TZD's do not decrease visceral or abdominal fat stores - Diabetes - thiazolidinediones

Nutrition Research Newsletter, Nov, 2003 by S. Shadid, M. Jensen

In recent years it has been well established that body fat distribution is an important aspect in the relationship between overweight and insulin resistance. Intra-abdominal or visceral fat accumulation is more highly associated with insulin resistance. This insulin resistance can be greatly improved by decreasing fat depot via diet, exercise, or surgery. Thiazolidinediones (TZDs) have also been shown to improve insulin sensitivity despite increasing total fat mass with usage. R is thought that redistribution of body fat may contribute to their insulin-sensitizing qualities.

In order to assess the effects of pioglitazone on fat distribution, fat cell size, and the relationship between fat distribution and insulin sensitivity in upper body obesity, researchers compared the effects of pioglitazone with diet and exercise, a standard intervention to improve insulin sensitivity. Thirty-nine subjects completed the study. Eligibility included being free of diabetes and other major health problems, weight stability, and being overweight with a BMI of 28 to 36, and having one of the following three items: 1) waist-to-hip ratio (WHR) greater than 0.85 (women) or greater than 0.95 (men); 2) computed tomography (CT)-measured visceral fat area greater than 120 [cm.sup.2] (women) or > 180 [cm.sup.2] (men); or 3) a ratio of visceral to total fat greater than 0.30 (women) or greater than 0.40 (men).

Subjects underwent blood testing (complete blood count, chemistry panel, and lipid profile), an insulin-modified intravenous glucose tolerance test, CT measures of visceral fat area, and dual-energy X-ray absorptiometry (DEXA) for body composition assessment before and after the intervention. Adipose tissue biopsies were taken from femoral and abdominal subcutaneous areas. Oxygen consumption ([Vo.sup.2peak]) and maximum heart rate were determined by a graded exercise tolerance test.

After baseline measurements, the subjects were randomized to receive 30 mg pioglitazone daily or a diet and exercise program for 18 to 20 weeks. The diet and exercise subjects were instructed in a 500-kcal per day deficit diet and in an exercise program.

Subjects in the diet and exercise group achieved an 11.8 1.1 kg weight Joss. Both diet and exercise, and pioglitazone improved insulin sensitivity, but only the former was associated with loss of intra-abdominal fat. Pioglitazone increased total body fat, which seemed to accumulate in the lower body depot in both the men and women. WHRs decreased in both groups. Abdominal fat cell size decreased (P = 0.06) following diet and exercise. No statistically significant changes in fat cell size were observed in pioglitazone-treated volunteers.

It appears that pioglitazone treatment improves insulin sensitivity and lowers WHR, similar to diet and exercise, but that this effect is due to selective increase in lower body fat and not a decrease in visceral or abdominal fat.

S. Shadid M. Jensen. Effects of pioglitazone versus diet and exercise on metabolic health and fat distribution in upper body obesity. Diabetes Care; 26:3148-5152 (November, 2003). [Correspondence: Michael D. Jensen, MD, Endocrine Research Unit, 5-194 Joseph, Mayo Clinic, Rochester, MN 55905. E-mail: Jensen.meichael@/mayo.edu].