Medication-induced diabetes during induction treatment for ALL, an early marker for future metabolic risk?

Abstract

Medication-induced diabetes (MID) is seen in children treated for acute lymphoblastic leukemia (ALL) mostly during induction, due to the use of l-asparaginase and glucocorticoids. Our objective was to assess whether MID during induction, is a risk factor for future impaired glucose tolerance (IGT), diabetes, or metabolic syndrome. Ninety survivors of pediatric ALL, ages 10 yr and older were recruited, 30 with history of MID and 60 controls. Waist/height ratio >0.5 was considered as an increased risk for central adiposity and insulin resistance. Lipid profile and an oral glucose tolerance test (OGTT) were performed. Study patients were older than controls (17.2 vs. 14.9, p < 0.05). The groups had similar sex distribution, body mass index (BMI) z-score, and Tanner staging. A waist/height ratio of >0.5 was seen in 60 and 31.7% of the study and control groups, respectively (p = 0.01). Increased frequency of IGT in the study group compared with the control group was seen (13.3 and 1%, respectively) (p = 0.07). We observed a trend toward higher proportion of patients with multiple features of metabolic syndrome in the study compared with control group (16.7 vs. 5%, p = 0.09). In conclusion, MID during induction may be an early marker for metabolic disturbances later in life. The higher rates of increased waist/height ratio, and subjects with multiple metabolic syndrome features, may predict a metabolic risk in children with history of MID. Rates of IGT were four fold higher in the study group although not statistically significant. MID may be a 'red flag' indicating the need for ongoing metabolic screening and lifestyle modifications to prevent future metabolic disease.

Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

“…The risk of corticosteroid-induced hyperglycemia is aggravated by asparaginase therapy 112, 113 . The prevalence of hyperglycemia during ALL therapy has been reported to be 10% to 20% during treatment with asparaginase and corticosteroids, most frequently in children above 10 years of age, with resolution after cessation or tapering down of these drugs 112– 116 . Medication-induced diabetes may be a marker for metabolic disease later in life 116 .…”

“…The prevalence of hyperglycemia during ALL therapy has been reported to be 10% to 20% during treatment with asparaginase and corticosteroids, most frequently in children above 10 years of age, with resolution after cessation or tapering down of these drugs 112– 116 . Medication-induced diabetes may be a marker for metabolic disease later in life 116 . Finally, hyperglycemia and obesity both have been associated with reduced event-free survival 117, 118 .…”

National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Cardiovascular Disease and Associated Risk Factors Working Group Report

“…13, 14, 62, 63 Additional risk factors include allogeneic HCT, 13, 14 grades II–IV acute GvHD, 13 cumulative prednisone dose, 40 unfavorable dietary habits, 43 lower physical activity 43 and family history of T2DM. 59 The contributions of therapeutic exposures prior to HCT 64 and acute phase hyperglycemia during HCT 40 to post-HCT risk of glucose metabolism dysregulation are not known. Patients treated with HCT and who developed DM, PDS or IR were more likely to experience changes in body composition and fat distribution rather than obesity based on body mass index (BMI).…”

Obesity and Metabolic Syndrome Among Adult Survivors of Childhood Leukemia

“…Other treatment-related risk factors independent of CRT that may impact adult obesity among survivors of childhood ALL include the type and dose of glucocorticoid exposure [25], the development of medication induced insulin resistance or diabetes during therapy [26, 27], and the amount of on therapy weight gain [25]. While the mechanisms underlying weight gain in children who do not receive CRT during treatment for ALL are unclear [28, 29], adiposity in these children is associated with increasing serum leptin levels and cumulative doses of glucocorticoids [26, 22].…”