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Duration of Insulin Action

By John Walsh, PA, CDE and Ruth Roberts, MA
Authors of Pumping Insulin
and Using Insulin

The duration of insulin action time (DIA, or active insulin time) is how long a bolus of insulin lowers your glucose. The DIA time starts when a bolus is given and ends when the bolus is no longer lowering the glucose. Like any medication you take, it is important to know whether insulin is still working or is “used up” before you take more. Boluses are frequently given before the previous bolus or boluses are used up. This is called insulin stacking. In the APP study, 64% of 132,000 bolus doses from 396 insulin pumps were delivered within 4.5 hours of a previous bolus, so most boluses involve some degree of insulin stacking.1 After a bolus is given, an accurate DIA minimizes insulin stacking and lessens hypoglycemia by accurately tracking how much insulin activity remains from previous boluses. This is reported as Insulin On Board or active insulin on a pump screen.

The DIA time is not arbitrary. It must correspond with how long insulin actually works in the body. An accurate DIA lets the Bolus Calculator accurately account for insulin stacking, calculate appropriate bolus recommendations, and track BOB so you can make reasonable judgements about bolus recommendations. An accurate DIA time becomes more important as glucose readings are brought into a desired target range, when boluses are given frequently, and with frequent physical activity. Different pumps estimate insulin action as a linear decline in bolus insulin activity, such as 20% or 25% each hour (Accu-Chek and Omnipod), or slightly more accurately as a curved line (Animas, Medtronic, and Tandem). Pumps provide the most accurate dose recommendations with DIAs of 4 to 6 hours.2-7 A time within this range should be used for the DIA setting.

Confusion is widespread among clinicians and pump wearers on how to select an accurate DIA time, partly because the insulin action time (IAT) of “3 to 5 hours” in insulin package inserts for today’s rapid insulins8 measures a different activity that has a shorter time period than the 4 to 6 hours during which a bolus of insulin actually lowers the glucose (DIA). The method used to measure IAT does not measure DIA accurately and makes smaller insulin doses appear to have an artificially short action time.

A person’s prior experience can make it seem like insulin works faster than it actually does. For example, insulin is often stacked without a person realizing it when they take a second bolus before the first one is used up. If the glucose suddenly goes low 30 minutes after a meal bolus, it seems logical to blame the bolus that was just given, even though the culprit is more likely the residual action of an earlier bolus. When boluses are excessive and rapidly lower the glucose, a person might also mistakenly conclude that insulin acts fast rather than that too many units were given. When the TDD is excessive, the frequent lows that result also make insulin appear to be fast.

Current insulin pumps allow the DIA time to be set by a clinician or user in a range from 2 to 8 hours. This wide time range encourages the setting of DIA times radically below an appropriate value.9 Even the slightly faster insulins now under development will have DIA times of 4 hours or longer once DIA times are accurately measured. Three hours is a common DIA time setting in current insulin pumps. An average time of 3.1 hours was found in our data of over 1,000 U.S. insulin pumps in 2007, and 3.4 hours was the average of Diasend data downloads of more than 1,000 U.S. and European pumps in 2014 (private communication). These relatively short DIA times can lead to excessive BC bolus recommendations. A DIA of 3 hours hides much of the insulin stacking and the BC will recommend much larger boluses than needed.

The unexplained hypoglycemia that short DIA times cause often lead to incorrect adjustments in other pump settings. When the short DIA time in a pump is corrected, the other BC settings that have been incorrectly adjusted to accommodate the short DIA time will need to be retested.10

If a pump BC’s recommenced boluses often fail to bring high glucose levels down to target in the presence of BOB, do not shorten the DIA. Never change the DIA time to “fix” a control problem. Instead, look at increasing the basal rates or carb boluses. Once these are appropriate, high readings become less common, and an appropriate DIA works fine.

