Heat-stability study of various insulin types in tropical temperature conditions: New insights towards improving diabetes care

Abstract

Strict storage recommendations for insulin are difficult to follow in hot tropical regions and even more challenging in conflict and humanitarian emergency settings, adding an extra burden to the management of people with diabetes. According to pharmacopeia unopened insulin vials must be stored in a refrigerator (2–8°C), while storage at ambient temperature (25–30°C) is usually permitted for the 4-week usage period during treatment. In the present work we address a critical question towards improving diabetes care in resource poor settings, namely whether insulin is stable and retains biological activity in tropical temperatures during a 4-week treatment period. To answer this question, temperature fluctuations were measured in Dagahaley refugee camp (Northern Kenya) using log tag recorders. Oscillating temperatures between 25 and 37°C were observed. Insulin heat stability was assessed under these specific temperatures which were precisely reproduced in the laboratory. Different commercialized formulations of insulin were quantified weekly by high performance liquid chromatography and the results showed perfect conformity to pharmacopeia guidelines, thus confirming stability over the assessment period (four weeks). Monitoring the 3D-structure of the tested insulin by circular dichroism confirmed that insulin monomer conformation did not undergo significant modifications. The measure of insulin efficiency on insulin receptor (IR) and Akt phosphorylation in hepatic cells indicated that insulin bioactivity of the samples stored at oscillating temperature during the usage period is identical to that of the samples maintained at 2–8°C. Taken together, these results indicate that insulin can be stored at such oscillating ambient temperatures for the usual four–week period of use. This enables the barrier of cold storage during use to be removed, thereby opening up the perspective for easier management of diabetes in humanitarian contexts and resource poor settings.

The Effect of high temperature on the stability of basal insulin in a pen: a randomized controlled, crossover, equivalence trial

“…This difference between studies could be due to differences in insulin formulation (regular and biphasic vs basal) and insulin container (vial vs cartridge). However, our study’s results are consistent with Kaufmann et al’s 13 findings in 2021. They investigated the effects of oscillating temperature (range: 25°C–37°C) on the stability of various insulin types.…”

“…The results demonstrated that insulin could be stored at oscillating ambient temperatures for 4 weeks. 13 The outcome of the present study provides reassuring evidence that an in-use insulin pen can be stored in RTs as high as 37°C for 28 days. These results remove cold storage as a significant barrier to the safe and effective use of an insulin pen for up to 4 weeks.…”

“…However, the biological activity of insulin was not evaluated in this study. To address this issue, Kaufmann et al 13 investigated the heat stability of human insulin formulations (rapid, NPH, and mixed insulin) and four analog insulin formulations (lispro, aspart, glargine, and mixed lispro analog) administered as vials and cartridges. They found that insulin exposed to temperatures fluctuating between 25°C and 37°C remained stable for 4 weeks, as evaluated by HPLC.…”

Diabetes Technology Meeting 2021

“…A study was performed which evaluated seven commercially available insulins in different storage conditions. 119 Insulin was analyzed by multiple methods: (1) high-performance liquid chromatography (HPLC), which is used for insulin quantification and potency determination; (2) circular dichroism, which is used to detect changes in 3D structures; (3) readout insulin receptors and Akt phosphorylation, which is used for bioactivity testing; and (4) visual inspection, which represents a simple and easily performed method. Using HPLC for insulin stored under oscillating conditions at 25°C to 37°C for four weeks showed stability and conformity to pharmacopeia guidelines.…”

Tropical medicine and diabetes: an integrative paradigm

“…Instead, they are forced to travel to clinics, sometimes under dangerous conditions, for therapy. This may soon change -an innovative new study by Médecins Sans Frontières (MSF) and the University of Geneva has shown that insulin can be stored at up to 37 o C. 35 Researchers tested insulin storage in real conditions, mirroring the temperature in the Dagahaley refugee camp in northern Kenya, which fluctuated between 25 o C at night and 37 o C during the day. The study reproduced these conditions in a laboratory environment where insulin storage conditions were tested over four weeks, which corresponds to the time it takes for a patient to finish one vial of insulin.…”