New Onset Persistent Hyperglycemia with Initiation of Brentuximab Treatment

Brentuximab is a CD-30-directed antibody-drug conjugate. The addition of brentuximab vedotin (BV) to adriamycin, vinblastine, and dacarbazine (AVD) has become a standard-of-care approach for advanced stage Hodgkin Lymphoma. BV has well known toxicities including peripheral neuropathy and infusion reactions. One emerging toxicity that is beginning to be recognized is new-onset hyperglycemia and diabetes mellitus. This case describes a rare presentation of new-onset diabetes mellitus one month after initiation of BV+AVD therapy in a patient with Hodgkin Lymphoma. A 41 year old previously healthy woman presented initially with complaints of chest and back pain. Cardiac etiology was ruled out, and lymphadenopathy was noted on chest imaging. Subsequent pathologic report from a robotic-assisted excision of a mediastinal mass and level five lymph node revealed Classical Hodgkin Lymphoma, nodular sclerosis type. Her baseline Hba1c was 5.8% at time of diagnosis. BV+AVD therapy was initiated about five weeks later. Six weeks after initiating treatment, she was admitted for abdominal pain secondary to constipation, at which time her blood glucose was noted to be 357 mg/dL. A repeated Hba1c was 8.1%. She required rapid acting insulin, and her glucoses ranged from 132-263 mg/dL. After discharge, a fasting glucose of over 250 mg/dL deemed her ineligible to have a PET/CT performed to assess disease status after completing cycle 2. She was referred urgently to the endocrinology clinic. She had been receiving dexamethasone 12mg every two weeks in conjunction with her chemotherapy, as well as additional lower doses for chemotherapy induced nausea. Thus, there was some thought she could have steroid-induced diabetes mellitus. However, her last dose of dexamethasone was given more than ten days prior to her most recent FSBG reading of 220 mg/dL, so steroid-induced diabetes was deemed less likely. The more likely etiology considered was BV-induced hyperglycemia. The patient was started on basal insulin, a DPP4i, and a meglitinide analog. Since initiation of this therapy, her glucose levels are now better controlled with readings consistently under 200 mg/dL. Furthermore, her lymphoma is in remission after three cycles of BV+AVD therapy, with a plan to complete six cycles. For many years, the standard of Hodgkin Lymphoma treatment consisted of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD). In 2017, the results of the ECHELON-1 phase 3 clinical trial demonstrated that a regimen with BV in conjunction with adriamycin, vinblastine, and dacarbazine (BV+AVD) has superior modified progression-free survival for patients with stage III/IV classical Hodgkin Lymphoma when compared to ABVD (Connors, NEJM, Jan, 2018). In a subsequent 3-year follow up study published in Blood, the authors demonstrated superior 3-year PFS for BV+AVD relative to ABVD. While BV has been a preferred treatment option to bleomycin, and one that avoids the dreaded complication of pulmonary fibrosis, we are learning more about other emerging toxicities related to its use. When the drug was first approved in 2011 for use in relapsed/refractory Hodgkin Lymphoma, the toxicity of hyperglycemia was not noted in the side effect profile. As the drug has now been in use for ten years, emerging data on other toxicities have been noted in trials and reported to the manufacturer. Hyperglycemia is a listed adverse effect in the prescribing label with an incidence of up to 8% of patients experiencing any grade hyperglycemia, and 6% experiencing Grade 3 or 4 hyperglycemia. The pathophysiology of hyperglycemia with BV administration is currently unclear. Interestingly, there is a paucity of literature describing this toxicity of the drug, and most incidence reports may be related to clinical trial data or post-approval reporting. An extensive literature search revealed only one other case report of new onset diabetes mellitus in patients receiving BV (Chiang, AACE, 2020). The authors suggest a general decrease in immune surveillance while on the drug leading to autoimmune conditions. Regardless of the mechanism of action, the above case report demonstrates a need to monitor blood glucose levels carefully during the initiation of BV therapy, especially in those individuals who have risk factors such as obesity or pre-diabetes mellitus. Future studies may further address the mechanism of hyperglycemia from BV and if the resultant diabetes is reversible. Disclosures No relevant conflicts of interest to declare.

