A Case of Doxorubicin and Cyclophosphamide Therapy-induced Type 1 Diabetes

A Case Report

Makoto Miyabayashi; Shunichiro Onishi; Tomohiko Yoshida; Minoru Takemoto

J Med Case Reports. 2023;17(26)

Abstract and Introduction

Abstract

Background: Patients receiving immune checkpoint inhibitors have been reported to develop autoimmune endocrine diseases, including type 1 diabetes, although few drugs have been shown to induce type 1 diabetes. Additionally, it is important to note that drugs other than immune checkpoint inhibitors could lead to the development of type 1 diabetes.

Case Presentation: A 54-year-old Filipino female patient underwent surgery for left-sided breast cancer. Postoperative chemotherapy was initiated, including doxorubicin (Adriamycin) and cyclophosphamide therapy. The patient was brought to our hospital by ambulance after consciousness disturbance following three courses of doxorubicin and cyclophosphamide therapy and was hospitalized. Her blood glucose and hemoglobin A1c levels were 1661 mg/dL and 11.9%, respectively. The patient was diagnosed with diabetic ketoacidosis after arterial blood gas analysis indicated a blood pH of 7.120. Her insulin secretion was impaired, and her anti-glutamic acid decarboxylase antibody test result was significantly positive.

Conclusions: The present case shows that doxorubicin and cyclophosphamide therapy may cause unexpected adverse responses, such as type 1 diabetes, though rarely, and highlights the importance of careful patient follow-up. This report is the first to present a case of type 1 diabetes that suddenly developed after doxorubicin and cyclophosphamide treatment.

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Table 1. Laboratory findings on admission as well as 6 months after hospitalization
	On admission	6 months after hospitalization	Normal range
WBC (/μ)	14,300	4980	3300–8600
RBC (×10⁶/μ)	4.32	4.72	3.86–4.92
Hb (g/dL)	12.5	12.7	11.6–14.8
Hct (%)	36.2	39.3	35.1–44,4
Platelets (×10³/μ)	121.0	231	158–348
Blood glucose (mg/dL)	1161	86	73–109
HbA1c (%)	11.9	6.6	4.9–6.0
AST (U/L)	30	18	13–30
ALT (U/L)	23	18	7–23
γ-GT (U/L)	61	23	9–32
LDH (U/L)	461	154	124–222
T-bilirubin (mg/dL)	0.4	0.3	0.4–1.5
ALP (U/L)	188	60	38–113
BUN (mg/dL)	88.1	14.7	8–20
Cre (mg/dL)	2.14	0.88	0.46–0.79
Na (mEq/L)	152	143	138–145
K (mEq/L)	4.3	4.7	3.6–4.8
Cl (mEq/L)	110	105	101–108
Acetoacetic acid (μmol/L)	562	NA	− 55
3-Hydroxybutyric acid (μmol/L)	1208	NA	− 85
Total ketone bodies (μmol/L)	1770	NA	− 130
CRP (mg/dL)	9.82	NA	0.0–0.2
U-ketone bodies	(1+)	(−)	(−)

HLA human leukocyte antigen

Table 2. The HLA type in the present patient
HLA-A	02:01:01	11:01:01
HLA-B	15:35	48:01:01
HLA-C	07:02:01	08:01:01
HLA-DRB1	09:01:02	15:02:01
HLA-DRB3/4/5	4 × 01:03:02	5 × 01:01:01
HLA-DQA1	01:02:01	03:02:01
HLA-DQB1	03:03:02	05:02:01
HLA-DPA1	02:02:02	–
HLA-DPB1	05:01:01	135:01

WBC white blood cell, RBC red blood cell, Hb hemoglobin, Ht hematocrit, HbA1c hemoglobin A1c, AST aspartate aminotransferase, ALT alanine aminotransferase, g-GT gamma-glutamyl transferase, T-bilirubin total-bilirubin, ALP alkaline phosphatase, BUN blood urea nitrogen, Cre creatinine, CRP c-reactive protein, U-ketone bodies urinary ketone bodies