One of the few attempts, if not the only one, to measure the insulin sensitivity of fat cells and muscle cells separately in human subjects was made by the University of Vermont investigator Ethan Sims, in his experimental obesity studies of the late 1960s. Sims and his colleagues surgically removed fat samples from their subjects before, during, and after the periods of forced overeating and weight gain. They reported that high-carbohydrate diets had the unique ability to increase the insulin sensitivity of fat cells, and particularly so in fat cells that were already large and overstuffed. They had no similar effect, however, on the insulin resistance of the muscle tissue.

If this observation is correct, it means carbohydrates are uniquely capable of prolonging this lipid-trapping condition by keeping the fat cells sensitive to insulin when they might otherwise become insulin-resistant. This might lower blood-sugar levels temporarily and delay or improve the appearance of diabetes—or “mask” the diabetes, as von Noorden put it—but would do so at the cost of increasing fat accumulation and obesity. Sims’s observation suggests that Neel’s third scenario for the genesis of obesity and diabetes was astute, and it suggests that a carbohydrate-rich diet might temporarily improve the symptoms of diabetes only by furthering the fattening process. Sims’s studies have not been repeated in humans, but they have been reproduced and confirmed in animals. Brunzell says he refuses to believe that Sims got this measurement correct, but he also says that he has never tried to do the measurements himself because they’re too difficult. But the question of whether Sims got it right requires a definitive answer. Without one, there’s no way to know if the ADA recommendations have been helping diabetics or hurting them, let alone to understand the pathology of obesity and diabetes. The impact on the public health could be immense.

Through the 1970s, physiologists and biochemists worked out the mechanisms by which insulin and other hormones regulate not just the amount of fat we carry, but its distribution throughout the body, independent of how much we might happen to eat or exercise. By the end of the decade, they could explain at both a hormonal and an enzymatic level all the vagaries of what Julius Bauer had called lipophilia, or the “exaggerated tendency of some tissues to store fat.”

A critical enzyme in this fat-distribution process is known technically as lipoprotein lipase, LPL, and any cell that uses fatty acids for fuel or stores fatty acids uses LPL to make this possible. When a triglyceride-rich lipoprotein passes by in the circulation, the LPL will grab on, and then break down the triglycerides inside into their component fatty acids. This increases the local concentration of free fatty acids, which flow into the cells—either to be fixed as triglycerides if these cells are fat cells, or oxidized for fuel if they’re not. The more LPL activity on a particular cell type, the more fatty acids it will absorb, which is why LPL is known as the “gatekeeper” for fat accumulation.