Skip to main content
Top
Published in: Endocrine 3/2019

01-03-2019 | Original Article

Impaired glucagon secretion in patients with fulminant type 1 diabetes mellitus

Authors: Hisako Komada, Yushi Hirota, Kazuhiko Sakaguchi, Yoko Okuno, Wataru Ogawa, Susumu Seino

Published in: Endocrine | Issue 3/2019

Login to get access

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.
Literature
1.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
2.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
3.
go back to reference 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)CrossRef 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)CrossRef
4.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
5.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
6.
go back to reference M. Taniyama, R. Katsumata, K. Aoki, S. Suzuki, A Filipino patient with fulminant type 1 diabetes. Diabetes Care 27, 842–843 (2004)CrossRefPubMed M. Taniyama, R. Katsumata, K. Aoki, S. Suzuki, A Filipino patient with fulminant type 1 diabetes. Diabetes Care 27, 842–843 (2004)CrossRefPubMed
7.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
8.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
9.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
10.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
11.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
12.
go back to reference D. D’Alessio, The role of dysregulated glucagon secretion in type 2 diabetes. Diabetes Obes. Metab. 13(Suppl 1), 126–132 (2011) D. D’Alessio, The role of dysregulated glucagon secretion in type 2 diabetes. Diabetes Obes. Metab. 13(Suppl 1), 126–132 (2011)
13.
go back to reference R.H. Unger, A.D. Cherrington, Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover. J. Clin. Invest. 122, 4–12 (2012)CrossRefPubMedPubMedCentral R.H. Unger, A.D. Cherrington, Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover. J. Clin. Invest. 122, 4–12 (2012)CrossRefPubMedPubMedCentral
14.
go back to reference 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)CrossRefPubMedPubMedCentral 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)CrossRefPubMedPubMedCentral
15.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
16.
go back to reference 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)CrossRefPubMedPubMedCentral 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)CrossRefPubMedPubMedCentral
17.
go back to reference R.H. Unger, L. Orci, Physiology and pathophysiology of glucagon. Physiol. Rev. 56, 778–826 (1976)CrossRefPubMed R.H. Unger, L. Orci, Physiology and pathophysiology of glucagon. Physiol. Rev. 56, 778–826 (1976)CrossRefPubMed
18.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
19.
go back to reference 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)CrossRefPubMedPubMedCentral 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)CrossRefPubMedPubMedCentral
20.
go back to reference W. Ogawa, K. Sakaguchi, Euglycemic diabetic ketoacidosis induced by SGLT2 inhibitors: possible mechanism and contributing factors. J. Diabetes Investig. 7, 135–138 (2016)CrossRefPubMed W. Ogawa, K. Sakaguchi, Euglycemic diabetic ketoacidosis induced by SGLT2 inhibitors: possible mechanism and contributing factors. J. Diabetes Investig. 7, 135–138 (2016)CrossRefPubMed
21.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
22.
go back to reference T. Hanafusa, A. Imagawa, Insulitis in human type 1 diabetes. Ann. NY Acad. Sci. 1150, 297–299 (2008)CrossRefPubMed T. Hanafusa, A. Imagawa, Insulitis in human type 1 diabetes. Ann. NY Acad. Sci. 1150, 297–299 (2008)CrossRefPubMed
23.
go back to reference Y. Cui, D.K. Andersen, Pancreatogenic diabetes: special considerations for management. Pancreatology 11, 279–294 (2011)CrossRefPubMed Y. Cui, D.K. Andersen, Pancreatogenic diabetes: special considerations for management. Pancreatology 11, 279–294 (2011)CrossRefPubMed
24.
go back to reference 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)CrossRefPubMedPubMedCentral 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)CrossRefPubMedPubMedCentral
Metadata
Title
Impaired glucagon secretion in patients with fulminant type 1 diabetes mellitus
Authors
Hisako Komada
Yushi Hirota
Kazuhiko Sakaguchi
Yoko Okuno
Wataru Ogawa
Susumu Seino
Publication date
01-03-2019
Publisher
Springer US
Published in
Endocrine / Issue 3/2019
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-018-1750-x

Other articles of this Issue 3/2019

Endocrine 3/2019 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.