Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 7-Day Trial for You or Your Team.

Learn More →

Commentary on a Case of Unexpected Hyperglycemia

Commentary on a Case of Unexpected Hyperglycemia This patient presented with symptoms typical of diabetes mellitus, namely polyuria, polydipsia, and weight loss. Together with the increased blood glucose concentration (≥200 mg/dL (11.1 mmol/L)), these findings establish the diagnosis of diabetes. The rapid onset combined with the magnitude of the glucose rise point to type 1 diabetes. This was confirmed by the presence of autoantibodies to glutamic acid decarboxylase (GAD) and decreased C-peptide concentration. Notwithstanding the glucose value of 947 mg/dL (52.5 mmol/L) and increased ketones (β-hydroxybutyrate), surprisingly the patient did not have metabolic acidosis, so did not meet the criteria for diabetic ketoacidosis (DKA). Type 1 diabetes generally results from autoimmune destruction of the insulin-secreting β-cells of the pancreas. Despite intensive research, the factor(s) that precipitate the autoimmunity are poorly understood and are rarely identified in an individual patient. Some patients develop secondary diabetes due to increased concentrations of insulin counter-regulatory hormones, often caused by endocrinopathies (e.g., Cushing’s syndrome, acromegaly), which manifest as type 2 diabetes. Certain drugs can cause secondary diabetes, most commonly by impairing insulin action. The increasing use of immunosuppressive drugs has resulted in β-cell destruction by autoantibodies, leading to type 1 diabetes. Checkpoint inhibitors, which reverse immune suppression in malignant cells, have been used for about 10 years for treating malignant neoplasms. Unfortunately, adverse effects occur in up to 90% of patients. Endocrine dysfunction is not infrequent, with thyroid disease reported in about 11% of patients. Approximately 1% of patients treated with anti-PD-1 agents (e.g., pembrolizumab) develop type 1 diabetes. Progression is more rapid than occurs in spontaneous type 1 diabetes, with onset usually <3 months after initiation of therapy (1). At presentation, glucose concentration is generally >550 mg/dL (30.6 mmol/L), HbA1c is 7.6%–8%, about 75% have DKA, and C-peptide is reduced in >85% (1, 2). The frequency of type 1 diabetes secondary to checkpoint inhibitors will increase as use of these agents expands. Nonstandard Abbreviations: GAD, glutamic acid decarboxylase; DKA, diabetic ketoacidosis. Author Contributions All authors confirmed they have contributed to the intellectual content of this paper and have met the following 4 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; (c) final approval of the published article; and (d) agreement to be accountable for all aspects of the article thus ensuring that questions related to the accuracy or integrity of any part of the article are appropriately investigated and resolved. Authors’ Disclosures or Potential Conflicts of Interest Upon manuscript submission, all authors completed the author disclosure form. Disclosures and/or potential conflicts of interest: Employment or Leadership: D.B. Sacks, Clinical Chemistry, AACC. Consultant or Advisory Role: None declared. Stock Ownership: None declared. Honoraria: None declared. Research Funding: Intramural Research Program of the NIH (to institution). Expert Testimony: None declared. Patents: None declared. References 1 Quandt Z , Young A, Perdigoto AL, Herold KC, Anderson MS. Autoimmune endocrinopathies: an emerging complication of immune checkpoint inhibitors . Annu Rev Med 2021 ; 72 : 313 – 30 . Google Scholar Crossref Search ADS PubMed WorldCat 2 Akturk HK , Kahramangil D, Sarwal A, Hoffecker L, Murad MH, Michels AW. Immune checkpoint inhibitor-induced type 1 diabetes: a systematic review and meta-analysis . Diabet Med 2019 ; 36 : 1075 – 81 . Google Scholar Crossref Search ADS PubMed WorldCat Published by Oxford University Press on behalf of the American Association for Clinical Chemistry 2021. This work is written by a US Government employee and is in the public domain in the US. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical Chemistry Oxford University Press

Commentary on a Case of Unexpected Hyperglycemia

Sacks, David B
Clinical Chemistry , Volume 67 (8): 2 – Aug 3, 2021
Download PDF
2 pages

Loading next page...
 
