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Hyperinsulinemia, Impaired Glucose Tolerance, and Diabetes Mellitus in Survivors of Childhood Cancer: Prevalence and Risk Factors

Department of Endocrinology (K.A.N., J.L.W.) and Center for Children’s Cancer and Blood Disorders (R.J.C., K.J.), Sydney Children’s Hospital, Sydney, New South Wales 2031, Australia; School of Women’s and Children’s Health (K.A.N., R.J.C., J.L.W.), University of New South Wales, Sydney, New South Wales 2052, Australia; Department of Endocrinology (K.S.S.), Royal Prince Alfred Hospital, Sydney, New South Wales 2050, Australia; and Faculty of Medicine (K.S.S.), University of Sydney, Sydney, New South Wales 2046, Australia

Address all correspondence and requests for reprints to: Dr. Kristen Neville, Department of Endocrinology, Sydney Children’s Hospital, High Street Randwick, New South Wales 2031, Australia. E-mail: kristen.neville{at}sesiahs.health.nsw.gov.au.

Context: Hyperinsulinism and its associated metabolic abnormalities, including diabetes mellitus (DM), have been reported in long-term survivors of childhood cancer, mainly after bone marrow transplant (BMT); however, the predisposing factors are unclear, and early markers have not been identified.

Methods: The prevalence of overweight/obesity, abdominal adiposity and hyperinsulinemia (HI), impaired glucose tolerance (IGT), or DM was examined prospectively in 248 survivors of childhood cancer (36 prepubertal, 88 pubertal, and 124 adult subjects; 67 BMT) at a median of 12.9 yr (2.3–33.6) after diagnosis and compared with healthy controls. Potential risk factors for the development of HI, IGT, or DM were sought.

Results: Overweight/obesity was not increased when comparing subjects with controls; however, the prevalence of abdominal adiposity in prepubertal and pubertal subjects was roughly doubled (P 0.04). Fasting insulin concentrations were higher in prepubertal and pubertal subjects compared with their controls (P < 0.001) and were similar in adult and pubertal subjects. HI, IGT, or DM was detected in 39 of 212 (18%) pubertal or adult subjects (23 BMT). Ten of 88 (11%) pubertal and 14 of 124 (11%) adult subjects had IGT/DM (vs. 0 and 4.9% controls, respectively; P < 0.001). Total body irradiation, untreated hypogonadism, and abdominal adiposity emerged as independent risk factors for the development of HI, IGT, or DM in multivariate regression analysis.

Conclusions: The risk factors identified suggest the need for reconsideration of BMT protocols and regular screening of survivors. The increased prevalence of abdominal adiposity among prepubertal subjects, none of whom had developed HI/IGT/DM, suggests that a waist to height ratio greater than 0.5 has potential as a clinical screening tool.

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