Treatment of obesity with diet/exercise versus pioglitazone has distinct effects on lipoprotein particle size

Objective: We compared the effects of diet/exercise induce weight loss versus pioglitazone on lipoprotein particle characteristics in non-diabetic, insulin resistant adults to determine whether the responses and potential mechanisms for improvement are similar between these two insulin sensitizing regimens. Methods and results: Thirty-seven obese, insulin resistant volunteers were randomized to 19 weeks of either pioglitazone or diet/exercise treatment. Insulin sensitivity (Si) by IVGTT and lipoprotein subclass particle profiles by NMR was measured. Only diet/exercise lowered TG (-40 ± 11 mg/dL), total (-29 ± 4 mg/dL) and LDL cholesterol (-20 ± 4 mg/dL; all p < 0.01). Both diet/exercise and pioglitazone improved Si (p < 0.05), decreased total LDL particles (-227 ± 40 and -149 ± 21 nmol/L, respectively, both p < 0.001) and small LDL particles (-242 ± 58 and -226 ± 36, respectively, both p < 0.001). Large LDL particle concentrations increased with both treatments. LDL particle subclasses changes correlated with changes in Si only in the diet/exercise group. Conclusion: In obese, insulin resistant non-diabetic adults, pioglitazone improved LDL particle characteristics in a manner similar to diet/exercise without changing TG, diabetic control, total or LDL cholesterol. This effect could have implications for atherosclerotic risk.