/lp/oxford-university-press/commentary-on-a-case-of-unexpected-hyperglycemia-gyw6AdYIU0

References (12)

Publisher
Oxford University Press
Copyright
Published by Oxford University Press on behalf of the American Association for Clinical Chemistry 2021. This work is written by a US Government employee and is in the public domain in the US.
ISSN
0009-9147
eISSN
1530-8561
DOI
10.1093/clinchem/hvab084
Publisher site
See Article on Publisher Site

Abstract

This patient presented with symptoms typical of diabetes mellitus, namely polyuria, polydipsia, and weight loss. Together with the increased blood glucose concentration (≥200 mg/dL (11.1 mmol/L)), these findings establish the diagnosis of diabetes. The rapid onset combined with the magnitude of the glucose rise point to type 1 diabetes. This was confirmed by the presence of autoantibodies to glutamic acid decarboxylase (GAD) and decreased C-peptide concentration. Notwithstanding the glucose value of 947 mg/dL (52.5 mmol/L) and increased ketones (β-hydroxybutyrate), surprisingly the patient did not have metabolic acidosis, so did not meet the criteria for diabetic ketoacidosis (DKA). Type 1 diabetes generally results from autoimmune destruction of the insulin-secreting β-cells of the pancreas. Despite intensive research, the factor(s) that precipitate the autoimmunity are poorly understood and are rarely identified in an individual patient. Some patients develop secondary diabetes due to increased concentrations of insulin counter-regulatory hormones, often caused by endocrinopathies (e.g., Cushing’s syndrome, acromegaly), which manifest as type 2 diabetes. Certain drugs can cause secondary diabetes, most commonly by impairing insulin action. The increasing use of immunosuppressive drugs has resulted in β-cell destruction by autoantibodies, leading to type 1 diabetes. Checkpoint inhibitors, which reverse immune suppression in malignant cells, have been used for about 10 years for treating malignant neoplasms. Unfortunately, adverse effects occur in up to 90% of patients. Endocrine dysfunction is not infrequent, with thyroid disease reported in about 11% of patients. Approximately 1% of patients treated with anti-PD-1 agents (e.g., pembrolizumab) develop type 1 diabetes. Progression is more rapid than occurs in spontaneous type 1 diabetes, with onset usually <3 months after initiation of therapy (1). At presentation, glucose concentration is generally >550 mg/dL (30.6 mmol/L), HbA1c is 7.6%–8%, about 75% have DKA, and C-peptide is reduced in >85% (1, 2). The frequency of type 1 diabetes secondary to checkpoint inhibitors will increase as use of these agents expands. Nonstandard Abbreviations: GAD, glutamic acid decarboxylase; DKA, diabetic ketoacidosis. Author Contributions All authors confirmed they have contributed to the intellectual content of this paper and have met the following 4 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; (c) final approval of the published article; and (d) agreement to be accountable for all aspects of the article thus ensuring that questions related to the accuracy or integrity of any part of the article are appropriately investigated and resolved. Authors’ Disclosures or Potential Conflicts of Interest Upon manuscript submission, all authors completed the author disclosure form. Disclosures and/or potential conflicts of interest: Employment or Leadership: D.B. Sacks, Clinical Chemistry, AACC. Consultant or Advisory Role: None declared. Stock Ownership: None declared. Honoraria: None declared. Research Funding: Intramural Research Program of the NIH (to institution). Expert Testimony: None declared. Patents: None declared. References 1 Quandt Z , Young A, Perdigoto AL, Herold KC, Anderson MS. Autoimmune endocrinopathies: an emerging complication of immune checkpoint inhibitors . Annu Rev Med 2021 ; 72 : 313 – 30 . Google Scholar Crossref Search ADS PubMed WorldCat 2 Akturk HK , Kahramangil D, Sarwal A, Hoffecker L, Murad MH, Michels AW. Immune checkpoint inhibitor-induced type 1 diabetes: a systematic review and meta-analysis . Diabet Med 2019 ; 36 : 1075 – 81 . Google Scholar Crossref Search ADS PubMed WorldCat Published by Oxford University Press on behalf of the American Association for Clinical Chemistry 2021. This work is written by a US Government employee and is in the public domain in the US. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Journal

Clinical Chemistry – Oxford University Press

Published: Aug 3, 2021

There are no references for this article.