Scott King

May 16, 2000. A question by e-mail:

Question 1: We studied PKU in our genetics course. On a genetic level, phenylallanine is not produced due to a stop codon on the gene. This can be compensated by diet, however, they have found a second codon that stops the porcess again leading to complications later in life. Is it possible that diabetes works this way on a genetic level? There may be a codon to start the autoimmune process and a second further along on the gene for complications. Wouldn't this help explain why some people are "lucky" and others aren't?,

Scott's reply: The genetic background of diabetes is the subject of intensive study. It is already known that it is more complicated that a single gene. At least three are involved, and probably many more. The most important is HLA-DR, and gene that determines the sort of protein that present antigen to immune cells -- such genes are often associated with "autoimmune" diseaes.

Question 2: In islet transplants, has anyone worked on changing the surface antigens on the islets so that the antibodies present won't attack them? Sort of tricking the antibodies in the plasma into thinking the islets or organs are "self" so they won't attack the new tissues. Wouldn't this eliminate the need for encapsulation and for anti-rejection medications?(not only in islets but in organ transplants, too.)

Scott's reply: Others are working on this approach. We think it unlikely to work. The
only way to do it would be to make custom islets for each diabetic, which
would be prohibitively expensive.

Scott King


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Carolyn Robertson

May 24, 2000. A question by e-mail:

Your credentials are certainly very impressive and I congratulate you on your contribution to spreading the word about good Diabetes management.

I do have a comment about your recent insulin article. It is my understanding that 75/25 is NOT 75% NPH but 75% lispro analogue (NPL - Neutral Protamine Lispro). Lispro is not stable when mixed with NPH therefore Lilly created the analogue to put into the new pen. Perhaps this is not a big thing - but it can lead to misunderstanding on the part of some uninformed people who will try to mix NPH + lispro in a vial (since mixture is currently only available in a pen)

Fran

Carol's reply: Francine, thanks for your email. You are right about the mixture that is being used by Lilly called 75/25. I should have made the distinction clearer. Humalog is mixed with a hybrid insulin called NPL. The new analogue produces an intermediate-acting insulin with an activity profile similar to that of NPH.

As you have noted the mixture with NPH and Humalog is not stable. The protamine binds with the Humalog when they are mixed together over a proglonged period. As per Eli Lilly, this period varies from a few weeks to months. Since this exchange occurs over a prolonged period of time, it is not an issue within the context of mixing insulin lispro and human NPH from separate vials for immediate injection.

Thanks again, I will make the clarification in the article.

Carol

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