Skip to main content
SpringerLink
Log in

Impaired glucagon secretion in patients with fulminant type 1 diabetes mellitus

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

Fulminant type 1 diabetes mellitus (FT1DM), characterized by rapid and almost complete destruction of pancreatic β-cells, is a newly identified subtype of type 1 diabetes mellitus. Although, the pathophysiology of this condition remains still unclear, histological evidence suggests that not only β-cells but also α-cells of pancreatic islets are reduced in number in FT1DM. However, the ability of glucagon secretion in patients with this condition has remained largely uncharacterized. We therefore examined glucagon secretion in patients with FT1DM and compared that with patients with other types of diabetes mellitus.

Methods

Fasting glucagon levels as well as glucagon secretion induced by intravenous administration of arginine were measured in hospitalized 83 patients with diabetes mellitus, including 4 with FT1DM, 18 with type 1 diabetes mellitus (T1DM), 40 with type 2 diabetes mellitus (T2DM), 5 with slowly progressive insulin-dependent diabetes mellitus (SPIDDM), and 16 with pancreatic diabetes mellitus (PDM).

Results

The area under the curve for serum glucagon levels after arginine infusion in FT1DM patients was significantly smaller than that in T1DM, T2DM, or SPIDDM patients but was similar to that in PDM patients. The fasting serum glucagon level of FT1DM patients was lower than that of T1DM or T2DM patients but did not significantly differ from that of SPIDDM or PDM patients.

Conclusions

These results suggest that glucagon secretion is impaired in patients with FT1DM.

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

Fig. 1

Similar content being viewed by others

References

  1. A. Imagawa, T. Hanafusa, J. Miyagawa, Y. Matsuzawa, A novel subtype of type 1 diabetes mellitus characterized by a rapid onset and an absence of diabetes-related antibodies. Osaka IDDM Study Group. N. Engl. J. Med. 342, 301–307 (2000)

    Article  CAS  PubMed  Google Scholar 

  2. T. Hanafusa, A. Imagawa, Fulminant type 1 diabetes: a novel clinical entity requiring special attention by all medical practitioners. Nat. Clin. Pract. Endocrinol. Metab. 3, 36–45 (2007)

    Article  CAS  PubMed  Google Scholar 

  3. L. Liu, L. Zeng, D. Sang, Z. Lu, J. Shen, Recent findings on fulminant type 1 diabetes. Diabetes Metab. Res. Rev. 34(1), e2928 (2018)

    Article  CAS  Google Scholar 

  4. C. Moreau, D. Drui, G. Arnault-Ouary, B. Charbonnel, L. Chaillous, B. Cariou, Fulminant type 1 diabetes in Caucasians: a report of three cases. Diabetes Metab. 34, 529–532 (2008)

    Article  CAS  PubMed  Google Scholar 

  5. R.A. McCauley, X. Wang, Fulminant type 1 diabetes mellitus-like presentation in a Hispanic woman in the United States. Diabetes Metab. 37, 356–358 (2011)

    Article  CAS  PubMed  Google Scholar 

  6. M. Taniyama, R. Katsumata, K. Aoki, S. Suzuki, A Filipino patient with fulminant type 1 diabetes. Diabetes Care 27, 842–843 (2004)

    Article  PubMed  Google Scholar 

  7. F. Tan, W.K. Loh, Fulminant type 1 diabetes associated with pregnancy: a report of 2 cases from Malaysia. Diabetes Res. Clin. Pract. 90, e30–e32 (2010)

    Article  PubMed  Google Scholar 

  8. A. Imagawa, T. Hanafusa, Y. Uchigata, A. Kanatsuka, E. Kawasaki, T. Kobayashi et al. Fulminant type 1 diabetes: a nationwide survey in Japan. Diabetes Care 26, 2345–2352 (2003)

    Article  PubMed  Google Scholar 

  9. Y.M. Cho, J.T. Kim, K.S. Ko, B.K. Koo, S.W. Yang, M.H. Park, et al. Fulminant type 1 diabetes in Korea: high prevalence among patients with adult-onset type 1 diabetes. Diabetologia 50, 2276–2279 (2007)

    Article  CAS  PubMed  Google Scholar 

  10. K. Sayama, A. Imagawa, K. Okita, S. Uno, M. Moriwaki, J. Kozawa et al. Pancreatic beta and alpha cells are both decreased in patients with fulminant type 1 diabetes: a morphometrical assessment. Diabetologia 48, 1560–1564 (2005)

    Article  CAS  PubMed  Google Scholar 

  11. S. Shibasaki, A. Imagawa, S. Tauriainen, M. Iino, M. Oikarinen, H. Abiru et al. Expression of toll-like receptors in the pancreas of recent-onset fulminant type 1 diabetes. Endocr. J. 57, 211–219 (2010)

