Insulin, as a peptide hormone drug, is susceptible to changes in stability when exposed to environmental factors under storage. Proper storage according to the manufacturer's recommendations is important to maintain its potency and enable precise dosing for people with diabetes (PwD). While it is reasonable to assume that transport conditions and temperature are well controlled during the supply chain, little is known about insulin storage after dispensing and insulin potency at the moment of administration. Insulin is exposed to various environmental factors when carried by PwD and storage recommendations are often not met when it is stored in household refrigerators. It is difficult to assess changes in insulin potency in clinical practice, and there is a gap in the current scientific literature on insulin stability. Package leaflet recommendations only give limited information on the impact of improper storage conditions on insulin stability and guidelines by health organizations are inconsistent. Given the importance of precise dosing in diabetes care, there is a need for more transparency on insulin stability, awareness for proper storage among health care professionals and PwD as well as clear guidelines and practical storage recommendations from manufacturers and health organizations.

Insulin Storage: A Critical Reappraisal:

Medical Devices, Smart Drug Delivery, Wearables and Technology for the treatment of Diabetes Mellitus.

Metformin is the first-line treatment for many people with type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) to maintain glycaemic control. Recent evidence suggests metformin can cross the placenta during pregnancy, thereby exposing the fetus to high concentrations of metformin and potentially restricting placental and fetal growth. Offspring exposed to metformin during gestation are at increased risk of being born small for gestational age (SGA) and show signs of ‘catch up’ growth and obesity during childhood which increases their risk of future cardiometabolic diseases. The mechanisms by which metformin impacts on the fetal growth and long-term health of the offspring remain to be established. Metformin is associated with maternal vitamin B12 deficiency and antifolate like activity. Vitamin B12 and folate balance is vital for one carbon metabolism, which is essential for DNA methylation and purine/pyrimidine synthesis of nucleic acids. Folate:vitamin B12 imbalance induced by metformin may lead to genomic instability and aberrant gene expression, thus promoting fetal programming. Mitochondrial aerobic respiration may also be affected, thereby inhibiting placental and fetal growth, and suppressing mammalian target of rapamycin (mTOR) activity for cellular nutrient transport. Vitamin supplementation, before or during metformin treatment in pregnancy, could be a promising strategy to improve maternal vitamin B12 and folate levels and reduce the incidence of SGA births and childhood obesity. Heterogeneous diagnostic and screening criteria for GDM and the transient nature of nutrient biomarkers have led to inconsistencies in clinical study designs to investigate the effects of metformin on folate:vitamin B12 balance and child development. As rates of diabetes in pregnancy continue to escalate, more women are likely to be prescribed metformin; thus, it is of paramount importance to improve our understanding of metformin’s transgenerational effects to develop prophylactic strategies for the prevention of adverse fetal outcomes.

Interaction between Metformin, Folate and Vitamin B12 and the Potential Impact on Fetal Growth and Long-Term Metabolic Health in Diabetic Pregnancies.

Objective: Not much is known about how people with diabetes store their insulin. Objective of our evaluation was to analyze at which temperature insulin is stored in domestic refrigerators...

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Storage Conditions of Insulin in Domestic Refrigerators and When Carried by Patients: Often Outside Recommended Temperature Range

Aims To evaluate the efficacy and safety of imeglimin for up to 52 weeks as combination therapy with insulin in Japanese patients with type 2 diabetes. Materials and Methods This double-blind, randomized, parallel-group phase 3 trial was performed at 35 sites in Japan. Eligible patients were individuals aged ≥20 years with type 2 diabetes and inadequate glycaemic control with insulin. Patients were randomly assigned (1:1) to either imeglimin (1000 mg twice daily) or matched placebo, in combination with insulin, for 16 weeks. In a subsequent 36-week, open-label extension period, all patients received imeglimin 1000 mg twice daily. The primary endpoint was change in mean glycated haemoglobin (HbA1c) from baseline to week 16. Results In all, 108 and 107 patients were randomly assigned to treatment with imeglimin 1000 mg twice daily or placebo, respectively. Compared with placebo, the adjusted mean difference in change from baseline HbA1c at Week 16 was −0.60% (95% confidence interval [CI] −0.80 to −0.40; P < 0.0001). This decrease was sustained up to 52 weeks with a mean decrease of −0.64% (95% CI −0.82 to −0.46) versus baseline. The incidence of patients experiencing adverse events and serious adverse events was similar in the two treatment groups. The number of patients experiencing hypoglycaemia was similar in the two treatment groups. In patients receiving imeglimin, all hypoglycaemic events were mild in severity; no episodes required assistance. Conclusions Imeglimin significantly improved HbA1c in Japanese patients with insufficiently controlled type 2 diabetes by insulin and had a similar safety profile to placebo. The efficacy of imeglimin on top of insulin was sustained for 52 weeks. Imeglimin represents a potential new treatment option for this population as add-on to insulin therapy. 

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/dom.14642

Efficacy and safety of imeglimin add‐on to insulin monotherapy in Japanese patients with type 2 diabetes ( <scp>TIMES</scp> 3): A randomized, double‐blind, placebo‐controlled phase 3 trial with a 36‐week open‐label extension period

To date, insulin therapy remains the cornerstone of diabetes management; but the art of injecting insulin is still poorly understood in many health facilities. To address this gap, the Forum for Injection Technique and Therapy Expert Recommendations (FITTER) published recommendations on injection technique after a workshop held in Rome, Italy in 2015. These recommendations are generally applicable to the majority of patients on insulin therapy, athough they do not explore alternative details that may be suitable for low- and middle-income countries. The East Africa Diabetes Study Group sought to address this gap, and furthermore to seek consensus on some of the contextual issues pertaining to insulin therapy within the East African region, specifically focusing on scarcity of resources and its adverse effect on the quality of care. A meeting of health care professionals, experts in diabetes management and patients using insulin, was convened in Kigali, Rwanda on 11 March 2018, and the following recommendations were made: (1) insulin should be transported safely, without undue shaking and exposure to high (> 32 °C) temperature environments. (2) Insulin should not be transported below 0 °C. (3) If insulin is to be stored at home for over 2 months, it should be stored at the recommended temperature of 2–8 °C. (4) Appropriate instructions should be given to patients while dispensing insulin. (5) Insulin in use should be kept at room temperature and should never be kept immersed under water. Immersing insulin under water after the vial has been pierced carries a high risk of contamination, leading to loss of potency and likelihood of causing injection abscesses. (6) The shortest available needles (4 mm for pen and 6 mm for insulin syringe) should be preferred for all patients. (7) In routine care, intramuscular injections should be avoided, especially with long-acting insulins, as it may result in severe hypoglycaemia. (8) The practice of slanting the needle excessively should be avoided as it results in sub-epidermal injection of insulin which leads to poor absorption and may cause “tattooing” of the skin and scarring. (9) In patients presenting in a wasted state, with “paper-like skin”, injections should, if possible, be initiated with pen injection devices, so as to utilise the 4-mm needle without lifting a skin fold (pinching the skin); otherwise lifting of a skin fold is required, if longer needles are utilised. (10) Reuse of needles and syringes is not recommended. However, as the reuse of syringes and needles is practiced for various reasons, and by many patients, individuals should not be given alarming messages; and usage should be limited to discarding when injections become more painful; but at any rate not to exceed reusing a needle more than 5 times.

/pdf/eadsg-guidelines-insulin-storage-and-optimisation-of-p1pmzcfwnd.pdf

Sanjay Kalra

Papers

EADSG Guidelines: Insulin Storage and Optimisation of Injection Technique in Diabetes Management.