Severe insulin resistance in long-term acute leukaemia survivors: lesson learned from a clinical case and review of the literature

Authors

  • Bilal Bashir Department of Diabetes, Endocrinology and Specialist Weight Management, Bolton NHS Foundation Trust, Bolton BL4 0JR UK
  • Moulinath Banerjee 1. Department of Diabetes, Endocrinology and Specialist Weight Management, Bolton NHS Foundation Trust, Bolton BL4 0JR UK 2. Centre for Endocrinology and Diabetes, Faculty of Medical and Human Sciences, The University of Manchester, Manchester M13 9PT UK

DOI:

https://doi.org/10.15277/bjd.2021.326

Keywords:

insulin resistance, metabolic syndrome, leukaemia, chemotherapy, radiotherapy, thiazolidinediones, metformin

Abstract

With the improvement of haematopoietic stem cell transplantation (HSCT) and radiotherapy, the population of cancer survivors is increasing and therefore increasing the number of patients living with late metabolic complications. We describe a case of a childhood acute lymphoblastic leukaemia survivor who developed insulin resistance 10 years after HSCT and total body radiation requiring a high dose of insulin (>1,500 IU). Using insulin-sensitising agents metformin and thiazolidinediones improved the control and reduced the insulin requirement – eventually stopping insulin. We describe for the first time the phenomenon of reverse diurnal variation in insulin sensitivity based on the clinical picture alone, which has not previously been described in the literature. We have reviewed the plausible mechanisms of developing insulin resistance, reverse diurnal variation and the role of thiazolidinediones in reducing lipotoxicity and adipocyte differentiation resulting in improved insulin sensitivity in such cases.

References

Inamoto Y, Lee SJ. Late effects of blood and marrow transplantation. Haematologica 2017;102(4):614–25. https://doi.org/10.3324/haematol.2016.150250

Turcotte LM, Yingst A, Verneris MR. Metabolic syndrome after hematopoietic cell transplantation: at the intersection of treatment toxicity and immune dysfunction. Biol Blood Marrow Transplant 2016; 22(7):1159–66. https://doi.org/10.1016/j.bbmt.2016.03.016

Link K, Moëll C, Garwicz S, et al. Growth hormone deficiency predicts cardiovascular risk in young adults treated for acute lymphoblastic leukemia in childhood. J Clin Endocrinol Metab 2004;89(10):5003–12. https://doi.org/10.1210/jc.2004-0126

Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996;334(5):292–5. https://doi.org/10.1056/NEJM199602013340503

Poglio S, Galvani S, Bour S, et al. Adipose tissue sensitivity to radiation exposure. Am J Pathol 2009;174(1):44–53. https://doi.org/10.2353/ajpath.2009.080505

Wei C, Thyagiarajan MS, Hunt LP, Shield JPH, Stevens MCG, Crowne EC. Reduced insulin sensitivity in childhood survivors of haematopoietic stem cell transplantation is associated with lipodystropic and sarcopenic phenotypes. Pediatr Blood Cancer 2015;62(11):1992–9. https://doi.org/10.1002/pbc.25601

Sutinen J. The effects of thiazolidinediones on metabolic complications and lipodystrophy in hiv-infected patients. PPAR Res 2009;2009: 373524. https://doi.org/10.1155/2009/373524

Thangavel N, Al Bratty M, Akhtar Javed S, Ahsan W, Alhazmi HA. Targeting peroxisome proliferator-activated receptors using thiazolidinediones: strategy for design of novel antidiabetic drugs. Int J Med Chem 2017;2017:1069718. https://doi.org/10.1155/2017/1069718

Phiske M. An approach to acanthosis nigricans. Indian Dermatol Online J 2014;5(3):239–49. https://doi.org/10.4103/2229-5178.137765

Yahagi E, Mabuchi T, Nuruki H, et al. A case of exogenous insulin- derived acanthosis nigricans caused by insulin injections. Tokai J Exp Clin Med 2014;39(1):5-9.

Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 2006;116(7):1784–92. https://doi.org/10.1172/JCI29126

Sheth SH, Larson RJ. The efficacy and safety of insulin-sensitizing drugs in HIV-associated lipodystrophy syndrome: a meta-analysis of randomized trials. BMC Infect Dis 2010;10(1):183. https://doi.org/10.1186/1471-2334-10-183

Wędrychowicz A, Ciechanowska M, Stelmach M, Starzyk J. Diabetes mellitus after allogeneic hematopoietic stem cell transplantation. Horm Res Paediatr 2013;79(1):44–50. https://doi.org/10.1159/000345547

Yoshino J, Almeda-Valdes P, Patterson BW, et al. Diurnal variation in insulin sensitivity of glucose metabolism is associated with diurnal variations in whole-body and cellular fatty acid metabolism in metabolically normal women. J Clin Endocrinol Metab 2014;99(9):E1666–70. https://doi.org/10.1210/jc.2014-1579

Carrasco-Benso MP, Rivero-Gutierrez B, Lopez-Minguez J, et al. Human adipose tissue expresses intrinsic circadian rhythm in insulin sensitivity. FASEB J 2016;30(9):3117–23. https://doi.org/10.1096/fj.201600269RR

Shih K-C, Liu L-Y, Kwok C-F, et al. Effect of reversing dark-light cycles on normal diurnal variation and related metabolic disturbance in rats. Chin J Physiol 2007;50(2):69–76. Available from: http://europepmc.org/abstract/MED/17608144

Ding G, Li X, Hou X, et al. REV-ERB in GABAergic neurons controls diurnal hepatic insulin sensitivity. Nature 2021;592(7856):763–7. https://doi.org/10.1038/s41586-021-03358-w

Yamaguchi S, Moseley AC, Almeda-Valdes P, et al. Diurnal variation in PDK4 expression is associated with plasma free fatty acid availability in people. J Clin Endocrinol Metab 2018;103(3):1068–76. https://doi.org/10.1210/jc.2017-02230

Stenvers DJ, Scheer FAJL, Schrauwen P, la Fleur SE, Kalsbeek A. Circadian clocks and insulin resistance. Nat Rev Endocrinol 2019;15(2):75-89. https://doi.org/10.1038/s41574-018-0122-1

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Published

2021-12-17

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Case Reports

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