Good Calories, Bad Calories

Noorden wrote, “but instead of excreting the sugar in the urine, they transfer it to the fat-producing parts of the body, whose tissues are still well prepared to receive it.” As the ability to burn blood sugar for energy further deteriorates and “the storage of the carbohydrates in the fat masses [also suffers] a moderate and gradually progressing impairment,” sugar appears in the urine, and the patient becomes noticeably diabetic. Using the modern terminology, this is the route from obesity to Type 2 diabetes. “The connection between diabetes and obesity,” as von Noorden put it, “ceases in the light of my theory to be any longer an enigmatical relation, and becomes a necessary consequence of the relationship discovered in the last few years between carbohydrate transformation and formation of fat.”

After the discovery of insulin in 1921, the potential role of insulin as a fattening hormone would become a long- running controversy. Those physicians who believed, as Louis Newburgh did without reservation, that obesity was an eating disorder, rejected the idea that insulin could fatten humans, if for no other reason than that this suggested the existence of a defective hormonal mechanism that could lead to obesity. The evidence, however, suggested exactly that. When insulin was injected into diabetic dogs in the laboratory, or diabetic human patients in the clinic, they put on weight and body fat. As early as 1923, clinicians were reporting that they had successfully used insulin to fatten chronically underweight children—patients who would be diagnosed today as anorexic—and to increase their appetite in the process.

In 1925, Wilhelm Falta, a student of von Noorden and a pioneer of the science of endocrinology in Europe, began using insulin therapy to treat underweight and anorexia in adults as well. Falta had argued, even in the pre- insulin era, that whatever pancreatic hormone was absent or defective in diabetes governed not only the use of carbohydrates for fuel, but also the assimilation of fat in adipose tissue. “A functionally intact pancreas is necessary for fattening,” Falta wrote. He also noted that the only way to fatten anyone efficiently was to include “abundant carbohydrates in the diet.” Otherwise, the body would adjust to eating “very much more than the appetite really craves,” by either lessening appetite still further or creating “an increased demand for movement.” The only way to get around this natural balance of intake and expenditure is by increasing the secretion from the pancreas. “We can conceive,” Falta speculated, “that the origin of obesity may receive an impetus through a primarily strengthened function of the insular apparatus, in that the assimilation of larger amounts of food goes on abnormally easily, and hence there does not occur the setting free of the reactions that in normal individuals work against an ingestion of food which for a long time supersedes the need.” After the discovery of insulin, Falta reported that giving it to patients would increase their appetite for carbohydrates specifically, and the carbohydrates in turn would stimulate the patient’s own insulin production. It would create a vicious cycle— although, in the case of anorexic and underweight patients, one that might return them to a normal appetite and normal weight.

By the 1930s, clinicians throughout Europe and the United States had taken to using insulin therapy to fatten their pathologically underweight patients. These patients could gain as much as six pounds a week eating meals “rich in carbohydrates” after receiving injections of small doses of insulin, reported Rony, who used insulin therapy on seven anorexic patients in his own clinic; it worked on five of them. None of these patients had been able to gain weight, but now they added an average of twenty pounds each in three months. “All reported a more or less pronounced increase of appetite,” Rony wrote, “and occasional strong feelings of hunger.” Until the 1960s, insulin was also used to treat severe depression and schizophrenia. Among the more renowned patients subjected to what was then called insulin-shock therapy was the Princeton mathematician John Nash, made famous by Sylvia Nasar’s 1998 biography, A Beautiful Mind. Its efficacy for treating mental illness was debatable, but as Nasar observed, “all the patients gained weight.” Another memorable recipient was the poet Sylvia Plath, who experienced a “drastic increase in weight” on the treatment. (In her autobiographical novel, The Bell Jar, Plath’s protagonist, Esther Greenwood, gains twenty pounds on insulin therapy—“I just grew fatter and fatter,” she says.)

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.”

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