||5R21CA261713-02 Interpret this number
||Dixon , Stephanie
||St. Jude Children'S Research Hospital
||PREDM: an Adaptive, Open-Label, Pilot Intervention Trial for Diabetes Prevention
Childhood cancer survivors have nearly twice the risk for developing diabetes compared to their siblings.
Diabetes is an established cardiovascular risk factor potentiating the risk for major cardiac events among
survivors, which is critical as cardiac death is the leading cause of non-cancer late mortality in this population.
Thus, diabetes is a major modifiable risk factor for cardiac risk reduction. Further, diabetes is known to increase
risk for other chronic health conditions, including chronic kidney disease, which survivors experience at higher
rates than the general population. Fortunately, prediabetes is easily diagnosed by fasting laboratory measures.
In the general population, pharmacologic therapy with metformin or intensive lifestyle intervention used in the
Diabetes Prevention Program (DPP) prevents progression to diabetes. Without intervention, it is estimated that
4-10% of adults with prediabetes in the general population will become diabetic each year. Yet, little is known
about prediabetes in survivors despite previous reports from the St. Jude Lifetime Cohort Study (SJLIFE) that
suggest up to one-third of adult survivors are prediabetic. Our preliminary data suggests that the prevalence of
prediabetes among childhood cancer survivors is near twice that of similarly aged controls among young adults
(18-<45 years). Further, survivors have unique, treatment-related risk for abnormalities in glucose control and
insulin homeostasis (including abdominal radiation, cranial radiation, hematopoietic cell transplant and
corticosteroid exposure). Therefore, it is unknown if interventions that are used in the general population to
prevent diabetes will be similarly efficacious and well tolerated among survivors. The SJLIFE cohort now contains
comprehensive treatment information and direct medical assessments for over 5,000 adult survivors. Leveraging
this resource, we aim to pilot an adaptive, open-label intervention to prevent diabetes using a combination of
daily metformin and a digitally-delivered lifestyle change program among adult survivors of childhood cancer with
prediabetes. All participants will initially take part in a lifestyle change program run-in period with the addition of
daily metformin among participants who remain at high-risk for prediabetes based on laboratory criteria. The
primary objective is to provide essential feasibility data as well as preliminary evidence for efficacy (improved
glycemic control and/or insulin resistance) for a future randomized intervention trial for prevention of diabetes
and associated cardiac complications in this high-risk population. Exploratory objectives are to evaluate the effect
of treatment on insulin sensitivity, anthropometric measures, physical activity, dietary change, health-related
quality of life and frailty.