Pioglitazone increases non-esterified fatty acid clearance in upper body obesity

Diabetologia. 2006 Jan;49(1):149-57. doi: 10.1007/s00125-005-0051-0. Epub 2005 Dec 2.


Aims/hypothesis: Plasma NEFA concentrations are largely determined by adipose tissue lipolysis. Insulin suppression of lipolysis is commonly impaired with insulin resistance and improves with thiazolidinedione treatment of type 2 diabetes. The present studies were designed to assess the effects of thiazolidinedione on NEFA (oleate) metabolism that are independent of improved glycaemic control.

Materials and methods: We measured plasma oleate concentration and flux ([(3)H]oleate), glucose kinetics ([6-(2)H(2)]glucose) and substrate oxidation (indirect calorimetry) before and after pioglitazone (30 mg/day for approximately 20 weeks) in 20 non-diabetic adults with upper body obesity. To assess the effects of improved insulin sensitivity per se we performed the same measurements in a matched group of volunteers treated with diet/exercise. Half of the two groups underwent these measurements during a hyperinsulinaemic-euglycaemic clamp, and the other half had their measurements taken during a (control) saline infusion before and after the intervention.

Results: Both interventions increased insulin-stimulated glucose disposal and reduced plasma oleate concentrations during the insulin clamp. After diet/exercise, oleate flux decreased (p=0.03) during the insulin clamp and oleate clearance remained unchanged (p=0.55), whereas in the pioglitazone group, oleate flux during the clamp was unchanged (p=0.97) and oleate clearance increased (p=0.003). Oleate clearance in the saline control condition was increased in the pioglitazone group compared with the diet/exercise group (p=0.02).

Conclusions/interpretation: In insulin-resistant, non-diabetic adults, pioglitazone increases NEFA clearance during physiological hyperinsulinaemia, whereas improved insulin sensitivity achieved by diet/exercise does not alter NEFA clearance but enhances insulin suppression of NEFA release. This action of pioglitazone may contribute to improved glucose metabolism in type 2 diabetes.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Body Mass Index
  • Body Weight
  • Diet, Reducing
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin / pharmacology
  • Male
  • Obesity / blood
  • Obesity / diet therapy
  • Obesity / drug therapy
  • Pioglitazone
  • Sex Characteristics
  • Thiazolidinediones / therapeutic use*


  • Hypoglycemic Agents
  • Insulin
  • Thiazolidinediones
  • Pioglitazone