187:drug effects
D052242:Adiponectin; D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D008055:Lipids; D008074:Lipoproteins; D052243:Resistin; D045162:Thiazolidinediones; D000077154:Rosiglitazone