The Insulin Sensitivity Factor (ISF) measures how much a unit of rapid-acting insulin can lower blood glucose levels in the body.
If the ISF is 1:2.0 mmol/L, a person would require 1 unit of Apidra, Fiasp, Humalog, or Novorapid for every 2 mmol/L drop in blood glucose level.
For instance, with a BGL of 15.2 mmol/L, an ISF of 1:2.0, and a target BGL of 6.5, the individual would need 4-4.5 units of rapid-acting insulin to reach the target. The calculation is: (15.2-6.5)/2.0 = 8.7/2.0 = 4.35 (rounded to 4.0 or 4.5).
(Current BGL – Target BGL) / ISF ISF Formula
Generally, the ISF is combined with the insulin-to-carbohydrate ratio (ICR) at meal times based on the pre-meal BGL.
It is important for individuals using insulin to work closely with their healthcare providers to determine their specific ISF and ICR in order to effectively manage their blood glucose levels. These factors can vary depending on a person’s age, weight, activity level, and overall health.
Individuals with diabetes can also adjust their ISF based on factors such as physical activity, stress, illness, and hormonal fluctuations. It is important to work closely with a diabetes healthcare professional to determine the most appropriate ISF for optimal blood sugar management.
Regular monitoring of blood sugar levels and making adjustments to insulin dosages as needed can help individuals maintain stable blood sugar levels and reduce the risk of complications associated with diabetes.
Understanding how ISF is calculated and how to make adjustments as needed is key to successful diabetes management.
Insulin resistance
Individuals with insulin resistance require higher insulin doses to correct elevated blood glucose levels, resulting in lower Insulin Sensitivity Factors (ISFs) like 1:0.5 mmol.
Factors such as stress and weight gain can decrease insulin sensitivity, while physical activity can boost ISF before and after exercise.
In addition to stress and weight gain, other factors that can contribute to insulin resistance include a diet high in sugar and unhealthy fats, lack of sleep, and genetics. It is important for individuals with insulin resistance to work with healthcare professionals to develop a comprehensive management plan that includes monitoring blood glucose levels, making dietary changes, and engaging in regular physical activity.
Regular exercise has been shown to improve insulin sensitivity and can help individuals with insulin resistance better manage their condition. Both aerobic exercise, such as running or cycling, and strength training exercises can be beneficial. It is important to consult with a healthcare provider before starting any new exercise regimen.
How do I now if the ISF is correct?
To assess the correction factor, monitor blood glucose levels (BGLs) 2-3 hours after administering a correction insulin dose. If the BGL does not return to the target range, adjust the correction factor accordingly.
It is important to regularly monitor blood glucose levels and work closely with your healthcare provider to ensure that your insulin sensitivity factor (ISF) is correctly adjusted to meet your individual needs. Making adjustments as needed can help to better manage your blood glucose levels and overall health.
Additional tips on the ISF:
- Insulin pumps calculate bolus insulin based on BGL, carbohydrate intake, target BGL, ISF, ICR, and IOB.
- To lower high BGLs within the target range, aim towards the upper limit.
- Low BGLs can be corrected using the ISF by subtracting the insulin quantity.
- Ensure the correct basal insulin dose by comparing pre-bed BGL with fasting BGL.
Explore our online educational program “Living with insulin online” for further details.
Insulin pumps utilize a bolus calculator (BC) to recommend insulin doses. Proper consideration of residual insulin activity is crucial to reduce subsequent boluses and minimize insulin stacking.
The BC assists in determining bolus insulin doses for carbohydrate intake and correcting hyperglycemia. The correct DIA setting in the BC ensures precise bolus recommendations.
Understanding the significance of DIA and selecting the appropriate DIA setting is vital, as incorrect settings may lead to hypoglycemic events and inaccurate bolus recommendations.
Keywords: duration of insulin action, insulin therapy, insulin pumps, insulin action time, pharmacodynamics, pharmacokinetics, rapid-acting insulin analogs
Basal insulin plays a crucial role in maintaining stable blood sugar levels during fasting.
Studies indicate that pump boluses are given less than 4.5 hours apart on average, with pump wearers administering an average of 4.14 carb and correction boluses daily. Data from Australia reveals a daily bolus frequency of 6.1, with intervals averaging between 2.95 to 3.93 hours between boluses. This suggests common insulin stacking, involving at least two-thirds of all boluses. However, no research has focused on the metabolic outcomes resulting from insulin stacking due to inappropriate DIA times.
Each insulin pump manufacturer has a unique configuration for their Bolus Calculator (BC). Clinicians must understand these differences, especially in calculating bolus doses after determining the Duration of Insulin Action (DOA) time. BCs are increasingly incorporated into blood glucose systems and mobile applications globally.
