Endocrinology and Metabolism

Review Articles

Adrenal gland
The Fascinating Interplay between Growth Hormone, Insulin-Like Growth Factor-1, and Insulin: Eline C. Nijenhuis-Noort, Kirsten A. Berk, Sebastian J. C. M. M. Neggers, Aart J. van der Lely; Endocrinol Metab. 2024;39(1):83-89. Published online January 9, 2024; DOI: https://doi.org/10.3803/EnM.2024.101

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This review intends to provide the reader with a practical overview of several (patho)physiological conditions in which knowledge of the interplay between growth hormone (GH), insulin-like growth factor-1 (IGF-1), and insulin is important. This might help treating physicians in making the right decisions on how to intervene and improve metabolism for the benefit of patients, and to understand why and how metabolism responds in their specific cases. We will specifically address the interplay between GH, IGF-1, and insulin in type 1 and 2 diabetes mellitus, liver cirrhosis, and acromegaly as examples in which this knowledge is truly necessary.

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IGF-1 and IGF-2 as Molecules Linked to Causes and Consequences of Obesity from Fetal Life to Adulthood: A Systematic Review
Justyna Szydlowska-Gladysz, Adrianna Edyta Gorecka, Julia Stepien, Izabela Rysz, Iwona Ben-Skowronek
International Journal of Molecular Sciences.2024; 25(7): 3966. CrossRef

Diabetes, obesity and metabolism
The Benefits Of Continuous Glucose Monitoring In Pregnancy: Jee Hee Yoo, Jae Hyeon Kim; Endocrinol Metab. 2023;38(5):472-481. Published online October 11, 2023; DOI: https://doi.org/10.3803/EnM.2023.1805

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Previous studies have consistently demonstrated the positive effects of continuous glucose monitoring (CGM) on glycemic outcomes and complications of diabetes in people with type 1 diabetes. Guidelines now consider CGM to be an essential and cost-effective device for managing type 1 diabetes. As a result, insurance coverage for it is available. Evidence supporting CGM continues to grow and expand to broader populations, such as pregnant people with type 1 diabetes, people with type 2 diabetes treated only with basal insulin therapy, and even type 2 diabetes that does not require insulin treatment. However, despite the significant risk of hyperglycemia in pregnancy, which leads to complications in more than half of affected newborns, CGM indications and insurance coverage for those patients are unresolved. In this review article, we discuss the latest evidence for using CGM to offer glycemic control and reduce perinatal complications, along with its cost-effectiveness in pregestational type 1 and type 2 diabetes and gestational diabetes mellitus. In addition, we discuss future prospects for CGM coverage and indications based on this evidence.

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Wearable devices for glucose monitoring: A review of state-of-the-art technologies and emerging trends
Mohammad Mansour, M. Saeed Darweesh, Ahmed Soltan
Alexandria Engineering Journal.2024; 89: 224. CrossRef

Original Article

Diabetes, Obesity and Metabolism
Human Leukocyte Antigens and Biomarkers in Type 1 Diabetes Mellitus Induced by Immune-Checkpoint Inhibitors: Hidefumi Inaba, Yosuke Kaido, Saya Ito, Tomonao Hirobata, Gen Inoue, Takakazu Sugita, Yuki Yamamoto, Masatoshi Jinnin, Hiroaki Kimura, Tomoko Kobayashi, Shintaro Iwama, Hiroshi Arima, Takaaki Matsuoka; Endocrinol Metab. 2022;37(1):84-95. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2021.1282

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Background
Type 1 diabetes mellitus induced by immune-checkpoint inhibitors (ICI-T1DM) is a rare critical entity. However, the etiology of ICI-T1DM remains unclear.
Methods
In order to elucidate risk factors for ICI-T1DM, we evaluated the clinical course and immunological status of patients with ICI-T1DM who had been diagnosed during 2016 to 2021.
Results
Seven of 871 (0.8%, six men and one woman) patients developed ICI-T1DM. We revealed that the allele frequencies of human leukocyte antigen (HLA)-DPA1*02:02 and DPB1*05:01 were significantly higher in the patients with ICI-T1DM In comparison to the controls who received ICI (11/14 vs. 10/26, P=0.022; 11/14 vs. 7/26, P=0.0027, respectively). HLA-DRB1*04:05, which has been found to be a T1DM susceptibility allele in Asians, was also observed as a high-risk allele for ICI-T1DM. The significance of the HLA-DPB1*05:01 and DRB1*04:05 alleles was confirmed by an analysis of four additional patients. The absolute/relative neutrophil count, neutrophils-lymphocyte ratio, and neutrophil-eosinophil ratio increased, and the absolute lymphocyte count and absolute/relative eosinophil count decreased at the onset as compared with 6 weeks before. In two patients, alterations in cytokines and chemokines were found at the onset.
Conclusion
Novel high-risk HLA alleles and haplotypes were identified in ICI-T1DM, and peripheral blood factors may be utilized as biomarkers.

