Metreleptin worked in a diabetic woman with a history of hematopoietic stem cell transplantation (HSCT) during infancy: further support for the concept of ‘HSCT-associated lipodystrophy’

Abstract

A 17-year-old woman with a history of childhood leukemia and hematopoietic stem cell transplantation (HSCT), preceded by total body irradiation, developed diabetes, dyslipidemia, fatty liver, and marked insulin resistance. Based on Dunnigan phenotype, HSCT-associated lipodystrophy was suspected. Because of rapid deterioration of diabetes control, metreleptin was introduced at 23 years of age upon receipt of her caregiver's documented consent. This trial was initially planned as a prospective 18 month-long study, with regular assessments of the patient's physical activity, food intake, and body composition analysis. However, because an abrupt and transient attenuation of the metreleptin effect occurred 16 months after the treatment initiation, the entire course of 28 months is reported here. Over the period, her HbA1c decreased from 10.9% to 6.7% despite no significant increase of physical activity and with a stable food intake. Decreased levels of triglyceride and non-HDL cholesterol were found. Her liver function improved, indicating the amelioration of fatty liver. In addition, a 25% reduction in the subcutaneous fat area at umbilical level was found, accompanied by a decrease in fat percentage of both total-body and trunk. The formation of neutralizing antibodies to metreleptin may be responsible for the transient loss of efficacy, considering a sudden elevation in her serum leptin level. In conclusion, metreleptin is useful for the management of HSCT-associated lipodystrophy, supporting the concept that adipose tissue dysfunction is responsible for diverse post-HSCT metabolic aberrations.

Case Report: Metreleptin and SGLT2 Inhibitor Combination Therapy Is Effective for Acquired Incomplete Lipodystrophy

“…We confirmed consistent improvement in the glucose metabolism with regard to insulin resistance and plasma glucose variability, evaluated by GIR and the homeostasis model assessment of insulin resistance (HOMA-IR), and FGM, respectively. Although metreleptin supplementation failed to improve the hyperglycemia in this study before SGLT2 inhibitor administration, a previous study demonstrated consistent improvement in glucose levels in a patient with CCS-related diabetic dystrophy (7). Leptin administration has been shown to improve insulin sensitivity through the activation of adenosine monophosphate-activated protein kinase (17).…”

Proceedings of the annual meeting of the European Consortium of Lipodystrophies (ECLip) Cambridge, UK, 7–8 April 2022

“…The introduction of dietary measures such as a low-fat diet was effective. The place of metreleptin in these situations remains to be defined [6]- [9].…”

Lipodystrophy as a Late Effect after Stem Cell Transplantation

“…So far, two cases with HSCT-associated lipodystrophy have been reported who were treated with metreleptin to overcome metabolic disease [ 24 , 25 ]. In the first report, a 28-year old female who developed partial lipoatrophy after receiving allogeneic BMT at the age of four years was treated with metreleptin due to poorly controlled hyperglycemia [ 24 ].…”

“…In the second study, a 17-year old woman with HSCT-associated LD who developed diabetes, dyslipidemia, fatty liver, and marked insulin resistance was treated with metreleptin for a period of 28 months [ 25 ]. Within the treatment period, her blood glucose and lipid parameters, as well as liver function, improved, while there was no significant change in physical activity or food intake.…”

“…The molecular mechanisms of pathogenesis in HSCT-associated LD are not well understood. From the above-mentioned risk factors potentially causing the development of HSCT-associated lipodystrophies, we would like to expand the current view on the underlying mechanisms [ 25 ] by the hypothesis that transplanted donor cells contribute to adipose tissue mass and function ( Figure 1 ). The major prerequisite for the development of the disease seems to be a damaging effect of TBI on adipose tissue.…”