Category: Diabetes/Prediabetes/Hypoglycemia

Monitor: 16

16 - PEMBROLIZUMAB-INDUCED FULMINANT DIABETES

Friday, Apr 26
12:30 PM – 1:00 PM

Objective :

Immune-checkpoint inhibitors (ICIs) have been associated with the development of various endocrinopathies. Herein, we report a case of fulminant insulin-deficient diabetes secondary to pembrolizumab.


Methods : n/a


Results :

n/a


Discussion : A 52-year-old man with metastatic lung adenocarcinoma was initiated on an immunochemotherapy regimen consistent of pembrolizumab, pemetrexed and carboplatin. Prior to this, he had been receiving afatinib for approximately 15 months. Six weeks after the initiation of the new medication regimen and just prior to receiving his third cycle of treatment, he was noted to have a random glucose level of 300 mg/dL (74 – 99). A comprehensive metabolic panel was otherwise unremarkable. The finding of new-onset hyperglycemia prompted a referral to Endocrinology and he was evaluated in our clinic the following day. He had no known history of diabetes mellitus. Physical exam was remarkable for obesity (BMI 36). Review of systems was positive for blurry vision, polyphagia and polydipsia. Laboratory studies revealed: random glucose 375 mg/dL, hemoglobin A1C 5.7% (4.2 - 5.6%), fructosamine 443 umol/L  (170 - 285), C-peptide 3.0 ng/mL (0.8 - 3.2), glutamic acid decarboxylase antibody 32.1 IU/mL (<5.0), islet cell antibodies <1:4 (<1:4), insulin antibodies <0.4 U/mL (<0.4). The patient was promptly started on insulin therapy given the concern for pembrolizumab-induced diabetes. Over the following days he was noted to have increasing insulin requirements, necessitating up to a total of 110 daily units of insulin to achieve adequate glycemic control. Pembrolizumab was discontinued by Oncology. C-peptide levels obtained 2, 4, 6, 9 and 20 weeks after the initiation of insulin therapy were 1.7, 0.2, <0.2, <0.2 and <0.2 ng/mL, respectively. At 9 months follow-up he remained fully insulin dependent.


Conclusion : ICIs have dramatically changed the treatment of malignancies that are resistant to conventional therapies. Since their introduction, the life expectancy of patients with lung cancer, renal cell carcinoma, melanoma and other malignancies has significantly increased. However, its use can be hindered by occurrence of serious adverse events related to induction of autoimmunity. For instance, ICIs have been associated with acute onset autoimmune diabetes in approximately 0.2% of patients. Currently there are no recommended treatments for these cases other than the prompt institution of insulin therapy. Biomarkers that could help predict the development of diabetes need to be elucidated, as they might assist in the development of strategies to prevent this serious adverse event.

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Vicente T. San Martin

Endocrinology Fellow
Cleveland Clinic
Beachwood, Ohio

Endocrinology Fellow, Cleveland Clinic

Alexandra Mikhael

Endocrinology Fellow
Department of Endocrinology, Diabetes and Metabolism; Cleveland Clinic
Beachwood, Ohio

Endocrinology Fellow, Cleveland Clinic

Divya Yogi-Morren

Staff Endocrinologist
Cleveland Clinic

Staff Endocrinologist, Cleveland Clinic

Betul Hatipoglu

Staff Endocrinologist
Cleveland Clinic

Staff Endocrinologist, Cleveland Clinic