title: 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.
authors.affiliation: Division of Endocrinology, Safra Children's Hospital, Ramat Gan, Israel; Department of Pediatrics, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Yeshayahu
authors.forename: Dror
authors.initials: D
authors.lastname: Koltin
authors.forename: Jill
authors.initials: J
authors.lastname: Hamilton
authors.forename: Paul C
authors.initials: PC
authors.lastname: Nathan
authors.forename: Stacey
authors.initials: S
authors.lastname: Urbach
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002648:Child; D003920:Diabetes Mellitus / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology; D006776:Hospitals, Pediatric; D006801:Humans; D060828:Induction Chemotherapy / Q000009:adverse effects*; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology; D056128:Obesity, Abdominal; D009864:Ontario / Q000453:epidemiology; D063766:Pediatric Obesity; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy*; D012074:Remission Induction; D012307:Risk Factors; D017741:Survivors; D065927:Waist-Height Ratio
chemical_list: D015415:Biomarkers
keywords: acute lymphoblastic leukemia; diabetes; impaired glucose tolerance; medication-induced diabetes; metabolic syndrome