GCBC Reference Check ~ Part II of ? ~ Insulin Resistance (again)

I have previously discussed the fact that in 2001, Keith Frayn laid out a progression of insulin resistance diametrically opposed to that proposed by Taubes in GCBC.  (See:  Insulin Resistance ~ Taubes v. Frayn)

This work, however wasn't referenced in GCBC, so this post addresses what Frayn had to say about the topic in the 1995 text that was:  Metabolic Regulation.

Let's review some GCBC excerpts:

The muscle cells become insulin-resistant in response to the "repeated high levels of insulinemia that result from excessive ingestion of highly refined carbohydratesand/or over-alimentation," but the fat cells fail to compensate.  They remain stubbornly sensitive to insulin.  So, as Neel explained, the fat tissue accumulates more and more fat, but "mobilization of stored fat would be inhibited." Now the accumulation of fat in the adipose tissue drives the vicious cycle.

"Over the years, prominent diabetologists and endocrinologists -- from Yalow and Berson in the 1960's through Dennis McGarry in the 1990's -- have speculated on this train of causation from hyperinsulinemia to Type 2 diabetes and obesity. Anything that increases insulin, induces insulin resistance, and induces the pancreas to compensate by secreting still more insulin, will also lead to an excess accumulation of body fat.

Taubes clearly presents the progression of this as follows:

Carb injestion --> insulin secretion --> hyperinsulinemia --> peripheral insulin resistance & fat accumulation --> eventual adipose insulin resistance.

Although not in great detail, Frayn does address insulin resistance on p. 243  of Metabolic Regulation:

Many of the metabolic changes in obesity seem to stem from the associated insulin resistance ...

Why does insulin resistance arise in obesity?  The answer is not entirely clear.  Many changes in insulin action have been shown in animal models of obesity:  a decrease in the number of insulin receptors on the cell surface, decreased activity of the insulin receptor tyrosine kinase, and changes in intracellular metabolic pathways which render them less sensitive to insulin.  To some extent there is a vicious spiral:  for instance, insulin resistance leads to inappropriately elevated non-esterified fatty acid concentrations in the fed state and these impair muscle glucose utilization by the glucose-fatty acid cycle.

OK, now there is certainly some ambiguity in Frayn's statements in this text, but this is on the two pages directly preceding the quoted "dieting is difficult" statement Frayn makes.  The description of IR, at the very least, does not jive with what Taubes presents, and the highlighted statement above would indicate a direction of causality directly opposite.  If Taubes had followed just Frayn's work to present day (being 2007 at the time), he would have come across a deluge of literature that contradicted his own pre-determined conclusion biased by his hypothesis.  Specifically, this 2001 Review:  Adipose tissue and the insulin resistance syndrome.  Taubes did actually look at some research of the 90's (McGarry), did none of that quote any of the references from that Frayn review paper, almost all of which date in the mid 90's or earlier.  

We know Taubes spoke with Keith Frayn sometime recently as regards the G3P part of his theories.  One wonders if he was one of those "clinical investigators and public-health authorities, those still active in research and those retired, who might point me to research I might have missed or provide further information and details on experimental methods and interpretation of the evidence"  Taubes consulted in writing GCBC.

One really has to ask themselves what Taubes did during his five years researching GCBC.  How much of Metabolic Regulation did he bother to read?  If he didn't read the entire book, surely he at least read Chapter 10 Energy Balance and Body Weight Regulation in its entirety?    Did he not bother to pursue contradictory evidence, or worse, did he come across it and simply choose to ignore it, knowingly perpetuating flawed theories?  This inquiring mind would love to know.

Just continuing to do my part in holding Taubes to the high standards he sets for others.