Research studies show that DIA times are identical between children and adults. One study of 18 children, 6 to 18 years of age, concluded that: “Insulin pharmacodynamics of Novolog® in children and adolescents were found to be similar to adults with Type 1 diabetes."11 A study of insulin action time in 9 children between 6 and 12 years old found no difference from adults,12 while another study at Stanford University of 8 children found their DIA to be slightly longer than adults.13 A larger study looked at the activity of Apidra insulin in 20 children aged 7 to 16 and found no difference between children and adults.14

If bolus doses are often larger than one tenth of a person’s weight in pounds (or one fifth of weight in kgs.), such as someone who weighs 150 pounds (68 kgs) and often boluses more than 15 units for meals, DIA times between 5 and 6 hours may be preferred.For those who use older human Regular insulin for cost savings, DIA times of 5 to 6.5 hours work well.

Read more about The Danger of Setting Duration of Insulin Action Pumps.

References:

  1. Walsh J, Wroblewski, D, and Bailey, TS: Disparate Bolus Recommendations In Insulin Pump Therapy. Poster at American Association of Clinical Endocrinology Meeting, 2007. Internet: www.diabetesnet.com/pdfs/AACE2007Poster.pdf.
  2. Heinemann L: Time-Action Profiles of Insulin Preparations, Kirchchem & C. GmbH, Mainz, Germany, 2004.
  3. Heinemann L, Weyer C, Rauhaus M, Heinrichs S, and Heise T: Variability of the metabolic effect of soluble insulin and the rapidacting insulin analog insulin aspart. Diabetes Care 21(11): 1910-4, 1998.
  4. Vaughn DE, Yocum RC, Muchmore DB, Sugarman BJ, Vick AM, Bilinsky IP, and Frost GI: Accelerated pharmacokinetics and glucodynamics of prandial insulins injected with recombinant human hyaluronidase. Diabetes Technol Ther. 11(6): 345-52, 2009.
  5. Steiner S, Hompesch M, Pohl R, Simms P, Flacke F, Mohr T, Pfützner A, and Heinemann L: A novel insulin formulation with a more rapid onset of action. Diabetologia 51(9): 1602-1606, 2008.
  6. Rave KM, Nosek L, de la Peña A, Seger M, Ernest CS 2nd, Heinemann L, Batycky RP, and Muchmore DB: Dose response of inhaled dry-powder insulin and dose equivalence to subcutaneous insulin lispro. Diabetes Care 28(10): 2400-2405, 2005.
  7. Rave K, Bott S, Heinemann L, Sha S, Becker RH, Willavize SA, and Heise T: Time-action profile of inhaled insulin in comparison with subcutaneously injected insulin lispro and regular human insulin. Diabetes Care 28(5): 1077-1082, 2005.
  8. Apidra Product Monograph; Version 9.0, April 4, 2011. Internet: products.sanofi.ca/en/apidra.pdf
  9. Heinemann L: The future of pumps and sensors, Chap. 9, pg.103, in Insulin Pump Therapy And Continuous Glucose Monitoring, edited by John Pickup. Oxford Diabetes Library, Oxford, 2009.
  10. Walsh J and Roberts R: Pumping Insulin, ed. 5.1, Torrey Pines Press; pgs. 93-112, 2013.
  11. NovoLog® Physician Insert – Approved October 21, 2005
  12. Mortensen HB, Lindholm A, Olsen BS, and Hylleberg B: Rapid appearance and onset of action of insulin aspart in paediatric subjects with type 1 diabetes. European Journal of Pediatrics 159(7);483-488, 2000.
  13. Buckingham BA, Block J, Wilson D, Rebrin K, and Steil G: Novolog Pharmacodynamics in Toddlers. Diabetes 54(Suppl 1): Abstract 1889-P, 2005.
  14. Becker R, Frick A, Heinemnn L, Nosek L, and Rave K: Dose response relation of insulin glulisine (GLU) in subjects with type 1 diabetes (T1DM). Diabetes 54 (Suppl. 1): A332 (Abstract 1367-P), 2005.

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