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Diabetes vignette EDN Autumn 2011 Vol. 8 No. 3 Copyright © 2011 John Wiley & Sons 119 Frequently doctors, specialist nurses and patients are unaware of the interaction between different insulins. We reviewed a needle phobic patient using a subcuta- neous cannula device. The patient was using insulin glargine (Lantus) and insulin aspart (Novorapid). He had been advised to use two separate devices to keep the insulins apart. However, he was using the one device to give both insulin types and had experienced no problems. Unlike most other insulins which are soluble at a neutral pH, insulin glargine is soluble at a pH of 4. The slightly acidic nature of glargine is the reason it can sting when injected. The manufacturer (Sanofi-Aventis) advises that it is never diluted or mixed with other insulins and that it should only be used if it is clear and colourless with no particles visible. We demonstrate the effects of mixing insulin glargine with short acting insulin analogues. In each of six 1ml syringes we mixed 50 units of a long acting insulin analogue, either glargine (Lantus) or detemir (Levemir), with 50 units of a short acting analogue: aspart (Novorapid), lispro (Humalog) or glulisine (Apidra). All of the short acting insulins mixed with insulin glargine imme- diately formed a cloudy white precipitate which gradually settled at the bottom of the syringe. In contrast, no precipitate was seen with the same short acting ana- logues mixed with detemir (see Figure 1). Adding an insulin with a slightly acidic pH on to an insulin with a neutral pH results in a solution with a pH part-way between the two (depending on the proportions of the two insulins). At the new pH, neither insulin will now be soluble. The insulin molecules form crystals which precipitate out of solution. This reduces the effectiveness of the insulin dose. Subcutaneous cannulae can be useful devices where patients might otherwise omit insulin doses because of needle phobia. Available brands include the Insuflon (Applied Medical Technology Ltd, Cambridge, UK) and the i-port (Patton Medical Devices, Austin, Texas, USA). These can be used for insulin but also for other repeated subcutaneous injections such as growth hormone, heparin, anal- gesics or G-CSF. These injection ports reduce pain and anxiety around repeated injections. 1 Studies in children show that their use can improve gly- caemic control. In one study, HbA 1c dropped from 9.4% (79mmol/mol) to 8.5% (69mmol/mol) over six months. 2 They are designed to be changed every three to five days. They are not available on prescrip- tion on the National Health Service but patients can purchase them. They are not widely used, either because of the cost or because doctors and specialist nurses are unfamiliar with them. We demonstrate why patients should be advised to use a separate injection port for the two different insulin types, especially if the long acting insulin is glargine. This advice is also relevant to patients injecting the two insulins with insulin pens. The two injections should be performed in two sepa- rate sites as precipitation of insulin crystals can occur within the sub- cutaneous layer. We hope that by publishing this we enlighten many more doctors and specialist nurses to ensure their patients are keeping the Lantus injection site rotation away from the short acting insulin injection site rotation. Jai Hill, Diabetes Specialist Nurse Dr Ruth Poole*, Diabetes Consultant Poole Hospital NHS Foundation Trust, Dorset, UK *Email: [email protected] Declaration of interests There are no conflicts of interest declared. References 1. Hanas R. Reducing injection pain in children and adolescents with diabetes: a review of indwelling catheters. Pediatr Diabetes 2004; 5(2):102–11. 2. Burdick P, Cooper S, Horner B, et al. Use of a subcutaneous injection port to improve glycemic control in children with type 1 diabetes. Pediatr Diabetes 2009;10(2):116–9. The effects of mixing different insulin analogues Figure 1. From top to bottom: (1) Lantus + Novorapid; (2) Lantus + Humalog; (3) Lantus + Apidra; (4) Levemir + Novorapid; (5) Levemir + Humalog; (6) Levemir + Apidra

The effects of mixing different insulin analogues

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Page 1: The effects of mixing different insulin analogues

Diabetes vignette

EDN Autumn 2011 Vol. 8 No. 3 Copyright © 2011 John Wiley & Sons 119

Frequently doctors, specialistnurses and patients are unaware ofthe interaction between differentinsulins. We reviewed a needle phobic patient using a subcuta-neous cannula device. The patientwas using insulin glargine (Lantus)and insulin aspart (Novorapid). He had been advised to use two separate devices to keep theinsulins apart. However, he wasusing the one device to give bothinsulin types and had experiencedno problems.

