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).