Good Calories, Bad Calories

Regarding the potential dangers of sugar in the diet, it is important to keep in mind that fructose is converted more efficiently into glycerol phosphate than is glucose. This is another reason why fructose stimulates the liver so readily to convert it to triglycerides, and why fructose is considered the most lipogenic carbohydrate. Fructose, however, does not stimulate the pancreas to secrete insulin, so glucose is still needed for that purpose. This suggests that the combination of glucose and fructose—either the 50–50 mixture of table sugar (sucrose) or the 55–45 mixture of high-fructose corn syrup—stimulates fat synthesis and fixes fat in the fat tissue more than does glucose alone, which comes from the digestion of bread and starches.

It is important also to know that the fat cells of adipose tissue are “exquisitely sensitive” to insulin, far more so than other tissues in the body. This means that even low levels of insulin, far below those considered the clinical symptom of hyperinsulinemia (chronically high levels of insulin), will shut down the flow of fatty acids from the fat cells. Elevating insulin even slightly will increase the accumulation of fat in the cells. The longer insulin remains elevated, the longer the fat cells will accumulate fat, and the longer they’ll go without releasing it.

Moreover, fat cells remain sensitive to insulin long after muscle cells become resistant to it. Once muscle cells become resistant to the insulin in the bloodstream, as Yalow and Berson explained, the fat cells have to remain sensitive to provide a place to store blood sugar, which would otherwise either accumulate to toxic levels or overflow into the urine and be lost to the body. As insulin levels rise, the storage of fat in the fat cells continues, long after the muscles become resistant to taking up any more glucose. Nonetheless, the pancreas may compensate for this insulin resistance, if it can, by secreting still more insulin. This will further elevate the level of insulin in the circulation and serve to increase further the storage of fat in the fat cells and the synthesis of carbohydrates from fat. It will suppress the release of fat from the fat tissue. Under these conditions—lipid trapping, as the geneticist James Neel described it—obesity begins to look preordained. Weights will plateau, as Dennis McGarry suggested in Science in 1992, only when the fat tissue becomes insulin-resistant as well, or when the fat deposits enlarge to the point where the forces working to release the fat and burn it for fuel—such as the increased concentration of fatty acids inside the fat cells—once again balance out the effect of the insulin itself.

By the mid-1960s, four facts had been established beyond reasonable doubt: (1) carbohydrates are singularly responsible for prompting insulin secretion; (2) insulin is singularly responsible for inducing fat accumulation; (3) dietary carbohydrates are required for excess fat accumulation; and (4) both Type 2 diabetics and the obese have abnormally elevated levels of circulating insulin and a “greatly exaggerated” insulin response to carbohydrates in the diet, as was first described in 1961 by the Johns Hopkins University endocrinologists David Rabinowitz and Kenneth Zierler.

The obvious implication is that obesity and Type 2 diabetes are two sides of the same physiological coin, two consequences, occasionally concurrent, of the same underlying defects—hyperinsulinemia and insulin resistance. This was precisely what von Noorden had suggested in 1905 with his diabetogenous-obesity hypothesis, even down to the notion that obesity would naturally result when muscle tissue becomes resistant to taking up glucose from the circulation before fat tissue does. Now the science had caught up to the speculation. “We generally accept that obesity predisposes to diabetes; but does not mild diabetes predispose to obesity?” as Yalow and Berson wrote in 1965. “Since insulin is a most lipogenic agent, chronic hyperinsulinism would favor the accumulation of body fat.”

When Yalow and Berson measured individual insulin and blood-sugar responses to the consumption of carbohydrates, they reported that even lean, healthy subjects exhibit “great biologic variation” in what they called the “insulin-secretory responses.” In other words, we secrete more or less insulin in response to the same amount of carbohydrates, or our insulin is more or less effective at lowering blood sugar or at promoting fat accumulation, or it remains elevated in the circulation for longer or shorter periods of time. And because variations of less than 1 percent in the partitioning of calories either for fuel or for storage as fat could lead to the accumulation of tens of pounds of excess fat over a decade, it would take only infinitesimal variations in these “insulin-secretory responses” to mark the difference between leanness and obesity, and between health and diabetes.