Splitting the Evening Insulin Dose To Avoid Low Blood Sugar Levels and To Improve Sugar Control in Patients with Type 1 Diabetes

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The summary below is from the full report titled "Administration of Neutral Protamine Hagedorn Insulin at Bedtime versus with Dinner in Type 1 Diabetes Mellitus To Avoid Nocturnal Hypoglycemia and Improve Control. A Randomized, Controlled Trial." It is in the 2 April 2002 issue of Annals of Internal Medicine (volume 136, pages 504-514). The authors are CG Fanelli, S Pampanelli, F Porcellati, P Rossetti, P Brunetti, and GB Bolli. The summaries may be reproduced for not-for-profit educational purposes only. Any other uses must be approved by the American College of Physicians-American Society of Internal Medicine.

What is the problem and what is known about it so far?

Type 1 diabetes mellitus (also called juvenile diabetes) occurs when the pancreas stops making insulin. Insulin helps the body use the energy in foods. Without insulin, blood levels of sugar become high. Over time, high blood sugar levels can lead to blindness, kidney failure, damage to nerves, and heart disease. To keep blood sugar levels in the normal range, people with type 1 diabetes must inject insulin several times each day and follow a special diet. There are several types of insulin. Short-acting (regular or lispro) insulins begin to act soon after injection. Long-acting (neutral protamine Hagedorn [NPH], lente, ultralente, or glargine) insulins do not begin to act until several hours after injection, but then they continue to act for many hours. For example, a dinnertime injection of long-acting insulin controls sugar levels throughout the night. A very low blood sugar level (hypoglycemia) is a dangerous complication of insulin treatment. To avoid hypoglycemia during the night, doctors often tell patients to "split" their evening insulin dose by taking short-acting insulin at dinner and long-acting insulin at bedtime instead of taking both forms of insulin at dinnertime ("mixing"). However, nobody has done a careful study to see whether "splitting" is truly better than "mixing" the evening insulin.

Why did the researchers do this particular study?

To see whether splitting the evening insulin dose decreases hypoglycemia and improves blood sugar control compared with mixing evening insulin at dinner.

Who was studied?

22 patients with type 1 diabetes, all of whom were injecting insulin four times daily at the beginning of the study.

How was the study done?

The researchers assigned patients at random to a 4-month period of either mixed (regular [short-acting] and NPH [long-acting] insulin at dinnertime) or split treatment (regular insulin at dinner and NPH insulin at bedtime). After 4 months, the patients switched to the other treatment. Patients measured their blood sugar levels before meals and at bedtime daily, at 3:00 a.m. every other day, and whenever they thought their sugar level was low. The researchers measured the number of hypoglycemic episodes and the general sugar control.

What did the researchers find?

Split treatment led to fewer episodes of nighttime hypoglycemia than mixed treatment. General sugar control was also better with split treatment.

What were the limitations of the study?

This study did not include the types of patients who are at greatest risk for hypoglycemia, such as young children or older adults. In addition, it is not known whether the study's results apply to patients who use types of short-acting and long-acting insulin other than regular and NPH insulin.

What are the implications of the study?

This study supports the common recommendation that patients split evening insulin doses into short-acting insulin with dinner and long-acting insulin at bedtime.