Sunday, March 18, 2012

Type 2 Diabetes or Just the Flu?

In a recent Cell article the senior researcher argues that he has identified that he has a gene for Type 2 Diabetes and after such a discovery he finds that after a year of monitoring he has actually shown signs of Type 2 Diabetes. Then after dieting it goes away. Really?

The details on the subject were:

Monitoring of glucose levels and HbA1c revealed the onset of T2D as diagnosed by the subject’s physician (day 369, Figures 2A and 2C). The subject lacked many known factors associated with diabetes (nonsmoker; BMI = 23.9 and 21.7 on day 0 and day 511, respectively) and glucose levels were  normal for the first part of the study. However, glucose levels elevated shortly after the RSV infection (after day 301) extending for several months (Figure 2D). High levels of glucose were further  confirmed using glycated HbA1c measurements at two time points (days 329, 369) during this period (6.4% and 6.7%, respectively). After a dramatic change in diet, exercise and ingestion of low doses of acetylsalicylic acid a gradual decrease in glucose (to 93 mg/dl at day 602) and HbA1c levels to 4.7% was observed. Insulin resistance was not evident at day 322. The patient was negative for anti-GAD and anti-islet antibodies, and insulin levels correlated well with the fasted and nonfasted states (Figure S2C), consistent with T2D. These results indicate that a genome sequence can be used to estimate disease risk in a healthy individual, and by monitoring traits associated with that disease, disease markers can be detected and the phenotype treated.

Now the patient did not have a high BMI but did have two viral attacks. As is well known obesity effects an immune like inflammatory response, chronically, and a viral attack has an acute response, yet both will effect an increase in blood glucose, often not suppressed by insulin in those with the potential for Type 2 Diabetes.

The problem with this patient is shown in Figure 2D where the blood glucose is measured, in somewhat of a random manner and where HbA1c is also shown. The problem is as follows. HbA1c reflects red cell glucose uptake and red cells last for 90 days and thus to reflect an elevated HbA1c one would expect an elevated level for 90 days, or at least for 45. That is not the case for this patient on the upside or on the down side. Also the glucose spikes as one would expect to find in acute inflammatory diseases or use of steroids and the like. In addition to do this properly one should be measuring fasting blood sugar and two hour post prandial and accounting for such exogenous factors as travel, stress, and excess carb intake. None of this was done.

The author and patient in question was interviewed and he states:

"I was not aware of any type-2 diabetes in my family and had no significant risk factors," said Snyder, "but we learned through genomic sequencing that I have a genetic predisposition to the condition. Therefore, we measured my blood glucose levels and were able to watch them shoot up after a nasty viral infection during the course of the study."

As a result, he was able to immediately modify his diet and exercise to gradually bring his levels back into the normal range and prevent the ongoing tissue damage that would have occurred had the disease gone undiagnosed. 

The question is was this Type 2 Diabetes or the flare seen in those with low insulin control when in an acute inflammatory state. Could one use a steroid to induce this and then watch blood sugar rise equally as well, and perhaps use that as a diagnostic. After all we use a classic glucose tolerance test to measure insulin response.

How does one define Type 2 Diabetes? Is it low insulin response? Or is it HbA1c above say 6.0? Is it the "potential" for the disease or the disease. The problem here in my opinion is that the author and patient in question may have crossed the line by saying if you have a genetic predisposition then you have the disease. A very slippery slope in my opinion.