ESPE Yearbook of Paediatric Endocrinology

PLoS ONE 2021;16: e0245372. doi: 10.1371/journal.pone.0245372

– According to pharmacopeia, unopened insulin vials must be stored in a refrigerator (2–8 °C) while storage at ambient temperature (25–28 °C) is usually permitted for the 4-week usage period during treatment– The authors investigated whether insulin remains stable and retains biological activity in oscillating tropical temperatures– They found that the structure of insulin and its efficiency on insulin receptor and Akt phosphorylation in hepatic cells remain stable at temperatures oscillating between 25 and 37 °C over a 4-week period, which enables the barrier of cold storage to be removed

The existing recommendations represent a significant hurdle to insulin-treated patients in low resource settings where strict storage at 2–8 °C is usually unavailable in their homes. While several studies have reported significant degradations of insulin preparations under high isothermal conditions, the originality of the study reported by Kaufmann et al. consisted of studying the stability and the biological activity of different insulin preparations stored and used by patients under continuously fluctuating temperatures between 25 and 37 °C. These temperatures were chosen following daily measurements performed in a refugee camp in Northern Kenya, run by MSF. Insulin potency was evaluated by high performance liquid chromatography, the 3-D structure by circular dichroism spectrometry and bioactivity by in vitro phosphorylation of the insulin receptor and the akt-signaling intracellular pathway of two different hepatocyte cell lines. The following insulin formulations used in the field by MSF in low resource countries were studied: rapid, NPH/isophane and premixed rapid/ NPH insulins. Measurements were performed at different time points up to 12 weeks on samples submitted to controlled temperature oscillations in the laboratory and on samples obtained up to 4 weeks from patients from the refugee camp and compared to formulations kept at 2–8 °C during the same time periods.

Under oscillating temperature conditions, the measured values of insulin quantification ranged between 98.3 and 99.9% of the initial concentrations and were all within the pharmacopeia acceptable range (100±10%) after 4 weeks and even after 12 weeks for the preparations tested under laboratory conditions. In addition, the three dimensional conformation of the mixed insulins as well as their biological activities were conserved under the same fluctuating storage conditions when compared to control samples stored at 2–8 °C. Furthermore, no significant difference in stability was found between insulin conditioned in pen cartridges and 10 ml vials. The authors conclude that insulin preparations may be kept for at least 4 weeks under fluctuating temperatures in patients’ homes, even in the absence of access to refrigeration, while retaining structural and efficacy integrity. These findings open new perspectives of diabetes care for tropical regions where refrigeration is not always available, affordable, or reliable. This does not preclude that the cold-chain of insulin prior to the period of use by the patient should be ensured as mentioned by the authors, although this remains an additional challenge for low resource countries.

(This commentary was prepared by Marc Maes, MD, PhD, Emeritus Professor of Pediatric Endocrinology and Diabetology, Cliniques Universitaires St Luc, 1200 Brussels, Belgium)