Monitoring for the development of DIDM during ALL directed therapy
It is important to plan screening and monitoring blood sugars taking into consideration the potency of steroids used, its dose, duration and peak action, dosing schedule, individual risk to develop DIDM, concomitant usage of other drugs which can synergistically result in DIDM.
Prednisolone, an intermediate-acting glucocorticoid when used as single morning dose likely to result in post lunch and night time hyperglycemia matching their peak (4-6 hours) and duration of action (12-16 hours). However, prednisolone when administered in divided doses can cause persistent hyperglycemia throughout the day with post prandial peak. Dexamethasone a long-acting steroid (duration of action >24 hours) will result in persistent hyperglycemia throughout the day with a slight decline after an overnight fast (25)(26)(27)(28).
Steroid induced hyperglycemia is known to occur acutely and transiently. Hence Endocrine Society guidelines on management of hyperglycaemia in earlier non-diabetic, non-critically ill hospitalised patients on steroid therapy advocates discontinuation of monitoring after 24-48 hours if all measured blood glucose values are normal(29)(30). But a recent study conducted in children with ALL noticed that, during Induction phase hyperglycemia can develop anywhere between first to fifth week after initiation of steroids(31). Similarly, non-diabetic adults with ALL on steroid therapy were shown to have hyperglycemic episodes between 2-4 weeks after initiation of induction chemotherapy(32). These findings were replicated in other studies involving adults, secondary to glucocorticoid exposure in non ALL settings(33)(34)(35). Diabetes Mellitus secondary to L-asparaginase occurs mostly within first week of initiation of treatment(36)(21)(37). Recently, PEG L-asparaginase usage in ALL has reduced the incidence of DIDM from 25% to 5-7 %(37).
Monitoring for DIDM should begin with documentation of baseline blood glucose levels before initiation of chemotherapy. We suggest glucose measurement for 2-3 days per week in all children on ALL directed chemotherapy (post lunch and/or pre dinner glucose when on intermediate-acting glucocorticoids as single morning dose and additional fasting glucose when on long-acting steroids or intermediate-acting steroids in divided doses) to diagnose DIDM throughout the period of steroid therapy, in addition to close watch for hyperglycemic symptoms. When on L-Asparaginase alone (without steroids), we suggest 2 to 3 random glucose testing routinely in the first week, followed by as and when required in case of hyperglycaemic symptoms, until completion of therapy.
We suggest the screening, diagnosis and treatment optimization using bedside Point Of Care (POC) capillary glucose monitoring (29). Diagnostic accuracy of POC meters should be at least 20% of real values(38). Due consideration to variables that can affect POC glucometer functioning like site and procedure of testing, high or low haemoglobin levels, low tissue perfusion and interaction with extraneous substances should be considered before interpreting values(39).