The Impact of New-Onset Diabetes Mellitus and Hypertension on All-Cause Mortality in an Apparently Healthy Population: A Ten-Year Follow-Up Study

Introduction. The comparative effect of new-onset diabetes mellitus (DM) and hypertension (HT) on long-term mortality is a matter of debate. Materials and Methods. From 2007 to 2017, a 10-year longitudinal retrospective cohort study was conducted in Thailand’s tertiary care setting. As baseline data, health check-up data from apparently healthy participants without underlying disease from 2007 were extracted. The vital status of all participants was determined in 2017, ten years after an initial examination. The impact of new-onset DM and HT at baseline on 10-year all-cause mortality was investigated using multivariable logistic regression analysis. Results. The prevalence of new-onset DM and HT was 6.4% and 28.8%, respectively, at baseline. Newly diagnosed diabetes increased the risk of all-cause mortality over 10 years (adjusted OR 4.77 and 95% CI 2.23-9.99). HT, on the other hand, did not increase the risk of death (adjusted OR 1.24 and 95% CI 0.65-2.35). Different HT and DM status combinations were compared to a nondiabetic, nonhypertensive reference. Individuals who were diabetic and hypertensive had a greater risk of death (adjusted OR 6.22 and 95% CI 2.22-17.00). Having DM without HT also increased the risk of death (adjusted OR 4.36 and 95% CI 1.35-12.87). However, having HT without DM did not result in a significant increase in 10-year mortality risk (adjusted OR 1.21 and 95% CI 0.57-2.56). Conclusion. In an apparently healthy population, new-onset DM is more strongly associated with 10-year all-cause mortality than new-onset HT. Having both DM and HT was associated with a greater risk of death when compared to having DM or HT alone.

Hyperglycemic Emergencies Associated With Covid-19 Vaccination: A Case Series And Discussion

Context Hyperglycemic emergencies such as diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS) and new-onset diabetes mellitus (DM) have been reported in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Hyperglycemia is a predictor of poor prognosis in COVID-19 disease. Objectives The objective of this work is to describe a case series of HHS and/or DKA likely triggered by the COVID-19 vaccine. The aim is to alert physicians of the potential hyperglycemic complications from the COVID-19 vaccination and to provide further insight into the underlying mechanism of the bidirectional relationship between SARS-CoV-2 and DM. Case description All 3 patients developed HHS and/or DKA within 2-10 days of the COVID-19 vaccination. PCR testing for SARS-CoV-2 was negative and other clinical precipitating factors were excluded. Two patients had a history of type 2 DM (T2DM) with pre-admission HbA1c levels of 7.0-7.5% while one patient was newly diagnosed with T2DM during the hospitalization. They were each treated with insulin infusion and were discharged on subcutaneous insulin therapy. Due to the rapid resolution of the hyperglycemia, insulin was discontinued in all patients within 8 weeks and they remain well-controlled on oral DM medications. Conclusion Severe hyperglycemia including HHS and DKA may be triggered by COVID-19 vaccination. Early evaluation and screening of patients with hyperglycemic symptoms after COVID-19 vaccination is recommended. The vaccine-induced hyperglycemia may provide further insight into the underlying pathogenesis caused by the SARS-CoV-2 infection itself. The underlying robust inflammatory response and “cytokine storm” may be the primary precipitant.

The association of new-onset diabetes mellitus and medical therapy for benign prostatic hyperplasia: A population-based study

Introduction: Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms are highly prevalent in the aging male. Similarly, the prevalence of metabolic syndrome is increasing worldwide, with mounting evidence that these two common conditions share more than age as a predisposing factor. The objective of this study was to determine if medical management of BPH is associated with an increased risk of new-onset diabetes mellitus (DM) in routine care. Methods: This population-based, retrospective cohort study expands on a parent study of linked administrative databases identifying patients diagnosed and treated for BPH between 2005 and 2015. The primary outcome of this secondary analysis was a new diagnosis of DM after the index date of BPH diagnosis. Covariates included age, dyslipidemia, hypertension, and vascular diseases. A Cox proportional hazards regression model was used for inferential statistical analysis. Results: A total 129 223 men were identified with a BPH diagnosis and no prior history of DM. Of those men, 6390 (5%) were exposed to 5-alpha-reductase inhibitor (5-ARI), 39 592 (31%) exposed to alpha-blocker (AB), and 30 545 (24%) exposed to combination therapy. Compared to those men with no BPH medication use, those exposed to drugs had an increased risk of new DM. Men treated with combination therapy of 5-ARI and AB (hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.25–1.35), 5-ARI monotherapy (HR 1.25, 95% CI 1.17–1.34), or AB monotherapy (HR 1.17, 95% CI 1.13–1.22) all were at higher risk of new DM diagnosis after adjusting for important covariates. When calculating the risk of a new diabetes diagnosis measured from the start of drug exposure, men treated with 5-ARIs had an increased risk of DM compared to AB monotherapy as the reference, with HR 1.12 (95% CI 1.03–1.21) for 5-ARI monotherapy and HR 1.20 (95% CI 1.14–1.25) for combination therapy. Conclusions: In this large, long-term, retrospective study of men with a BPH diagnosis in routine practice, the risk of a new diagnosis of DM was greater in patients receiving medical management compared to controls. This modest but significant increased risk was highest in men treated with any 5-ARIs, in combination as well as monotherapy, compared to the ABs.