Insulin: How To Restore A Tarnished Miracle

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By: James S. Hirsch

It was hailed as a "miracle cure," restoring life to the "erstwhile dead" anddelivering not just health, but "salvation." Discovered in 1922, insulin did notlive up to the initial euphoria – it didn't cure anything – but the life-savingelixir still stands as one of the greatest breakthroughs in medical history.

But a funny thing happened to insulin's halo. It's been replaced by analbatross. Though the product is purer and better than ever before, insulin isoften underused by type 1 diabetics and frequently avoided by type 2 patientswho should be taking it. Insulin is often feared, reviled, misunderstood, poorlytaught, used incorrectly, or neglected. At the January 2007 ADA post-gradmeeting in New York, Dr. Arturo Rollo of Harvard Medical School said thatdelaying insulin therapy for type 2 patients was the greatest disaster inprimary care.

Even when insulin is used properly, sometimes it has to be called a differentname. Dr. Lois Jovanovic, the director of research and chief scientific officerof Sansum Diabetes Research Institute in Santa Barbara, California, realizedthat many of her Mexican-American patients feared insulin because they recalledthat it had been given to an aging diabetic ancestor long after it could do muchgood. Insulin seemed like a precursor to death. "The word was terrifying,because it's the drug that killed everyone in the family," said Dr. Jovanovic,who has type 1 herself. To convince these patients to accept insulin therapy,she uses insulin pens, calling them las plumas.

Ironically, the need for insulin has never been greater. Type 1 patients, ofcourse, whose numbers are growing, need the injected hormone to live. But thereal epidemic is occurring in type 2 diabetes – and that's where insulin'sunderuse is most glaring. An estimated thirty percent of type 2 patients takeinsulin, but David M. Nathan, head of the diabetes unit at Massachusetts GeneralHospital, believes that sixty percent need it to achieve near-normal bloodsugars.

What makes insulin's fall from grace so jarring is that it was once the verysymbol of modern science defeating an ancient disease. After its discovery,widely published photographs demonstrated insulin's miraculous power toliterally restore flesh to bones. "A Boon to the Human Race," shouted an earlyad from Eli Lilly, which was the first company to mass produce insulin. Anotherad by Eli Lilly showed a beautiful bride kissing her beaming father, the happygroom in the background, with the tagline: "Our favorite picture of insulin."

To be sure, many patients remain grateful for this "miracle," and I, for one,remain in awe. When I took injections (I now use a pump), I would sometimesparaphrase Shakespeare with the words "Insulin, do thy deed." Which was, keep mealive for another day. And when my young son took his first shot, the heartbreakof his diagnosis was leavened by the knowledge that insulin would save him fromdeath.

So how did insulin lose its groove? Some concerns are longstanding. Insulinsometimes causes weight gain because patients now retain their nutrients, andexcessive insulin can cause hypoglycemia, which itself can be a killer.(Nietzsche said, "That which does not kill me, makes me stronger." With insulin,the inverse is true: "That which makes me stronger, can also kill me.")

The more pressing issue is with type 2 diabetics. It was long assumed that theyavoided insulin because they feared the injections, but the extraordinarysuccess of Byetta, an injectable drug for type 2 patients, has undermined thatargument. The real problem with insulin is that it is equated with failure orpunishment. According to this view, type 2 patients who can't maintain goodcontrol with diet, exercise, and oral agents must suffer the consequences withinsulin. Some doctors reinforce this perception by threatening their patientsthat they will have to start shots unless they lose weight. Insulin can alsorepresent the needs of a body in its final throes, so avoiding it is a form ofdenial.

"There is a fear of insulin in that it represents the final stage," said Paul S.Jellinger, president of the American College of Endocrinology. "The connotationis that you're about to lose a leg, or whatever."

This view is both shortsighted and wrong. Type 2 diabetes is a "progressive"disease, which means that beta cells become increasingly impaired over time. Ifa type 2 patient lives long enough, in most cases that individual willessentially have the same beta cell function – little or none – as a type 1patient. Thus, the goal of every type 2 patient should be to live long enough torequire insulin.

Healthcare providers also shoulder some of the blame. Initiating insulin therapyfor any patient is time consuming, so doctors who receive no extra compensationfor good care may prefer to delay the burdens (their own) of insulin. (Somedoctors also delay type 2 oral agents because they then have to deal withpatients' adverse side effects.) Doctors also underprescribe insulin for type 1patients because they fear getting sued over a severe hypoglycemic incident, orperhaps they just don't want to be bothered with late-night phone calls."Hyperglycemia is considered the patient's fault; hypoglycemia, the doctor'sfault," said Dr. John Holcombe, Medical Fellow at Eli Lilly.

To restore insulin's luster, at minimum healthcare providers need to be taughthow to use it. Many in training don't even know what it looks like. My brother,Dr. Irl Hirsch, runs a diabetes clinic for the University of Washington inSeattle, and when students or residents assist him, he has to show them what avial of insulin looks like. "Even the fellows are clueless," he said.

Patients must also be convinced about the indispensability of the product,particularly in the high-tech age of insulin analogs: rapid-acting, peakless,inhaled, and formulations we've not yet envisioned. I would love to see theprincipal manufacturers – Novo Nordisk, Eli Lilly, and sanofi-aventis – sponsor amarketing campaign to remind patients that insulin is not a sign of weakness orfailure, but a product with a glorious history and marvelous future. I would puta tall vial next to a precious child, with the tagline: "Insulin. The MiracleKeeps Getting Better."

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