Diabetes and Blood Glucose Disorders Under Anti-PD1

Abstract

Acute type 1 diabetes (AD1) is a rare but definitive immune-related adverse event associated with anti-PD1. Most of the reported cases are close to what has been described as "fulminant type 1 diabetes." We sought to determine whether anti-PD1 could impair glycoregulation and whether occurrence of AD1 could be anticipated by prior glycemic changes. Fasting glycemia collected before, under, and after treatment in melanoma patients treated with anti-PD1 over a period of 36 months were retrospectively analyzed. Glycemic trend analyses were performed using linear regression analysis. In total, 1470 glucose values were monitored in 163 patients treated for a mean duration of 5.96 months. Three patients developed an AD1 (1, 84%). Two other cases were observed in the same period in a still-blinded trial of anti-PD1 versus ipilimumab. All cases of AD1 occurred in patients with a normal pretreatment glycemia, and there was no detectable drift of glycemia before ketoacidosis onset. In 4 of 5 cases of AD1, the HLA subgroups were DRB01* 03 or 04, known to increase type 1 diabetes risk in the general population. In the 28 patients with preexisting type 2 diabetes, there was a slight trend for glycemia increase with anti-PD1 infusions (0.05 mmol/L/infusion P=0.004). In the 132 patients with normal pretreatment glycemia, there was a slight trend for a decrease of glycemia with anti-PD1 infusions (-0.012/mmol/L/infusion P=0.026). These data suggest that the monitoring of glycemia under anti-PD1 cannot help to anticipate AD1, and there is no general tendency to glycemic disorder. HLA genotyping before treatment may help to focus surveillance in patients with the HLA DRB1*03/04 group.

Rapid onset type 1 diabetes with anti-PD-1 directed therapy

“…Our findings are consistent with the results of a retrospective study done by Magis et al that looked at the fasting glucose of patients before, during and after anti-PD-1 treatment and found that all cases of type 1 diabetes occurred in patients with normoglycemia prior to DKA occurrence [23]. In the setting of these findings, Magis et al advises against monitoring of blood glucose in patients on immunotherapy [23]. Patients in our case series had their blood glucose checked as part of the basic metabolic panel to assess glycemia, renal function and other electrolytes while on immunotherapy.…”

“…However, a review of glycemia in our case series did not show any sustained elevations in blood glucose levels preceding newly diagnosed diabetes. Our findings are consistent with the results of a retrospective study done by Magis et al that looked at the fasting glucose of patients before, during and after anti-PD-1 treatment and found that all cases of type 1 diabetes occurred in patients with normoglycemia prior to DKA occurrence [23]. In the setting of these findings, Magis et al advises against monitoring of blood glucose in patients on immunotherapy [23].…”

“…Our findings are consistent with the results of a retrospective study done by Magis et al . that looked at the fasting glucose of patients before, during and after anti-PD-1 treatment and found that all cases of type 1 diabetes occurred in patients with normoglycemia prior to DKA occurrence [ 23 ]. In the setting of these findings, Magis et al .…”

Is immune checkpoint inhibitor-associated diabetes the same as fulminant type 1 diabetes mellitus?

“…61,68 Pre-existing type 2 diabetes did not appear to predict occurrence. 52 It is however important to note that these studies are mostly cross-sectional and retrospective in nature. Prospective studies are needed before any conclusions can be drawn regarding the risk factors of developing ICIinduced diabetes.…”

Treatment of Advanced Melanoma: Past, Present and Future

“…The correlation between human leukocyte antigen (HLA) subtypes and several irAEs caused by ICIs has been investigated in various studies [47,[75][76][77][78][79]. For example, Fujimura et al reported two cases of advanced melanoma patients who possessed HLA-DRB1*04:05, which is strongly associated with VKH disease, developing VKH-like uveitis after sequential administration of nivolumab and D + T combination therapy [47].…”