Insulin’s fattening properties have long been particularly obvious to diabetics and the physicians who treat them. Because diabetics will gain weight with insulin therapy, even those who are obese to begin with, clinicians have always had difficulty convincing their patients to continue taking their insulin. When they start to fatten, they naturally want to slack off on the therapy, so the need to control blood sugar competes with the desire to remain lean, or at least relatively so. This is also a clinical dilemma, because the weight gain will also increase the risk of heart disease. In the chapter on insulin therapy in the 1994 edition of Joslin’s Diabetes Mellitus, the Harvard diabetologist James Rosenzweig portrayed this insulin-induced weight gain as uncontroversial: “In a number of studies of patients treated with insulin for up to 12 months, weight gains of 2.0 to 4.5 kg [roughly four to ten pounds] were reported….” This weight gain, he wrote, then leads to “the often-cited vicious cycle of increased insulin resistance, leading to the need for more exogenous insulin, to further weight gain, which increases the insulin resistance even more.”*109

If insulin fattens those who receive it, as the evidence suggests, then how does it work? The prewar European clinicians who used insulin therapy to treat anorexics accepted the possibility, as Falta suggested, that the hormone can directly increase the accumulation of fat in the fat tissues. Insulin was “an excellent fattening substance,” Erich Grafe wrote in Metabolic Diseases and Their Treatment. Grafe believed that the fattening effect of insulin is likely “due to improved combustion of carbohydrate and increased synthesis of glycogen and fat.” In the United States, however, the conventional wisdom came from Louis Newburgh and his colleagues at the University of Michigan. When insulin increases weight, Newburgh said, it does so either through the power of suggestion—a placebo effect—or by a reduction of blood sugar to the point where the patient eats to avoid very low blood sugar (hypoglycemia) and the accompanying symptoms of dizziness, weakness, and convulsions.

When Rony reviewed the experimental and clinical reports in 1940, he considered any conclusion to be premature. Because obese individuals tend to have high blood sugar, rather than low, Rony said, it was hard to imagine how insulin, which lowered blood sugar, could cause obesity. “Still,” he noted, “it might be possible that in obese subjects a latent or conditional form of hyperinsulinism exists which would promote fat deposition without causing hypoglycemia.” This was not supported by conclusive evidence, he added, and so it “remains, for the time being, at best a working hypothesis.”