Fast-Acting Insulin

By Hope Warshaw, MMSc, RD, BC-ADM, CDE | June 6, 2005 12:00 am

Even when you think you’re doing everything right with your diabetes care regimen, it can sometimes seem like your blood glucose levels are hard to control. One potential source of difficulty that you may not have thought of is how you time your injections or boluses of rapid-acting insulin with respect to meals.

Since the first rapid-acting insulin, insulin lispro (brand name Humalog), came on the market in 1996, most diabetes experts have recommended taking it within 15 minutes of starting a meal (any time between 15 minutes before starting to eat to 15 minutes after starting to eat). This advice is based on the belief that rapid-acting insulin is absorbed quickly and begins lowering blood glucose quickly. However, several years of experience and observation suggest that this advice may not be ideal for everyone who uses rapid-acting insulin. As a result, the advice on when to take it needs updating.


Insulin basics

The goal of insulin therapy is to match the way that insulin is normally secreted in people without diabetes.

Basal insulin. Small amounts of insulin are released by the pancreas 24 hours a day. On average, adults secrete about one unit of insulin per hour regardless of food intake.

Bolus insulin. In response to food, larger amounts of insulin are secreted and released in two-phase boluses. The first phase starts within minutes of the first bite of food and lasts about 15 minutes. The second phase of insulin release is more gradual and occurs over the next hour and a half to three hours. The amount of insulin that is released matches the rise in blood glucose from the food that is eaten.

In people with normal insulin secretion, insulin production and release is a finely tuned feedback system that maintains blood glucose between about 70 mg/dl and 140 mg/dl at all times, no matter what or when a person eats or when he engages in physical activity. During illness, when insulin needs may rise, the pancreas just produces more.

People whose pancreas does not secrete insulin normally often must inject insulin or infuse it with an insulin pump. People who have Type 1 diabetes, in which the pancreas secretes no insulin or virtually no insulin, must inject or infuse insulin. But learning when to take insulin and how much to take is challenging, because injected or infused insulin does not act exactly like insulin released from the pancreas. The first step to figuring out when to take insulin and how much to take is understanding an insulin’s action curve.

Insulin action

An insulin’s action curve has the following three phases:

Rapid-acting insulin is often called mealtime insulin because its action curve most closely resembles the body’s normal release of insulin at mealtimes. (However, most people who use an insulin pump use rapid-acting insulin as a basal insulin as well, infusing small amounts 24 hours a day.) The three rapid-acting insulins currently approved by the US Food and Drug Administration — lispro, aspart (NovoLog), and glulisine (Apidra ) — have similar action curves, with an onset occurring in 5–15 minutes, a peak in 45– 90 minutes, and an overall duration of about 3–4 hours.

However, Howard Wolpert, MD, editor of the book Smart Pumping and Senior Physician and Director of the Insulin Pump Program at Joslin Diabetes Center, cautions against blind-faith acceptance of insulin action curves or standard advice about when insulin works, noting that insulin can show “a lot of variability…between individuals and even within the same person from day to day.” The time ranges given for an insulin to reach its peak action are averages, so they may not fit everyone or every situation. You may find through blood glucose monitoring and experience that rapid-acting insulin typically reaches peak effectiveness within 45–90 minutes or possibly sooner or later. This information can affect when you take your premeal doses.

Matching insulin and food

In addition to understanding an insulin’s action curve, it’s important to understand how the food you eat affects your blood glucose level so that you can match your insulin’s action to the expected rise in blood glucose level following a meal. In general, people with normal stomach emptying can expect some glucose from the carbohydrate they’ve eaten to start raising their blood glucose level within minutes of starting to eat. Blood glucose level tends to peak about one to two hours after the start of a meal and gradually drops over the next three hours.

When to inject. If rapid-acting insulin always started working almost immediately and peaked one to two hours later, injecting it anytime within 15 minutes of starting to eat would work well. But newer observations suggest that rapid-acting insulin doesn’t get absorbed and start working that quickly in all people. John Walsh, PA, CDE, coauthor of the book Using Insulin, for example, believes the maximum blood-glucose-lowering effect of rapid-acting insulin may occur much closer to two hours after an injection rather than 45–90 minutes. If this is the case, the optimal time to take rapid-acting insulin is on the earlier end of the spectrum — about 10 to 15 minutes before eating — rather than with the first bite or 15 minutes after starting a meal. Walsh’s belief is based on research suggesting that insulin’s pharmacodynamics (when, how much, and how long insulin seems to be acting on cells, working to reduce blood glucose levels) may be different from its pharmacokinetics (when, how much, and how long insulin is detectable in the bloodstream). In other words, insulin may be measurable in the bloodstream before it begins actively lowering blood glucose.

Some other factors that may cause insulin action to differ from the action curve given in product literature or to vary from person to person include thickness of the subcutaneous fatty layer at an injection site, temperature, blood flow, exercise, and dose size. (The choice of injection site — abdomen, thigh, arm, buttock — does not seem to affect the absorption rate of rapid-acting insulin as it does for slower-acting insulins.) Injecting into areas that have more subcutaneous fat tends to slow insulin absorption. Widened blood vessels (caused by higher temperatures or exercise) allow insulin to be absorbed more quickly; constricted blood vessels (caused by colder temperatures or smoking) can cause slower absorption. Large doses of insulin may also be absorbed somewhat more slowly than smaller doses.

