Skip to main content
SpringerLink
Log in

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

  • Original Article
  • Published:
Diabetology International Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Mazzone T, Meyer PM, Feinstein SB, Davidson MH, Kondos GT, D’Agostino RB Sr, Perez A, Provost JC, Haffner SM. Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial. JAMA. 2006;296:2572–81.

    Article  CAS  PubMed  Google Scholar 

  2. Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, Skene AM, Tan MH, Lefèbvre PJ, Murray GD, Standl E, Wilcox RG, Wilhelmsen L, Betteridge J, Birkeland K, Golay A, Heine RJ, Korányi L, Laakso M, Mokán M, Norkus A, Pirags V, Podar T, Scheen A, Scherbaum W, Schernthaner G, Schmitz O, Skrha J, Smith U, Taton J. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study: a randomized controlled trial. Lancet. 2008;366:1279–89.

    Article  Google Scholar 

  3. Wilcox R, Bousser MG, Betteridge DJ, Schernthaner G, Pirags V, Kupfer S, Dormandy J. Effects of pioglitazone in patients with type 2 diabetes with or without previous stroke. Stroke. 2007;38:865–73.

    Article  CAS  PubMed  Google Scholar 

  4. Erdmann E, Dormandy JA, Charbonnel B, Massi-Benedetti M, Moules IK, Skene AM. The effect of pioglitazone on recurrent myocardial infarction in 2,445 patients with type 2 diabetes and previous myocardial infarction. J Am Col Cardiol. 2007;49:1772–80.

    Article  CAS  Google Scholar 

  5. Kawamori R, Kadowaki T, Onji M, Seino Y, Akanuma Y. Hepatic safety profile and glycemic control of pioglitazone in more than 20,000 patients with type 2 diabetes mellitus: postmarketing surveillance study in Japan. Diab Res Clin Pract. 2007;76:229–35.

    Article  CAS  Google Scholar 

  6. Nissen SE, Nicholls SJ, Wolski K, Nesto R, Kupfer S, Perez A, Jure H, De Larochellière R, Staniloae CS, Mavromatis K, Saw J, Hu B, Lincoff AM, Tuzcu EM, PERISCOPE intervention. Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis on patients with type 2 diabetes: the PERISCOPE randomized controlled trial. JAMA. 2008;299:1561–73.

    Article  CAS  PubMed  Google Scholar 

  7. Miyazaki Y, Mahankali A, Matsuda M, Mahankali S, Hardies J, Cusi K, Mandarino LJ, DeFronzo RA. Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab. 2002;87:2784–91.

    Article  CAS  PubMed  Google Scholar 

  8. Kadowaki K, Fukino K, Negishi E, Ueno K. Sex differences in PPAR gamma expressions in rat adipose tissues. Biol Pharm Bull. 2007;30:818–20.

    Article  CAS  PubMed  Google Scholar 

  9. Ueno K, Sugai H, Sato H. Mechanism of sex differences and the clinical significance of PPARγ targeted drugs. Jap J Clin Med. 2010;68:224–8.

    Google Scholar 

  10. Igarashi M, Jimbu Y, Hirata A, Tominaga M. Characterization of plasma brain natriuretic peptide level in patients with type 2 diabetes. Endocr J. 2005;52:353–62.

    Article  CAS  PubMed  Google Scholar 

  11. Makino N, Sugano M, Satoh S, Oyama J, Maeda T. Peroxisome proliferator-activated receptor-gamma ligands attenuate brain natriuretic peptide production and affect remodeling in cardiac fibroblasts in reoxygenation after hypoxia. Cell Biochem Biophys. 2006;44:65–71.

    Article  CAS  PubMed  Google Scholar 

  12. Tokunaga K, Matsuzawa Y, Ishikawa K, Tarui S. Novel technique for determination of body fat by computed tomography. Int J Obes. 1983;7:437–45.

    CAS  PubMed  Google Scholar 

  13. Tsuchiya K, Akaza I, Yoshimoto T, Hirata Y. Pioglitazone improves endothelial function with increased adiponectin and high-density lipoprotein cholesterol levels in type 2 diabetes. Endocr J. 2009;56:691–8.

    Article  CAS  PubMed  Google Scholar 

  14. Aso Y, Hara K, Ozeki N, Yatsuka C, Nakano T, Matsumoto S, Suetsugu M, Nakamachi T, Takebayashi K, Haruki K, Inukai T. Low-dose pioglitazone increases serum high molecular weight adiponectin and improves glycemic control in Japanese patients with poorly controlled type 2 diabetes. Diabetes Res Clin Pract. 2009;85:147–52.

    Article  CAS  PubMed  Google Scholar 

  15. Lefebvre AM, Laville M, Vega N, Riou JP, Gaal L, Auwerx J, Vidal H. Depot-specific differences in adipose tissue gene expression in lean and obese subjects. Diabetes. 1998;47:98–103.

    Article  CAS  PubMed  Google Scholar 

  16. Yasue H, Obata K, Okumura K, Kurose M, Ogawa H, Matsuyama K, Jougasaki M, Saito Y, Nakao K, Imura H. Increased secretion of atrial natriuretic polypeptide from the left ventricle in patients with dilated cardiomyopathy. J Clin Invest. 1989;83:46–51.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Arnetz L, Dorkhan M, Alvarsson M, Brismar K, Ekberg NR: Gender differences in non-glycemic responses to improved insulin sensitivity by pioglitazone treatment in patients with type 2 diabetes. Acta Dibetol. 2013. doi:10.1007/s00592-013-0457-y

Download references

Author information

Authors and Affiliations

  1. Diabetes Center, Manda Memorial Hospital, Sapporo, Hokkaido, Japan

    Shinji Taneda, Hidenori Bando, Kazushi Misawa, Kennichi Tuchida, Yuko Akimoto, Tomoyasu Nawa, Seiya Hagiwara, Minoru Kikuchi, Toshiaki Sasaki, Toshi Niizuma, Hidetaka Nakayama & Naoki Manda

Authors
  1. Shinji Taneda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hidenori Bando
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kazushi Misawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kennichi Tuchida
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuko Akimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tomoyasu Nawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Seiya Hagiwara
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Minoru Kikuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Toshiaki Sasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Toshi Niizuma
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hidetaka Nakayama
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Naoki Manda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shinji Taneda.

About this article

Cite this article

Taneda, S., Bando, H., Misawa, K. et al. Prospective study (Manda study 1) on the clinical effects of pioglitazone in relation to gender differences in Japanese patients with type 2 diabetes. Diabetol Int 5, 92–97 (2014). https://doi.org/10.1007/s13340-013-0136-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13340-013-0136-9

Keywords

Search

Navigation