When To Give Pre-Meal Insulin   (February 3, 2013)

Another diabetes myth just bit the dust: the idea that pre-meal (bolus) injections of regular human insulin should be given thirty minutes before eating. This is a myth that I grew up with, and one that I had religiously taught my insulin-using patients back in the days before insulin analogs became available. But it wasn’t just me: the ADA still says “Insulin shots are most effective when you take them so that insulin goes to work when glucose from your food starts to enter your blood. For example, regular insulin works best if you take it 30 minutes before you eat.”

Before continuing, let me add a few points of clarification about types of insulin and when they became commercially available.  Insulin progressed from initially being “animal insulins,” which were obtained (ever since the 1920’s) from beef or pork pancreases. All insulins were short-duration-of-action, with their effects on glucose levels lasting only a few hours, until NPH  became available in about 1950 (NPH lasts about half-a-day). In 1983, semi-synthetic “human insulin” (Humulin) first became commercially available.  All short-duration insulins were frequently called “regular insulin” – and the regular insulin vials had a big letter “R” printed on the label. In 1996, Humalog, the first of  the “insulin analogs,” became available; the rapid-acting insulin analogs now also include Novolog, NovoRapid, and Apidra.

It was always obvious ever since insulin therapy was available that short-acting insulin should be given before meals. In 1925, Dr. Banting, one of the co-discoverers of insulin, described giving insulin “from one-half to three-quarters of an hour before meals.”

This concept of building in a window of time between the injection of short-acting insulin and starting to eat continued unchanged until the insulin analogs became available in 1996: one of the positive attributes touted for the new analog products was their ability to be more rapidly absorbed -- so that it was considered appropriate to recommend giving the insulin injection at mealtime (or even after the meal).  

I do recall asking a lot of patients whom I was advising to switch from human insulin to insulin analogs about when they were actually taking their human insulin – and many of them sheepishly replied that they were indeed taking the insulin at mealtime for convenience. I, with great superiority, was able to assure them that their sins were now forgiven with the insulin analogs, as these new wonder drugs are able to be given with meals rather than a half-hour before.

In a study just published in Diabetes Care, Randomized Crossover Study to Examine the Necessity of an Injection-to-Meal Interval in Patients With Type 2 Diabetes Mellitus and Human Insulin , researchers set up a prospective, randomized, open-label, single-center crossover study of 100 patients with T2DM who had been using insulin therapy with regular human insulin, and who had been taking their insulin doses an average of 17 minutes before eating. Half the patients started the study with a 20-minute gap between shots and meals, and half started the study with no gap between shots and meals. After 12 weeks, the patients switched: those who had been gapping become no-gappers, and vice versa, and the study continued for another 12 weeks.

The researchers  looked at A1C changes, blood glucose profile, hypoglycemia, and asked about quality of life, treatment satisfaction, and patient preference. They found no clinically relevant difference in A1C, BGP, or hypos, and... insulin therapy without a gap was preferred by 86.5% of patients. BTW, I really don’t understand why 13.5% would want a gap, except maybe that they were used to it before entering the study.  The authors conclude that “An IMI [injection-to-meal interval] for patients with T2DM and preprandial insulin therapy is not necessary.” (I’ll add a necessary disclaimer: If you are taking short-acting insulin 15-30 minutes before meals and want to switch your timing to immediately before eating, please discuss with your physician or diabetes educator before doing so!)

I think we can safely add “the gap” to the ever-expanding list of diabetes myths: it’s okay to inject immediately before eating, whether taking an insulin analog (which has always been known) or the older regular insulin varieties where some authorities suggest a 30-minute delay.