July 5, 2006

A Diabetes Gene Found in Type 2 Jews

Lately I've learned that there is one gene that appears to cause both MODY-1 and a kind of Type 2 diabetes. What's important about it, is that when it's broken, it mostly affects post-meal insulin secretion, not your fasting blood sugar. That means if your defect lies in this gene, you're going to have the kind of diabetes that is tougher to diagnose because most doctors just do a fasting test.

Eventually people with this particular kind of diabetes do become fully diabetic, because the elevated postprandial blood sugars will destroy beta cells over time. But, if I am reading the research reports correctly, with this kind of diabetes you are more likely to end up with the cardiovascular complications (i.e. heart attack) which come at lower A1cs, rather than the classic, high A1c, complications of retinopathy and kidney failure.

This might sound great, except that often the first symptom that you have developed a cardiovascular diabetic complication is a fatal heart attack. It's little consolation to know that you're going to die in your 60s with no retinopathy!

The gene is HNF4-a. I originally noticed it because it both the MODY-1 gene AND it several studies have found problems with it occur with some frequency in Jewish Type 2s. It is also found frequently in Finnish type 2s and in several other ethnic groups.

The HNF4-a gene secretes a protein that switches on other genes in the pancreas and liver, and among those genes it affects are those that cause insulin secretion in response to a glucose load and those that produce aldehyde dehydrogenase, the enzyme which breaks down alcohol, and which, if you don't have it, gives you "Asian flush". It also affects prothrombin which helps your blood coagulate, and some of the genes that affect lipid production.

There are dozens of different genetic errors which can affect HNF4-a. How your diabetes will behave depends on what exactly is broken.

This is fascinating stuff and still not much reported on. It is not possible to get screening for this gene outside of studies right now, unless you have severe symptoms of MODY-1.

Just remember that the typical pattern for this kind of diabetes is that for years your post-meal blood sugars will be high--over 200 mg/dl when you eat a meal containing a normal amount of carbohydrate, while your fasting blood sugar and A1c test may be normal or only mildly elevated. If you are Jewish and suspect you might be diabetic. Make sure your doctor tests your post-meal blood sugars, not just the fasting blood sugar or you might be falsely assured you are "just fine" when you aren't.