August 31, 2011

Six New Diabetes Gene Varients Identified in South Asian Populations

A new study, published in Nature Genetics, emphasizes the diversity of the many physiological breakdowns doctors lump together under the title "Type 2 Diabetes."

You can read a good summary of the study here:

Six New Genetic Variants Linked to Type 2 Diabetes Discovered in South Asians

View the abstract of the actual study here:

Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci. Jaspal S. Kooner, et al. Nature Genetics, 2011; DOI: 10.1038/ng.921

The genes involved are GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A. Of these I recognize HNF4A, which is a gene that has also been identified as the cause of MODY-1 and of the diabetes found in Danish and Ashkenazi Jewish populations. It causes diabetes because when it is damaged, it disturbs the sequence by which a normal pancreatic beta cell is induced to secrete insulin when blood sugars rise over a threshold.

People who have a damaged HNF4A gene respond very strongly to drugs that stimulate insulin secretion because they bypass the stage of the insulin secretion function where HNF4A plays a part. Of these drugs, Prandin and Gliclazide have been found to be the safest. The other sulfonylurea drugs are cheaper, but they are associated with an increased risk of heart attack because they also stimulate a receptor in heart muscle. (Details Here.)

Note: Gliclazide is not sold in the United States. It is marketed as Glizid, Glyloc and Reclide in India and as Diamicron in most other parts of the world.

GRB14 affects insulin receptor signaling and when it is broken it appears to increase insulin resistance.

HMG20A has previously been associated with a greater incidence of diabetes in obese subjects. (Details here.)

This study also identifies a gene that is new to me, ST6GAL1, as affecting the ability to secrete insulin.

ST6GAL1, AP3S2 and VPS26A have something to to with Golgi bodies and do not seem to have been hitherto associated with diabetes. Gogli bodies are parts of the cell that process and assemble proteins for secretion. Perhaps when this gene is damaged insulin secretion is, too. The Nature study abstract reports that ST6GAL1 is associated with impaired insulin secretion but doesn't comment on the others.

What really sticks out here, though, which has been the case with all the genes identified in studies of all populations with "Type 2 diabetes" is that most of the genes identified impact on insulin secretion, NOT insulin resistance and most have nothing to do with obesity.

People mostly seem to get Type 2 diabetes because they don't have a normal ability to secrete insulin. As documented HERE, people with these defective genes often do get fat, but they get fat after their blood sugar starts to rise, probably in response to the ravenous hunger that comes with high blood sugars as they drop back to normal.

As is the case world wide, most people who are obese, even morbidly so don't develop Type 2 diabetes. Only about 10% of any population does, while in some parts of the world, including sections of the U.S. well over 50% of the population is obese.

That said, the question no one in the scientific establishment is asking is this: is it possible that the genetic damage we are seeing which underlies Type 2 diabetes is coming from toxic exposures in our environment? South Asia industrialized very quickly and is notorious for the horrendous environmental conditions that have accompanied this industrialization. We know that herbicides like atrazine, and chemicals used in industrial processes like arsenic, are associated with high rates of both obesity and diabetes. But is anyone looking at what genetic changes these compounds and hundreds of others make?

It's time that we stopped blaming people for causing their diabetes by overeating. Yes, people are overeating, but this is almost always because something major is broken in the built-in systems that regulate appetite. The rise in obesity and in diabetes incidence (which, by the way is a much smaller rise than the rise in obesity), goes back to 1970, which is, coincidentally about a decade after the world replaced wood, metal and glass with plastic for most objects in our immediate environment.

This is not a coincidence, folks. I'm old enough to remember the pre-plastic days, and to remember that people did not walk everywhere or eat small portions back then. That is a fantasy created by the industrial powers who want you to blame yourself for your diabetes and ignore the massive pollution of our environment with the toxic chemicals that make their companies rich.

You can learn about the many chemicals, pharamceuticals, and pollutants that have been linked to causing diabetes HERE.



RB said...

" people with these defective genes often do get fat, but they get fat after their blood sugar starts to rise, probably in response to the ravenous hunger that comes with high blood sugars as they drop back to normal."

Exactly what Taubes proposes. Maybe we're not fat because we eat too much, but maybe we eat too much because we're fat.

Jenny said...


High blood sugars make people eat too much LONG before they're fat.

Jan Blawat said...

You are totally right that people are not eating more today. I'm 64. When I was a kid people ate 3 huge meals a day. Kids got a lot more exercise than they do now, there was no homework and there were no computers to keep them inside, but the adults were not that active. We seldom had green salad, and vegetables were cooked to the slime stage and weren't popular. Meat, bread, potatoes and jello were the staples. Everything was homemade, but it was calorie-heavy. If I ate that now I'd weigh 400 in a year.

Helen said...

Interesting indeed that all the genetic defects involved insulin secretion, rather than insulin resistance. Makes sense, as you said, as so many are insulin resistant in the U.S. and still a minority has diabetes. And then there are those who aren't (apparently, since this usually isn't tested) particularly insulin resistant who do have (apparent) Type II diabetes. I have heard that South Asians often develop diabetes when thin.

Is it clear that these defects are from toxic exposures, or are some inherited? I know you can only go so far back to find out, so it's possible the initial genetic defect was caused by an exposure.

In addition to the estrogen-like substances in plastics, have you researched arsenic much? It has been epidemiologically associated with diabetes and is a widespread contaminant of drinking water worldwide. Less so in the U.S., but a threat to those who get their drinking water from wells. I am going to get ours tested.

In laboratory animals, arsenic does cause a type of diabetes and appears to affect mitochondrial function.

Congratulations on your novel! I know what I'm getting Mom for her birthday.

Jenny said...


One of the genes was associated with insulin resistance, but more with secretion failures.

I have written about arsenic as a cause of diabetes on this page:

You Did Not Eat Your Way to Diabetes.