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Table of contents
Endocrine Press | Endocrine Society
Nonrandomized studies have shown significant improvement in glycemic control comparing pre- and post-intervention periods in patients switched from U prandial insulin preparations to U regular insulin. For patients and providers who opt for a trial of regular U insulin, a number of issues need to be considered to mitigate risks and optimize benefits of using this concentrated insulin.
First and foremost is the frequent confusion in the communication between provider, pharmacy, and patient regarding the correct insulin dose to be administered. Because regular U insulin is administered with U insulin syringes, a 1-unit measure of U corresponds to a 5-unit delivery of regular insulin.
Overview of Insulin
To minimize confusion, regular U prescriptions should be made out in volume rather than units, but this difference must be clearly explained to patients to avoid overdosing. For example, 0. Newer concentrated insulin preparations on the market have avoided this confusion by providing measured doses in an insulin pen delivery system. For example, insulin lispro U Humalog U , a twofold concentration of insulin lispro U with similar pharmacodynamics, is only available in a prefilled pen. Using insulin pen technology, a 1-unit dose of insulin actually corresponds to 1 unit of insulin, thereby removing any possible confusion regarding the prescription or administration of the correct insulin dose.
Insulin lispro U offers the convenience of holding more insulin per pen; it contains units of insulin per pen compared with units in the lispro U pen. In the years since the discovery of insulin in , our understanding of diabetes and the development of treatments have greatly improved the With so much importance placed on one laboratory value, it is imperative to remember that the test is imperfect, with pitfalls both in accuracy A complex and controversial relationship exists between intensive glycemic control and cardiovascular outcomes.
With several new therapeutic drug classes available, successful management strategies require a balancing of multiple agents to achieve target Hyperglycemia in hospitalized patients, with or without diabetes, is associated with adverse outcomes including increased rates of infection and Skip to main content. New insulin preparations: A primer for the clinician.
Insulin is considered the therapeutic standard in patients with advanced insulin deficiency. Types of available insulin products have differing onset, peak, and duration of action ranging from ultra-short-acting to ultra-long-acting. The US Food and Drug Administration approved an inhaled insulin product in ; all other products are administered subcutaneously. Concentrated insulin preparations provide an alternative for patients requiring consistently high daily doses of insulin.
Data from Afrezza insulin human inhalation powder [package insert]. Figure 1. Serum insulin concentrations and glucose infusion rate of inhaled insulin for inhaled vs insulin lispro in patients with type 1 diabetes. Next Article: Inpatient hyperglycemia management: A practical review for primary medical and surgical teams.
Cecilia Lansang, MD, MPH In the years since the discovery of insulin in , our understanding of diabetes and the development of treatments have greatly improved the McDonnell, MD With so much importance placed on one laboratory value, it is imperative to remember that the test is imperfect, with pitfalls both in accuracy Ganda, MD A complex and controversial relationship exists between intensive glycemic control and cardiovascular outcomes. Hermayer, MD, MS Andrew Dake, MD With several new therapeutic drug classes available, successful management strategies require a balancing of multiple agents to achieve target Read More Article Inpatient hyperglycemia management: A practical review for primary medical and surgical teams Author: M.
Umpierrez, MD, CDE Hyperglycemia in hospitalized patients, with or without diabetes, is associated with adverse outcomes including increased rates of infection and Read More. Images are hypothetical cartoons based on data from Havelund et al 34 and Whittingham et al.
Studies of disappearance rates of radiolabelled insulin analogues in porcine models were used to gauge the relative importance of self-association and albumin binding in depot protraction. Thus, the likely mechanism of protracted absorption is self-association of insulin detemir causing retention in the depot for long enough to establish albumin binding, which further delays absorption. As insulin detemir also binds reversibly to albumin in the circulation, it could be speculated that further protraction of the pharmacodynamic effect might occur through retention in the plasma compartment.
However, comparisons of plasma residence times with other acylated analogues with differing albumin-binding affinities suggest that while there is some retention of insulin detemir in the circulation, the contribution of this to the overall protraction of action is much lower than that attributable to depot retention. This is because the absorption rate mainly depends on the concentration difference of free insulin between the interstice and the capillary as insulin can diffuse both into and out of the capillary lumen.
For human insulin, the capillary concentration is relatively high and flow dependent. A high flow will decrease the capillary concentration and increase the absorption rate. Similarly, a low flow will decrease the concentration difference and the absorption rate. In contrast, absorbed insulin detemir is immediately and almost completely bound by circulating albumin in the capillary lumen, so the free concentration is kept very low and albumin-bound detemir complexes are too large to readily re-exit the capillary.
Thus, the free concentration difference effectively becomes more or less constant and independent of the flow rate. Second, data from pharmacokinetic experiments in dogs describing half-lives in different tissues as well as transcapillary transport 37 , 38 , 39 predict that even if the plasma concentration of insulin detemir were to rise, the effect of this at target tissues would be reduced.
Thus, changes in plasma concentration are slow to affect target tissue interstitial concentrations, whereas there will be an almost immediate increase in the interstitial concentration should circulating insulin levels rise Figure 2. These two buffering properties might explain a significant reduction in the within-subject variability of pharmacokinetic and pharmacodynamic profiles from injection to injection seen in comparison to more conventional basal insulins. Interstitial rise in insulin concentration in response to increased subcutaneous absorption rate.
The insulin detemir response is greatly buffered as a result of albumin binding. An important consideration with the reversible albumin-binding principle is whether it might pose a risk of interaction with other albumin-bound compounds. The potential of insulin detemir to interact competitively with other albumin-bound drugs has nevertheless been studied in vitro , and at drug:albumin concentration ratios as high as , there were no interactions between insulin detemir and a series of free fatty acids, nor with phenylbutazone, warfarin, ibuprofen, diazepam, tolbutamide, glibenclamide, aspirin or valproate.
The receptor interaction profile of insulin detemir has been studied in several in vitro cell models. In vivo , a reduced receptor affinity should not affect molar potency, because the physiological clearance of insulin is predominantly via its receptor. Receptor residence time and the relative affinity for the IGF-I receptor were not increased for insulin detemir relative to human insulin, hence insulin detemir did not display an increased mitogenic potency Table 1.
This pharmacokinetic and glucose-lowering time—action profile of subcutaneously injected insulin detemir has been assessed comparatively in h isoglycaemic clamp studies. Insulin detemir was shown to have an equivalent total blood glucose-lowering action to NPH insulin on a unit basis, but with a longer duration of action and reduced maximal effect Table 2.
At a dose of 0. Another pharmacodynamic study specifically assessed the within-subject variability of insulin detemir in comparison to NPH insulin and insulin glargine. Other pharmacological studies have shown that insulin detemir is more consistent in its pharmacokinetic profile across- and within-age groups than NPH insulin, 47 and that the pharmacokinetic profile is unaffected by renal or moderate hepatic impairment.
In summary, a thorough programme of pharmacological assessment of insulin detemir has suggested that acylation of the insulin molecule to enable albumin binding is an effective principle for engineering protraction and predictability, with a good safety profile. Protraction is achieved primarily through retention in the injection depot, with plasma albumin binding mediating an important buffering mechanism.
This, together with the avoidance of precipitation, might underpin the remarkably low within-subject variability seen in repeat glucose clamp studies. The obvious advantage that the smooth and flat kinetic profile with reduced variability should bring to the clinical arena is a reduced risk of hypoglycaemia, which in turn should allow more aggressive titration towards lower glycaemic targets. Davies M. The reality of glycaemic control in insulin treated diabetes: defining the clinical challenges.
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Types of insulin
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