Table 3

Disease characteristics and course of individual patients with PD-1 inhibitor induced new-onset insulin-dependent diabetes

PtBMIICIPre-ICI laboratory dataPresentationC-peptide (ng/mL), PG (mg/dL)Doses/
time (months) to presentation
AntibodiesOther IRAETherapy
125PembrolizumabFPG 95 mg/dL, RPG 96 mg/dL. Mild DKA: RPG 580 mg/dL, HbA1c 8.6%, urine ketone 40, and β-OHB 1.3 mmol/L.0.9, 1292/2.1GAD65 0.06; IAA and IA-2A negative.Thyroiditis.MDI.
235PembrolizumabFPG 78 mg/dL. Severe DKA: RPG 971 mg/dL, HbA1c 10.7%, β-OHB 10.8 mmol/L, and lipase 661 IU/L.<0.1, 1471/2.2GAD65 0.21; IAA and IA-2A negative.Thyroiditis.MDI →
insulin pump.
338PembrolizumabFPG 83 mg/dL, RPG 108 mg/dL. DKA/HHS: RPG 972 mg/dL, HbA1c 7.8%, and β-OHB 3.7 mmol/L.<0.1, 2781/0.6GAD65 15.4, IAA 0.05, IA-2A 0.17; ZnT8A negative.Thyroiditis.MDI.
425PembrolizumabNot tested.RPG 600 mg/dL, HbA1c 10.5%, and trace urine ketone.0.3, 2503/4.8IAA 0.14; GAD 65, IA-2A, ZnT8A negative.Metformin → MDI.
523NivolumabFPG tested once 105 mg/dL.RPG 600 mg/dL.4/5.5Thyroiditis.MDI.
635Ipilimumab → PembrolizumabFPG 108 mg/dL, RPG tested once 140 mg/dL, HbA1c 5.4%.RPG 377 mg/dL, FPG 321, and HbA1c 9.7%.5.2, 3216/4.9Metformin → MDI.
731PembrolizumabFPG 86 mg/dL, RPG tested once 141 mg/dL. Severe DKA: RPG 644 mg/dL, HbA1c 9.7%, and β-OHB 6.8 mmol/L.5/7.8GAD65 negative.Thyroiditis and hypophysitis.MDI.
833PembrolizumabFPG tested once 106 mg/dL. Mild DKA: RPG 460 mg/dL, FPG 311 mg/dL, HbA1c 7.8, urine ketone 750, β-OHB 0.2 mmol/L, and lipase 120 IU/L.0.7, 14217/9.7GAD65 0.05; IAA, IA-2A, ZnT8A negative.Metformin basal insulin → MDI.
945PembrolizumabFPG 96 mg/dL, RPG 114 mg/dL. Severe DKA: RPG 429 mg/dL, FPG 236 mg/dL, HbA1c 11.3%, urine ketone 750, and β-OHB 8 mmol/L.16/23.6Dermatitis, hypophysitis, and arthritis.MDI.
1025PembrolizumabFPG tested once 126 mg/dL. Mild DKA: RPG 426 mg/dL, FPG 335 mg/dL, HbA1c 11.2%, β-OHB 1.9 mmol/L, and increased pancreas FDG uptake.4/3MDI.
1123PembrolizumabRPG 84 mg/dL. Severe DKA: RPG 1389 mg/dL, HbA1c 8.8%, β-OHB 14 mmol/L, lipase 226, and GGT 227.0.4, 8662/0.7MDI.
1246PembrolizumabFPG 99 mg/dL. Mild ketosis: FPG 448 mg/dL, and HbA1c 10.6 β-OHB 1.2 mmol/L.4/8.2GAD65, IAA, IA-2A, ZnT8A negative.MDI.
  • BMI, body mass index; DKA, diabetic ketoacidosis; FPG, fasting plasma glucose; GAD65, glutamic acid decarboxylase 65; GGT, gamma-glutamyl transferase; HHS, hyperglycemic hyperosmolar state; HbA1c, hemoglobin A1c; IA-2, islet antigen 2; IAA, insulin autoantibodies; ICI, immune checkpoint inhibitor; IRAE, immune-related adverse event; MDI, multiple daily injections of insulin; β-OHB, beta-hydroxybutyrate; PD-1, programmed cell death protein 1; RPG, random plasma glucose; ZnT8A, Zinc transporter 8 antibody.