Good Calories, Bad Calories

Over the years, prominent diabetologists and endocrinologists—from Yalow and Berson in the 1960s through Dennis McGarry in the 1990s—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.

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.^*118

Neel suggested three scenarios of these insulin-secretory responses that could constitute 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 the refined carbohydrates/over-alimentation of many civilized diets.” Genetic variations in these responses would determine how long it would be before obesity or diabetes appears, and which of the two appears first. The one important caveat about these three scenarios, Neel added, is that they “should not be thought of as mutually exclusive or as exhausting the possible biochemical and physiological sequences” that might induce obesity and/or diabetes once populations take to eating modern Western 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 sensitivity 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-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.

This scenario is the most difficult to sort out clinically, because when these investigators measure insulin resistance in humans they invariably do so on a whole-body level, which is all the existing technology allows. Any disparities between the responsiveness of fat and muscle tissue to insulin cannot be measured. This is critical, because for the past thirty-five years the American Diabetes Association has recommended that diabetics eat a diet relatively rich in carbohydrates based on the notion that this makes them more sensitive to insulin, at least temporarily, so the diet appears to ameliorate the diabetes. This effect was initially reported in 1971, by the University of Washington endocrinologists Edwin Bierman and John Brunzell,^*119 who then waged a lengthy and successful campaign to persuade the American Diabetes Association to recommend that diabetics eat more carbohydrates rather than less. If Neel’s third scenario is correct, however, a likely explanation for why carbohydrate-rich diets appear to facilitate blood-sugar control after meals is that they increase the insulin sensitivity of the fat cells specifically, while the muscle tissue remains insulin-resistant.