Ultralente and Pre Meal Lispro or Aspart


• Provides flexibility for varying dietary habits

• Short duration of action of lispro and aspart results in fewer between-meal "hypos"

• Insulin coverage for snacks or extra meals is easily provided by additional injections of the rapid-acting insulin

• No waiting time between the lispro or aspart injection and the meal


• Ultralente is the most variable of the available insulin preparations in terms of day-to-day consistency in insulin kinetics, and thus glycemic control

• Nocturnal hypoglycemia in some patients

• Difficult to compensate for variance in physical activity


The use of Ultralente insulin for basal coverage and a rapid-acting insulin at meals has been the mainstay approach for intensive insulin therapy in the United States for many years. Figure 2A shows how it is generally done: Ultralente with lispro or aspart when beginning breakfast, lispro or aspart at lunch, and Ultralente with lispro or aspart at supper. Before the rapid-acting insulin analogs became available, Regular insulin was used for the mealtime coverage, and it was generally recommended that the Ultralente and Regular insulins be given as separate injections (five shots per day) to avoid the effect of Ultralente's slowing the kinetics of action of the Regular (15). This is now a moot issue because lispro and aspart are resistant to this effect (three shots each day). Also, the analogs provide other important benefits such as no waiting time between the injection and eating the meal, and a shorter duration of action for more focused mealtime insulin delivery and less risk of between-meal hypoglycemia than Regular insulin.

It confuses some practitioners that Ultralente is given twice daily, because they were taught it has a 24-36-hour duration of action. That was when the insulin in Ultralente was of beef origin. Human-based Ultralente has been available for several years, and its duration of action is considerably shorter. Further, many physicians believe that Ultralente is a peakless insulin when in fact there is a sizable peak effect, as shown in Figure 2A, that causes some patients to experience nocturnal hypoglycemia. Because of this, many experts advise a four-shot variation on this regimen: Ultralente and lispro or aspart at breakfast, Huma-log or aspart at lunch, Humalog or aspart at supper, and NPH at bedtime.


This program is one of the best for patients who want flexibility for dietary habits in both when they eat and what they eat. By taking rapid-acting insulin for each meal, they can take exactly the right amount of insulin at exactly the right time. Also, snacks or extra meals are easily covered with additional injections of rapid-acting insulin. Furthermore, the use of separate basal and bolus insulin coverage means patients have near-total freedom over the timing of when they eat. Thus, this regimen is particularly useful for anyone with erratic eating habits.

The main disadvantages are twofold. Ultralente is the most inconsistent of the available insulin preparations in terms of its absorption (16), causing considerable day-to-day variability in insulin action and thus glycemia in some patients. This can be particularly problematic for patients who are highly physically active, and is generally not the best choice for them. The second issue regards the substantial peak effect of this insulin. Trying to optimize fasting blood glucose values by upward adjustments of the p.m. Ultralente dose causes nighttime hypoglycemia (with or without symptoms) in approximately 25% of patients. Changing to the four-shot variation listed above often eliminates this problem.

Is it necessary to use rapid-acting insulin analogs for the mealtime coverage over Regular insulin? Generally the answer is yes, as it has been repeatedly shown that there is less postprandial and middle-of-the-night hypoglycemia with the analogs (17-19). When should the analogs be injected? While there has been some disagreement, most studies suggest injecting anywhere from 15 minutes before the meal to when the patient starts to eat (20).

A complex issue is when to perform SBGM—pre-meal or post-meal? Because of the targeted effect of lispro and aspart for postprandial glycemic control, pre-meal glucose monitoring does not provide optimal information for determining the mealtime insulin dosages. Thus, when beginning the program, it is useful on some days to measure blood glucose values before a meal (goal 80-120 mg/ dl) and other days 2 hours after meals (goal <140 mg/dl). However, once the program has been established, the use of algorithms for adjustments in the mealtime insulin dosage based on the glycemia at that time means that most testing is done pre-meaJ.

How do you do it?

Calculate the 24-hour insulin need as described in Table 4.

Give 50% of the 24-hour dosage as Ultralente split equally between breakfast and supper.

Give the remaining 50% of the 24-hour dosage at meals with, on average, 30-40% at breakfast, 30% at lunch, and 30-40% at dinner depending on the patient's eating habits.

Adjust these starting dosages if the patient has unusual eating, exercise, or work habits.

Table 4 Sensitivity Factors for Calculating 24-Hour Insulin Needs (approximate figures to be used in calculating the starting 24-hour insulin needs)

Phenotype Normal weight Extremely physically active Moderately physically active Minimally active Obese

Extremely physically active Moderate physically active Minimally active

0.3 units/kg 0.4 units/kg 0.5 units/kg

0.5 units/kg 0.6 units/kg 0.8 units/kg

Renal failure

Coexisting illness raising risk of hypoglycemia

Eating habits ("big eater")

New-onset type 1 diabetes <30 years old

Subtract 0.2 units/kg Subtract 0.2 units/kg Add 0.1 unit/kg 0.3 units/kg

5. Perform daily fasting, pre-meal or 2-hour postmeal, and bedtime SBGM along with weekly middle-of-the-night SBGM.

6. Example: 70-kg male who is moderately physically active. Total daily insulin dose is 70 kg X 0.4 units/kg = 28 units. Total Ultralente: 28 X 50% = 14 units, a.m. and p.m. Ultralente: 14 X 50% = 7 units each. Total lispro or aspart: 28 X 50% = 14 units. Pre-breakfast lispro or aspart: 14 X 40% = 6 units. Pre-lunch and pre-supper lispro or aspart: 14 X 30% = 4-5 units. Final: 7 units Ultralente and 6 units lispro or aspart pre-breakfast, 4 units lispro or aspart pre-lunch, 6 units Ultralente and 4-5 units lispro or aspart pre-dinner. Adjust insulin doses as needed based on the SBGM values to attain the glycemia goals in Table 2.

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Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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