Risk factors for medication-induced diabetes mellitus

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To the Editor:

Amed et al¹ compared risk factors for children with type 2 diabetes mellitus and medication-induced diabetes mellitus. Their conclusion that “there is no consistent risk profile for children” to develop medication-induced diabetes is not surprising, given the heterogeneity of underlying medical conditions and diabetogenic agents. Children with medication-induced diabetes mellitus have variable underlying medical conditions. Variable risk profiles have been described even in analyses of groups with a single diagnosis, such as liver transplantation.², ³ Could Amed et al provide the frequency of primary diagnoses in their survey? Grouping patients by underlying condition may help determine a risk profile.

The role of obesity in the development of medication-induced diabetes mellitus merits further investigation. Amed et al hypothesized that their “lean” subset of patients with medication-induced diabetes mellitus exhibit primarily defects in β-cell function, rather than insulin resistance.¹ Do the authors have baseline C-peptide values at onset of diabetes to help differentiate insulin-deficient from insulin-resistant diabetes mellitus? Obesity was present in only 53.4% of the patients with medication-induced diabetes mellitus in the survey; however, insulin resistance may be influenced by other factors, such as exposure to glucocorticoids.⁴ Preliminary data from a cohort of children with diabetes mellitus after liver transplantation have shown a lack of obesity with normal to elevated C-peptide levels, suggesting insulin resistance as a possible underlying mechanism for diabetes mellitus.⁵

To help guide preventive interventions, we suggest that a risk profile for medication-induced diabetes mellitus might be more easily found by matching those individuals with medication-induced diabetes mellitus to a control group with the same underlying medical condition and of the same sex and pubertal stage. Furthermore, obtaining insulin or C-peptide levels at the time of diagnosis may help determine whether insulin deficiency or insulin resistance contributes to the diabetes mellitus and may help direct therapeutic interventions.

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References 

1. Amed S, Dean H, Sellers EA, Panagiotopoulos C, Shah BR, Booth GL, et al. Risk factors for medication-induced diabetes and type 2 diabetes. J Pediatr. 2011;159:291–296
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2. Hathout E, Alonso E, Anand R, Martz K, Imseis E, Johnston J, et al. Post-transplant diabetes mellitus in pediatric liver transplantation. Pediatr Transplant. 2009;13:599–605
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3. Kuo HT, Lau C, Sampaio MS, Bunnapradist S. Pretransplant risk factors for new-onset diabetes mellitus after transplant in pediatric liver transplant recipients. Liver Transplant. 2010;16:1249–1256
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4. Schacke H, Docke WD, Asadullah K. Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther. 2002;96:23–43
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5. Kerkar N, Akler G, Annunziato R, Miloh T, Arnon R, Rapaport R, et al. Diabetes in pediatric liver transplant recipients: endocrine perspective (abstract). Am J Transplant. 2011;11(Suppl 2):497
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