Prospective study (Manda study 1) on the clinical effects of pioglitazone in relation to gender differences in Japanese patients with type 2 diabetes

Aims We investigated the mechanism underlying body weight (BW) gain after pioglitazone administration in type 2 diabetes in relation to gender differences in abdominal fat distribution and congestive factors. Materials and methods Seventy-five patients without insulin treatment took 15 or 30 mg pioglitazone plus their current medication; abdominal visceral (V) and subcutaneous (S) fat tissues and clinical parameters were compared before and after the 24-week intervention. Results Eleven patients withdrew. Of the remaining 64 patients, hemoglobin A1c improved in 52, indicating that most were pioglitazone responders for glycemic control. Mean BW increased from 64.0 to 66.0 kg. There were gender differences in BW gain. In women, V decreased and S increased; in men, V did not decrease and S markedly increased. Atrial natriuretic peptide increased more significantly than brain natriuretic peptide in women. This suggested that pioglitazone induced a V-to-S abdominal fat distribution shift only in women. In men, the main weight gain mechanism was believed to be an S increase. Adiponectin increase was observed in both groups; however, high-sensitive C-reactive protein decreased only in women. Triglyceride and free fatty acid decreased significantly only in women. Conclusion A pioglitazone-induced V-to-S distribution shift of tissue adipocytes occurred only in women. Pioglitazone may be more beneficial for atherosclerotic and metabolic factors in women despite the smaller dose administered. The pioglitazone dose should be carefully considered in women, whereas the beneficial effects of pioglitazone may be limited in men.