Thursday, December 9, 2010

Obesity and Type 2 Diabetes: Blame the Genes!

In a recent article in NEJM the author present a long list of genes associated with Obesity and Type 2 Diabetes. Now he states:

The increasing global prevalence of type 2 diabetes is tied to rising rates of obesity — in part a consequence of social trends toward higher energy intake and reduced energy expenditure. However, the mechanisms that underlie individual differences in the predisposition to obesity remain obscure.

 Now obesity in almost all cases is an energy balance issue, which he alludes to:

Input - Output = Net Accumulation
1 pound = 3500 kcal

That is it, plain and simple. Perhaps there is some imbalance that changes the second equation, a bit, but not by much. We know we can get a mouse to have a predisposition to just sit in their cage and eat and eat, that is the genetic changing of some hypothalamic set point. You see as fundamentally an engineer, one of the most annoying features of engineers in med school is their unending asking of why! The Liberal Arts types never ever understood that.

He continues:

For type 2 diabetes and obesity, the discovery of causal genes has followed three main waves. 

The first wave consisted of family-based linkage analyses (see the Glossary) and focused candidate-gene studies....

second wave of discovery involved a switch to tests of association. Although intrinsically more powerful than linkage analysis, association analysis suffers from the disadvantage that the signal can be detected only if one examines the causal variant itself or a nearby marker with which it is tightly correlated. Until the advent of methods that enabled genomewide surveys of association, researchers were therefore obliged to direct their attention to specific candidate variants or genes of interest...

The third, and most successful, wave of discovery has been driven by systematic, large-scale surveys of association between common DNA sequence variants and disease. The first demonstration that unbiased discovery efforts could reveal new insights into the pathogenesis of type 2 diabetes resulted from identification of the association between type 2 diabetes and variants within TCF7L2 .

I would agree that Type 2 Diabetes has a genetic predisposition. His chart later in his paper does outline what can happen. There is a small group of people who get Type 2 Diabetes late in life and are not obese. The insulin production just drops and that is most likely a genetic factor also associated with aging, like many cancers are. However that is uncommon, not necessarily rare, but uncommon. There may be a few who through genetic reasons somehow mess up one of the basic laws of physics and can add weight on even a 900 kcal a day diet. I have never seen a study on this but I would admit it may be possible. But for the most part, food in is weight on. If one has a genetic predisposition for overwhelming the pancreas and its insulin producing ability then there you go!

The problem for the most part starts with self selected obesity. A human cannot and should not blame their genes. We prepared a report on this almost half a year ago after much debate. This paper just muddies the water by almost always linking Obesity and Type 2 Diabetes as genetic. Humans have free will, and we are influenced both positively and negatively by what we eat. We can in many ways control obesity. That in almost all cases reduces glucose loads and even with diminished insulin production reduces or eliminates Type 2 Diabetes.

The above is the list of genes for obesity from the article. They are all ex post facto and for the most part no one ever told the patients to just stop eating.

The author ends with:

An improved understanding of fundamental disease mechanisms is already emerging; this will underpin future therapeutic advances. But the expansion of personalized medicine beyond monogenic forms of disease awaits a more complete description of predisposition. The boundaries of personalized medicine will be much clearer in a few years, after large-scale genomewide resequencing efforts (now under way) provide a systematic, comprehensive description of the relations between genome sequence variation and major clinical phenotypes.

We see in this article the extension of the concept of the Victim Society, it is not my fault it is my genes, so we all must spend our money making them better because it is never their fault!