interesting article about rebuttal of last week

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This article originally posted 17 December, 2010 and appeared in

Type 2 Diabetes,

Type 1 Diabetes,

Issue 552

Rebuttal to the Analysis that the Cause of Diabetes is Not Genetic

From Constantin Polychronakos, M.D., F.R.C.P.C., Professor, Departments of

Pediatrics and Human Genetics, Director, Division of Endocrinology, McGill

University

Health Centre, comes a response to last week's article,

New Analysis Concludes Cause of Diabetes Not Genetic....

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I think that your uncritical and unbalanced presentation of a non-peer

reviewed analysis of the role of genes in diabetes, by total scientific

unknowns

with an agenda, was a great disservice to your audience.

Genetic analysis will not tell us all about the causes of diabetes but it is

putting in place a very important piece of this multi-piece puzzle.

The statements made in this article are blatantly false for both types of

diabetes, but especially for Type 1, where genetic analysis has been a

resounding

success.

In Type 1 diabetes, the concordance in identical twins is >50% if you follow

them long enough (Redondo et al., N Engl J Med. 2008 Dec

25;359(26):2849-50),

while in dizygotic twins, exposed to exactly the same environment, it is ten

times less (and not different from ordinary siblings, shooting down

intrauterine

environment as a possible difference between mono- and di-zygotic twins).

Currently known genetic loci can identify, at birth, from a drop of blood,

more

than 90% of diabetics within the 20% of the general population with the

highest risk. These are percentages that begin to be useful at the

individual level.

Suppose that one of the immune interventions currently tried by TrialNet and

others to prevent T1DM in antibody-positive individuals is proven effective.

Are we going to screen the entire population of children with antibodies

yearly? This is logistically impossible but if we can confine this screening

to

only 20% of the population it is brought to the realm of the feasible.

By contrast, although we know that environment is also important in Type 1

diabetes, not a single environmental factor, modifiable or otherwise, has

been

identified to date. The recent publication of the TRIGR pilot data (N Engl J

Med. 2010 Nov 11;363(20):1900-8) pours a lot of cold water on the cow's milk

theory. Intervention to remove cow's milk from infant feeding made no

difference in rates of diabetes in (genetically) high-risk infants and the

(barely

significant) difference in antibody positivity can be trivially explained by

an unusually high rate of missing antibody data from children who ended up

developing diabetes anyway. The literature on viral causes is a mess of half

the papers contradicting the other half.

Here, I might also mention that genetic study of a very rare form of

neonatal diabetes has discovered RFX6, a previously unstudied gene that is

absolutely

necessary for the development of the pancreatic beta cells and, likely, has

been a crucial " missing link " in efforts to cure common types of diabetes by

generating new beta cells. (See

http://www.nature.com/nature/journal/v463/n7282/full/7282708a.html)

For Type 2 diabetes, it is true that environment is supremely important.

There, genetics is called to explain why, from individuals exposed to

exactly the

same environment, some get diabetes but most don't. The problem in T2DM is

that genetic risk is due to a very large number (thousands) of genes, each

contributing

very small effects. This is not at all the same thing as saying that genes

have no role in determining the disease. It will be closer to truth to say

that,

unlike the situation in T1DM, no single gene has an effect large enough to

be useful in genetic prediction. This is not because these genes are not

important,

but simply because they are not different enough amongst individuals to

account for relative risk. Their knowledge can still serve in the

development of

new treatments.

I think you owe it to your audience to publish a more balanced view of the

issue.

Sincerely,

Constantin Polychronakos M.D., F.R.C.P.C.

Professor, Departments of Pediatrics and Human Genetics

Director, Division of Endocrinology

McGill University Health Centre (Children's Hospital)

Editor, Journal of Medical Genetics