Table 3.
Disease characteristics and course of individual patients with PD-1 inhibitor induced new-onset insulin-dependent diabetes
| Pt | BMI | ICI | Pre-ICI laboratory data | Presentation | C-peptide (ng/mL), PG (mg/dL) | Doses/ time (months) to presentation |
Antibodies | Other IRAE | Therapy |
| 1 | 25 | Pembrolizumab | FPG 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, 129 | 2/2.1 | GAD65 0.06; IAA and IA-2A negative. | Thyroiditis. | MDI. |
| 2 | 35 | Pembrolizumab | FPG 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, 147 | 1/2.2 | GAD65 0.21; IAA and IA-2A negative. | Thyroiditis. | MDI → insulin pump. |
| 3 | 38 | Pembrolizumab | FPG 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, 278 | 1/0.6 | GAD65 15.4, IAA 0.05, IA-2A 0.17; ZnT8A negative. | Thyroiditis. | MDI. |
| 4 | 25 | Pembrolizumab | Not tested. | RPG 600 mg/dL, HbA1c 10.5%, and trace urine ketone. | 0.3, 250 | 3/4.8 | IAA 0.14; GAD 65, IA-2A, ZnT8A negative. | – | Metformin → MDI. |
| 5 | 23 | Nivolumab | FPG tested once 105 mg/dL. | RPG 600 mg/dL. | 4/5.5 | – | Thyroiditis. | MDI. | |
| 6 | 35 | Ipilimumab → Pembrolizumab | FPG 108 mg/dL, RPG tested once 140 mg/dL, HbA1c 5.4%. | RPG 377 mg/dL, FPG 321, and HbA1c 9.7%. | 5.2, 321 | 6/4.9 | – | – | Metformin → MDI. |
| 7 | 31 | Pembrolizumab | FPG 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. | – | 5/7.8 | GAD65 negative. | Thyroiditis and hypophysitis. | MDI. |
| 8 | 33 | Pembrolizumab | FPG 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, 142 | 17/9.7 | GAD65 0.05; IAA, IA-2A, ZnT8A negative. | – | Metformin basal insulin → MDI. |
| 9 | 45 | Pembrolizumab | FPG 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. | – | 16/23.6 | – | Dermatitis, hypophysitis, and arthritis. | MDI. |
| 10 | 25 | Pembrolizumab | FPG 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. | – | 4/3 | – | – | MDI. |
| 11 | 23 | Pembrolizumab | RPG 84 mg/dL. | Severe DKA: RPG 1389 mg/dL, HbA1c 8.8%, β-OHB 14 mmol/L, lipase 226, and GGT 227. | 0.4, 866 | 2/0.7 | – | – | MDI. |
| 12 | 46 | Pembrolizumab | FPG 99 mg/dL. | Mild ketosis: FPG 448 mg/dL, and HbA1c 10.6 β-OHB 1.2 mmol/L. | – | 4/8.2 | GAD65, 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.