    Article  CAS  PubMed  Google Scholar 

  12. D. D’Alessio, The role of dysregulated glucagon secretion in type 2 diabetes. Diabetes Obes. Metab. 13(Suppl 1), 126–132 (2011)

  13. R.H. Unger, A.D. Cherrington, Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover. J. Clin. Invest. 122, 4–12 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. A. Imagawa, T. Hanafusa, T. Awata, H. Ikegami, Y. Uchigata, H. Osawa et al. Report of the Committee of the Japan Diabetes Society on the research of fulminant and acute-onset type 1 diabetes mellitus: new diagnostic criteria of fulminant type 1 diabetes mellitus. J. Diabetes Investig. 3, 536–539 (2012)

    Article  PubMed  PubMed Central  Google Scholar 

  15. T. Kobayashi, S. Tanaka, N. Harii, K. Aida, H. Shimura, M. Ohmori et al.Immunopathological and genetic features in slowly progressive insulin-dependent diabetes mellitus and latent autoimmune diabetes in adults. Ann. NY Acad. Sci. 1079, 60–66 (2006)

    Article  CAS  PubMed  Google Scholar 

  16. R.H. Unger, E. Aguilar-Parada, W.A. Müller, A.M. Eisentraut, Studies of pancreatic alpha cell function in normal and diabetic subjects. J. Clin. Invest. 49, 837–848 (1970)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. R.H. Unger, L. Orci, Physiology and pathophysiology of glucagon. Physiol. Rev. 56, 778–826 (1976)

    Article  CAS  PubMed  Google Scholar 

  18. D. Yabe, A. Kuroe, M. Ohya, K. Watanabe, N. Kitatani, M. Oku et al.A case of fulminant type 1 diabetes mellitus with exocrine pancreatic insufficiency and enhanced glucagon response to meal ingestion. Diabetes Res. Clin. Pract. 82, e1–e4 (2008)

    Article  PubMed  Google Scholar 

  19. T. Katsura, D. Kawamori, E. Aida, T.A. Matsuoka, I. Shimomura, Glucotoxicity induces abnormal glucagon secretion through impaired insulin signaling in InR1G cells. PLoS ONE 12, e0176271 (2017)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. W. Ogawa, K. Sakaguchi, Euglycemic diabetic ketoacidosis induced by SGLT2 inhibitors: possible mechanism and contributing factors. J. Diabetes Investig. 7, 135–138 (2016)

    Article  CAS  PubMed  Google Scholar 

  21. A.K. Foulis, J.A. Stewart, The pancreas in recent-onset type 1 (insulin-dependent) diabetes mellitus: insulin content of islets, insulitis and associated changes in the exocrine acinar tissue. Diabetologia 26, 456–461 (1984)

    Article  CAS  PubMed  Google Scholar 

  22. T. Hanafusa, A. Imagawa, Insulitis in human type 1 diabetes. Ann. NY Acad. Sci. 1150, 297–299 (2008)

    Article  PubMed  Google Scholar 

  23. Y. Cui, D.K. Andersen, Pancreatogenic diabetes: special considerations for management. Pancreatology 11, 279–294 (2011)

    Article  PubMed  Google Scholar 

  24. S. Shibasaki, A. Imagawa, J. Terasaki, T. Hanafusa, Endogenous insulin secretion even at a very low level contributes to the stability of blood glucose control in fulminant type 1 diabetes. J. Diabetes Investig. 1, 283–285 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank Naoko Hashimoto, Tomoko Nishiumi, Ayumi Kanno, and Kentaro Suda for assistance with data collection as well as Yutaka Takahashi and Genzo Iguchi of Kobe University Graduate School of Medicine for helpful discussion.

Funding

This study was supported by a Research Grant from the Ministry of Education, Culture, Sports, Science, and Technology of Japan to S.S. and Y.H.

Author information

Authors and Affiliations

  1. Division of Diabetes and Endocrinology, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan

    Hisako Komada, Yushi Hirota, Kazuhiko Sakaguchi, Yoko Okuno & Wataru Ogawa

  2. Division of General Internal Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan

    Kazuhiko Sakaguchi

  3. Division of Molecular and Metabolic, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan

    Susumu Seino

Authors
  1. Hisako Komada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yushi Hirota
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kazuhiko Sakaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yoko Okuno
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wataru Ogawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Susumu Seino
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yushi Hirota.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the ethics committee of Kobe University Graduate School of Medicine (approval no. 180044). All patients provided written consent to the analysis and publication of their clinical data for scientific purposes.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Komada, H., Hirota, Y., Sakaguchi, K. et al. Impaired glucagon secretion in patients with fulminant type 1 diabetes mellitus. Endocrine 63, 476–479 (2019). https://doi.org/10.1007/s12020-018-1750-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-018-1750-x

Keywords

Search

Navigation