Exposure and outcomes definitions
While debate exists among clinicians and statisticians about the best
representation of GV, CV has begun to emerge as the preferred metric due
to its advantage of being relative to mean glucose and thus more
descriptive of hypoglycemic excursions than SD, which is largely only
reflective of hyperglycemic excursions.4-7 Therefore,
CV was used to measure GV for each subject using laboratory-measured
serum glucose values over pre-transplant (day -14 to 0) and post-HSCT
(days 0-30) intervals to evaluate for HSCT-related stress GV and its
effects. Because glucose CV is meant to reflect nonfasting glucose over
an extended period, all glucose values were included, exceptglucose
values within one hour of a previous glucose value were censored to
reduce oversampling. Evaluation of potential outliers did not
significantly impact results. Whole blood glucose measurements were
typically performed daily in the early morning (between 12 and 3 A.M.)
during hospital admission, and typically one to three daytime
measurements per week after discharge. Because natural glucose CV
categories are not clearly defined, we analyzed glucose CV continuously
for all models. However, for descriptive purposes, glucose CV was
categorized into four groups approximating published nonfasting CV
ranges in various populations. The groups are: healthy adults (Grade 1,
<20%), adults who are obese or receive aggressive oral
therapy for type 2 diabetes (Grade 2, ≥20 and <27%), adults
with type 1 or 2 diabetes that is well-controlled with insulin (Grade 3,
≥27 and <36%) and adults with poorly controlled type 1
diabetes (Grade 4, ≥36%).5,8
Post-HSCT outcomes included time to: death from any cause,
transplant-related mortality (TRM), diagnosis of severe GVHD (defined as
acute grades III-IV or chronic) 9,10, clinically
significant infection in the first 100 days, and ICU admission in the
first 100 days post-HSCT. Clinically significant infections were defined
by hospitalization for a positive microbiology result or
diagnostic/problem list code. Infections were further categorized by
serious bacterial infection (SBI), viremia/viruria, or invasive fungal
infection. Serious bacterial infections included infections such as
bacteremia, bacterial peritonitis, meningitis, and pneumonia with
hypoxemia. To be classified as clinically significant for
viremia/viruria, we required both positive high viral load (of Ebstein
Barr virus, Human herpes virus 6, adenovirus, cytomegalovirus, and BK
virus) and symptoms requiring hospitalization and treatment, when
available. To reduce the risk of misclassification bias, subjective
outcomes (infection, GVHD) were reviewed by at least one study
physician; any unclear outcomes were classified by 1-3 additional study
physicians.
A list of exposure variables/covariates and their definitions is
provided in the appendix (Table S1). Data were censored at the time of
any recurrence/progression of primary disease, graft failure, or second
HSCT. Because of the nature of HSCT care, there was not a notable amount
of missing data or loss to follow-up.