According to Good Calories, Bad Calories
by Gary Taubes, gwa is right on target in her post!
From page 395:
One of the more insightful of these analyses was by the geneticist James Neel in 1982, when he "revisited" his thrifty-gene hypothesis and rejected the idea (which has since been embraced so widely by public-health authorities and health writers) that we evolved through periods of feast and famine to hold on to fat. Neel suggested three scenarios of these insulin-secretory responses that could consitiute a predisposition to obesity and/or Type 2 diabetes--each of which, he wrote, would be a physiological "response to the excessive glucose pulses that result from refined carbohydrates/over-alimentation of many civilized diets.".......
The first of these scenarios was what Neel called a "quick insulin trigger." By this Neel meant that the insulin-secreting cells in the pancreas are hypersensitive to the appearance of glucose in the bloodstream. They secrete too much insulin in response to the rise in blood sugar during a meal; that encourages fat deposition and induces a compensatory insulin resistance in the muscles. The result will be a vicious circle: excessive insulin secretion stimulates insulin resistance, which stimulates yet more insulin secretion. In this scenario, we gain weight until the fat cells eventually become insulin-resistant. When the "overworked" pancreatic cells "lose their capacity to respond" to this insulin resistance, Type 2 diabetes appears.
In Neel's second scenario, there is a tendency to become slightly more insulin-resistant than would normally be the case when confronted with a given amount of insulin in the circulation. So even an appropriate insulin response to the waves of blood sugar that appear during meals will result in insulin resistance, and that in turn requires a ratcheting up of the insulin response. Once again, the result is the vicious cycle.
Neel's third scenario is slightly more complicated, but there's evidence to suggest that this one comes closest to reality. Here an appropriate amount of insulin is secreted in response to the "excessive glucose pulses" of a modern meal, and the response of the muscle cells to the insulin is also appropriate. The defect is in the relative insensitivity of muscle and fat cells to the insulin. The muscle cells become insulin-resistant in response to the "repeated high levels of insulinemia that result from excessive ingestion of highly refined carbohydrates and/or over-alimentaion," 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.
There is so much good info in Taubes' book; once again I urge everyone to add it to your library.