How Does Type 2 Develop?

Gretchen Becker Health Guide
  • A nifty study of a personal genome was published in the journal Cell last week. What makes it fascinating is that the subject of the study apparently developed type 2 diabetes during the study and the researchers were able to follow its progress.


    You can see a popular summary of the study or read the full article if you wish.


    During the course of the study, the subject had a couple of viral infections, and after the second infection, his blood glucose (BG) levels, which were normal at the beginning of the study, started rising. Because of this, the researchers started monitoring his BG levels and A1c more often than before.

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    The subject had nonfasting BG levels below 100 mg/dL when the study began, and after the second viral infection, they went up to about 150 and he was diagnosed with diabetes. At this point, his hemoglobin A1c was 6.4. According to the article, the man then changed his lifestyle, and by the end of the study, his BG levels were below 100 again, and his A1c was 4.7.


    Unfortunately, because the focus of the study was on the genes, although the article says that most BG measurements were "at a fixed time after a constant meal," they don't reveal what the time or meal were. A BG of 150 mg/dL at 60 minutes after a carby meal wouldn't be very unusual in a nondiabetic, especially during or after an infection. A BG of 150 2 hours after a noncarby meal would.


    The final A1c of 4.7 is interesting because it agrees with Dr. Richard K Bernstein's assertion that really normal A1cs are in the 4s, not just below 6.


    You can see a graph of the BG results in the full article.


    According to the popular press article, "with dramatic changes in diet, exercise and a regular low dose of aspirin, his glucose levels dropped back down." Unfortunately, they didn't say what the dramatic changes in diet consisted of. Presumably the aspirin was because he showed signs of inflammation after the infection.


    The genetic analysis showed that the man was at high risk for type 2 diabetes, but the article in Cell said there was no evidence of insulin resistance when his BG levels were rising. Type 2 diabetes is currently defined by insulin resistance, so it's not clear why he was given that diagnosis except that he was at risk for the disease and was still producing insulin. The man had no anti-GAD or anti-islet antibodies, which suggests that he didn't have early type 1 diabetes, although it's always possible that antibodies could show up later.


    The man had a body mass index (BMI) of 24 at the beginning of the study and reduced that to 22 by the end of the study, which is consistent with type 2 caused by being slightly overweight. But then why no insulin resistance?


    It's unlikely that he had MODY as the more common MODY genes are known and should have been picked up by the detailed genetic analysis.


    Maybe non-type 2, non-type 1 would have been a better diagnosis.


    However, despite the lack of anti-GAD or anti-islet antibodies, the man did show some autoantibodies to a protein involved with insulin binding. There seems to be more and more evidence that what is currently diagnosed as type 2 diabetes includes some autoimmune antibodies as well as insulin resistance.


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    Another possibility is that it's normal for BG levels to go up after infections even in people without diabetes. We know that they can go up dramatically in people with diabetes after an infection or stress like steroid hormone therapy. Could it be that they increase in nondiabetics as well but then go down when the infection is gone? Most people without diabetes don't measure their BG levels regularly, especially when they're sick with an infection.


    Type 1 diabetes sometimes follows a viral infection, but it has never been noted before that type 2 diabetes can also be caused by a viral infection. After the second infection, the results showed an increase in the activity of about 2000 genes and a decrease in the activity of about 2000 other ones, indicating how complex this all is.


    It's pure chance that the subject of this study turned out to have a risk for type 2 diabetes and developed high BG levels during the study. One assumes he will continue to monitor his BG levels over time and perhaps more in-depth studies will be done.


    If so, we may get more clues about how diabetes develops. If you have high risk of type 2, can you keep it away forever if it's caught early and you modify your lifestyle? Does taking an anti-inflammatory drug like aspirin in the early stages help?


    Are there common types of diabetes that we are not yet aware of? This man has none of the antibodies characteristic of type 1 but none of the insulin resistance characteristic of type 2. He did have evidence of some autoantibodies that would affect insulin secretion. In type 2 diabetes, is the insulin resistance sometimes not commonly present in the early stages of the disease?  Or is this an unusual form of the disease?


    We know that nondiabetic relatives of people with type 2 often do have insulin resistance. But no one agrees on which occurs first: insulin resistance or a defect in insulin secretion. It's possible that different people develop the disease in different ways.


    Whatever, this is a fascinating study that should lead to breakthroughs in our understanding of this complex disease.



Published On: March 19, 2012