Thursday, December 18, 2008

Pioglitazone and changes in body fat distribution.

This topic just came up in one a paper and I thought I might dig up some details about it. We all know that the TZDs tend to change fat distribution but may not have looked into the details of it. Dr. Jensen (my mentor) in 2003 published a paper on this topic in Diabetes Care. Here are the details: (its freely available from Diabetes Care) I've added in details that I thought were interesting and put them in italics.

Shadid S, Jensen MD. Effects of Pioglitazone Versus Diet and Exercise on Metabolic Health and Fat Distribution in Upper Body Obesity. Diabetes Care. 2003;26(11):3148-3152.

Thirty-nine upper body obese (BMI of 28-36 and waist to hip ratio >0.85 for women and >0.95 for men), insulin-resistant, nondiabetic men and premenopausal women were randomly assigned to receive either 30 mg/day pioglitazone or a diet (500kcal/day deficit) and exercise program for 20 weeks. The exercise regimen consisted of 15 mins of aerobic exercise 3x/week and increased gradually to 45 minutes of aerobic exercise 4 times a week. Before and after the intervention, insulin sensitivity, body composition, body fat distribution (waist-to-hip ratio [WHR], computed tomography abdomen, and dual-energy X-ray absorptiometry), and abdominal and femoral fat cell size were assessed.

Diet and exercise resulted in an 11.8 ± 1.1 kg weight loss. Both diet and exercise and pioglitazone improved insulin sensitivity, but only diet and exercise were associated with loss of intra-abdominal fat. Pioglitazone increased total body fat, which preferentially accumulated in the lower body depot in both men and women. WHRs decreased in both groups although in the pioglitazone group, the waist circumference did not decrease. Abdominal fat cell size decreased (P = 0.06) after diet and exercise. No statistically significant changes in fat cell size were observed in pioglitazone-treated volunteers.
Another interesting change was in terms of the cholesterol. Only the diet/exercise group had a reduction in the total cholesterol while pio group did not.
BP reductions were also more significant for the diet/exercise group than pioglitazone group.

Dr. Jensen did not find a decrease in visceral fat area. In comparison to other publications, no change has been reported in the intra-abdominal adipose tissue area by 4 reports with pio. Three have reported a decrease and most have reported a decrease in the visceral to subcutaneous fat area ratio. Just note that some of the investigators reporting decreases in visceral fat area did combine TZD with diet.
The gain in insulin sensitivity may be due to the decrease in fat cell size and an increase in their numbers instead.


  1. That's very interesting. Did they really lose 11.8 +/- 1.1 kg? Seems like a lot. To me this is another vote against TZDs - which I tend not to use - and for caloric restriction and exercise for DM2 patients.

  2. They did lose that much weight. It's a unique environment here because so many people work for the Mayo and volunteer for these studies. The follow-up and compliance can be great. We'll have to talk more about it some time if you guys ever come to Rochester. The change in fat distribution or fat cell size is very interesting and would love to get others to see if they find any other articles on the subject.


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