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Type 1 diabetes mellitus affected by potential toxicity from long-term use of nivolumab
Yuma Motomura, Shin Urai, Yushi Hirota, Naoki Takegawa, Hironori Bando, Masaaki Yamamoto, Hidenori Fukuoka, Masahiro Tsuda, Wataru Ogawa
Diabetology International.2024; 15(1): 130. CrossRef
Review – The impact of pharmacogenetics on the outcome of immune checkpoint inhibitors
Karlijn de Joode, Niels Heersche, Edwin A. Basak, Sander Bins, Astrid A.M. van der Veldt, Ron H.N. van Schaik, Ron H.J. Mathijssen
Cancer Treatment Reviews.2024; 122: 102662. CrossRef
Reaching the Diagnosis of Checkpoint Inhibitor-Induced Diabetes Mellitus in Different Clinical Scenarios: A Real-World Application of Updated Diagnostic Criteria
Anna Angelousi, Dimitrios C. Ziogas, Vasiliki Siampanopoulou, Chrysoula Mytareli, Amalia Anastasopoulou, George Lyrarakis, Helen Gogas
Diseases.2024; 12(2): 40. CrossRef
Non-Invasive Predictive Biomarkers for Immune-Related Adverse Events Due to Immune Checkpoint Inhibitors
Ben Ponvilawan, Abdul Wali Khan, Janakiraman Subramanian, Dhruv Bansal
Cancers.2024; 16(6): 1225. CrossRef
A case of rapidly progressive insulin-dependent diabetes mellitus without islet autoantibodies developed over two years after the first dose of nivolumab
Kota Nishihama, Yuko Okano, Chisa Inoue, Kanako Maki, Kazuhito Eguchi, Soichiro Tanaka, Atsuro Takeshita, Mei Uemura, Taro Yasuma, Toshinari Suzuki, Esteban C. Gabazza, Yutaka Yano
Diabetology International.2024;[Epub] CrossRef
A single center case series of immune checkpoint inhibitor-induced type 1 diabetes mellitus, patterns of disease onset and long-term clinical outcome
John Marsiglio, Jordan P. McPherson, Magdalena Kovacsovics-Bankowski, Joanne Jeter, Christos Vaklavas, Umang Swami, Douglas Grossmann, Alyssa Erickson-Wayman, Heloisa P. Soares, Katie Kerrigan, Berit Gibson, Jennifer Anne Doherty, John Hyngstrom, Sheetal
Frontiers in Immunology.2023;[Epub] CrossRef
Predictive Biomarkers for Immune-Related Endocrinopathies following Immune Checkpoint Inhibitors Treatment
Almog Shalit, Panagiotis Sarantis, Evangelos Koustas, Eleni-Myrto Trifylli, Dimitris Matthaios, Michalis V. Karamouzis
Cancers.2023; 15(2): 375. CrossRef
Predictive Biomarkers for Checkpoint Inhibitor Immune-Related Adverse Events
Iñigo Les, Mireia Martínez, Inés Pérez-Francisco, María Cabero, Lucía Teijeira, Virginia Arrazubi, Nuria Torrego, Ana Campillo-Calatayud, Iñaki Elejalde, Grazyna Kochan, David Escors
Cancers.2023; 15(5): 1629. CrossRef
Amino acid polymorphisms in human histocompatibility leukocyte antigen class II and proinsulin epitope have impacts on type 1 diabetes mellitus induced by immune-checkpoint inhibitors
Hidefumi Inaba, Shuhei Morita, Daisuke Kosugi, Yuki Asai, Yosuke Kaido, Saya Ito, Tomonao Hirobata, Gen Inoue, Yuki Yamamoto, Masatoshi Jinnin, Hiroaki Kimura, Masao Ota, Yuko Okudaira, Hiroyasu Nakatani, Tomoko Kobayashi, Shintaro Iwama, Hiroshi Arima, T
Frontiers in Immunology.2023;[Epub] CrossRef
Clinical characteristics and human leukocyte antigens in patients with immune checkpoint inhibitor-induced type 1 diabetes and pituitary dysfunction: a single center prospective study
Natsuko Hara, Hirotsugu Suwanai, Fumiyoshi Yakou, Keitaro Ishii, Hajime Iwasaki, Hironori Abe, Jumpei Shikuma, Hiroyuki Sakai, Takashi Miwa, Ryo Suzuki
Endocrine.2023; 81(3): 477. CrossRef
Autoimmunity in immune checkpoint inhibitor‐induced immune‐related adverse events: A focus on autoimmune skin toxicity and pneumonitis
Fiamma Berner, Lukas Flatz
Immunological Reviews.2023; 318(1): 37. CrossRef
Prediction-based prompt levothyroxine replacement to prevent a hypothyroid state after immune-related adverse events involving the thyroid gland
Ichiro Yamauchi, Takuro Hakata, Taku Sugawa, Daisuke Kosugi, Haruka Fujita, Kentaro Okamoto, Yohei Ueda, Toshihito Fujii, Daisuke Taura, Norio Harada, Nobuya Inagaki
Endocrine Journal.2023; 70(10): 987. CrossRef
Key Determinants of Immune-Mediated Adverse Reactions to Oncology Drugs
Yihan Zhou, Shan Ding
Cancers.2023; 15(23): 5622. CrossRef
Risk factors and predictors of immune-related adverse events: implications for patients with non-small cell lung cancer
Majd Issa, Joy Tang, Yizhen Guo, Chris Coss, Thomas A. Mace, Jason Bischof, Mitch Phelps, Carolyn J Presley, Dwight H Owen
Expert Review of Anticancer Therapy.2022; 22(8): 861. CrossRef
Risk Factors and Biomarkers for Immune-Related Adverse Events: A Practical Guide to Identifying High-Risk Patients and Rechallenging Immune Checkpoint Inhibitors
Adithya Chennamadhavuni, Laith Abushahin, Ning Jin, Carolyn J. Presley, Ashish Manne
Frontiers in Immunology.2022;[Epub] CrossRef
Flash Glucose Monitoring and Diabetes Mellitus Induced by Immune Checkpoint Inhibitors: An Approach to Clinical Practice
Pablo Rodríguez de Vera-Gómez, Ana Piñar-Gutiérrez, Raquel Guerrero-Vázquez, Virginia Bellido, Cristóbal Morales-Portillo, María Pilar Sancho-Márquez, Pablo Espejo-García, Noelia Gros-Herguido, Gema López-Gallardo, María Asunción Martínez-Brocca, Alfonso
Journal of Diabetes Research.2022; 2022: 1. CrossRef