The importance of staying ahead. Fine-tuning the timing of your premeal boluses or injections is important, but it should not overshadow one of the basics of blood glucose control: counting the carbohydrates in a meal or snack and using enough insulin to cover the anticipated rise in blood glucose. (If you don’t know how to count carbohydrates or to match your insulin dose to the amount of carbohydrate you plan to eat, speak to your health-care provider.) Many people find themselves in a reactive mode when it comes to dosing insulin, taking it in response to high blood glucose rather than using enough of it before a meal to cover the rise of blood glucose in the hours after a meal or snack. Experts agree that it’s much harder to bring high blood glucose back down than to control blood glucose levels with sufficient insulin in the first place.

Variable impact of food

To achieve a good match between the amount of insulin you take and an anticipated rise in your blood glucose level, you need to know how much carbohydrate you intend to eat, because carbohydrate has the greatest effect on blood glucose level. Some experts also encourage people to take into account the type of carbohydrate consumed as well as the amount.

Walsh, Wolpert, and Gary Scheiner, a certified diabetes educator in private practice in Pennsylvania, agree that the glycemic index of the foods in a meal or snack as well as the fiber and fat content can dramatically affect how quickly or slowly blood glucose level rises. (The glycemic index ranks foods based on how quickly they raise a person’s blood glucose.) “Using this knowledge is especially helpful at breakfast,” adds Wolpert, because “some people are more insulin-resistant in the morning and therefore have more of a problem controlling blood glucose around the breakfast hours.” For these reasons, both Wolpert and Scheiner suggest that people have foods with a lower glycemic index such as yogurt or a bowl of oatmeal with a piece of fruit for breakfast rather than foods with a higher glycemic index such as some cold cereals, pancakes, or muffins.

In general, foods and combinations of foods that have a low glycemic index and high fiber content will raise blood glucose more slowly. Meals and snacks that have a higher glycemic index and are lower in fiber will raise blood glucose more quickly. Meals and snacks that are high in fat content tend to cause a delayed rise in blood glucose.

The extent to which the glycemic index or fat content of a meal speeds or slows the rise in blood glucose following a meal varies from person to person. If you find that certain meals affect your postmeal blood glucose levels in a predictable fashion, you may be able to fine-tune the timing of your premeal injections or boluses accordingly.

Practical tips

Meticulously timing your rapid-acting insulin dose and carefully calculating your dose according to the carbohydrate you will eat is usually best for blood glucose control, but it may not always be possible. There are times when you know exactly when and how much you will eat and times when you don’t. For example, if you are trying out a new restaurant, eating at a friend’s home, or not feeling well, you may not know exactly when or what you will be eating, which can make it difficult to know how much insulin you’ll need and when to take it. In addition, if your blood glucose level is low before a meal, you may have to give the food, not the insulin, a head start. The following practical tips may help you adjust for the realities of daily life:

High blood glucose before a meal. If your blood glucose is high before a meal, use your insulin sensitivity factor (how much your blood glucose level falls in response to one unit of insulin) to calculate a dose of rapid-acting insulin to cover the high, then wait until that insulin begins to lower your blood glucose before you eat. This method is easier and more convenient for insulin pump users. (For people who are willing to take an extra injection but who don’t want the hassle of carrying a vial of insulin and syringes, an insulin pen may also add some convenience.)

Claudia Shwide-Slavin, a dietitian and certified diabetes educator in private practice in New York City, advises the following: “If your blood glucose level is between 140 mg/dl and 180 mg/dl, take the rapid-acting insulin and wait half an hour before eating. If it’s between 180 mg/dl and 200 mg/dl, wait 45 minutes. If it’s higher than 200 mg/dl, wait at least an hour.” She also notes, however, “I have seen it take two hours after an injection for blood glucose levels to budge.” If a person is hungry or must eat at a specific time, Shwide-Slavin recommends limiting the amount of carbohydrate at the meal by eating mainly protein and nonstarchy vegetables.

Another suggestion from Shwide-Slavin if you can’t delay a meal is to “check your blood glucose an hour before you think you will eat. If it is high, take a correction dose so that your blood glucose will be on the downswing by the time you eat.”

Low blood glucose before a meal. If your blood glucose is low before a meal (below about 80 mg/dl), “Wait to take your insulin,” says Shwide-Slavin. “Let the food have 15 minutes to raise your blood glucose before taking your insulin.”

Low glycemic index foods. On a related note, Wolpert advises, “If your blood glucose is less than 100 mg/dl before a meal and you plan to have a meal with a low glycemic index, wait until you start to eat to take your rapid-acting insulin.”

