The sad thing about doctors is that they aren't engineers, and this is doubly true for lawyers. So when you read about medications, everything's written by people who (a) don't think in terms of getting results out of feedback control systems, though that's what the body's all about, and (b) do think in terms of, "If I say something blatantly wrong, I'll get sued, but if I'm mealy-mouthed, I'm safe." This means that the dosage adjustment (titration) instructions for Karl's long-acting Lantus insulin are vague and simplistic, even by the standards of the intelligent layman: http://www.lantus.com/hcp/titration.aspx. Thanks, health-care industry!
So let's talk about feedback control systems, which is a fancy term for something that everyone already knows a lot about. If you set the cruise control on your car, the car will run at the speed you set, increasing the throttle when you're going uphill, decreasing it when you're going downhill, etc. Going up a really steep hill, you might not have enough horsepower to maintain your speed, so you slow down: "flat out" is all you've got. On a downslope, you might go faster than the speed you selected. So cruise control keeps everything constant under a certain range of conditions, but outside this range, you get what you get.
Karl's pancreas is still making some insulin. The pancreas has a very cool feedback control loop which, like cruise control, puts insulin into Karl's system at the right rate to keep his blood-sugar levels constant, within a certain range. The problem is that his pancreas can't make enough insulin to keep his blood sugar under control under most conditions. His pancreas' accelerator is pressed all the way to the floor and he's still not at cruising speed.
If we get his dosage right, injected insulin acts like a strong tailwind, allowing Karl to get up to speed without making his pancreas run flat-out. To continue the auto analogy, this reduces wear and allows it to cool off, so it will last longer.
Not only that, but by allowing the engine run most of the time at, say, 50% power instead of 100% power, if we get an unexpected hill, we can get over some hills without slowing down, because we have reserve capacity. Turning the analogy back to diabetes, if Karl eats a larger portion than we had calculated, so he receives less insulin than he should, or sneaks a snack without any insulin at all, his body has reserves that will cover it without spiking his blood sugar. Sweet!
Because Karl's pancreas is producing some insulin on its own, he can receive different doses of long-acting insulin and arrive at the same average blood-sugar levels. If he gets a low-ish does, his pancreas will provide more insulin, and if he gets a high-ish does, it will provide less. So within this range, the results will be equivalent -- except to his pancreas!
Since the goal is to keep his pancreas from being overloaded, we're aiming for a dose on the high side of this range. So far, we've determined that a dose of Lantus anywhere between 6 and 8 units per day gives about the same results, and we'll probably test 9 units soon. We're adjusting no more often than once a week, since day-to-day variations are wide enough to obscure the results.