Brief Report

Diabetes, Obesity and Metabolism
Growth in Children with HLA-Conferred Susceptibility to Type 1 Diabetes: Liisa Saare, Aleksandr Peet, Vallo Tillmann; Endocrinol Metab. 2022;37(1):175-179. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2021.1262

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Abstract PDF PubReader ePub: The incidence of type 1 diabetes (T1D) is increasing throughout the world. This trend may be explained by the accelerator hypothesis. Our study investigated growth, its biochemical markers, and their associations with the development of diabetes-associated autoantibodies (DAAB) in 219 children with genetic risk for T1D. Subjects were divided into risk groups based on their human leukocyte antigen genotype. Children in the moderate- to high-risk group were significantly taller when corrected to mid-parental height and had a lower insulin-like growth factor 1 (IGF-1)/IGF-1 binding protein (IGFBP-3) molar ratio than those in the low-risk group (corrected height standard deviation score 0.22±0.93 vs. –0.04±0.84, P<0.05; molar ratio 0.199±0.035 vs. 0.211+0.039, P<0.05). Children with DAAB tended to be taller and to have a higher body mass index than those with no DAAB. Our results suggest that the accelerator hypothesis explaining the increasing incidence of T1D may not solely be dependent on environmental factors, but could be partially genetically determined.

Review Articles

Miscellaneous
Clinical Characteristics, Management, and Potential Biomarkers of Endocrine Dysfunction Induced by Immune Checkpoint Inhibitors: Shintaro Iwama, Tomoko Kobayashi, Hiroshi Arima; Endocrinol Metab. 2021;36(2):312-321. Published online April 27, 2021; DOI: https://doi.org/10.3803/EnM.2021.1007

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Immune-related adverse events (irAEs) affecting the endocrine glands are among the most frequent irAEs induced by immune checkpoint inhibitors (ICIs) and include hypopituitarism, primary adrenal insufficiency, thyrotoxicosis, hypothyroidism, hypoparathyroidism, and type 1 diabetes mellitus. Since the incidence and clinical features of endocrine irAEs vary according to the ICI used, it is important to understand the characteristics of these irAEs and to manage each one appropriately. Since some endocrine irAEs, including adrenal crisis and diabetic ketoacidosis, are potentially life-threatening, predicting the risk of endocrine irAEs before their onset is critical. Several autoantibodies have been detected in patients who develop endocrine irAEs, among which anti-thyroid antibodies may be predictive biomarkers of thyroid dysfunction. In this review, we describe the clinical features of each endocrine irAE induced by ICIs and discuss their potential biomarkers, including autoantibodies.

