Good Calories, Bad Calories

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.”

Only Newburgh’s interpretation of the evidence, however (and only the obesity research community in the United States), survived the war years. Afterward, clinical investigators would state unambiguously—as Edward Rynearson and Clifford Gastineau did in their 1949 clinical manual Obesity…—that insulin puts weight on only by lowering blood sugar to the point where patients overeat to remain conscious. This hypoglycemia was considered a rare pathological condition, one with no relevance to everyday life, and so only in that condition were elevated insulin levels to be considered a causal agent in weight gain and common obesity.

In 1992, the University of Texas diabetologist Denis McGarry published an article in Science with the memorably idiosyncratic title “What If Minkowski Had Been Ageusic? An Alternative Angle on Diabetes.” The German physiologist Oskar Minkowski was the first to identify the role of the pancreas in diabetes. The word “ageusic” refers to a condition in which the sense of taste is absent. “Legend has it,” McGarry wrote, “that on a momentous day in 1889 Oskar Minkowski noticed that urine collected from his pancreatectomized^*110 dogs attracted an inordinate number of flies. He is said (by some) to have tasted the urine and to have been struck by its sweetness. From this simple but astute observation he established for the first time that the pancreas produced some entity essential for control of the blood sugar concentration, which, when absent, resulted in diabetes mellitus.” Some thirty years later, when Frederick Banting and Charles Best in Toronto identified insulin as the relevant pancreatic secretion, McGarry wrote, they naturally did so in the context of Minkowski’s observations about blood sugar, and thus “diabetes mellitus has been viewed ever since as a disorder primarily associated with abnormal glucose metabolism.” But if Minkowski had been ageusic and so missed the sweet taste of the urine, McGarry speculated, he might have noticed instead the smell of acetone, which is produced in the liver from the conversion of fat into ketone bodies. “He would surely have concluded that removal of the pancreas causes fatty acid metabolism to go awry,” McGarry wrote. “Extending this hypothetical scenario, the major conclusion of Banting’s work might have been that the preeminent role of insulin is in the control of fat metabolism.”

McGarry’s parable focused on diabetes, but the point he made extends to virtually everything having to with insulin. Just as diabetes has traditionally been perceived as a disorder of carbohydrate metabolism—even though fat metabolism is also dysfunctional—insulin has always been perceived as a hormone that primarily functions to regulate blood sugar, though, as we’ve discussed, it regulates the storage and use of fat and protein in the body as well. Because blood sugar could be measured easily through the first half of the twentieth century, but not yet the fats in the blood, the focus of research rested firmly on blood sugar.