Combined diabetic ketoacidosis and hyperosmolar hyperglycemic state in type 1 diabetes mellitus induced by immune checkpoint inhibitors: Underrecognized and underreported emergency in ICIs-DM

Abstract

BackgroundCombined diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) secondary to immune checkpoint inhibitors (ICIs) is extremely rarely reported among ICIs- diabetes mellitus (DM) cases and is always ignored by physicians. This study aimed to conduct a systematic review to recognize better the rare adverse event of combined DKA-HHS associated with immune checkpoints.MethodsA electronic search in Pubmed/Cochrane/Web of Science, complemented by manual searches in article references, was conducted to identify clinical features of ICIs-combined DKA-HHS.Resultswe identified 106 patients with ICIs- type 1 diabetes mellitus (T1DM) from 82 publications: 9 patients presented a coexistence of metabolic acidosis, severe hyperglycemia, and/or DKA; All patients were not diagnosed as combined DKA-HHS. Compared with ICIs-DKA patients, combined DKA-HHS cases were prone to higher hyperglycemia (1020 ± 102.5 vs 686.7 ± 252.6mg/dL). Moreover, acute kidney injury (87.5% vs 28.6%) and prior chemotherapy (66.7% vs 31.6%) showed higher occurrences with the onset of ICIs-HHS or combined DKA-HHS.BConclusionsCombined DKA-HHS portends a poor diagnosis in patients with coexistence features of DKA and HHS, which healthcare professionals and patients should be aware of due to differences in treatment. Our observational retrospective case series shows that patients with more risk factors were more likely to develop combined DKA-HHS. We are the first to report this group of patients’ clinical characteristics and outcomes.

Cemiplimab-Induced Hyperosmolar Hyperglycemic State With Concurrent Diabetic Ketoacidosis in a Patient Receiving Treatment for Cutaneous Squamous Cell Carcinoma

“…Aggressive fluid hydration, IV insulin, and electrolyte repletion led to a rapid recovery of the patient’s clinical status and cemiplimab was discontinued after discharge. Our findings highlight an extremely rare yet underrecognized and underreported emergency in ICI-DM: HHS-DKA in type 1 DM (T1DM) induced by ICIs [ 9 ].…”

“…However, no accepted definition currently exists to identify patients presenting with HHS and DKA due to a lack of sufficient data regarding patients' clinical characteristics, frequency, and prognosis [ 13 ]. One recent study sought to define HHS-DKA as follows: plasma osmolarity ≥320 mOsm/kg, initial blood sugar ≥600 mg/dL, pH ≤7.3, and ketonuria and/or ketonemia [ 9 ]. Based on this current definition, our patient exhibited HHS-DKA induced by cemiplimab use.…”

“…Although cemiplimab-induced DKA has been described before [ 17 ], our findings differ in that our patient displayed cemiplimab-induced HHS-DKA. This is significant because compared with ICI-DKA patients, ICI-induced HHS-DKA patients are prone to have higher hyperglycemia, significantly higher HbA1C levels, more likely to experience acute kidney injury, and more likely to have received chemotherapy before immunotherapy [ 9 ].…”

Guideline for the Management of Diabetes Mellitus in the Elderly in China (2024 Edition)

“…In recent years, with the use of immune checkpoint inhibitors, diabetes onset following the use of these inhibitors is often characterized by the onset of DKA 222 and may also be accompanied by HHS. 223 Therefore, older patients with diabetes using immune checkpoint inhibitors should be vigilant for both DKA and HHS. Older patients with diabetes using SGLT-2 inhibitors should also be aware of the potential occurrence of DKA.…”

“…It should be noted that co‐existence of DKA and HHS is not rare. In recent years, with the use of immune checkpoint inhibitors, diabetes onset following the use of these inhibitors is often characterized by the onset of DKA 222 and may also be accompanied by HHS 223 . Therefore, older patients with diabetes using immune checkpoint inhibitors should be vigilant for both DKA and HHS.…”