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Clinical characteristics and potential biomarkers of thyroid and pituitary immune-related adverse events
Tomoko Kobayashi, Shintaro Iwama, Hiroshi Arima
Endocrine Journal.2024; 71(1): 23. CrossRef
A case of rapidly progressive insulin-dependent diabetes mellitus without islet autoantibodies developed over two years after the first dose of nivolumab
Kota Nishihama, Yuko Okano, Chisa Inoue, Kanako Maki, Kazuhito Eguchi, Soichiro Tanaka, Atsuro Takeshita, Mei Uemura, Taro Yasuma, Toshinari Suzuki, Esteban C. Gabazza, Yutaka Yano
Diabetology International.2024;[Epub] CrossRef
Endocrinopathies associated with immune checkpoint inhibitor use
Anupam Kotwal, Randol Kennedy, Nupur Kikani, Sonali Thosani, Whitney Goldner, Afreen Shariff
Endocrine Practice.2024;[Epub] CrossRef
Recovery from insulin dependence in immune checkpoint inhibitor‐associated diabetes mellitus: A case report
Marie Okubo, Yuji Hataya, Kanta Fujimoto, Toshio Iwakura, Naoki Matsuoka
Journal of Diabetes Investigation.2023; 14(1): 147. CrossRef
Case Report: A Rising Cause of New-Onset Endocrinopathies After Immunotherapy
Charity Tan, Sarah Hendricks, Kristina Hernandez, Martha Benavides, Rupinderjit Samra
The Journal for Nurse Practitioners.2023; 19(5): 104582. CrossRef
Risk of Thyroid Dysfunction in PD-1 Blockade Is Stratified by the Pattern of TgAb and TPOAb Positivity at Baseline
Xin Zhou, Shintaro Iwama, Tomoko Kobayashi, Masahiko Ando, Hiroshi Arima
The Journal of Clinical Endocrinology & Metabolism.2023; 108(10): e1056. CrossRef
Severe thyrotoxicosis induced by tislelizumab: a case report and literature review
Liman Huo, Chao Wang, Haixia Ding, Xuelian Shi, Bin Shan, Ruoying Zhou, Ping Liang, Juan Hou
Frontiers in Oncology.2023;[Epub] CrossRef
Life-Threatening Endocrinological Immune-Related Adverse Events of Immune Checkpoint Inhibitor Therapy
Aleksandra Basek, Grzegorz K. Jakubiak, Grzegorz Cieślar, Agata Stanek
Cancers.2023; 15(24): 5786. CrossRef
Increased Risk of Thyroid Dysfunction by PD-1 and CTLA-4 Blockade in Patients Without Thyroid Autoantibodies at Baseline
Shintaro Iwama, Tomoko Kobayashi, Yoshinori Yasuda, Takayuki Okuji, Masaaki Ito, Masahiko Ando, Xin Zhou, Ayana Yamagami, Takeshi Onoue, Yohei Kawaguchi, Takashi Miyata, Mariko Sugiyama, Hiroshi Takagi, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Tets
The Journal of Clinical Endocrinology & Metabolism.2022; 107(4): e1620. CrossRef
Biomarkers and risk factors for the early prediction of immune-related adverse events: a review
Ying Zhang, Xiaoling Zhang, Weiling Li, Yunyi Du, Wenqing Hu, Jun Zhao
Human Vaccines & Immunotherapeutics.2022;[Epub] CrossRef
Immune Checkpoint Inhibitors as a Threat to the Hypothalamus–Pituitary Axis: A Completed Puzzle
Agnese Barnabei, Andrea Corsello, Rosa Maria Paragliola, Giovanni Maria Iannantuono, Luca Falzone, Salvatore Maria Corsello, Francesco Torino
Cancers.2022; 14(4): 1057. CrossRef
Elevated TSH Level, TgAb, and Prior Use of Ramucirumab or TKIs as Risk Factors for Thyroid Dysfunction in PD-L1 Blockade
Tomoko Kobayashi, Shintaro Iwama, Ayana Yamagami, Yoshinori Yasuda, Takayuki Okuji, Masaaki Ito, Xin Zhou, Masahiko Ando, Takeshi Onoue, Takashi Miyata, Mariko Sugiyama, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Tetsunari Hase, Masahiro Morise, Taka
The Journal of Clinical Endocrinology & Metabolism.2022; 107(10): e4115. CrossRef
Preconditioning of the immune system modulates the response of papillary thyroid cancer to immune checkpoint inhibitors
Fabiana Pani, Yoshinori Yasuda, Sylvie T Rousseau, Kevin C Bermea, Solmaz Roshanmehr, Rulin Wang, Srinivasan Yegnasubramanian, Patrizio Caturegli, Luigi Adamo
Journal for ImmunoTherapy of Cancer.2022; 10(12): e005538. CrossRef
Survival benefit of endocrine dysfunction following immune checkpoint inhibitors for nonthyroidal cancers
Anupam Kotwal, Mabel Ryder
Current Opinion in Endocrinology, Diabetes & Obesity.2021; 28(5): 517. CrossRef

