PD-1 inhibitor-induced fulminant type 1 diabetic ketoacidosis：a case report and literature review

doi:10.16150/j.1671-2870.2026.02.015

Abstract

Abstract:

Programmed death receptor 1 (PD-1) inhibitors are a type of immune checkpoint inhibitors (ICI), which are widely used in cancer therapy, but can easily trigger immune-related adverse events, among which fulminant type 1 diabetic ketoacidosis (DKA) is relatively rare. As of February 2025, a search was conducted on PubMed, and a total of 59 cases of fulminant type 1 diabetes ketoacidosis (DKA) induced by ICI with complete data were summarized, including 31 males and 28 females. The median age at onset was 61 years (range: 14-87 years), and the primary tumors were mainly melanoma (27.1%) and non-small cell lung cancer (18.6%). Among the therapeutic agents, PD-1 monoclonal antibodies account for the highest proportion (67.8%), with pembrolizumab (18 cases) and nivolumab (17 cases). This paper reports a case of fulminant type 1 diabetic ketoacidosis in a patient with malignant gastric antrum tumor after treatment with the PD-1 inhibitor tirelizumab. At present, it is believed that its pathogenesis may be related to abnormal activation of the immune system. Diagnosis is mainly based on clinical symptoms and signs, laboratory tests, and relevant medical history. For cancer patients receiving PD-1 inhibitor therapy, a rapid rise in blood glucose and the onset of DKA symptoms in the short term should raise a high level of concern for this condition after excluding other common causes of diabetes. In terms of treatment, timely fluid resuscitation, ketone clearance, short-term insulin therapy, and active symptomatic management are crucial. ICI-related diabetes is not an absolute contraindication for PD-1 inhibitor therapy. Once the patient's condition stabilizes, it can be continued under close monitoring. In this case, this patient was diagnosed timely and accurately. After insulin therapy, blood glucose was well controlled. PD-1 inhibitors could be continued under strict monitoring after discharge. This case report provides clinical experience, reminding clinicians that when using PD-1 inhibitors, in addition to monitoring thyroid and pituitary function, blood glucose fluctuations should be monitored simultaneously, and multidisciplinary collaboration should be emphasized to avoid serious consequences of acute complications of diabetes.

Key words: Diabetes, Immune checkpoint inhibitors, Fulminant type 1 diabetes, Diabetic ketoacidosis, Programmed death receptor 1 inhibitors

CLC Number:

R587.2
R445

WEN Bin, ZHU Hong, LIU Shi, QIN Feixue, HE Juankun, GUI Li. PD-1 inhibitor-induced fulminant type 1 diabetic ketoacidosis：a case report and literature review[J]. Journal of Diagnostics Concepts & Practice, 2026, 25(02): 232-238.

Figures/Tables 7

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References 20

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时间	项目	结果	参考值
入院前23 d	血清葡萄糖（mmol/L）	7.14	3.9~6.1
入院前9 d	血清葡萄糖（mmol/L）	6.51	3.9~6.1
	淋巴细胞亚群检测
	T细胞比率（%）	59.4	61.5~76.3
	T₄细胞比率（%）	20.4	31.4~43.8
	T₈细胞比率（%）	37.1	18~27.8
	T₄/T₈比值	0.55	1.19~2.27
	NK细胞比率（%）	31.1	9.5~21.9
	细胞因子诱导性杀伤细胞比率（%）	2.13	0.05~5.05
	CTL细胞比率（%）	3.03	8.1~15.7
	PD-1阳性细胞比率（%）	0.33	0.45~3.03
	CTLA-4阳性细胞比率（%）	0.33	0.64~3.30
	甲状腺功能
	三碘甲状腺原氨酸（ng/mL）	1.24	0.8~1.9
	甲状腺激素（μg/dL）	9.37	5~13
	血清促甲状腺激素（μIU/mL）	2.07	0.27~4.20
	甲状腺球蛋白（ng/mL）	50.38	3.5~77.0
	抗甲状腺球蛋白抗体（U/mL）	264.70	<115
	抗甲状腺过氧化物酶抗体（U/mL）	237.38	<40
	游离三碘甲状腺原氨酸（pmol/L）	5.29	3.5~7.0
	游离甲状腺素（pmol/L）	17.53	8.5~22.5

