When Type 2s Take Insulin – A History of Insulin

While someone with type 1 diabetes needs insulin from the beginning of the disease, people with type 2 diabetes have some residual insulin secretion. However, first-phase insulin response-the initial surge of insulin that normally occurs when food is ingested-is lost, resulting in high blood-glucose levels after meals. Nat-ural insulin production also is insufficient to handle insulin resistance.

“Early insulin replacement is an evolving strategy for optimal metabolic control of patients with type 2 diabetes,” says Rosenstock. “The ultimate goal of management is the same as for type 1 diabetes-to prevent acute and long-term complications by improving glycemic control.”

Kirkman says the most common reason she starts a type 2 on insulin is if the person’s A1C is above his or her goal despite maximum doses of two oral agents. But she tries to talk to type 2s about insulin from the start, so that it doesn’t come as a shock to them later if they need to begin injections.

“I stress to type 2s that there is beta-cell dysfunction in type 2 diabetes, and that it’s a progressive thing. I present insulin as a necessary and logical next step to preserve their long-term health, not as a punishment or sign of failure.”

Kirkman adds that she has rarely found it helpful to have a type 2 on three oral agents. “I think it’s mainly a delaying tactic.”

Although there is no consensus, Einhorn believes that “most of us will turn to Lantus early” and use it to get fasting blood glucose under control, expecting that oral agents will work to handle prandial needs during the day. “Lantus is such a good insulin that many of us would consider using it as a first line [of defense]. An argument can be made that its action is such that it can take the place of multiple oral agents.”

In the beginning, there was Regular. Manufactured from beef or pig pancreases, the elixir was “rough” and unrefined, with a dirty, brown appearance. Regular had to be injected several times a day. Despite its drawbacks, it was the “time in a bottle” that gave people with diabetes the substance they needed to live. Diabetes was no longer a death sentence.

The first insulin hurt. Faced with its impurity and the large needles used to inject the life-giving substance, people clamored for an insulin that lasted longer, one that could do the job without several painful injections every day.

The ’30s and ’40s

The “magic bullet” was protamine, derived from salmon sperm. Added to insulin, it lengthened insulin action time. Pro-tamine zinc insulin was introduced in 1936, with NPH (neutral protamine Hagedorn) coming along a decade later.

The ’50s and ’60s

Adding zinc to insulin to form crystals in varying sizes produced the Lente family-including Ultralente-in 1951. The size of the insulin crystals determined the length of the insulin’s action: the larger the crystal, the longer it took to disperse insulin from the injection site.

At first, it was believed that only one shot a day of a longer-acting insulin was needed, freeing people with diabetes from the burden of multiple daily shots.

“It was like injecting a time bomb every morning,” one diabetes educator said of the low blood glucose that occurred several hours after people took a massive dose of NPH each morning. Only when home blood-glucose testing came along was it learned that the longer-acting insulins were unable to maintain good glucose control. Short-acting insulins were needed to control post-meal glucose rises.

The ’70s, ’80s and Today

In the 1970s, the animal insulins used at the time were purified. Then, in the 1980s, “human” insulin was developed through recombinant DNA technology, which uses bacteria or yeast to grow insulin akin to that produced by the human body. It was the beginning of the end of animal insulins, which didn’t have as strong an action as the manufactured substances.

But in addition to Regular, only three intermediate-acting preparations were made with the human insulins-NPH, Lente, and Ultralente. While human Regular lasted longer than the animal-based version, people discovered that the shot of human intermediate-acting insulin they took at dinner no longer lasted throughout the night, prompting some to move the dinner shot to bedtime. Many people, frustrated with these limits, returned to using the animal insulins. Still, human insulins were marketed as “better,” though no studies ever proved this.

Now it looks as if the best insulins are no longer “human.” In the new analogs (or mutant insulins) made possible by the development of recombinant DNA insulins-the insulin molecule is changed in a way that either speeds up or slows down the action.

We’re also back to where we started: multiple injections each day to regulate blood-glucose levels-albeit with insulins that better mimic normal insulin action.

Although our knowledge has evolved, the ultimate in blood-glucose control has not yet arrived, even with today’s combinations of long-acting and rapid-acting insulins. Rosenstock wrote in the April 2001 issue of Diabetes: “Unfortunately, no combination of available insulin preparations possesses the characteristics necessary to simulate normal insulin secretion. However, recent advancesÉ have resulted in insulin analogs with properties that may significantly improve insulin replacement therapy.”