DIA Versus IAT
Several factors influence glucose outcomes, underscoring the importance for clinicians to eliminate errors contributing to glycemic fluctuations. The absence of clear definitions for insulin action times leads to confusion regarding DOA. Researchers often draw from glucose clamp studies to describe insulin properties, which measure the metabolic impact of test insulins graphically for comparative purposes.
The DOA in daily life differs from the Insulin Action Time (IAT) observed in glucose clamp studies. IAT commences with the rise in glucose infusion post a test insulin injection and concludes when the glucose infusion rate returns to baseline. While IAT aids in insulin comparisons, it does not establish the DOA needed to prevent insulin stacking in BC calculations.
Figure 1.
IAT is measured between points A and B, involving the suppression of basal insulin delivery. Glucose clamp studies assist in determining the Glucose Infusion Rate (GIR) required to maintain blood glucose at a target level after administering a test insulin dose in healthy or diabetic subjects.
In contrast, DOA in daily life denotes the duration from the test insulin injection until the metabolic influence ends, based on simultaneous basal insulin delivery. Unlike glucose clamp studies, daily life insulin therapy does not provide standard basal insulin coverage.
Figure 2.
DOA is gauged between points C and D, where consistent basal insulin delivery enables the direct measurement of bolus insulin pharmacodynamics. Statistical smoothing methods address differences in calculating IAT and DOA to obtain precise values for pharmacodynamic parameters.
In pump insulins, maintaining basal insulin delivery yields realistic DOA values, typically longer than IAT times. Data suggests DOA estimates range from 5 to 6 hours for most bolus insulin doses.
Insulin Variability May Be Magnified by Current Clamp Studies
In glucose clamp studies, varying test insulin doses alter IAT times, with larger doses extending the times. However, the clamp methodology affects time variability, complicating comparisons between test doses and daily insulin therapy. Larger doses divert more test insulin towards basal functions than smaller doses, influencing IAT durations.
Figure 3.
Diverse insulin doses impact pharmacodynamics, where larger doses prolong IAT times. Factors like hepatic glucose production and basal insulin secretion notably influence the apparent IAT of insulin doses.
Maintaining basal insulin delivery may reduce variability in pharmacodynamic measurements, providing more accurate calculations for DOA and IAT. Nevertheless, daily elements like activity and temperature can introduce insulin absorption variability beyond controlled settings.
Why Do Clinicians and Patients Use Inappropriately Short DIA Times?
Users must select a suitable DIA without a clear basis. Personal experiences may lead to misunderstandings about insulin speed, attributing low blood glucose to recent boluses rather than residual activity from prior doses. The most common mistake is opting for a short DIA, with an average of 3.4 hours reported by pump wearers in online forums.
Parents of children with diabetes and physicians assume that small insulin doses taken by children have a short DIA of around 3 hours. However, research indicates that children exhibit insulin activity similar to adults, with potential persistence for at least 5 hours. Children often experience insulin stacking due to brief DIA times in bolus calculators.
Many patients and healthcare providers confuse DIA with insulin pharmacokinetics (PK) and overlook the continued metabolic impact of insulin post-PK decline. With a wide range of DIA times offered by insulin pump manufacturers, there is no standardized approach, leading to incorrect settings input by users and clinicians.
Problematic Adjustments That Arise When a Short DIA Is Used
Short DIA times can conceal insulin activity and influence bolus recommendations. Inaccurate DIA settings may result in hypoglycemia and complexity in making adjustments for improved metabolic management.
Table 1.
Impact of DIA settings on residual insulin activity after 3 hours.
| Time of Day | Amount of Insulin Remaining after 3 Hours |
|---|---|
| A total of 3.0 hours | 0.0 Units |
| 4.0 hours | 1.8 units |
| Duration: 4.5 hours | Difficulty level: 2.5 out of 5 |
Insufficient duration of insulin action (DIA) can result in the accumulation of insulin doses and hidden insulin effects, leading to unexplained episodes of low blood sugar. Conducting further investigations on DIA durations is crucial to better comprehend and tackle this clinical challenge.
Additional Considerations for BCs
Accurate settings for DIA are vital for appropriate recommendations on insulin doses. Comparing recent blood sugar readings with insulin activity can assist individuals in making necessary adjustments or decisions on additional carbohydrate intake.
After mealtime insulin doses, making timely corrections is essential for sustaining optimal management of blood sugar levels. Having a clear understanding of the current insulin activity enables individuals to plan for physical activities and effectively manage their blood sugar levels.
Figure 4.
Evaluating the insulin activity from the bolus dose after 2 hours can help determine whether a correction dose of insulin or additional carbohydrate intake is needed to stabilize blood sugar levels. Monitoring the Bolus On Board (BOB) and blood sugar levels offers guidance for optimizing settings on insulin pumps.
Understanding the factors that influence the effectiveness of insulin is pivotal for establishing precise DIA settings and achieving optimal metabolic control. Clinical research studies on DIA durations under real-world conditions are essential for enhancing the management of diabetes.
