scholarly journals Immune Checkpoint Inhibitor-Associated Type 1 Diabetes Mellitus: Case Series, Review of the Literature, and Optimal Management

2017 ◽  
Vol 10 (3) ◽  
pp. 897-909 ◽  
Author(s):  
Jonathan Kapke ◽  
Zachary Shaheen ◽  
Deepak Kilari ◽  
Paul Knudson ◽  
Stuart Wong
Keyword(s):  
Diabetes Mellitus ◽  
Monoclonal Antibody ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Immune Checkpoint ◽  
Autoimmune Diabetes ◽  
Human Monoclonal Antibody ◽  
Programmed Death ◽  
Autoimmune Diabetes Mellitus

With the introduction of immune checkpoint inhibitors into clinical practice, various autoimmune toxicities have been described. Antibodies targeting the receptor:ligand pairing of programmed death receptor-1 (PD-1) and its cognate ligand programmed death-ligand 1 (PD-L1) in rare reports have been associated with autoimmune diabetes mellitus. We report 2 cases of rapid-onset, insulin-dependent, type 1 diabetes mellitus in the setting of administration of nivolumab, a fully human monoclonal antibody to PD-1, and atezolizumab, a humanized monoclonal antibody to PD-L1. This appears to be the first report of autoimmune diabetes mellitus associated with atezolizumab. In addition, we provide a brief review of similar cases reported in the literature and a discussion of potential mechanisms for this phenomenon and propose a diagnostic and treatment algorithm.

Teplizumab for Treatment of Type 1 Diabetes Mellitus

2012 ◽  
Vol 46 (10) ◽  
pp. 1405-1412 ◽  
Author(s):  
Jessica W Skelley ◽  
Lindsey K Elmore ◽  
Jeffrey A Kyle
Keyword(s):  
Diabetes Mellitus ◽  
Monoclonal Antibody ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Human Monoclonal Antibody ◽  
Clinical Trial Data ◽  
Data Sources ◽  
Β Cells ◽  
Phase 3

Objective: To review the pharmacology, pharmacokinetics, safety, and efficacy of teplizumab and evaluate relevant clinical trial data. Data Sources: Searches of MEDLINE, International Pharmaceutical Abstracts, ClinicalTrials.gov, American Diabetes Association scientific posters, and Google Scholar (1966-May 2012) were conducted using the key words teplizumab. anti-CD3 monoclonal antibody, MGA031, and hOKT3γ1 (Ala-Ala). Searches were limited to articles published in English. Study Selection and Data Extraction: Clinical trials evaluating teplizumab for type 1 diabetes mellitus (T1DM) published in English were selected from the data sources. All published relevant abstracts were included. References cited in identified articles were used for additional citations. Data Synthesis: T1DM accounts for up to 10% of all cases of diabetes mellitus, T1DM is characterized as a chronic and progressive autoimmune disease leading to the destruction of insulin-producing β-cells of the pancreas. Teplizumab is a humanized Fc-mutated anti-CD3 monoclonal antibody that alters the function of the T-lymphocytes that mediate the destruction of the insulin-producing β-cells. While clinical data are limited, both Phase 2 and Phase 3 studies have demonstrated preserved C-peptide response as a measure of insulin production, decreased exogenous insulin use, and improved grycemic control following a 12- to 14-day teplizumab infusion in patients diagnosed with T1DM within the previous 6 weeks. However, 1 Phase 3 trial tailed to find the same benefits in those diagnosed with T1DM within the previous 12 weeks when a lower cumulative teplizumab dose was used. Initial studies indicated that teplizumab is well tolerated, with a self-limiting rash as the most commonly reported adverse effect. Conclusions: Teplizumab is an anti-CD3 human monoclonal antibody with promising activity in treatment of patients with T1DM, Results from Phase 3 trials are needed to further determine safety, efficacy, and dosing frequency.

Type I Diabetes Mellitus

2019 ◽  
Author(s):  
Joseph I. Wolfsdorf ◽  
Katharine Garvey
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Glycemic Control ◽  
Type 1 Diabetes Mellitus ◽  
Diabetic Ketoacidosis ◽  
Autoimmune Diabetes ◽  
Type I ◽  
Insulin Deficiency ◽  
Glucose Levels

Type 1 diabetes mellitus is characterized by severe insulin deficiency, making patients dependent on exogenous insulin replacement for survival. These patients can experience life-threatening events when their glucose levels are significantly abnormal. Type 1 diabetes accounts for 5 to 10% of all diabetes cases, with type 2 accounting for most of the remainder. This review details the pathophysiology, stabilization and assessment, diagnosis and treatment, disposition and outcomes of patients with Type 1 diabetes mellitus. Figures show the opposing actions of insulin and glucagon on substrate flow and plasma levels; plasma glucose, insulin and C-peptide levels throughout the day; the structure of human proinsulin; current view of the pathogenesis of Type 1 autoimmune diabetes mellitus; pathways that lead from insulin deficiency to the major clinical manifestations of Type 1 diabetes mellitus; relationship between hemoglobin A1c values at the end of a 3-month period and calculated average glucose levels during the 3-month period; different combinations of various insulin preparations used to establish glycemic control; and basal-bolus and insulin pump regimens. Tables list the etiologic classification of Type 1 diabetes mellitus, typical laboratory findings and monitoring in diabetic ketoacidosis, criteria for the diagnosis of Type 1 diabetes, clinical goals of Type 1 diabetes treatment, and insulin preparations. This review contains 10 figures, 9 tables, and 40 references. Keywords: Type 1 diabetes mellitus, optimal glycemic control, hypoglycemia, hyperglycemia, polyuria, polydipsia, polyphagia, HbA1c, medical nutrition therapy, Diabetic Ketoacidosis

Differences in the genetic background of latent autoimmune diabetes in adults (LADA) and type 1 diabetes mellitus

2002 ◽  
Vol 84 (2) ◽  
pp. 109-115 ◽  
Author(s):  
Ágnes Vatay ◽  
Katalin Rajczy ◽  
Éva Pozsonyi ◽  
Nóra Hosszúfalusi ◽  
Zoltán Prohászka ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Genetic Background ◽  
Autoimmune Diabetes ◽  
Latent Autoimmune Diabetes
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