项目	结果	参考值
血清葡萄糖（mmol/L）	34.27	3.8~6.1
糖化血红蛋白（%）	8.32	4.0~6.4
血清果糖胺测定（mmol/L）	0.338	0~0.286
尿常规
尿蛋白	1+	阴性
尿葡萄糖	4+	阴性
尿酮体	3+	阴性
血气分析
酸碱度	7.092	7.35~7.45
二氧化碳分压（mmHg）	15.4	35~48
氧分压（mmHg）	116.5	80~100
实际碳酸氢根（mmol/L）	4.6	21~26
乳酸（mmol/L）	4.40	0~2.2
血常规
白细胞（10⁹/L）	25.78	3.5~9.5
红细胞（10¹²/L）	4.35	4.3~5.8
血小板（10⁹/L）	209.0	125~350
血红蛋白（g/L）	137	130~175
超敏C反应蛋白（mg/L）	4.91	0~3.0
白细胞介素6（pg/mL）	27.685	<7

血生化	结果	参考值
谷丙转氨酶（U/L）	26.6	0~41
谷草转氨酶（U/L）	15.7	0~40
碱性磷酸酶（U/L）	229	40~130
白蛋白（g/L）	46.4	35~52
γ谷氨酰转肽酶（U/L）	45	8~58
尿素（mmol/L）	11.26	2.8~8.3
肌酐（mmol/L）	106	50~130
尿酸（mmol/L）	479	150~417
钾（mmol/L）	5.56	3.5~5.5
钠（mmol/L）	131.9	136~155
氯（mmol/L）	97.2	90~110
钙（mmol/L）	2.34	2.09~2.54
镁（mmol/L）	1.18	0.67~1.04
磷（mmol/L）	1.84	0.8~1.5

项目	结果	参考值
糖尿病三抗体
抗谷氨酸脱羧酶抗体（IU/mL）	0.85	<10.00
胰岛素自身抗体（COI）	0.14	<1.10
胰岛细胞抗体（COI）	0.05	<1.10
甲状腺功能
三碘甲状腺原氨酸（nmol/mL）	1.3	1.2~2.9
甲状腺素（nmol/mL）	183.35	64.4~167.3
促甲状腺激素（mIU/L）	0.016	0.35~4.75
抗甲状腺球蛋白抗体（IU/mL）	63.8	0~75
抗甲状腺过氧化物酶抗体（IU/mL）	236.9	0~30
游离三碘甲状腺原氨酸（pmol/L）	3.94	3.5~7.0
游离甲状腺素（pmol/L）	31.92	10~22
性激素
催乳素（ng/mL)	31.11	男性：4.04~15.2
睾酮（ng/mL）	6.500	男性：1.66~8.11
雌二醇（pg/mL）	26.85	男性：25.8~60.7
促卵泡生成素（IU/L）	33.37	男性：1.5~12.4
促黄体生成素（IU/L）	16.92	男性：1.7~8.6
孕酮（ng/mL）	0.32	男性：≤0.149

病例特征	结果（n=59）
性别
男/女	31/28
中位发病年龄（范围）	68（14~87）岁
原发肿瘤
黑色素瘤	16（27.1%）
非小细胞肺癌	11（18.6%）
免疫检查点抑制剂
帕博利珠单抗	18（30.5%）
纳武利尤单抗	17（28.8%）
纳武利尤单抗+伊匹木单抗	9（15.3%）
PD-1	40（67.8%）
PD-L1	10（16.9%）
CTLA-4	0（0%）
PD-1+CTLA-4	9（15.3%）
DKA	58（98.3%）
中位血糖	33.83 mmol/L
开始治疗到出现DKA中位时间（范围）	9（0.7~84.0）周
C肽
低水平/未提及	36（61.0%）/16（27.1%）
平均糖化血红蛋白	8.17%
糖尿病相关抗体（检测率)
GADA	53（89.8%）
ICA	25（42.4%）
IAA	18（30.5%）
IA2A	23（39%）
ZnT8	13（22.0%）