Moreover, it is important for individuals with diabetes to communicate with their healthcare providers regularly to review their insulin regimen and make necessary adjustments. Engaging in regular physical activity and following a well-balanced diet are also key components in managing blood sugar levels effectively. By staying informed about the latest developments in diabetes management, individuals can take proactive steps in improving their overall health and well-being.
Limits of Existing IAT and DIA Research
Various factors, including the type of insulin dose, the duration of infusion set usage, and the site of insulin delivery, can influence DIA settings. Reliable data from studies using the glucose clamp technique provide valuable insights into the properties of insulin formulations and their metabolic effects in pump therapy.
Table 2.
Examining the Pharmacokinetic and Pharmacodynamic characteristics of rapid-acting insulins used in insulin pumps from studies conducted at a single research center involving subcutaneous insulin injections.
| Insulin Exposure Duration (Pharmacokinetics, minutes) | Insulin Effectiveness (Glucose Infusion Rate, minutes) | |||||
|---|---|---|---|---|---|---|
| Source | Number of participants | Amount of medication | Time to reach peak concentration | Time to reach half of peak concentration | Peak concentration time | Time to return to half of peak concentration after peak period |
The protocol involves administering a bolus of fast-acting insulin and monitoring blood glucose levels every 15 minutes for a period of 2-3 hours. During this time, it is important to closely monitor for any hypoglycemic events and adjust insulin dosages as needed. The DIA time can be estimated by observing the time at which blood glucose levels start to rise after reaching their lowest point post-insulin administration.
It is recommended to repeat the protocol multiple times to ensure accuracy and consistency in determining DIA times for individual patients. This information can help healthcare providers make informed decisions about insulin dosing strategies and assist patients in managing their diabetes effectively.
Experimental Study Design
Standardizing activities of study participants in the days leading up to the experimental study is crucial to eliminate any variables influencing the results. Evaluation of basal insulin requirements for each enrolled C-peptide-negative subject with type 1 diabetes is necessary. Participants should be in good control to minimize the impact of insulin resistance due to high blood sugar levels.
On study days, regular insulin can be administered subcutaneously to provide basal insulin coverage, while rapid-acting insulin is used to determine its DIA. Different insulin doses should be tested on separate days to understand the concentration effects on DIA. The study period must allow the glucose infusion rate to return to baseline levels for accurate DIA measurement.
Stable isotopes can be used to assess the suppression of hepatic glucose production during experiments. Maintaining normal blood sugar levels overnight before the study starts is crucial. This protocol aims to offer realistic DIA times that reflect the actual action times of insulins commonly used in pumps.
Glucose clamp studies can validate DIA estimates by comparing them to data from patient pump usage. Investigating basal replacement and insulin stacking with different insulins can provide valuable insights into finding optimal settings. Further research on pump practices can help in understanding DIA better.
Additional Pump and DIA Research
Research on pump practices to evaluate DIA includes:
- Bolus insulin doses (U/kg)
- Time intervals between bolus doses
- Anatomic sites for infusion sets
- Time required to infuse large insulin boluses
The current utilization of DIA times is of particular interest. Research data can shed light on the impact of DIA on recommended insulin doses, although there is limited information available on this topic.
Further studies on the effectiveness of different types of infusion sets and their impact on DIA would be beneficial for improving insulin delivery and patient outcomes. Additionally, exploring the optimal timing of bolus doses in relation to meals and physical activity could provide valuable insights for managing blood sugar levels more effectively with insulin pumps.
Recommendations for Selecting DIA Times in Current Practice
Due to the lack of reliable data on DIA, using pharmacodynamic data with higher insulin doses can help estimate DIA settings. DIA settings between 4.5 and 6.5 hours may be more accurate, especially for larger boluses. It is crucial to adjust DIA time settings for bigger boluses and address insulin deficit directly when blood glucose levels are high.
Conclusions
There is confusion among healthcare providers and patients regarding accurate DIA settings. Research studies are needed to determine DIA times for fast-acting insulins and eliminate incorrect DIA time choices for more precise adjustments in pump settings. Adequate training on all pump settings, including DIA, is essential.
Footnotes
Abbreviations: BC, bolus calculator; BOB, bolus insulin on board; carb, carbohydrate; CGM, continuous glucose monitor; DIA, duration of insulin action; GIR, glucose infusion rate; HGP, hepatic glucose production; IAT, insulin action time; IOB, insulin on board; PD, pharmacodynamic; PK, pharmacokinetic; SC, subcutaneous.
Declaration of Conflicting Interests: The authors declare no conflicts of interest. LH has stakes in Profil Institute for Metabolic Research and Profil Institute for Clinical Research. The authors are consultants for companies developing treatments for diabetes.
Funding: This article received no financial support.
References
Articles from the Journal of Diabetes Science and Technology are provided courtesy of Diabetes Technology Society