Unlike most other insulinswhich are soluble at a neutral pH,insulin glargine is soluble at a pH of 4. The slightly acidic nature ofglargine is the reason it can stingwhen injected. The manufacturer(Sanofi-Aventis) advises that it isnever diluted or mixed with otherinsulins and that it should only beused if it is clear and colourless withno particles visible.

We demonstrate the effects ofmixing insulin glargine with shortacting insulin analogues. In each ofsix 1ml syringes we mixed 50 unitsof a long acting insulin analogue,either glargine (Lantus) ordetemir (Levemir), with 50 units ofa short acting analogue: aspart(Novorapid), lispro (Humalog) orglulisine (Apidra).

All of the short acting insulinsmixed with insulin glargine imme-diately formed a cloudy white precipitate which gradually settledat the bottom of the syringe. Incontrast, no precipitate was seenwith the same short acting ana-logues mixed with detemir (seeFigure 1).

Adding an insulin with a slightlyacidic pH on to an insulin with aneutral pH results in a solution with

a pH part-way between the two(depending on the proportions ofthe two insulins). At the new pH,neither insulin will now be soluble.The insulin molecules form crystalswhich precipitate out of solution.This reduces the effectiveness of theinsulin dose.

Subcutaneous cannulae can beuseful devices where patients mightotherwise omit insulin dosesbecause of needle phobia. Availablebrands include the Insuflon(Applied Medical Technology Ltd,Cambridge, UK) and the i-port(Patton Medical Devices, Austin,Texas, USA). These can be used forinsulin but also for other repeatedsubcutaneous injections such asgrowth hormone, heparin, anal-gesics or G-CSF.

These injection ports reducepain and anxiety around repeatedinjections.1 Studies in children showthat their use can improve gly-caemic control. In one study, HbA1cdropped from 9.4% (79mmol/mol)to 8.5% (69mmol/mol) over sixmonths.2 They are designed to bechanged every three to five days.

They are not available on prescrip-tion on the National Health Servicebut patients can purchase them.They are not widely used, eitherbecause of the cost or because doctors and specialist nurses areunfamiliar with them.

We demonstrate why patientsshould be advised to use a separateinjection port for the two differentinsulin types, especially if the longacting insulin is glargine. Thisadvice is also relevant to patientsinjecting the two insulins withinsulin pens. The two injectionsshould be performed in two sepa-rate sites as precipitation of insulincrystals can occur within the sub-cutaneous layer.

We hope that by publishing thiswe enlighten many more doctorsand specialist nurses to ensure theirpatients are keeping the Lantusinjection site rotation away from the short acting insulin injectionsite rotation.

Jai Hill, Diabetes Specialist Nurse Dr Ruth Poole*, DiabetesConsultantPoole Hospital NHS FoundationTrust, Dorset, UK *Email: [email protected]

Declaration of interestsThere are no conflicts of interestdeclared.

References1. Hanas R. Reducing injection pain

in children and adolescents with diabetes: a review of indwellingcatheters. Pediatr Diabetes 2004;5(2):102–11.

2. Burdick P, Cooper S, Horner B, et al.Use of a subcutaneous injectionport to improve glycemic control inchildren with type 1 diabetes. PediatrDiabetes 2009;10(2):116–9.

The effects of mixing different insulin analogues

Figure 1. From top to bottom: (1) Lantus + Novorapid; (2) Lantus +Humalog; (3) Lantus + Apidra; (4) Levemir + Novorapid; (5) Levemir+ Humalog; (6) Levemir + Apidra