Flash Glucose Monitoring and Diabetes Mellitus Induced by Immune Checkpoint Inhibitors: An Approach to Clinical Practice

Abstract

Objectives. The aim of this study is to investigate in depth diabetes mellitus associated with immune checkpoint inhibitors (DM-ICIs) by analysing a case series. We also evaluated the clinical impact of flash glucose monitoring (FGM) systems in the management of this entity. Methods. We conducted an observational cohort study of DM-ICIs diagnosed in two hospitals in Seville (Spain). Patients with a new diagnosis of diabetes mellitus (DM) or with sudden worsening of preexisting DM after starting treatment with ICIs, with a random 5 hour-postprandial C-peptide value of <0.6 nmol/L and without possibility of subsequent withdrawal of insulin treatment, were included. Results. A total of 7 cases were identified, mostly males ( $n=6$ ; 85.7%), with a mean age of 64.9 years. The mean glycated hemoglobin (HbA1c) upon diagnosis was 8.1%, with diabetic ketoacidosis (DKA) observed in 6 cases (85.7%). Subcutaneous flash glucose monitoring (FGM) systems were used in six cases, with a mean follow-up period of 42.7 weeks. During the first 90 days of use, mean average glucose was 167.5 mg/dL, with a coefficient of variation (CV) of 34.6%. The mean time in the range 70-180 mg/dL (TIR) was 59.7%, with a mean time above range (TAR) 181-250 mg/dL of 27.8% and a mean $\text{TAR}>250\text{mg}/\text{dL}$ of 10.2%. The mean time below range (TBR) 54-69 mg/dL was 2%, while the mean $\text{TBR}<54\text{mg}/\text{dL}$ was 0.3%. The mean glucose management indicator (GMI) was 7.3%. No significant differences were observed in FGM values for the following 90 days of follow-up. A progressive improvement in all parameters of glycaemic control was observed between the first month of FGM use and the sixth month of FGM use. Of note, there was a decrease in mean CV (40.6% to 34.1%, $p=0.25$ ), mean TAR 181-250 (30.3% to 26%, $p=0.49$ ), mean $\text{TAR}>250\text{mg}/\text{dL}$ (16.3% to 7.7%, $p=0.09$ ), mean TBR 54-69 mg/dL (5.2% to 2%, $p=0.16$ ), and mean $\text{TBR}<54\text{mg}/\text{dL}$ (1.8% to 0.2%, $p=0.31$ ), along with an increase in mean values of TIR 70-180 mg/dL (46.5% to 60.5%, $p=0.09$ ). The lack of statistical significance in the differences observed in the mean FGM values over the follow-up period may be related to the small sample size. Conclusion. DM-ICI is recognised by a state of sudden-onset insulinopenia, often associated with DKA. The use of FGM systems may be a valid option for the effective management of DM-ICIs and for the prevention of severe hyperglycaemic and hypoglycaemic episodes in this condition.