Uncertain carbohydrate intake. If you don’t know how much carbohydrate you will eat at a meal, consider splitting your rapid-acting insulin dose. Take enough insulin before the meal to cover the amount of carbohydrate you are sure you will eat. Then as the meal goes on and you know how much more carbohydrate you will eat, take more insulin to cover that amount. This method is easiest if you are on an insulin pump.

Large meals. Splitting your rapid-acting insulin dose can also work well for meals that are larger than normal. It has been shown that large meals can delay the rise of blood glucose regardless of the nutrient composition of the meal.

Drawn-out meals. Pump users who are planning to have a meal that is eaten over time, such as a cocktail party or Thanksgiving dinner or a meal that is higher in fat or lower in glycemic index and high in fiber, may want to consider using one of the optional bolus delivery tools on their insulin pump. Most insulin pumps allow you to deliver a bolus over time rather than all at once or to deliver some of the bolus immediately and the rest over the next few hours. People who inject insulin could take half their bolus at the start of a meal and the other half an hour or two later.

Snacks. Regardless of whether the carbohydrate you eat is part of a meal or snack, it has the potential to raise your blood glucose level. Alison Evert, RD, CDE, a diabetes educator at the University of Washington Medical Center, advises people to “take rapid-acting insulin with any amount of carbohydrate over 10 grams.” Although it is common to think that a few grams won’t make a big difference, the reality is that 10 grams of carbohydrate can raise many peoples’ blood glucose 30 or more points.

Unused bolus insulin

While the duration of action of rapid-acting insulin is usually given as 3–4 hours, some diabetes experts believe it may continue to lower blood glucose level for as long as 5 hours. Walsh believes that a good rule of thumb is to assume that about 20% of a dose of rapid-acting insulin is used each hour after it is given. In his book Using Insulin and on his Web site, he provides a table that shows insulin activity at 1, 2, 3, 4, and 5 hours after bolus doses of insulin from 1 to 10 units.

This information becomes important if you give bolus doses of rapid-acting insulin less than four to five hours apart. When two doses of rapid-acting insulin overlap, their effects overlap, too, and the result can be hypoglycemia. Therefore, when you’re considering the size of a bolus dose of insulin, it is critical that you factor in what Walsh calls “the unused insulin” or “bolus [insulin] on board.” This is the amount of “active” rapid-acting insulin left from a previous injection or bolus dose from a pump that continues to lower your blood glucose.

To illustrate this idea, consider the following example. Before lunch, you take a bolus of rapid-acting insulin. Three hours later you decide to have a snack with 30 grams of carbohydrate. You check your blood glucose and find that it’s high at 195 mg/dl. Assuming your insulin sensitivity factor is 45 mg/dl, you calculate you’ll need two units of insulin to bring your blood glucose level down to your premeal target of 100 mg/dl and another two units to cover the snack you’re about to eat (assuming an insulin-to-carbohydrate ratio of 1:15). You take the insulin, and several hours later, your blood glucose has dropped to 55 mg/dl. Why? Because you didn’t factor in the hour or so of action left on the bolus you took at lunch.

To prevent hypoglycemia from unused insulin, get in the habit of thinking about when you took your last bolus dose and how much (if any) action is still left before taking another bolus to “correct” high blood glucose.

The latest generation of insulin pumps, which some people call “smart pumps,” has a built-in feature that keeps track of how much of a previous bolus dose is still active. If the user attempts to administer a bolus dose while a previous bolus is still active, the pump will suggest subtracting the amount of insulin still “on board” from the requested amount.

How are you doing?

Measuring and observing your postmeal (postprandial) blood glucose values will help you to determine how well you are timing your rapid-acting insulin and figuring your doses. Walsh suggests that “much of the postprandial high blood glucose values observed are because people aren’t giving rapid-acting insulin long enough before a meal to act in tandem with their food. Most foods affect the blood glucose within two hours, while most of the effect of rapid-acting insulin is seen over five hours.”

The American Diabetes Association advises that postprandial blood glucose shouldn’t exceed 180 mg/dl (plasma value) at two hours after the start of a meal. Other associations and experts believe the two-hour postmeal goal should be less than 140 mg/dl. Occasionally checking your blood glucose after a meal at hours one, two, and three can help you determine when your blood glucose level peaks and starts to come down again. According to Scheiner, “Research shows that it is common for people to have elevated blood glucose levels after meals.” One key to controlling these highs is better timing of rapid-acting insulin.

Because responses to insulin and carbohydrate can vary (because of, say, activity level or meal composition), some people find it helpful to record their experiences for future reference in a notebook, computer file, or logbook. Chart the foods you eat and the amounts, the amount of insulin you take to cover the food, your blood glucose levels before and after you eat, when you exercise and how vigorously, and any lessons you learn. Although perfect control is impossible, your personal database can help you obtain a better understanding of your blood glucose readings and how to fine-tune your diabetes control.

The right time

Delivering rapid-acting insulin at the proper time can help you to achieve optimal blood glucose control. It’s not easy, but by learning when it’s best for you to take your insulin and putting a few tips into practice, you can increase your chances of hitting your blood glucose targets more regularly. For more information about insulin, click here[1].

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