Diabetes
Latent Autoimmune Diabetes in Adults: Current Status and New Horizons: Paolo Pozzilli, Silvia Pieralice; Endocrinol Metab. 2018;33(2):147-159. Published online June 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.147

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Autoimmune diabetes is a heterogeneous disease which can arise at any age. Subjects with adult-onset autoimmune diabetes who do not necessitate insulin-therapy for at least 6 months after diagnosis are demarcated as having latent autoimmune diabetes in adults (LADA). This condition is more heterogeneous than young-onset autoimmune diabetes and shares clinical and metabolic characteristics with both type 2 and type 1 diabetes. Patients with LADA are considered by having highly variable β-cell destruction, different degrees of insulin resistance and heterogeneous titre and pattern of islet autoantibody, suggesting different pathophysiological pathways partially explaining the heterogeneous phenotypes of LADA. To date the heterogeneity of LADA does not allow to establish a priori treatment algorithm and no specific guidelines for LADA therapy are available. These subjects are mostly treated as affected by type 2 diabetes, a factor that might lead to the progression to insulin-dependency quickly. A personalised medicine approach is necessary to attain optimal metabolic control and preserve β-cell function to decrease the risk of long-term diabetes complications. Recent data concerning the use of oral antidiabetic agents as dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists indicate up-and-coming results in term of protect C-peptide levels and improving glycaemic control. This review summarises current knowledge on LADA, emphasising controversies regarding its pathophysiology and clinical features. Moreover, we discuss data available about novel therapeutic approaches that can be considered for prevention of β-cell loss in LADA.

Citations

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Drug candidates and potential targets of Curculigo spp. compounds for treating diabetes mellitus based on network pharmacology, molecular docking and molecular dynamics simulation
Abdul Halim Umar, Diah Ratnadewi, Mohamad Rafi, Yohana Caecilia Sulistyaningsih, Hamim Hamim, Wisnu Ananta Kusuma
Journal of Biomolecular Structure and Dynamics.2023; 41(17): 8544. CrossRef
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Pilar Vich-Pérez, Juan Carlos Abánades-Herranz, Gustavo Mora-Navarro, Ángela María Carrasco-Sayalero, Miguel Ángel Salinero-Fort, Ignacio Sevilla-Machuca, Mar Sanz-Pascual, Cristina Álvarez Hernández-Cañizares, Carmen de Burgos-Lunar, Vijayaprakash Suppia
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Current Diabetes Reviews.2023;[Epub] CrossRef
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The role of cholecalciferol deficiency in the development of latent autoimmune diabetes in adults
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Two Fifth-Generation Fighter Pilots Discovered with Latent Autoimmune Diabetes
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Bewusstseinsstörung, Tachypnoe und Tachykardie bei einem 71-jährigen Patienten mit Diabetes mellitus Typ 2
S. Großmann, U. Hoffmann, C. Girlich
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Good Glycemic Outcomes Following Bariatric Surgery Among Patients With Type 2 Diabetes, Obesity, and Low-Titer GAD Antibodies
Ruveena Kaur, David Kim, Richard Cutfield, Michael Booth, Lindsay Plank, Rinki Murphy
Diabetes Care.2021; 44(2): 607. CrossRef
Slowly evolving, immune-mediated diabetes in 14-year-old patient: a case report
M. R. Ragimov, D. D. Omelchuk, L. I. Ibragimova, O. S. Derevyanko, T. V. Nikonova
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Combination of vitamin D and dipeptidyl peptidase-4 inhibitors (VIDPP-4i) as an immunomodulation therapy for autoimmune diabetes
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