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Pathophysiology/Complications
Hepatic insulin clearance is increased in patients with high HbA1c type 2 diabetes: a preliminary report
  1. Tsuyoshi Okura1,
  2. Yohei Fujioka1,
  3. Risa Nakamura1,
  4. Mari Anno1,
  5. Yuichi Ito1,
  6. Sonoko Kitao1,
  7. Kazuhisa Matsumoto1,
  8. Kyoko Shoji1,
  9. Keisuke Sumi1,
  10. Kazuhiko Matsuzawa1,
  11. Shoichiro Izawa1,
  12. Hiroko Okura1,
  13. Etsuko Ueta2,
  14. Hisashi Noma3,
  15. Masahiko Kato4,
  16. Takeshi Imamura5,
  17. Shin-Ichi Taniguchi6,
  18. Kazuhiro Yamamoto1
  1. 1Division of Endocrinology and Metabolism, Tottori University, Tottori, Japan
  2. 2School of Health Science, Tottori University, Tottori, Japan
  3. 3Institute of Statistical Mathematics, Minato-ku, Tokyo, Japan
  4. 4School of Health Science Major in Clinical Laboratory Science, Tottori University, Tottori, Japan
  5. 5Division of Molecular Pharmacology, Tottori University, Tottori, Japan
  6. 6Department of Regional Medicine, Tottori University, Tottori, Japan
  1. Correspondence to Dr Tsuyoshi Okura; ohkura{at}med.tottori-u.ac.jp

Abstract

Introduction Hepatic insulin clearance (HIC) is an important pathophysiology of type 2 diabetes. HIC was reported to decrease in patients with type 2 diabetes and metabolic syndrome. However, hyperglycemia was suggested to enhance HIC, and it is not known whether poorly controlled diabetes increases HIC in patients with type 2 diabetes. We investigated whether HIC was increased in patients with poorly controlled diabetes, and whether HIC was associated with insulin resistance and incretins.

Research design and methods We performed a meal tolerance test and the hyperinsulinemic–euglycemic clamp in 21 patients with type 2 diabetes. We calculated the postprandial C-peptide area under the curve (AUC)-to-insulin AUC ratio as the HIC; measured fasting and postprandial glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon levels and analyzed serum adiponectin and zinc transporter-8 (ZnT8) gene polymorphism.

Results The HIC significantly correlated with glycated hemoglobin (HbA1c) (r_S=0.58, p<0.01). In patients with high HIC above the median of 6.5, the mean HbA1c was significantly higher compared with low HIC below the median. Homeostatic model assessment (HOMA)-beta (r_S=−0.77, p<0.01) and HOMA-IR (r_S=−0.66, p<0.005) were correlated with HIC. The M/I value in the clamp study was correlated with HIC. GLP-1-AUC and GIP-AUC were not correlated with HIC. Glucagon-AUC was negatively correlated with HIC, but there were no significant differences between the high and low HIC groups. Adiponectin was positively correlated with HIC. The ZnT8 gene polymorphism did not affect HIC.

Conclusions These results suggest that HIC was increased in patients with high HbA1c type 2 diabetes, low insulin secretion, low insulin resistance and high adiponectin conditions.

  • insulin
  • clearance and action
  • type 2 diabetes
  • insulin clamp
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjdrc-2019-001149

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    Footnotes

    • Contributors TO participated in the design of the study and performed the statistical analysis. YF, RN, MA, YI, SK, KMatsumoto, KyS, KeS, KMatsuzawa, SI, HO and EU collected the data. HN helped with the statistical analysis. MK, TI, S-IT and KY conceived the study, participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.

    • Funding This work was supported by a JSPS KAKENHI Grant-in-Aid for Scientific Research (C) Grant Number 16K08935 (2016–2018), a JSPS KAKENHI Grant-in-Aid for Young Scientists (B) Grant Number 26870373 (2014–2015) and grants for young researchers from the Japan Association for Diabetes Education and Care (2014).

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Ethics approval This study was conducted in accordance with the principles of the Declaration of Helsinki. This study was approved by the Ethics Committee of the Faculty of Medicine, Tottori University (approval number G161). Informed consent was obtained from all of the participants using a procedure that was approved by the Ethics Committee.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement All data relevant to the study are included in the article.