Effect of insulin sensitizer therapy on atherothrombotic and inflammatory profiles associated with insulin resistance.
OBJECTIVE
To determine whether targeted pharmacological improvement of insulin sensitivity will normalize the associated elevations of thrombotic and inflammatory cardiovascular disease (CVD) biomarkers in individuals with insulin resistance.


METHODS
Study 1 was a cross-sectional study of Asian Indians with and without diabetes mellitus and Northern European Americans without diabetes (n=14 each) conducted between December 11, 2003, and July 14, 2006. Study 2 was a secondary analysis of a double-blind randomized controlled study conducted between August 19, 2005, and August 24, 2010, that included 25 individuals with untreated diabetes or impaired fasting glucose who were randomized to receive placebo (n=13) or a combination of metformin, 1000 mg twice daily, and pioglitazone, 45 mg daily (n=12), for 3 months. In both studies, measurements of insulin sensitivity (euglycemic-hyperinsulinemic clamp) and plasma inflammatory and thrombotic factor concentrations were obtained on enrollment (studies 1 and 2) and after intervention (study 2).


RESULTS
Study 1 demonstrated significant correlations between insulin sensitivity and plasma adiponectin, high-density lipoprotein cholesterol, plasminogen activator inhibitor 1, interleukin 6, tumor necrosis factor α, and triglycerides. Insulin sensitizer therapy significantly improved insulin sensitivity, inflammatory cytokines except interleukin 6, and thrombotic factors except fibrinogen, without concomitant changes in weight, blood pressure, or body composition.


CONCLUSIONS
Insulin sensitizer therapy ameliorates inflammatory and thrombotic factors implicated in developing CVD. Interventions to improve insulin sensitivity may thus be considered as therapeutic options to reduce CVD burden in insulin-resistant states, although further research is needed to determine long-term effects on morbidity and mortality.
Department of Internal Medicine, Mayo School of Graduate Medical Education, Mayo Clinic, Rochester, MN 55905, USA.
Rozalina G
RG
McCoy
Brian A
BA
Irving
Mattias
M
Soop
Manivanan
M
Srinivasan
Laura
L
Tatpati
Lisa
L
Chow
Audrey J
AJ
Weymiller
Rickey E
RE
Carter
K Sreekumaran
KS
Nair
D002318:Cardiovascular Diseases / Q000097:blood / Q000517:prevention & control; D003430:Cross-Sectional Studies; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000503:physiopathology*; D004359:Drug Therapy, Combination; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D018836:Inflammation Mediators / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D008687:Metformin / Q000008:administration & dosage; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage
D007004:Hypoglycemic Agents; D018836:Inflammation Mediators; D045162:Thiazolidinediones; D008687:Metformin; D000077205:Pioglitazone